The practice of using herbal supplements dates back thousands of years. Today, there is a renewal in the use of herbal supplements among American consumers. However, herbal supplements are not for everyone. In fact, some herbal products may cause problems for people treatments for chronic ailments. Because they are not subject to scrutiny by the FDA or other governing agencies, the use of herbal supplements is controversial. 

Herbal supplements are products made from plants for use in the treatment and management of certain diseases and medical conditions. Many prescription drugs and over-the-counter medicines are also made from plant derivatives. These products contain only purified ingredients and, unlike herbal supplements, are closely regulated by the FDA. Herbal supplements may contain entire plants or plant parts. Herbal supplements come in all forms: dried, chopped, powdered, capsule, or liquid, and can be used in various ways. Please address the followings: 

Discuss advantages and disadvantages of dietary supplements, including adverse reactions, drug-drug interactions, drug-food interactions, and specific laboratory issues that may arise from using these products. 

Discuss the position of the FDA and other governmental agencies on over the counter herbal supplements. Support your post with at least 2 evidenced-based guidelines published within the last 5 years. 

The posts must be referenced as mentioned above and written in APA 6th edition format. 

Books: 

Teri Moser Woo & Marylou V. Robinson (4th ed.). Pharmacotherapeutics for  

Advanced Practice Nurse Prescribers. Davis   

Chapters 7, 10, 12, 13: Cultural &  

Ethnic Influences in  

Pharmacotherapeutics; Herbal &  

Nutritional Therapies;  

Pharmacoeconomics; Over-the 

Counter Medications  

Recommended reading: Adams et al.  

chapters 7,8,10,11 

FOURTH EDITION
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vii
T
ORGANIZATION
The Foundation
PREFACE
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Pharmacotherapeutics With Single Drugs
Pharmacotherapeutics
With Multiple Drugs
Special Drug Treatment Considerations
FEATURES
Unit I chapters
Unit II chapters
Unit III chapters
viii
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Unit IV chapters
SUMMARY
ACKNOWLEDGMENTS
ix
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xi
MARYLOU V. ROBINSON, PHD, FNP-CTERI MOSER WOO, RN, PHD,
CPNP-PC, FAANP
ABOUT THE AUTHORS
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xiii
Lorena C. Guerrero, PhD, MN, ARNP, FNP-BC
Anne Hedger, DNP, ACNP-CS, ANP-CS,
CPNP-AC, ENP-BC, CCRN
Leila N. Jones, MSN, BA, RN
Jennifer Jordan, RPh, PharmD, BCPS
Tracy Klein, PhD, FNP, ARNP, FAANP, FRE,
FAAN
Ashim Malhotra, BPharm, PhD
Theresa Mallick-Searle, MS, RN-BC, ANP-BC
Erin Anderson, MSN, CPNP
Cally Bartley, MSN, FNP-C
Jane M. Carrington, PhD, RN
Diana L. Dewell, ARNP, ANP
Gina Dobbs, MSN, CRNP
Krista Estes, DNP, FNP-C
Teral Gerlt, MS, RN, WHCNP-E
Theresa Granger, PhD, ARNP, FNP
CONTRIBUTORS
3827_FM_i-xviii 03/07/15 10:26 AM Page xiii

Fujio McPherson, RN, DAOM, MSN, FNP, LAC
Benjamin J. Miller, PhD, MN, ARNP, FNP, ACNP
Anne E. Morgan, PharmD
Joan Nelson, DNP, RN
Patricia Nodine PhD, CNM
Kristen Lambert Osborn, MSN, CPNP–AC/PC
James L. Raper, DSN, CRNP, JD, FAANP, FAAN
Peter J. Rice, PharmD, PhD, BCPS
Laura Rosenthal, DNP, ACNP
Ruth Schaffler, PhD, FNP
Tracy Scott, DNP, FNP
Kathy Shaw, DNP, RN, CDE
R. Brigg Turner, PharmD, BCPS
Connie Valdez, PharmD, MSEd, BCPS
Mary Weber, PhD, PMHNP-BC, FAANP
xiv
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xv
Joan Parker Frizzell, PhD, CRNP, ANP-BC
Tammy Gilliam, DNP, APRN-BC, FNP
Cathy R. Kessenich, DSN, ARNP, FAANP
Pamela King, PhD, APRN, FNP, PNP
Angela I. Kulesza, DNP, NP-C
Christine Nelson-Tuttle, DNS, RN, PNP-BC
David G. O’Dell, DNP, ARPN, FNP-BC
JoAnne Pearce, MS, PhDc, RN, APRN
Marianne Adam, PhD, RN, CRNP
Nancy Beckham, PhD, FNP-C
Christopher W. Blackwell, PhD, ARNP, ANP-BC,
AGACNP-BC, CNE
Sharon Chalmers, PhD, CNE, APRN-BC
Patsy E. Crihfield, DNP, APRN, FNP-BC,
PMHNP-BC, PMHS
Linda Dayer-Berenson, PhD, MSN, CRNP, CNE,
FAANP
Carolynn A. DeSandre, PhD, CNM, FNP-BC
Abimbola Farinde, PharmD, MS
REVIEWERS
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Julie Ponto, PhD, RN, ACNS-BC, AOCNS
Susan Quisenberry, DNP, APRN, CNP, FNP-C
Sandra Restaino, DNP, NP-C, FAANP, CSC
Maria Rosen, PhD, RN, PNP-BC
Kathleen R. Sheikh, MSN, FNP-BC
Jennifer Sipe, RN, MSN, APRN-BC
Angela Thompson, PhD, PharmD
Diane Yorke, MSN, MBA, PhD, RN, CPNP
xvi
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xvii
Chapter 16 Drugs Affecting the Cardiovascular
and Renal Systems 295
Marylou V. Robinson, PhD, FNP-C
Chapter 17 Drugs Affecting the Respiratory
System 361
Teri Moser Woo, PhD, CPNP
Chapter 18 Drugs Affecting the
Hematopoietic System 415
Teri Moser Woo, PhD, CPNP and
Kristen Lambert Osborne MSN, CPNP AC/PC
Chapter 19 Drugs Affecting the Immune
System 447
Teri Moser Woo, PhD, CPNP
Chapter 20 Drugs Affecting the
Gastrointestinal System 497
Teri Moser Woo, PhD, CPNP
Chapter 21 Drugs Affecting the Endocrine
System 541
Marylou Robinson, PhD, FNP
and Kathy Shaw, DNP, RN, CDE
Chapter 22 Drugs Affecting the
Reproductive System 615
Diana L. Dewel, ARNP, ANP
Chapter 23 Drugs Affecting the
Integumentary System 647
Cally Bartley, MSN, FNP-C
Chapter 24 Drugs Used in Treating Infectious
Diseases 691
Jennifer Jordan, RPh, PharmD, BCPS;
R. Brigg Turner, PharmD, BCPS; and
Teri Moser Woo, PhD, CPNP
Chapter 25 Drugs Used in Treating
Inflammatory Processes 801
Teri Moser Woo, PhD, CPNP
Chapter 26 Drugs Used in Treating Eye
and Ear Disorders 837
Teri Moser Woo, PhD, CPNP
UNIT III. PHARMACOTHERAPEUTICS
WITH MULTIPLE DRUGS 863
Chapter 27 Anemia 865
Teri Moser Woo, PhD, CPNP and
Kristen Osborn MSN, CPNP AC/PC
Chapter 28 Chronic Stable Angina and
Low-Risk Unstable Angina 881
Laura D. Rosenthal, DNP, ACNP
Chapter 29 Anxiety and Depression 897
Mary Weber, PhD, PMHNP-BC, FAANP
and Krista Estes, DNP, FNP-C
UNIT I. THE FOUNDATION 1
Chapter 1 The Role of the Nurse Practitioner
as Prescriber 3
Teri Moser Woo, PhD, CPNP and
Marylou V. Robinson, PhD, FNP-C
Chapter 2 Review of Basic Principles
of Pharmacology 11
Peter J. Rice, PharmD, PhD, BCPS
Chapter 3 Rational Drug Selection 29
Teri Moser Woo, PhD, CPNP
Chapter 4 Legal and Professional Issues in
Prescribing 37
Tracy Klein, PhD, FNP
Chapter 5 Adverse Drug Reactions 51
Connie A. Valdez, PharmD, MSEd, BCPS;
Anne E. Morgan, PharmD; and
Peter J. Rice, PharmD, PhD, BCPS
Chapter 6 Factors That Foster Positive
Outcomes 61
Marylou V. Robinson, PhD, FNP-C and
Teri Moser Woo, PhD, CPNP
Chapter 7 Cultural and Ethnic Influences in
Pharmacotherapeutics 75
Lorena C. Guerrero, PhD, MS, ARNP, FNP-BC and
Leila M. Jones, RN, MSN
Chapter 8 An Introduction to
Pharmacogenomics 103
Ashim Malhotra, BPharm, PhD
Chapter 9 Nutrition and Neutraceuticals 115
Teri Moser Woo, PhD, CPNP
Chapter 10 Herbal Therapy and Nutritional
Supplements 129
Fujio McPherson, RN, DAOM, MSN, FNP, LAC
Chapter 11 Information Technology and
Pharmacotherapeutics 151
Jane M. Carrington, PhD, RN
Chapter 12 Pharmacoeconomics 159
Teri Moser Woo, PhD, CPNP
Chapter 13 Over-the-Counter Medications 165
Teri Moser Woo, PhD, CPNP
UNIT II. PHARMACOTHERAPEUTICS
WITH SINGLE DRUGS 171
Chapter 14 Drugs Affecting the Autonomic
Nervous System 173
Tracy Scott, DNP, FNP
Chapter 15 Drugs Affecting the Central
Nervous System 225
Teri Moser Woo, PhD, CPNP
CONTENTS
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Chapter 30 Asthma and Chronic Obstructive
Pulmonary Disease 913
Benjamin J. Miller, PhD, MN, ARNP, FNP, ACNP
Chapter 31 Contraception 943
Teri Gerlt, MS, RN, WCHNP
Chapter 32 Dermatological Conditions 957
Teri Moser Woo, PhD, CPNP
Chapter 33 Diabetes Mellitus 991
Kathy Shaw, DNP, RN, CDE and
Marylou Robinson, PhD, FNP-C
Chapter 34 Gastroesophageal Reflux
and Peptic Ulcer Disease 1021
Teri Moser Woo, PhD, CPNP
Chapter 35 Headaches 1035
Theresa Mallick-Searle, MS, RN-BC, ANP-BC
Chapter 36 Heart Failure 1063
Laura Rosenthal, DNP, ACNP
Chapter 37 Human Immunodeficiency Virus
Disease and Acquired
Immunodeficiency Syndrome 1081
James Raper, DSN, CRNP, JD, FAANP, FAAN and
Gina Dobbs, MS, CRNP
Chapter 38 Hormone Replacement Therapy
and Osteoporosis 1103
Marylou V. Robinson, PhD, FNP-C
Chapter 39 Hyperlipidemia 1129
Marylou V. Robinson, PhD, FNP-C
Chapter 40 Hypertension 1155
Marylou V. Robinson, PhD, FNP-C
Chapter 41 Hyperthyroidism and
Hypothyroidism 1179
Marylou V. Robinson, PhD, FNP
Chapter 42 Pneumonia 1195
Anne Hedger, DNP, ACNP-CS, ANP-CS,
CPNP-AC, ENP-BC, CCRN
Chapter 43 Smoking Cessation 1205
Benjamin J. Miller, PhD, MN, ARNP, FNP, ACNP
Chapter 44 Sexually Transmitted
Diseases and Vaginitis 1217
Theresa Granger, PhD, ARNP, FNP
Chapter 45 Tuberculosis 1237
Teri Moser Woo, PhD, CPNP
Chapter 46 Upper Respiratory Infections,
Otitis Media, and Otitis Externa 1253
Teri Moser Woo, PhD, CPNP
Chapter 47 Urinary Tract Infections 1267
Erin Anderson, MSN, CPNP
UNIT IV. SPECIAL DRUG TREATMENT
CONSIDERATIONS 1281
Chapter 48 Women as Patients 1283
Priscilla M. Nodine, PhD, CNM
Chapter 49 Men as Patients 1303
James Raper, DNS, CRNP, JD, FAANP, FAAN
Chapter 50 Pediatric Patients 1321
Teri Moser Woo, PhD, CPNP
Chapter 51 Geriatric Patients 1337
Joan M. Nelson, DNP, RN
Chapter 52 Pain Management: Acute
and Chronic Pain 1351
Ruth L. Schaffler, PhD, FNP
INDEX 1373
xviii
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UNIT I
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3
CHAPTER 1
Teri Moser Woo • Marylou Robinson
Other APRNs
Physician Assistants
Nurses Not in Advanced Practice Roles
CANADIAN NURSE PRACTITIONER PRACTICE, 8
CURRENT ISSUES AND TRENDS IN HEALTH CARE
AND THEIR EFFECT ON PRESCRIPTIVE AUTHORITY, 8
Autonomy and Prescriptive Authority
Interdisciplinary Teams
Level of Education of Team Members
Reimbursement
N
ROLES OF REGISTERED NURSES
IN MEDICATION MANAGEMENT
Registered Nurses
ROLES OF REGISTERED NURSES IN MEDICATION
MANAGEMENT, 3
Registered Nurses
Advanced Practice Registered Nurses
ROLES AND RESPONSIBILITIES OF APRN
PRESCRIBERS, 4
ADVANCED KNOWLEDGE, 4
BENEFITS OF AN APRN AS PRESCRIBER, 5
CLINICAL JUDGMENT IN PRESCRIBING, 5
COLLABORATION WITH OTHER PROVIDERS, 7
Physicians
Pharmacists
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Advanced Practice Registered Nurses
ROLES AND RESPONSIBILITIES
OF APRN PRESCRIBERS
ADVANCED KNOWLEDGE
4
3827_Ch01_001-010 01/07/15 12:33 PM Page 4

BENEFITS OF AN APRN AS
PRESCRIBER
CLINICAL JUDGMENT IN
PRESCRIBING
5
3827_Ch01_001-010 01/07/15 12:33 PM Page 5

Is There a Clear Indication for Drug Therapy?
What Drugs Are Effective in Treating
This Disorder?
What Is the Goal of Therapy With This Drug?
Under What Conditions Is It Determined That
a Drug Is Not Meeting the Goal and a Different
Therapy or Drug Should Be Tried?
Are There Unnecessary Duplications With
Other Drugs That the Patient Is Already Taking?
Would an Over-the-Counter Drug Be Just
as Useful as a Prescription Drug?
What About Cost?
Where Is the Information to Answer These
Questions?
6
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7
COLLABORATION WITH OTHER
PROVIDERS
Physicians
Pharmacists
Other APRNs
Physician Assistants
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8
Nurses Not in Advanced Practice Roles
CANADIAN NURSE PRACTITIONER
PRACTICE
CURRENT ISSUES AND TRENDS IN
HEALTH CARE AND THEIR EFFECT
ON PRESCRIPTIVE AUTHORITY
Autonomy and Prescriptive Authority
Interdisciplinary Teams
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9
Level of Education of Team Members
Reimbursement
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10
REFERENCES
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11
CHAPTER 2
Peter J. Rice
Intracellular Receptors Regulating Gene Expression
Enzymes
Drug Action at Receptors
Disease States and Receptors
Non-receptor Mechanisms
PHARMACOKINETICS, 18
Absorption
Distribution
Metabolism
Drug Interactions
Excretion
SUMMARY, 27
PHARMACOLOGY—THE STUDY
OF DRUGS
HOW NEW DRUGS ARE DEVELOPED
PHARMACOLOGYTHE STUDY OF DRUGS, 11
HOW NEW DRUGS ARE DEVELOPED, 11
DRUG RESPONSES, 12
Dose–Response Curves
Types of Drug Responses
Expressing Drug Responses
Drug Selectivity
Drug Responses in the Real World
Brand Versus Generic Drugs
RECEPTORS, 15
Ion Channel Receptors
Receptors Coupled to G Proteins
Transmembrane Receptors
3827_Ch02_011-028 01/07/15 12:33 PM Page 11

DRUG RESPONSES
Dose–Response Curves
Types of Drug Responses
12
BOX 2–1 IDEAL DRUG PROPERTIES
• Convenient route of administration, probably taken
by mouth
• Established dosage
• Immediate onset of action
• Produces a single desired biological action
• Produces no unwanted effects
• Convenient duration of action
• Dosage unaffected by loss of kidney or liver function
or by disease state
• Improves quality of life
• Prolongs patient survival
3827_Ch02_011-028 01/07/15 12:33 PM Page 12

Expressing Drug Responses
13
BOX 2–2 EXAMPLES OF GRADED
RESPONSES TO DRUGS
• Blood pressure
• Heart rate
• Diuresis
• Bronchodilation
• FEV1
• Pain (scale 1–10)
• Coma score
BOX 2–3 EXAMPLES OF QUANTAL
RESPONSES TO DRUGS
• Convulsions
• Pregnancy
• Rash
• Sleep
• Death
Potency differences
Drug concentration (Molar)
R
es
po
ns
e
pe
rc
en
ta
ge
o
f m
ax
im
um
100
75
50
25
0
10-9 10-8 10-7 10-6 10-5
Figure 2–1. Concentration–effect curves for three drugs that differ
in potency (i.e., the dose or concentration required to produce an
effect). The drug concentration on the x-axis is expressed in molar units,
representing the number of molecules in each liter of solution. The
graded response is expressed as a percentage of maximum effect.
3827_Ch02_011-028 01/07/15 12:33 PM Page 13

Drug Selectivity
Drug Responses in the Real World
Brand Versus Generic Drugs
14
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15
RECEPTORS Ion Channel Receptors
“Real world” drug responses
Drug concentration (µg/mL)
R
es
po
ns
e
pe
rc
en
ta
ge
o
f m
ax
im
um
100
75
50
25
0
0.1 1 10 100 1000
Desired
effect
Placebo
effect
Toxicity
Ineffective
Figure 2–2. Theoretical representation of how drugs produce effects
in clinical practice. Drug concentration (x-axis) increases from left to
right. Some patients will respond at low dosages, either because of
the placebo effect or sensitivity to the drug. As drug concentrations
increase, greater numbers of patients will respond favorably but
some will also respond adversely. At some dosage or concentration,
the presence of toxic effects precludes the use of higher doses in
patients.
3827_Ch02_011-028 01/07/15 12:33 PM Page 15

Receptors Coupled to G Proteins
16
ACh
Na+
K+
ACh
Figure 2–3. The nicotinic acetylcholine (ACh) receptor comprises five
subunits that come together to form an ion channel receptor. When
ACh binds to two sites on the receptor, the ion channel opens to let
sodium (Na+) and potassium (K+) cross the cell membrane to initiate
a response.
Drug
G protein
Effector
protein
Figure 2–4. G-protein–coupled receptors are proteins that cross the
cell membrane 7 times, creating a pocket in which drugs can interact.
Bound drugs may stimulate the receptor to release a G protein that
can interact with various effector proteins to produce physiological
responses.
3827_Ch02_011-028 01/07/15 12:33 PM Page 16

Transmembrane Receptors
Intracellular Receptors Regulating
Gene Expression
17
Drug
-p
-pp-
-p
-pp-
Figure 2–5. The insulin receptor is prototypical of tyrosine kinase re-
ceptors. These receptors are brought together by extracellular drug
binding (insulin in the case of the insulin receptor), which activates
the intracellular enzyme tyrosine kinase. Tyrosine kinase receptors
activate one another by adding a phosphorus (P) to select sites on
cellular proteins, which in turn activates a physiological response.
Steroid
hormone
RNA
DNA
Protein
Receptor
Figure 2–6. Steroid hormones diffuse through the cell membrane
to interact with steroid receptors in the cytoplasm. The hormone–
receptor pair relocates to the nucleus, where it can interact with
DNA to effect RNA transcription and the synthesis of proteins.
Binding
“Transition state” Products
Enzyme
Substrate
Active site
Enzyme Enzyme
Figure 2–7. Enzymes bind to substrates and speed up biochemical
reactions. Enzymes can serve as receptors to the substrate, which
binds at the active site, or to drugs that control enzyme activity
through binding at a different site.
Enzymes
Drug Action at Receptors
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Non-receptor Mechanisms
PHARMACOKINETICS
Absorption
Disease States and Receptors
18
BOX 2–4 EFFECTS OF ROUTE OF
ADMINISTRATION
• Compliance
• Bioavailability
• Onset of action
• Duration of action
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19
Site of Administration
Bioavailability
Peak Blood Levels
Parenteral Administration
Oral Administration
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Distribution
Properties That Affect Distribution
20
Time (hours)
Bl
oo
d
le
ve
l (
ar
bi
tra
ry
)
100
80
60
40
20
0
0 63 129 15 18 21 24
20 min
60 min
120 min
Figure 2–8. Blood levels for the same dose absorbed with peak-times
of 20 minutes, 60 minutes, or 120 minutes. Rapid absorption results
in faster effect, but blood levels are higher with a greater likelihood of
toxicity.
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21
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Metabolism
Phase I and Phase II Metabolism
22
Extracellular fluid
~1/3 of total bodyPl
as
m
a
Extracellular fluid
~1/3 of total bodyPl
as
m
a
Intracellular fluid
~2/3 of total
body water
Extracellular fluid
~1/3 of total bodyPl
as
m
a
Intracellular fluid
~2/3 of total
body water
Intracellular fluid
~2/3 of total
body water
A B
Concentration = amount/volume
C
Phenobarbital
Phase 1 Phase 2
O
O
O
NH
NH
p-hydroxy-phenobarbital
O
OHO
O
NH
NH
p-OH-phenobarbital
glucuronide
O
OOO
O
HO
OH
OHHO
O
NH
NH
Figure 2–10. Metabolism of phenobarbital. Phase I metabolism adds an –OH to the molecule. A water-soluble glucuronide molecule is linked
to this site during phase II metabolism.
Figure 2–9. Drug concentration in
the plasma following administra-
tion depends on the volume of dis-
tribution. If a drug is confined to
plasma (A), then plasma concentra-
tion will be higher compared with
distribution into extracellular fluid
(B) or intracellular fluid (C). Dilution
in increasing volumes is shown by
shading of the areas containing a
drug.
3827_Ch02_011-028 01/07/15 12:33 PM Page 22

Cytochrome P450
Metabolism and Half-Life
23
BOX 2–5 DRUG-METABOLIZING ENZYMES
(LISTED IN ORDER OF
IMPORTANCE)
CYP3A
CYP2C
CYP1A
CYP2E
CYP2D
3827_Ch02_011-028 01/07/15 12:33 PM Page 23

Patterns of Metabolism
Drug Interactions
24
Metabolism
Dr
ug
a
ct
ivi
ty
Active
drug
Prodrug
Active
metabolite
Inactive
metabolite
Phase 1
metabolism
Phase 2
metabolism
Active
metabolite
(greater solubility)
Inactive
metabolite
(greater solubility)
Figure 2–11. Typical effect of metabolism (solid arrows) on drug
activity. Prodrugs are metabolized to active drugs that can undergo
phase I and phase II metabolism, with metabolites varying in activity,
compared with the parent drug, and in solubility, which increases the
likelihood of renal elimination. Sometimes metabolism produces
unusual effects (dashed arrows), such as drug metabolites that retain
drug activity or accumulate in the body.
3827_Ch02_011-028 01/07/15 12:33 PM Page 24

Excretion
Renal Excretion
25
Glomerulus
Proximal tube Distal tube
Loop of
Henle
Reabsorption
Secretion Collecting
duct
Urine
Figure 2–12. Diagram of the nephron, the functional unit of the
kidney. Blood vessels flowing into the glomerulus provide blood,
which is filtered into the lumen, the inner opening of the nephron. As
fluid passes along the nephron, transporters can either reabsorb
drugs (dark arrow) back into the blood or secrete (light arrow) drugs
from blood into the lumen.
3827_Ch02_011-028 01/07/15 12:33 PM Page 25

Tubular Reabsorption
Tubular Secretion
Renal Excretion of Drugs
Biliary Excretion
Other Sites of Excretion
26
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SUMMARY
REFERENCES
27
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29
CHAPTER 3
Teri Moser Woo
Therapeutic Factors
Safety
Cost
Patient Factors
Provider Factors
INFLUENCES ON RATIONAL PRESCRIBING, 34
Pharmaceutical Promotion
When Prescribing Recommendations Change
THE PROCESS OF RATIONAL DRUG PRESCRIBING, 29
Define the Patient’s Problem
Specify the Therapeutic Objective
Choose the Treatment
Start the Treatment
Educate the Patient
Monitor Effectiveness
DRUG FACTORS INFLUENCING DRUG SELECTION, 32
Pharmacodynamic Factors
Pharmacokinetic Factors
T
THE PROCESS OF RATIONAL DRUG
PRESCRIBING
Define the Patient’s Problem
3827_Ch03_029-036 01/07/15 12:32 PM Page 29

Specify the Therapeutic Objective
Choose the Treatment
Start the Treatment
30
BOX 3–1 WORLD HEALTH
ORGANIZATION’S SIX-STEP
MODEL OF RATIONAL
PRESCRIBING
Step Description
Step 1 Define the patient’s problem.
Step 2 Specify the therapeutic objective.
Step 3 Choose the treatment.
Step 4 Start the treatment.
Step 5 Educate the patient.
Step 6 Monitor effectiveness.
Source: de Vries, T. P., Henning, R. H., Hogerzeil, H. V., & Fresle,
D. A. (1994). Guide to good prescribing. WHO/DAP/94.11.
Geneva, Switzerland: World Health Organization.
Diagnosis Treatment
Treatment
script
Analytic
Slow, conscious,
systematic,
evidence-based,
novice
Non-analytic
Fast, unconscious,
heuristic,
experience-based,
expert
Figure 3–1. Hypothetical model of therapeutic reasoning. Bissessur
et al, 2009.
BOX 3–2 THE ‘I Can PresCribE A Drug’
MNEMONIC
Indication
Contraindications
Precautions
Cost/Compliance
Efficacy
Adverse effects
Dose/Duration/Direction
Source: Iglar, K., Kennie, N., & Bajcar, J. (2007). I Can PresCribE a
Drug: Mnemonic-based teaching of rational prescribing. Family
Medicine, 39(4), 236–240.
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Educate the Patient
Monitor Effectiveness
31
CLINICAL PEARL
Drugs don’t work in patients who don’t take them.
—C. Everett Koop, MD
Table 3–1 Example of the Use of the ‘I Can PresCribE a Drug’ Mnemonic
3827_Ch03_029-036 01/07/15 12:32 PM Page 31

DRUG FACTORS INFLUENCING
DRUG SELECTION
Pharmacodynamic Factors
Pharmacokinetic Factors
Therapeutic Factors
Safety
Cost
32
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33
Patient Factors
Previous Adverse Drug Reactions
Health Beliefs
Current Drug Therapy
Patient Age
Pregnancy
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Provider Factors
Ease of Prescribing or Monitoring
Formularies
INFLUENCES ON RATIONAL
PRESCRIBING
Pharmaceutical Promotion When Prescribing Recommendations
Change
34
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REFERENCES
35
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37
CHAPTER 4
Tracy Klein
Systemic Solutions to Problems of Controlled Substance
Prescribing
STATE LAW, 45
Jurisdiction
Writing and Transmitting the Prescription
ETHICAL ASPECTS OF PRESCRIBING, 47
Informed Consent
Prescribing for Self, Family, or Friends
Sale of Pharmaceuticals and Supplements
NURSE PRACTITIONER ROLE OUTSIDE THE UNITED
STATES, 48
FEDERAL DRUG LAW, 37
History
U.S. Food and Drug Administration Regulatory Jurisdiction
The New Drug Approval Process
Official Labeling
Controlled Substance Laws
Controlled Substance Prescribing Precautions
CONTROLLED SUBSTANCE MISUSE: PRESCRIBER
EDUCATION, 43
Behavioral Red Flags
Pressure to Prescribe
Enabling
When You Suspect a Patient Is Misusing Medications
FEDERAL DRUG LAW
History
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U.S. Food and Drug Administration
Regulatory Jurisdiction
The New Drug Approval Process
Preclinical Research
38
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Clinical Studies
39
Adverse reaction
reporting
Preclinical
Investigation
(Stage 1)
Range:
1–3 years
Average:
18 months
Range:
2–10 years
Average:
5 years
Range:
2 months to 10 years
Average:
24 months
Initial
Synthesis
Animal
Testing
Inspections
Surveys/
sampling/
testing
Clinical
Investigation
(Stage 2)
Clinical Phase I Trials
Short
Term
Long Term
Clinical Phase III Trials
Clinical Phase II Trials
NDA
Review
(Stage 3)
Postmarketing
studies
(Stage 4)
30-day safety review NDA submitted NDA approved
Industry time FDA time
Figure 4–1. New drug development timeline.
3827_Ch04_037-050 01/07/15 12:31 PM Page 39

Bioavailability Studies
Regulatory Review: New Drug Application
Accelerated Approval of a New Drug
Application
Postapproval Research
Official Labeling
Off-Label Use
40
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Controlled Substance Laws
Controlled Substance Prescribing
Precautions
41
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42
Table 4–1 Controlled Drug Schedules
Schedule Controls Required Drug Examples
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CONTROLLED SUBSTANCE MISUSE:
PRESCRIBER EDUCATION
Behavioral Red Flags
43
BOX 4–1 WEB RESOURCES FOR LEGAL
AND ETHICAL ISSUES IN
PRESCRIBING
National Cancer Institute Clinical Trials: http://www
.cancer.gov/clinicaltrials
National Institute of Health Clinical Trials: http://
clinicaltrials.gov/ct2/home
FDA MedWatch: http://www.fda.gov/Safety/MedWatch/
default.htm
U.S. Drug Enforcement Administration: http://www
.dea.gov
National Provider Identifier Number application:
https://nppes.cms.hhs.gov/NPPES/Welcome.do
National Council of State Boards of Nursing: www
.ncsbn.org
Institute for Safe Medication Practices: www.ismp.org
Opioid Assessment, Medication Agreement and Man-
agement Tools: http://www.painedu.org/tools
.asp?Tool=11
Table 4–2 Behaviors More and Less Predictive of Addiction
Probably More Predictive Probably Less Predictive
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Pressure to Prescribe
Enabling
When You Suspect a Patient
Is Misusing Medications
Communication Barriers
Communication Skills
Systemic Solutions to Problems of
Controlled Substance Prescribing
44
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Prescription Drug Monitoring Programs
STATE LAW
Jurisdiction
45
PRESCRIBING TIPS
A few prescribing tips can help the practitioner reduce
environmental facilitation of prescription misuse. First,
collect and document a complete history and examina-
tion before prescribing controlled substances. Do not
rely on patient-supplied history, x-rays, or medical records
to confirm your assessment—obtain this information di-
rectly from the primary source. Passik and Weinreb
(2000) advise use of the four “A’s” to guide initial and on-
going assessment of medication efficacy: (1) analgesia
measurement by use of pain scales or other assessment
tools, (2) activities of daily living (ADLs) as measured by
levels of physical and psychological functioning, (3) ad-
verse effects, and (4) abuse issues.
Prescribe limited quantities without refills on a first
visit, allowing additional time for patient assessment and
confirmatory documentation. Educate medical and as-
sistive staff in reinforcement of consistent clinic policies
and procedures related to scheduling, forms, urine drug
screening, records review and release, and refills. It is
not uncommon for patients who do misuse substances
to quickly identify the “weak link” among the treatment
team and focus their energies on this person or process.
Standardize expectations regarding after-hours calls, use
of multiple providers, and weekend or early refills and
post them where they are readily available.
Patients covered by insurance plans, including Med-
icaid and Medicare, can be limited to one pharmacy or
one prescriber through their payment plan. Case man-
agers can often be utilized to help review and manage
medication use and advocate for access to additional
options for pain management and control. Other tips in-
clude prescribing generic, longer-acting formulations of
drugs that have less street value and writing out the
quantity prescribed rather than using only numerals,
which can be altered.
Medication Agreements
3827_Ch04_037-050 01/07/15 12:31 PM Page 45

Writing and Transmitting
the Prescription
The Prescription Format
46
Health and Wellness Clinic
5000 N. Willamette Blvd.
Portland, Oregon
503-555-1111
Anita Lee Wynne PhD, FNP-C Teri Woo, CPNP
Jane Doe DOB: 4/18/01
Amoxicillin 250 mg per 5 mL
Disp: 300 mL. Give pediatric dosing spoon.
Sig: 15 mL po bid X 10 days for otitis media.
No refills
Teri Woo, CPNP
Wt. 48 lb
Date:
Figure 4–2. Sample prescription.
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What May Be Prescribed
State-Specific Elements
Electronic Prescribing and Secure Prescribing
ETHICAL ASPECTS OF PRESCRIBING
Informed Consent
47
Figure 4–3. Sample prescription for controlled substance.
Date:
Health and Wellness Clinic
5000 N. Willamette Blvd.
Portland, Oregon
503-555-1111
Anita Lee Wynne PhD, FNP-C Teri Woo, CPNP
John Doe DOB: 6/5/51
Oxycodone 5 mg
Disp: 30 (thirty)
Sig: 1 tablet q4–6h pm back pain.
Do not drive or use hazardous machinery until response
is known. May produce drowsiness. Do not exceed
6 tablets per day.
No refills
Anita Lee Wynne, FNP-C DEA # on file in pharmacy
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Prescribing for Self, Family, or Friends
Sale of Pharmaceuticals
and Supplements
NURSE PRACTITIONER ROLE
OUTSIDE THE UNITED STATES
48
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REFERENCES
49
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51
CHAPTER 5
Connie A. Valdez • Anne E. Morgan • Peter J. Rice
Gender
Drug Interactions
Medical Conditions
DETECTION AND ASSESSMENT OF ADRS, 56
Responding to ADRs and Warnings
Narranjo ADR Probability Scale
ADR REPORTING, 57
SUMMARY, 59
A
MECHANISTIC CLASSIFICATION
OF ADRS
MECHANISTIC CLASSIFICATION OF ADRS, 51
TIMERELATED CLASSIFICATION OF ADRS, 53
DOSERELATED ADRS, 54
SEVERITY OF ADRS, 54
COMMON CAUSES OF ADRS, 55
RISK FACTORS, 55
Genetics
Age
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52
Table 5–1 Pharmacological Adverse Drug Reactions Table 5–2 Immune-Mediated Adverse Drug
Reactions
3827_Ch05_051-060 01/07/15 12:30 PM Page 52

TIME-RELATED CLASSIFICATION
OF ADRS
53
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DOSE-RELATED ADRS
SEVERITY OF ADRS
54
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55
COMMON CAUSES OF ADRS
RISK FACTORS
Genetics
Age
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Gender
Drug Interactions
Medical Conditions
DETECTION AND ASSESSMENT
OF ADRS
56
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Responding to ADRs and Warnings
Naranjo ADR Probability Scale
ADR REPORTING
57
Table 5–3 Naranjo Adverse Drug Reaction Scoring
Naranjo Adverse Drug Reaction Scoring Yes No Not Known Score
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Figure 5–1. The FDA MedWatch form provides a mechanism for health professionals to report ADRs. Source: U.S. Food and Drug Administration,
www.fda.gov/Safety/MedWatch
58
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SUMMARY
REFERENCES
59
BOX 5–1 COMMON DRUGS WITH REMS
• Isotretinoin
• Extended-release and long-acting opioid analgesics
• Rosiglitazone
• Testosterone
• Verenicline
• Metoclopramide
• Mifepristone
• Buprenorphine and naloxone
• Naltrexone
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60
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61
CHAPTER 6
Marylou V. Robinson • Teri Moser Woo
FINANCIAL IMPACTS, 67
Cost Versus Complications
Out-of-Pocket Versus Insurance
Family Versus Self
Generic Versus “New and Improved” Brand Name
Public and Private Assistance
COMMUNICATION DIFFICULTIES, 68
Non–English Speakers and Interpreters
Speech and Hearing Issues
COMMUNICATION BETWEEN PROVIDERS, 68
PATIENT’S RESPONSIBILITIES, 68
MEASURING ADHERENCE, 69
Patient Reports
Clinical Outcomes
Pill Counts
Refill Records
Biological and Chemical Markers
Medication Adherence Scales
PREDICTORS OF ADHERENCE, 70
SUMMARY, 70
OVERVIEW OF NONADHERENCE, 62
Intentional Versus Nonintentional Nonadherence
ADVERSE DRUG REACTIONS, 62
ASYMPTOMATIC CONDITIONS, 62
CHRONIC CONDITIONS, 63
KNOWLEDGE DEFICIT AND PATIENT
PERCEPTION, 63
Keys to Patient Education
Health and Cultural Beliefs
Medical Terminology Literacy
Written Handouts
COGNITIVE IMPAIRMENT
AND PSYCHIATRIC ILLNESS, 65
Longer-Acting Drugs
Use of Reinforcements
CAREGIVER’S ROLES, 65
The Pediatric Patient
Caregiver’s Quality of Life
Behavioral Therapy
COMPLEXITY OF DRUG REGIMEN
AND POLYPHARMACY, 66
Personalized Drug Schedules
Simplifying the Regimen
T
3827_Ch06_061-074 01/07/15 12:38 PM Page 61

OVERVIEW OF NONADHERENCE Intentional Versus Nonintentional
Nonadherence
ADVERSE DRUG REACTIONS
ASYMPTOMATIC CONDITIONS
62
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CHRONIC CONDITIONS
KNOWLEDGE DEFICIT AND PATIENT
PERCEPTION
63
Table 6–1 Factors Contributing to Medication
Adherence With Chronic Illness
3827_Ch06_061-074 01/07/15 12:38 PM Page 63

Keys to Patient Education
Health and Cultural Beliefs
Medical Terminology Literacy
Written Handouts
64
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COGNITIVE IMPAIRMENT AND
PSYCHIATRIC ILLNESS
Longer-Acting Drugs
Use of Reinforcements
CAREGIVER’S ROLES
The Pediatric Patient
Caregiver’s Quality of Life
Behavioral Therapy
65
3827_Ch06_061-074 01/07/15 12:38 PM Page 65

COMPLEXITY OF DRUG REGIMEN
AND POLYPHARMACY
Personalized Drug Schedules
Simplifying the Regimen
Sensory or Mobility Challenges
Cues as Reminders
66
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Scheduling Visits for Medication Follow-Up
FINANCIAL IMPACTS
Cost Versus Complications
Out-of-Pocket Versus Insurance
Family Versus Self
Generic Versus “New and Improved”
Brand Name
67
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Public and Private Assistance
COMMUNICATION DIFFICULTIES
Non–English Speakers
and Interpreters
Speech and Hearing Issues
COMMUNICATION BETWEEN
PROVIDERS
PATIENT’S RESPONSIBILITIES
68
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MEASURING ADHERENCE
Patient Reports
Clinical Outcomes
Pill Counts
Refill Records
Biological and Chemical Markers
Medication Adherence Scales
69
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!
PREDICTORS OF ADHERENCE
SUMMARY
70
BOX 6–1 MORISKY SIMPLIFIED
SELF-REPORT MEASURE
OF ADHERENCE
Scoring: 0 = High Adherence; 1–2 Medium Adherence;
3–4 Low Adherence
1. Do you ever forget to take your medicine?
2. Are you careless at times about taking your
medicine?
3. When you feel better do you sometimes stop
taking your medicine?
4. Sometimes if you feel worse when you take your
medication, do you stop taking it?
Adapted from Jani, A. A., Stewart, A., Nolen, R. D., & Tavel, L.
(2002). Medication adherence and patient education. Florida
AIDS Education & Training Center. In HIV/AIDS primary care
guide (p 87). Gainesville, FL: University of Florida Press.
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71
Patient
Five spheres of influence and multiple factors that impact
adherence and self-management. M. Robinson, 2015.
Personal Influences
Psychological well-being
Self-efficacy
Health beliefs
Spiritual beliefs
Prior success
Willingness
Ability to trust
Health System Influences
Access to care
Availability of specialty care
Self-management support
Continuity of care providers
Continuity of insurance plan coverage
Wait times
Insurance coverage for medications
Pharmacy access
Automatic renewals
Personalize messaging
concerning adherence
Biomedical Influences
Timing of diagnosis
Duration of impact
Degree of physical impact
Comorbidities
Polypharmacy
Functional impact
Anticipated trajectory of impact
Frequency of dosing
Drug-to-drug interactions
Socioeconomic Influences
Occupational support
Occupational demands
Financial stability
Educational level
Impact of costs on prior lifestyle
Impact of costs on other family members
Cost of medications
Transportation access
Cultural barriers and considerations
Religious barriers and considerations
Rural locations
Living arrangements
Housing stability
Legal status
Formal dependency status
Interpersonal Influences
General external social support
Familial support
Familiarity with others
with similar circumstances
Changes in above factors
after diagnosis
Language barriers
Patient provider relationship
Patient provider stability
Figure 6–1. Five spheres of influence and multiple factors that impact adherence and self-management. Robinson, M. (2015). Derived from
Wheeler, K. J., Roberts, M. E., & Neiheisel, M. B. (2014). Medication adherence part two: Predictors of nonadherence and adherence. Journal
of the American Association of Nurse Practitioners,26(4), 225–232.
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REFERENCES
72
Table 6–2 Factors Influencing Adherence
General Health Status Medical History, Nutritional Assessment, and Comorbidities
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73
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75
CHAPTER 7
Lorena C. Guerrero • Leila M. Jones
ASIAN AMERICANS, 87
Cultural Factors
Racial Differences in Drug Pharmacokinetics and
Response
NATIVE HAWAIIAN/PACIFIC ISLANDERS, 90
Cultural Factors
Racial Differences in Drug Pharmacokinetics and
Response
HISPANIC AMERICANS, 92
Cultural Factors
Racial Differences in Drug Pharmacokinetics and
Response
NONHISPANIC WHITES, 95
SUMMARY, 96
U.S. DEMOGRAPHICS, 75
U.S. Demographic Groupings
Health Disparities in the United States
Cultural Influences on Care
TRANSCULTURAL NURSING CARE THEORIES, 77
STANDARDS OF CULTURAL COMPETENCY, 77
ELIMINATING HEALTH DISPARITIES, 79
ETHNOPHARMACOLOGY, 79
AFRICAN AMERICANS, 80
Cultural Factors
Racial Differences in Drug Pharmacokinetics and Response
AMERICAN INDIAN/ALASKA NATIVE GROUPS, 84
Cultural Factors
Racial Differences in Drug Pharmacokinetics and Response
T U.S. DEMOGRAPHICS
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U.S. Demographic Groupings
Health Disparities in the United States
Cultural Influences on Care
76
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TRANSCULTURAL NURSING CARE
THEORIES
STANDARDS OF CULTURAL
COMPETENCY
77
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78
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ELIMINATING HEALTH DISPARITIES
ETHNOPHARMACOLOGY
79
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AFRICAN AMERICANS
Cultural Factors
Demographics
Education and Employment
Family Relationships
Health-Care Utilization
80
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Health Status and Other Biological Variables
81
3827_Ch07_075-102 01/07/15 12:38 PM Page 81

Health Beliefs and Practices
82
3827_Ch07_075-102 01/07/15 12:38 PM Page 82

Racial Differences in Drug
Pharmacokinetics and Response
83
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AMERICAN INDIAN/ALASKA
NATIVE GROUPS
Cultural Factors
Demographics
Education and Employment
84
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Family Relationships
Health-Care Utilization
Health Status and Other Biological Variables
85
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Health Beliefs and Practices
86
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Racial Differences in Drug
Pharmacokinetics and Response
ASIAN AMERICANS
Cultural Factors
Demographics
Education and Employment
Family Relationships
87
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Health-Care Utilization
Health Status and Other Biological Variables
Health Beliefs and Practices
88
3827_Ch07_075-102 01/07/15 12:38 PM Page 88

Racial Differences in Drug
Pharmacokinetics and Response
89
3827_Ch07_075-102 01/07/15 12:38 PM Page 89

NATIVE HAWAIIAN AND PACIFIC
ISLANDERS
Cultural Factors
Demographics
Education and Employment
90
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Family Relationships
Health-Care Utilization
Health Status and Other Biological Variations
91
3827_Ch07_075-102 01/07/15 12:38 PM Page 91

Health Beliefs and Practices
Racial Differences in Drug
Pharmacokinetics and Response
HISPANIC AMERICANS
Cultural Factors
Demographics
Education and Employment
92
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Family Relationships
Health-Care Utilization
Health Status and Other Biological Variations
93
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Health Beliefs and Practices
94
3827_Ch07_075-102 01/07/15 12:38 PM Page 94

Racial Differences in Drug
Pharmacokinetics and Response NON-HISPANIC WHITES
95
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SUMMARY
96
BOX 7–1 RESOURCES FOR CULTURALLY COMPETENT CARE
Center for Cross-Cultural Research
WESTERN WASHINGTON UNIVERSITY
Housed within an integral part of the Department of Psychology at Western Washington University, the Center for Cross-
Cultural Research was started in response to the Euro-American bias in psychological theory, research, and practical applica-
tions. The mission of the Center for Cross-Cultural Research is to promote culture-related research, offer courses on culture,
promote exchange between cultural scientists, and disseminate the results of culture research. http://www.wwu.edu/culture/
Cross Cultural Health Care Program
The mission of the Cross Cultural Health Care Program is to serve as a bridge between communities and health-care institu-
tions to ensure full access to quality health care that is culturally and linguistically appropriate. http://www.xculture.org
Diversity Rx
Diversity Rx promotes language and cultural competence to improve the quality of health care for minority, immigrant, and
ethnically diverse communities. http://www.diversityrx.org
National Center for Cultural Competence
The mission of the National Center for Cultural Competence (NCCC) is to increase the capacity of health and mental health
programs to design, implement, and evaluate culturally and linguistically competent service delivery systems to address
growing diversity, persistent disparities, and to promote health and mental health equity. http://nccc.georgetown.edu/
PharmGKB
The PharmGKB is managed by Stanford University and is a pharmacogenomics knowledge resource that encompasses clini-
cal information including dosing guidelines and drug labels, potentially clinically actionable gene-drug associations and
genotype-phenotype relationships. PharmGKB collects, curates and disseminates knowledge about the impact of human ge-
netic variation on drug responses.
Transcultural Nursing Society
The mission of the Transcultural Nursing Society (TCNS) is to enhance the quality of culturally congruent, competent, and
equitable care that results in improved health and well-being for people worldwide. The TCNS seeks to provide nurses and
other health-care professionals with the knowledge base necessary to ensure cultural competence in practice, education,
research, and administration. www.tcns.org
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REFERENCES
97
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98
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99
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100
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101
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103
CHAPTER 8
Ashim Malhotra
PGLYCOPROTEIN, 111
CLINICAL IMPLICATIONS OF
PHARMACOGENOMICS, 111
Adverse Drug Reactions
Warfarin
Pharmacogenetic Testing Prior to Prescribing
SUMMARY, 113
A
GENETICS REVISITED, 104
HISTORY OF PHARMACOGENETICS, 105
PHARMACOGENOMICS, 105
GENETIC DIFFERENCES OF DRUG METABOLISM, 105
Genetic Polymorphism
Phase I and Phase II Metabolism
Specific CYP450 Enzymes
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GENETICS REVISITED
104
BOX 8–1 DEFINITIONS
Genetic polymorphism: multiple differences of a DNA
sequence found in at least 1% of the population
Genetics: the study of heredity and its variations
Genomics: the study of the complete set of genetic in-
formation present in a cell, an organism, or species
Pharmacogenetics: the study of the influence of hered-
itary factors on the response of individual organisms
to drugs (Venes, 2005); the study of variations of DNA
and RNA characteristics as related to drug response
(U.S. Food and Drug Administration, 2010b)
Pharmacogenomics: the study of the effects of genetic
differences among people and the impact that these
differences have on the uptake, effectiveness, toxic-
ity, and metabolism of drugs
SNP: single-nucleotide polymorphism
Source: Venes, D. (2005). Taber’s cyclopedic medical dictionary
(21st ed.). Philadelphia: FA Davis; U.S. Food and Drug Adminis-
tration. (2010b). Table of valid genomic biomarkers in the
context of approved drug labels. Retrieved from http://www
.fda.gov/RegulatoryInformation/Guidances/ucm129286.htm
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HISTORY OF PHARMACOGENETICS
PHARMACOGENOMICS
GENETIC DIFFERENCES IN DRUG
METABOLISM
Genetic Polymorphism
Phase I and Phase II Metabolism
105
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106
Figure 8–2. Pharmacogenomics of acetylation in isoniazid. Plasma
isoniazid concentrations in 267 patients measured 6 hours post-
dose. The bimodal distribution shows the effect of an NAT-2 genetic
polymorphism.
No
. s
ub
je
ct
s
0
24
12
0
4 8 12
Fast rate of acetylation
Slow rate of acetylation
Plasma isoniazid (mcg/mL)
Table 8–1 Clinical Implications of Genetic
Polymorphisms
Metabolizer Effect on Clinical
Phenotype Drug Metabolism Implications
Specific CYP450 Enzymes
CYP2D6
30
65
100
50
0
0
wt/wt
24 h
Dr
ug
C
on
c. 100
50
0
0 50
wt/wt
wt/m
m/m
100
Ef
fe
ct
(%
)
100
50
0
0
wt/m
24 h
Dr
ug
C
on
c. 100
50
0
0 50
wt/wt
wt/m
m/m
100
Ef
fe
ct
(%
)
99
100
50
0
0
m/m
24 h
Dr
ug
C
on
c. 100
50
0
0 50
wt/wt
Drug ConcentrationTime
wt/m
m/m
100
Ef
fe
ct
(%
)
Drug Metabolism
Genotypes
Drug Receptor
Genotypes
+ =
Therapeutic
Effect (%)
Toxicity
(%)
Genetic Polymorphism
of Drug Exposure
Genetic
Polymorphism
of Drug Sensitivity
Genetically Regulated
Heterogeneity
in Drug Effects
Efficacy
Toxicity
A
75 1
35 1
10 1
B
85 <10 45 <10 10 <10 C 95 >80
50 >80
10 >80
Figure 8–1. Genetic polymorphisms and drug metabolism/receptors.
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107
Figure 8–3. Proportion of drugs metabolized by CYP450 isoenzymes.
CYP2D6
19%
CYP3A4
36%
CYP1A2
CYP2A6CYP2B6
CYP2E1
CYP2C9
CYP2C19
Table 8–2 Medications and Their Receptors
Gene Medications Drug Effect Linked to Polymorphism
Drug-Metabolizing Enzymes
Drug Targets
3827_Ch08_103-114 01/07/15 12:37 PM Page 107

CYP2C9
108
Table 8–3
Substrate Inhibitors Inducers
60
30
0
0 24 48 72
Pl
as
m
a
no
rtr
ip
ty
lin
e
(n
m
ol
/L
)
Hours
0 Functional CYP2D6 genes
1 Functional CYP2D6 genes
2 Functional CYP2D6 genes
3 Functional CYP2D6 genes
13 Functional CYP2D6 genes
Figure 8–4. European population and the CYP2D6 substrate
nortriptyline.
3827_Ch08_103-114 01/07/15 12:37 PM Page 108

109
Table 8–4 ( and )
Substrate Inhibitors Inducers
35
30
25
20
15
10
5
0
2
3.7
10
20
29
Pe
rc
en
ta
ge
o
f i
nd
ivi
du
al
s
Percentage Duplication of CYP2D6 Across Different Populations
Sweden Germany Spain Saudi Arabia Ethiopia
Figure 8–5. Percentage distribution of individ-
uals across countries showing a duplication of
an allele of CYP2D6. The figure explains the
exaggerated metabolism of some drugs in the
specified percentage of individuals belonging
to certain ethnic backgrounds (generously as-
suming ethnic homogeneity in some coun-
tries) due to increased 2D6 activity.
3827_Ch08_103-114 01/07/15 12:37 PM Page 109

CYP3A4
110
Table 8–5
Substrate Inhibitors Inducers
12
10
8
6
4
2
0
Pe
rc
en
ta
ge
o
f A
lle
lic
F
re
qu
en
cy
Percentage of Allelic Variation CYP2C9
Across Different Ethnicities
CYP2C9*2
CYP2C9 Allelic Mutations
CYP2C9*3
Caucasians Africans Asians
Figure 8–6. Percentage distribution of individuals across ethnicities
exhibiting polymorphism in CYP2C9.
120
100
80
60
40
20
0
Pe
rc
en
ta
ge
o
f A
lle
lic
F
re
qu
en
cy
Percentage of Allelic Variation VKORC1
Across Different Ethnicities
VKORC1 Allelic Variant (–1639)
VKORC1
Caucasians Africans Asians
Figure 8–7. Percentage distribution of individuals across ethnicities
showing variation in VKORC1.
3827_Ch08_103-114 01/07/15 12:37 PM Page 110

P-GLYCOPROTEIN
111
Parent
Drug
CYP3A4
Metabolite
P-Glycoprotein
Intestinal WallSmall Intestine Enteric Blood Flow
Figure 8–8. Drug–metabolism interactions.
CLINICAL IMPLICATIONS
OF PHARMACOGENOMICS
Adverse Drug Reactions
Warfarin
Pharmacogenetic Testing Prior
to Prescribing
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112
Table 8–6 U.S. Food and Drug Administration
Positions on Necessity of
Pharmacogenetic Testing as
Indicated on Drug Labeling
Pharmacogenetic
Biomarker Drug
Test Required
Test Recommended
Information Only
3827_Ch08_103-114 01/07/15 12:37 PM Page 112

SUMMARY
REFERENCES
113
Table 8–7 FDA-Approved Diagnostic Test
Commercially Available for Commonly
Prescribed Pharmacologic Therapies
Genetic Test Drug Benefit of Genetic Test
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114
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115
Teri Moser Woo
NUTRIENTDRUG INTERACTIONS, 115
Influence of Diet on the Pharmacokinetics of Drugs
Drug-Induced Nutrient Depletion
Outcomes of Nutrient–Drug Interactions
NUTRITIONAL MANAGEMENT, 118
NUTRACEUTICALS, 119
Fiber
Vitamins and Minerals
Fatty Acids
Plant Sterols
Pre-, Pro-, and Symbiotics
E
NUTRIENT–DRUG INTERACTIONS
Influence of Diet on the Pharmacokinetics
of Drugs
Drug Absorption
CHAPTER 9
3827_Ch09_115-128 01/07/15 12:35 PM Page 115

Drug Metabolism
116
3827_Ch09_115-128 01/07/15 12:35 PM Page 116

Drug Excretion
Drug-Induced Nutrient Depletion
Outcomes of Nutrient–Drug Interactions Clinical Decision Making
117
3827_Ch09_115-128 01/07/15 12:35 PM Page 117

NUTRITIONAL MANAGEMENT
118
Table 9–1 Vitamin K Content in Common Foods
Food Serving Size Daily Value (%)
Foods High in Vitamin K (more than Eat No More Than 1 Serving per Day
or equal to 200% DV)
Foods Moderately High in Vitamin K Eat No More Than 2 Servings per Day
(60% to 199% DV)
3827_Ch09_115-128 01/07/15 12:35 PM Page 118

NUTRACEUTICALS
Fiber
119
3827_Ch09_115-128 01/07/15 12:35 PM Page 119

Vitamins and Minerals
Vitamin A
120
Table 9–2 Recommended Fiber Intake
Gender/Age Fiber (g/d)
Table 9–3 Recommended Reference Intakes of Vitamins and Minerals
Nutrient Age RDA Food Sources
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121
Table 9–3 Recommended Reference Intakes of Vitamins and Minerals—cont’d
Nutrient Age RDA Food Sources
Vitamin B1
3827_Ch09_115-128 01/07/15 12:35 PM Page 121

Vitamin B2
Vitamin B3
Vitamin B6
Vitamin B12
Vitamin C
122
3827_Ch09_115-128 01/07/15 12:35 PM Page 122

Vitamin D
Vitamin K
Folate
123
Table 9–4 Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health*
ng/mL** nmol/L** Health Status
3827_Ch09_115-128 01/07/15 12:35 PM Page 123

Calcium
Iron
Fatty Acids
124
BOX 9–1 MEDICATIONS INTERFERING
WITH FOLATE UTILIZATION
Antiepileptic drugs (phenytoin, primidone)
Metformin
Sulfasalazine
Triamterene
Methotrexate
Barbiturates
Trimethoprim
Pyrimethamine
Isoniazid
Oral contraceptives
3827_Ch09_115-128 01/07/15 12:35 PM Page 124

Plant Sterols
Pre-, Pro-, and Symbiotics
125
3827_Ch09_115-128 01/07/15 12:35 PM Page 125

REFERENCES
126
BOX 9–2 RESOURCES
American Dietetic Association
http://www.eatright.org
Drugs.com Drug Interaction Checker
http://www.drugs.com/drug_interactions.php
Food and Medication Interactions
http://www.foodmedinteractions.com
Medscape Drug Interaction Checker
www.medscape.com
National Institutes of Health Office of Dietary
Supplements
http://ods.od.nih.gov/Health_Information/Health_
Information.aspx
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127
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128
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129
CHAPTER 10
Fujio McPherson
Ayurvedic Herbs
Herbs for Common Disorders
HERBAL PREPARATIONS, 147
CONSIDERATIONS FOR THE APN PRESCRIBER, 147
SUGGESTED READING, 148
Western Herbs
Chinese Medicine
Ayurvedic Medicine
General Recommendations
P
OVERVIEW OF HERBAL MEDICINE, 130
DEFINITIONS, 130
Western Herbal Medicine
Traditional Chinese Medicine
Ayurvedic Medicine
HERBAL SAFETY, 133
Evidence Grading
Matrix for Evidence Grading
Challenges to Using an Evidence-Based Method
COMMON HERBS, 138
Western Herbs
Traditional Chinese Herbs
3827_Ch10_129-150 01/07/15 12:34 PM Page 129

OVERVIEW OF HERBAL MEDICINE
DEFINITIONS
130
3827_Ch10_129-150 01/07/15 12:34 PM Page 130

Western Herbal Medicine
Traditional Chinese Medicine
131
3827_Ch10_129-150 01/07/15 12:34 PM Page 131

Ayurvedic Medicine
132
3827_Ch10_129-150 01/07/15 12:34 PM Page 132

133
HERBAL SAFETY
3827_Ch10_129-150 01/07/15 12:34 PM Page 133

Evidence Grading
Natural Standard
Healthnotes
Rakel Evidence Versus Harm Scale
Cochrane Database of Systematic Reviews
German Commission E Monographs
134
3827_Ch10_129-150 01/07/15 12:34 PM Page 134

Matrix for Evidence Grading
135
Hypertension
CAM Therapy Natural Standard Healthnotes Rakel WHO Commission- E
Cochrane Summary:
Clinical Implications for Practice: Hypertension
Herb/Supplement Indications Contraindications Dose Rakel Harm Scale
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136
Hypertension Commentary
Hyperlipidemia
CAM Therapy Natural Standard Healthnotes Rakel WHO Commission- E
Cochrane Summary:
Clinical Implications for Practice: Hyperlipidemia
Herb/Supplement Indications Contraindications Dose Rakel Harm Scale
3827_Ch10_129-150 01/07/15 12:34 PM Page 136

Hyperlipidemia Commentary
Challenges to Using an Evidenced-
Based Model
137
3827_Ch10_129-150 01/07/15 12:34 PM Page 137

COMMON HERBS
Western Herbs
Mental Health Symptoms
138
3827_Ch10_129-150 01/07/15 12:34 PM Page 138

139
3827_Ch10_129-150 01/07/15 12:34 PM Page 139

140
3827_Ch10_129-150 01/07/15 12:34 PM Page 140

141
3827_Ch10_129-150 01/07/15 12:34 PM Page 141

Traditional Chinese Herbs
The Four Energies
142
3827_Ch10_129-150 01/07/15 12:34 PM Page 142

The Five Flavors
The Four Movements
Meridian Routes
Actions
Herbal Formulas
How to Take Chinese Herbs
Rules for Taking a Formula
143
3827_Ch10_129-150 01/07/15 12:34 PM Page 143

Insomnia
Heart–Spleen Deficiency
144
CLINICAL PEARL
TCM diagnosis
Although this text does not cover TCM diagnosis or an
explanation of the disorder mentioned (e.g., spleen de-
ficiency, heart fire, etc.), the general purpose of includ-
ing the differential diagnosis is to demonstrate how
diverse TCM diagnosis is and how it applies to the
choice of herbal medicine prescribed. Please refer to
TCM textbooks to further understand TCM diagnosis.
3827_Ch10_129-150 01/07/15 12:34 PM Page 144

Ayurvedic Herbs
Additional Approach to Choosing
Digestive Disorders
Rejuvenative Disorders
145
3827_Ch10_129-150 01/07/15 12:34 PM Page 145

Herbs for Common Disorders
146
Table 10–1 Selective Herbal Agents Used for Common Conditions
Condition Treatment
Pain
3827_Ch10_129-150 01/07/15 12:34 PM Page 146

HERBAL PREPARATIONS
CONSIDERATIONS FOR THE APRN
PRESCRIBER
147
BOX 10–1 WEB-BASED RESOURCES FOR
HERBS AND ALTERNATIVE
THERAPIES
• American Botanical Council, http://www
.herbalgram.org
• American Herbalist Guild, http://www
.americanherbalistsguild.com
• Biofeedback Certification Institute of America,
http://www.bcia.org
• National Center for Complementary and Alternative
Medicine, http://nccam.nih.gov
• Natural Standard: The Authority on Integrative
Medicine, http://www.naturalstandard.com/
• Cochrane Database of Systematic Reviews, http://
www.cochran.org
3827_Ch10_129-150 01/07/15 12:34 PM Page 147

SUGGESTED READING
Western Herbs
Chinese Medicine
Ayurvedic Medicine
General Recommendations
REFERENCES
148
BOX 10–2 HERBAL RESOURCES
East West School of Herbology
P.O. Box 275
Ben Lomond, CA 95005
1-800-717-5010
herbcourse@planetherbs.com or www
.planetherbs.com
Sponsor of planetary herbal formulas that supplies
Western, Eastern, and Ayurvedic herbs.
Herb Pharm
Box 116
Williams, OR 97544
1-800-348-4372
Specializing in herbal tinctures.
www.herb-pharm.com
Spring Wind Herb Company
2325 4th Street #6
Berkeley, CA 94710
Good source for Chinese herbs.
Banyan Botanical
6705 Eagle Rock Ave, NE
Albuquerque, NM 87113
1-800-953-6424
www.banyanbotanicals.com
Good source for Ayurvedic herbs.
Mountain Rose Herbs
P.O. Box 50220
Eugene, OR 97405
1-800-879-3337
www.mountainroseherbs.com
Large selection of bulk organic herbs, spices, teas, es-
sential oils, and bulk ingredients.
The Tao of Tea
3430 SE Belmont Street
Portland OR 97214
1-503-736-0198
www.taooftea.com
Good selection of herbal teas.
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149
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150
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151
CHAPTER 11
Jane M. Carrington
MEDICATION RECONCILIATION, 154
PATIENT PRIVACY, 155
PATIENT EDUCATION, 155
QUALITY IMPROVEMENT, 156
CONCLUSION, 157
OVERVIEW INTRODUCTION
OVERVIEW, 151
INTRODUCTION, 151
THE ELECTRONIC HEALTH RECORD, 152
Information Storage and Exchange
Computerized Provider Order Entry
CLINICAL DECISION SUPPORT SYSTEMS, 154
PATIENT SAFETY, 154
3827_Ch11_151-158 01/07/15 12:58 PM Page 151

THE ELECTRONIC HEALTH RECORD
152
Information Storage and Exchange
Table 11–1 Core Elements for Meaningful Use for Providers
Associated with
Core Element Measures Pharmacotherapeutics
3827_Ch11_151-158 01/07/15 12:58 PM Page 152

Computerized Provider Order Entry
153
Table 11–2 Advantages and Disadvantages of Computerized Provider Order Entry
Resource Advantages Resource Advantages
3827_Ch11_151-158 01/07/15 12:58 PM Page 153

CLINICAL DECISION SUPPORT
SYSTEMS
PATIENT SAFETY
MEDICATION RECONCILIATION
154
3827_Ch11_151-158 01/07/15 12:58 PM Page 154

PATIENT PRIVACY
PATIENT EDUCATION
155
3827_Ch11_151-158 01/07/15 12:58 PM Page 155

QUALITY IMPROVEMENT
156
Table 11–3 Suggestions for Screening Web Sites
Web Site/Source Screening Suggestions
3827_Ch11_151-158 01/07/15 12:58 PM Page 156

CONCLUSION
REFERENCES
157
BOX 11–1 SAMPLE QUESTIONS FOR
QUALITY IMPROVEMENT
1. In this practice, are we consistent in ordering specific
laboratory tests at specific time intervals for patients
on medication XXX with a diagnosis of XXX?
2. Are patients who take medication XXX receiving
education about nutrition, what to exclude from
a diet?
3. For this diagnosis, are patients avoiding readmission
with XXX medication?
4. In this practice, are we consistent in how we educate
patients about medication XXX?
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158
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159
CHAPTER 12
Teri Moser Woo
APPLYING PHARMACOECONOMICS
TO PRACTICE, 163
Prescribing Generic Versus Brand-Name Medications
Medicare Part D
CONCLUSION, 164
T
PHARMACOECONOMIC STUDIES
PHARMACOECONOMIC STUDIES, 159
Components of Well-Designed Studies
Cost-of-Illness Analysis
Cost-Minimization Analysis
Cost-Effectiveness Analysis
Cost-Benefit Analysis
Cost-Utility Analysis
IMPACT OF GENERIC DRUGS ON DRUG THERAPY, 162
Generic Substitution
Generic Bioequivalence
3827_Ch12_159-164 01/07/15 12:57 PM Page 159

Components of Well-Designed
Studies
160
Table 12–1 Factors Influencing Pharmacoeconomic
Outcomes
Research Type
Table 12–2 Commonly Used Pharmacoeconomic Research Methodologies
Method Outcome Examples
3827_Ch12_159-164 01/07/15 12:57 PM Page 160

Cost-of-Illness Analysis
Cost-Minimization Analysis
Cost-Effectiveness Analysis
Cost-Benefit Analysis
Cost-Utility Analysis
161
3827_Ch12_159-164 01/07/15 12:57 PM Page 161

IMPACT OF GENERIC DRUGS
ON DRUG THERAPY Generic Substitution
Generic Bioequivalence
162
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163
Pharmaceutical Equivalents
Therapeutic Equivalents
Bioequivalence
APPLYING PHARMACOECONOMICS
TO PRACTICE
Prescribing Generic Versus
Brand-Name Medications
Medicare Part D
3827_Ch12_159-164 01/07/15 12:57 PM Page 163

CONCLUSION
REFERENCES
164
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165
CHAPTER 13
Teri Moser Woo
ABUSE OF OTC MEDICATIONS, 168
PATIENT EDUCATION REGARDING OTC
MEDICATIONS, 168
SUMMARY, 169
P
OVER-THE-COUNTER MEDICATIONS
OVERTHECOUNTER MEDICATIONS, 165
OTC MEDICATION SALES, 166
SELFPRESCRIBING OF OTC MEDICATIONS, 166
HAZARDS OF OTC SELFMEDICATION, 167
ADVERSE EFFECTS OF OTC SELFMEDICATION, 167
Adverse Effects
Drug Interactions
3827_Ch13_165-170 01/07/15 12:57 PM Page 165

OTC MEDICATION SALES
166
SELF-PRESCRIBING OTC
MEDICATIONS
Table 13–1 Conditions for Which OTC Drugs
Are Marketed
3827_Ch13_165-170 01/07/15 12:57 PM Page 166

HAZARDS OF OTC SELF-MEDICATION
ADVERSE EFFECTS OF OTC
SELF-MEDICATION
Adverse Effects
167
Table 13–2 Over-the-Counter Medications That May Impair Driving or Operating Machinery
Medication OTC Products
3827_Ch13_165-170 01/07/15 12:57 PM Page 167

Drug Interactions
Antacids
Anticholinergics
Central Nervous System Depressants
NSAIDS and Aspirin
ABUSE OF OTC MEDICATIONS
PATIENT EDUCATION REGARDING
OTC MEDICATIONS
168
3827_Ch13_165-170 01/07/15 12:57 PM Page 168

SUMMARY
REFERENCES
169
BOX 13–1 PATIENT EDUCATION
REGARDING OTC MEDICATIONS
• Read the label of the medication to determine dose,
duration of treatment, adverse effects, and drug
interactions.
• If you do not understand the label information, ask
a pharmacist or your health-care provider to clarify.
• Inform your provider and the pharmacist of any OTC
medications you are taking, even medications you
only take occasionally.
• Do not drive or operate machinery if you take sedating
OTC medications. You may be charged with driving
under the influence.
• Inform your provider if you have any adverse effects
from the OTC medication.
BOX 13–2 OVER-THE-COUNTER
MEDICATION RESOURCES
American College of Preventive Medicine
Over the Counter Medications Time Tool
http://www.acpm.org/?OTCMeds_ClinRef
Consumer Healthcare Products Association
www.chpa.org
http://otcsafety.org/
Scholastic OTC Literacy for Teachers
http://www.scholastic.com/otcliteracy/
U.S. Food and Drug Administration
Educational Resources: Understanding Over-the-
Counter Medicine
http://www.fda.gov/Drugs/ResourcesForYou/
Consumers/
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170
3827_Ch13_165-170 01/07/15 12:57 PM Page 170

UNIT II
3827_Ch14_171-224 01/07/15 12:55 PM Page 171

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173
T
CHAPTER 14
Tracy Scott
ADRENERGIC AGONISTS, 174
ALPHA2 AGONISTS: CENTRAL, 174
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ADRENERGIC ANTAGONISTS, 181
ALPHA1 ANTAGONISTS, 181
Nonselective Alpha Antagonists
Selective Alpha1 Antagonists
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
BETAADRENERGIC ANTAGONISTS
BLOCKERS, 187
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
COMBINED ALPHA AND BETAADRENERGIC
ANTAGONISTS, 196
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CHOLINERGIC AGONISTS, 200
MUSCARINIC AGONISTS, 200
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CHOLINESTERASE INHIBITORS, 202
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CHOLINERGIC BLOCKERS, 213
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
3827_Ch14_171-224 01/07/15 12:55 PM Page 173

ALPHA2 AGONISTS: CENTRAL
Pharmacodynamics
174
Resting
activity
+–
+–
+–
Resting
activity
PNS SNS
PNS SNS
PNS SNS
Resting
activity
Figure 14–1. Resting activity and the autonomic nervous system.
ADRENERGIC AGONISTS
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175
Table 14–1 Actions of Autonomic Nervous System Based on Receptor
Organ or Tissue Receptor Adrenergic Effect Receptor Cholinergic Effect
3827_Ch14_171-224 01/07/15 12:55 PM Page 175

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
176
Table 14–1 Actions of Autonomic Nervous System Based on Receptor—cont’d
Organ or Tissue Receptor Adrenergic Effect Receptor Cholinergic Effect
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177
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Table 14–2 ! Pharmacokinetics: Selected Centrally Acting Alpha2 Agonists
Protein
Drug Onset Peak Duration Binding Bioavailability Half-Life Elimination
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178
Table 14–3 ” Drug Interactions: Centrally Acting Alpha2 Agonists
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 178

179
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
3827_Ch14_171-224 01/07/15 12:55 PM Page 179

180
Table 14–4 # Schedule: Centrally Acting Alpha2 Agonists
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 180

ADRENERGIC ANTAGONISTS
ALPHA1 ANTAGONISTS
Nonselective Alpha Antagonists
Selective Alpha1 Antagonists
Pharmacodynamics
181
3827_Ch14_171-224 01/07/15 12:55 PM Page 181

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
182
Table 14–5 Selected Alpha1-Adrenergic Antagonists
Protein
Drug Onset Peak Duration Binding (%) Bioavailability (%) Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 182

Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
183
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184
Table 14–6 # Dosage Schedule: Selected Alpha1-Adrenergic Antagonists
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 184

185
Table 14–7 ” Drug Interactions: Selected Alpha1-Adrenergic Antagonists
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 185

Rational Drug Selection
Monitoring
Patient Education
186
3827_Ch14_171-224 01/07/15 12:55 PM Page 186

BETA-ADRENERGIC ANTAGONISTS
(BLOCKERS)
Pharmacodynamics
Cardiovascular Effects
Renal Effects
Respiratory Effects
Ocular Effects
Metabolic and Endocrine Effects
187
3827_Ch14_171-224 01/07/15 12:55 PM Page 187

Effects on Other Systems
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
188
Table 14–8 ! Pharmacokinetics: Selected Beta Blockers
Protein
Drug Onset Peak Duration Binding (%) Bioavailability (%) Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 188

Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
189
3827_Ch14_171-224 01/07/15 12:55 PM Page 189

Drug, Food, and Laboratory Test Interactions
190
CLINICAL PEARL
For patients with diabetes who must take a beta
blocker, the diaphoresis associated with hypoglycemia
is not masked by these drugs. Patients should be
taught to recognize this indication of possible hypo-
glycemia and test their blood glucose levels whenever
unexplained diaphoresis occurs.
Table 14–9 ” Drug Interactions: Selected Beta Blockers
Drug Interacting Drug Possible Effect Implications
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191
Table 14–9 ” Drug Interactions: Selected Beta Blockers—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 191

Clinical Use and Dosing
192
3827_Ch14_171-224 01/07/15 12:55 PM Page 192

Rational Drug Selection
Monitoring
Patient Education
193
3827_Ch14_171-224 01/07/15 12:55 PM Page 193

194
Table 14–10 # Dosage Schedule: Selected Beta Blockers
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 194

195
Table 14–10 # Dosage Schedule: Selected Beta Blockers—cont’d
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 195

COMBINED ALPHA- AND
BETA-ADRENERGIC ANTAGONISTS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
196
3827_Ch14_171-224 01/07/15 12:55 PM Page 196

Adverse Drug Reactions
Drug, Food, and Laboratory Test Interactions
197
Table 14–11 ! Pharmacokinetics: Combined Alpha-Beta Blockers
Protein
Drug Onset Peak Duration Binding Bioavailability Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 197

Clinical Use and Dosing
198
Table 14–12 ” Drug Interactions: Combined Alpha-Beta Blockers
Drug Interacting Drug* Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 198

199
Table 14–13 # Dosage Schedule: Combined Alpha-Beta Blockers
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 199

Monitoring
Patient Education
CHOLINERGIC AGONISTS
MUSCARINIC AGONISTS
Pharmacodynamics
200
3827_Ch14_171-224 01/07/15 12:55 PM Page 200

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
201
3827_Ch14_171-224 01/07/15 12:55 PM Page 201

Clinical Use and Dosing
Patient Education
CHOLINESTERASE INHIBITORS
Pharmacodynamics
202
3827_Ch14_171-224 01/07/15 12:55 PM Page 202

Pharmacokinetics
Absorption and Distribution
203
Table 14–14 ! Pharmacokinetics: Selected Acetylcholinesterase Inhibitors
Protein
Drug Onset Peak Duration Binding (%) Bioavailability Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 203

Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
204
3827_Ch14_171-224 01/07/15 12:55 PM Page 204

Adverse Drug Reactions
Drug Interactions
205
3827_Ch14_171-224 01/07/15 12:55 PM Page 205

206
Table 14–15 ” Drug Interactions: Selected Acetylcholinesterase Inhibitors
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 206

207
Table 14–15 ” Drug Interactions: Selected Acetylcholinesterase Inhibitors—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 207

Clinical Use and Dosing
208
3827_Ch14_171-224 01/07/15 12:55 PM Page 208

Rational Drug Selection
209
3827_Ch14_171-224 01/07/15 12:55 PM Page 209

210
Table 14–16 # Dosage Schedule: Acetylcholinesterase Inhibitors
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 210

Monitoring
211
Table 14–16 # Dosage Schedule: Acetylcholinesterase Inhibitors—cont’d
Drug Indication Form Initial Dose Maintenance Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 211

Patient Education
212
Table 14–17 ! Pharmacokinetics: Selected Cholinergic Blockers
Drug Onset Peak Duration Half-Life Elimination
3827_Ch14_171-224 01/07/15 12:55 PM Page 212

CHOLINERGIC BLOCKERS
Pharmacodynamics
213
3827_Ch14_171-224 01/07/15 12:55 PM Page 213

Cardiovascular Effects
Respiratory Effects
Exocrine Gland Effects
Urinary and Gastrointestinal Effects
Central Nervous System Effects
Optic Effects
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
214
3827_Ch14_171-224 01/07/15 12:55 PM Page 214

Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
215
3827_Ch14_171-224 01/07/15 12:55 PM Page 215

216
Table 14–18 ” Drug Interactions: Selected Cholinergic Blockers
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 216

Clinical Use and Dosing
217
Table 14–18 ” Drug Interactions: Selected Cholinergic Blockers—cont’d
Drug Interacting Drug Possible Effect Implications
3827_Ch14_171-224 01/07/15 12:55 PM Page 217

218
Table 14–19 # Dosage Schedule: Selected Cholinergic Blockers
Drug Indication Form Initial Dose Maintenance and Maximum Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 218

219
Table 14–19 # Dosage Schedule: Selected Cholinergic Blockers—cont’d
Drug Indication Form Initial Dose Maintenance and Maximum Dose
3827_Ch14_171-224 01/07/15 12:55 PM Page 219

220
3827_Ch14_171-224 01/07/15 12:55 PM Page 220

Rational Drug Selection
221
3827_Ch14_171-224 01/07/15 12:55 PM Page 221

Monitoring
Patient Education
REFERENCES
222
3827_Ch14_171-224 01/07/15 12:55 PM Page 222

223
3827_Ch14_171-224 01/07/15 12:55 PM Page 223

224
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225
T
CHAPTER 15
Teri Moser Woo
ANOREXIANTS
ANTICONVULSANTS, 228
HYDANTOINS
IMINOSTILBENES
SUCCINIMIDES
DRUGS THAT AFFECT GABA
LEVETIRACETAM
LAMOTRIGINE
ANTIDEPRESSANTS, 245
TRICYCLIC ANTIDEPRESSANTS TCAs
MONOAMINE OXIDASE INHIBITORS MAOIs
SELECTIVE SEROTONIN REUPTAKE INHIBITORS SSRIs
SEROTONINNOREPINEPHRINE REUPTAKE
INHIBITORS SNRIs
ANTIPSYCHOTICS APs, 255
TYPICAL ANTIPSYCHOTICS
ATYPICAL ANTIPSYCHOTICS
DOPAMINERGICS
ANXIOLYTICS ANTIANXIETY AND HYPNOTICS, 267
BENZODIAZEPINES
SEROTONERGIC ANXIOLYTICS
BARBITURATES
SEDATIVEHYPNOTICS
BENZODIAZEPINE HYPNOTICS
NONBENZODIAZEPINE HYPNOTICS
MOOD STABILIZERS, 276
LITHIUM
VALPROATES
NONCLASSIFIED MOOD STABILIZERS
MUSCLE RELAXANTS AND ANTISPASMOTICS, 281
CENTRALLY ACTING MUSCLE RELAXANTS
DIRECTACTING ANTISPASMOTICS
OPIOID ANALGESICS AND THEIR ANTAGONISTS
STIMULANTS
3827_Ch15_225-294 02/07/15 2:48 PM Page 225

ANOREXIANTS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
226
Table 15–1 ! Pharmacokinetics: Anorexiants
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 226

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
ANTICONVULSANTS
227
Table 15–2 ” Drug Interactions: Anorexiants
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 227

HYDANTOINS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Pharmacotherapeutics
Precautions and Contraindications
228
Table 15–3 # Dosage Schedule: Anorexiants
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 228

229
Table 15–4 ! Pharmacokinetics: Antiepileptic Drugs
Drug Onset Peak Duration Half-Life Excretion
Adverse Drug Reactions
3827_Ch15_225-294 02/07/15 2:48 PM Page 229

Drug Interactions
230
Possible Effect Implications
Table 15–5 ” Drug Interactions: Hydantoins (Anticonvulsants
Drug Interacting Drug
3827_Ch15_225-294 02/07/15 2:48 PM Page 230

231
Table 15–5 ” Drug Interactions: Hydantoins (Anticonvulsants)—cont’d
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
3827_Ch15_225-294 02/07/15 2:48 PM Page 231

232
Table 15–6 # Dosage Schedule: Selected Anticonvulsants
Drug Indications Dosage Available Dosage Forms
Drugs That Affect GABA
3827_Ch15_225-294 02/07/15 2:48 PM Page 232

233
Table 15–6 # Dosage Schedule: Selected Anticonvulsants—cont’d
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 233

234
Table 15–6 # Dosage Schedule: Selected Anticonvulsants—cont’d
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 234

IMINOSTILBENES
Pharmacodynamics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
235
3827_Ch15_225-294 02/07/15 2:48 PM Page 235

Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
236
Table 15–7 ” Drug Interactions: Carbamazepine and Oxcarbazepine (Anticonvulsants)
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 236

237
Table 15–8 # Dosage Schedule: Carbamazepine and Oxcarbazepine (Anticonvulsants)
Drug Indications Dosage Available Dosage Forms
Patient Education
SUCCINIMIDES
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion.
3827_Ch15_225-294 02/07/15 2:48 PM Page 237

Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
DRUGS THAT AFFECT GABA
Pharmacodynamics
238
Table 15–9 # Dosage Schedule: Succinimides (Anticonvulsants)
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 238

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
239
Table 15–10 ! Pharmacokinetics: Tricyclic Antidepressants
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 239

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
240
3827_Ch15_225-294 02/07/15 2:48 PM Page 240

Rational Drug Selection
Monitoring
Patient Education
LEVETIRACETAM
Pharmacodynamics
241
3827_Ch15_225-294 02/07/15 2:48 PM Page 241

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
242
3827_Ch15_225-294 02/07/15 2:48 PM Page 242

LAMOTRIGINE
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
243
3827_Ch15_225-294 02/07/15 2:48 PM Page 243

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
244
3827_Ch15_225-294 02/07/15 2:48 PM Page 244

Rational Drug Selection
Monitoring
Patient Education
ANTIDEPRESSANTS
TRICYCLIC ANTIDEPRESSANTS TCAs
245
3827_Ch15_225-294 02/07/15 2:48 PM Page 245

Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
246
3827_Ch15_225-294 02/07/15 2:48 PM Page 246

247
Table 15–11 ” Drug Interactions: Tricyclic Antidepressants
Drug Interacting Drug Possible Effect Implications
Table 15–12 # Dosage Schedule: Tricyclic Antidepressants
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 247

Rational Drug Selection
Monitoring
Patient Education
MONOAMINE OXIDASE INHIBITORS
MAOIs
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics
Precautions and Contraindications
248
Table 15–12 # Dosage Schedule: Tricyclic Antidepressants—cont’d
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 248

Adverse Drug Reactions
Clinical Use and Dosing
Drug and Food Interactions
Rational Drug Selection
Monitoring
Patient Education
SELECTIVE SEROTONIN REUPTAKE
INHIBITORS SSRIs
249
Table 15–13 ” Drug Interactions: Monoamine Oxidase Inhibitors
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 249

Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
250
Table 15–14 ! Pharmacokinetics: SNRIs, SSRIs, and Other Antidepressants
Drug Peak Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 250

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosages
Rational Drug Selection
Monitoring
Patient Education
251
3827_Ch15_225-294 02/07/15 2:48 PM Page 251

252
Table 15–15 ” Drug Interactions: Selective Serotonin Reuptake Inhibitors (SSRIs)
Drug Interacting Drug Possible Effect Implications
Table 15–16 # Dosage Schedule: Non-TCA Antidepressants
Drug Indications
Neurotransmitters
Affected Dosage
Available Dosage
Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 252

253
Table 15–16 # Dosage Schedule: Non-TCA Antidepressants—cont’d
Drug Indications
Neurotransmitters
Affected Dosage
Available Dosage
Forms
SEROTONINNOREPINEPHRINE
REUPTAKE INHIBITORS SNRIs
3827_Ch15_225-294 02/07/15 2:48 PM Page 253

Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
254
3827_Ch15_225-294 02/07/15 2:48 PM Page 254

Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
ANTIPSYCHOTICS (APS)
255
3827_Ch15_225-294 02/07/15 2:48 PM Page 255

TYPICAL ANTIPSYCHOTICS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
256
Table 15–17 ! Pharmacokinetics: Typical Antipsychotics
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 256

Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
257
Table 15–18 ” Drug Interactions: Typical Antipsychotics
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 257

258
Table 15–19 # Dosage Schedule: Typical Antipsychotics
Drug Indications*
Available Dosage
FormsDosage
3827_Ch15_225-294 02/07/15 2:48 PM Page 258

Patient Education
ATYPICAL ANTIPSYCHOTICS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
259
Table 15–20 Abnormal Involuntary Movement Scale (AIMS) Checklist
Abnormal Involuntary Movement Scale Notes
3827_Ch15_225-294 02/07/15 2:48 PM Page 259

Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
260
3827_Ch15_225-294 02/07/15 2:48 PM Page 260

261
Table 15–21 ” Drug Interactions: Atypical Antipsychotics
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 261

262
Table 15–22 # Dosage Schedule: Atypical Antipsychotics
Drug Indications Dosage
Available Dosage
Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 262

263
Table 15–22 # Dosage Schedule: Atypical Antipsychotics—cont’d
Available Dosage
Drug Indications Dosage Forms
Monitoring
Patient Education
3827_Ch15_225-294 02/07/15 2:48 PM Page 263

DOPAMINERGICS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
264
Table 15–23 ! Pharmacokinetics: Dopaminergics
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 264

265
Table 15–24 ” Food and Drug Interactions: Dopaminergics
Drug Interacting Drug or Food Possible Effect Implications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
3827_Ch15_225-294 02/07/15 2:48 PM Page 265

266
Table 15–25 # Dosage Schedule: Dopaminergics
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 266

Patient Education
ANXIOLYTICS (ANTIANXIETY)
AND HYPNOTICS
BENZODIAZEPINES
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
267
3827_Ch15_225-294 02/07/15 2:48 PM Page 267

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
268
Table 15–26 ! Pharmacokinetics: Benzodiazepines
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 268

269
Table 15–27 ” Drug Interactions: Benzodiazepines
Drug Interacting Drug Possible Effect Implications
SEROTONERGIC ANXIOLYTICS
Pharmacodynamics Pharmacokinetics
Absorption and Distribution
3827_Ch15_225-294 02/07/15 2:48 PM Page 269

270
Table 15–28 # Dosage Schedule: Benzodiazepines
Drugs Indications Dosage Available Dosage Forms
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reaction
3827_Ch15_225-294 02/07/15 2:48 PM Page 270

Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
BARBITURATES
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
271
3827_Ch15_225-294 02/07/15 2:48 PM Page 271

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
272
Table 15–29 ! Pharmacokinetics: Barbiturates
Drug Onset Peak Duration Half-Life Excretion
Table 15–30 ” Drug Interactions: Barbiturates
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 272

Rational Drug Selection
273
Table 15–31 # Dosage Schedule: Barbiturates
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 273

Monitoring
Sedative-Hypnotics
BENZODIAZEPINE HYPNOTICS
NONBENZODIAZEPINE HYPNOTICS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
274
3827_Ch15_225-294 02/07/15 2:48 PM Page 274

Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
275
3827_Ch15_225-294 02/07/15 2:48 PM Page 275

MOOD STABILIZERS
LITHIUM
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics
Precautions and Contraindications
276
3827_Ch15_225-294 02/07/15 2:48 PM Page 276

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
277
Table 15–32 ” Drug Interactions: Lithium
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 277

Monitoring
Patient Education
VALPROATES
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Onset, Peak, and Duration
Pharmacotherapeutics
Precautions and Contraindications
278
Table 15–33 # Dosage Schedule: Lithium
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 278

Adverse Drug Reactions
Drug Interactions
Clinical Uses and Dosages
Rational Drug Selection
279
Table 15–34 ” Drug Interactions: Valproates
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 279

Monitoring
Patient Education
NONCLASSIFIED MOOD STABILIZERS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
280
Table 15–35 # Dosage Schedule: Valproates
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 280

Drug Interactions
Clinical Use and Dosing
Rationale Drug Selection
Monitoring
Patient Education
MUSCLE RELAXANTS AND
ANTISPASMOTICS
CENTRALLY ACTING MUSCLE
RELAXANTS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
281
3827_Ch15_225-294 02/07/15 2:48 PM Page 281

Adverse Drug Reactions
282
3827_Ch15_225-294 02/07/15 2:48 PM Page 282

Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
283
3827_Ch15_225-294 02/07/15 2:48 PM Page 283

Monitoring
Patient Education
DIRECTACTING ANTISPASMOTICS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
284
3827_Ch15_225-294 02/07/15 2:48 PM Page 284

Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
OPIOID ANALGESICS AND THEIR
ANTAGONISTS
Pharmacodynamics
285
3827_Ch15_225-294 02/07/15 2:48 PM Page 285

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
286
Table 15–36 ! Pharmacokinetics: Opioid Analgesics and Antagonists
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 286

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
287
Table 15–37 ” Drug Interactions: Opioid Analgesics and Antagonists
Drug Interacting Drug Possible Effect Implications
3827_Ch15_225-294 02/07/15 2:48 PM Page 287

288
Table 15–38 # Dosage Schedule: Opioid Analgesics and Antagonists
Drug Indications Dosage Available Dosage Forms
3827_Ch15_225-294 02/07/15 2:48 PM Page 288

Table 15–38 # Dosage Schedule: Opioid Analgesics and Antagonists—cont’d
Drug Indications Available Dosage Forms Dosage
289
3827_Ch15_225-294 02/07/15 2:48 PM Page 289

Monitoring
Patient Education
STIMULANTS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
290
3827_Ch15_225-294 02/07/15 2:48 PM Page 290

Table 15–40 ” Drug Interactions: Stimulants
Drug Interacting Drug Possible Effect Implications
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
291
Table 15–39 ! Pharmacokinetics: Stimulants
Drug Onset Peak Duration Half-Life Excretion
3827_Ch15_225-294 02/07/15 2:48 PM Page 291

292
Table 15–41 # Dosage Schedule: Stimulants
Drug Indications Dosage Available Dosage Forms
Dosage
3827_Ch15_225-294 02/07/15 2:48 PM Page 292

293
Table 15–41 # Dosage Schedule: Stimulants—cont’d
Drug Indications Dosage Available Dosage Forms
Monitoring
Patient Education
REFERENCES
3827_Ch15_225-294 02/07/15 2:48 PM Page 293

294
3827_Ch15_225-294 02/07/15 2:48 PM Page 294

295
ANGIOTENSIN-CONVERTING ENZYME
INHIBITORS, ANGIOTENSIN II
RECEPTOR BLOCKERS, AND DIRECT
RENIN INHIBITORS
CHAPTER 16
Marylou V. Robinson
ANGIOTENSINCONVERTING ENZYME INHIBITORS,
ANGIOTENSIN II RECEPTOR BLOCKERS, AND DIRECT
RENIN INHIBITORS, 295
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CALCIUM CHANNEL BLOCKERS, 308
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
CARDIAC GLYCOSIDES, 316
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTIARRHYTHMICS, 323
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
NITRATES, 333
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
PERIPHERAL VASODILATORS PADs, 338
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
ANTILIPIDEMICS, 340
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
DIURETICS, 350
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
3827_Ch16_295-360 01/07/15 5:26 PM Page 295

Pharmacodynamics
296
Angiotensinogen
Renin
Angiotensin I
Potent vasoconstriction
Aldosterone
Sodium and water
retention
Increased blood pressure
Adrenal gland
Angiotensin-converting
enzyme
Kininogen
Kallikrein
Inactive fragments
Increased
prostaglandin
synthesis
Vasodilation
Decreased blood pressure
Bradykinin
Angiotensin II
Increased intravascular
volume
Figure 16–1. Renin-angiotensin-aldosterone system. Renin acts on angiotensinogen to create the inactive decapeptide angiotensin I.
Angiotensin I is then converted, primarily in the lung, to angiotensin II, a potent vasoconstrictor, through the activity of angiotensin-converting
enzyme (ACE). Angiotensin II stimulates aldosterone secretion, causing retention of sodium and water and loss of potassium by the kidney.
ACE is also involved in the inactivation of bradykinin, a vasodilator. Together, these systems help to control blood pressure.
3827_Ch16_295-360 01/07/15 5:26 PM Page 296

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
297
3827_Ch16_295-360 01/07/15 5:26 PM Page 297

298
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f F
oo
d
A
ct
iv
e
D
ru
g
O
ns
et
(h
)
Pe
ak
(h
)
(h
)
Bi
nd
in
g
(B
A
)
on
A
bs
or
pt
io
n
M
et
ab
ol
it
e
H
al
f-
Li
fe
(h
)
El
im
in
at
io
n
A
CE
In
hi
bi
to
rs
3827_Ch16_295-360 01/07/15 5:26 PM Page 298

299
A
RB
s
D
ir
ec
t R
en
in
In
hi
bi
to
r
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300
Table 16–2 ” Dosage Schedules: Angiotensin-Converting-Enzyme Inhibitors and Angiotensin II
Receptor Blockers and Direct Renin Inhibitors
Drug Indication Dose Form Initial Dose Maintenance Dose
ACEI
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301
Table 16–2 ” Dosage Schedules: Angiotensin-Converting-Enzyme Inhibitors and Angiotensin II
Receptor Blockers and Direct Renin Inhibitors—cont’d
Drug Indication Dose Form Initial Dose Maintenance Dose
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302
Table 16–2 ” Dosage Schedules: Angiotensin-Converting-Enzyme Inhibitors and Angiotensin II
Receptor Blockers and Direct Renin Inhibitors—cont’d
Drug Indication Dose Form Initial Dose Maintenance Dose
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303
Table 16–2 ” Dosage Schedules: Angiotensin-Converting-Enzyme Inhibitors and Angiotensin II
Receptor Blockers and Direct Renin Inhibitors—cont’d
Drug Indication Dose Form Initial Dose Maintenance Dose
DRI
Drug Interactions
Table 16–3 # Drug Interactions: Angiotensin-Converting-Enzyme Inhibitors, Angiotensin II Receptor
Antagonists, and Direct Renin Inhibitors
Drug Interacting Drug Possible Effect Implications
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Clinical Use and Dosing
304
Table 16–3 # Drug Interactions: Angiotensin-Converting-Enzyme Inhibitors, Angiotensin II Receptor
Antagonists, and Direct Renin Inhibitors—cont’d
Drug Interacting Drug Possible Effect Implications
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305
Table 16–4 $ Indication and Dosage Forms: Selected ACEI and ARB Combinations
Drug Indication Dosage Form Initial Dosing Maintenance Dosing
ACEI
ARB
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306
Table 16–4 $ Indication and Dosage Forms: Selected ACEI and ARB Combinations—cont’d
Drug Indication Dosage Form Initial Dosing Maintenance Dosing
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Rational Drug Selection
Monitoring
307
CLINICAL PEARL
Many brand-name ACEIs have the same cost for dif-
ferent strengths. It is possible to prescribe a high
strength of the drug and have the patient halve it to
achieve the desired dose, resulting in considerable
cost savings.
CLINICAL PEARL
If you hear an abdominal bruit in a patient known to
have vascular disease, give captopril, a short-acting
ACEI, and measure serum creatinine prior to the dose
and within 1 or 2 days after the dose. A rapid rise in the
creatinine level suggests renal artery stenosis. A slower
rise probably indicates a problem with poor hydration
that can be corrected by rehydrating the patient and
discontinuing or lowering the dose of any diuretics the
patient is taking.
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Patient Education
CALCIUM CHANNEL BLOCKERS
Pharmacodynamics
308
CLINICAL PEARL
Patients should be monitored for indications of an-
gioedema. Suspect angioedema in any patient who calls
the next morning after taking the first dose and com-
plains of voice changes or swollen lips or tongue. Stop
the drug immediately. The symptoms recede as the drug
is eliminated. Protection of the airway is rarely needed,
but careful assessment of airway status is required.
3827_Ch16_295-360 01/07/15 5:26 PM Page 308

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
309
Ca2+ channels
Ca2+ channel blockers
Intracellular Ca2+ ATP
Beta2 agonists
(+)
(+)
Calmodulin
Ca2+-calmodulin complex
MLCK Myosin-LC kinase MLCK-(PO4)2
Myosin
light
chain
Myosin-LC-PO4 Myosin-LC
Actin
Relaxation
cAMP
Contraction
(–)
Figure 16–2. Control of smooth muscle contraction. Contraction is triggered by the influx of calcium (Ca) through transmembrane calcium
channels. The calcium combines with calmodulin to form a complex that converts the enzyme myosin light-chain kinase (MLCK) to its active
form. The latter phosphorylates the myosin light chains, initiating the interaction of myosin with actin that produces contraction. Relaxation
begins with the reabsorption of calcium, removing it from interaction with the myosin system. Substances that increase cyclic adenosine
monophosphate (cAMP), including beta agonists, may cause relaxation in smooth muscle by accelerating the inactivation of MLCK.
3827_Ch16_295-360 01/07/15 5:26 PM Page 309

310
Table 16–5 ! Pharmacokinetics: Calcium Channel Blockers
Onset Duration Protein Oral
Drug (h) Peak (h) (h) Binding Bioavailability Half-Life (h) Elimination
Dihydropyridines
Type 1 CCB
Pharmacotherapeutics
Precautions and Contraindications
3827_Ch16_295-360 01/07/15 5:26 PM Page 310

Adverse Drug Reactions
Drug Interactions
311
Table 16–6 # Drug Interactions: Selected Calcium Channel Blockers
Drug Interacting Drug Possible Effect Implications
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312
Table 16–6 # Drug Interactions: Selected Calcium Channel Blockers—cont’d
Drug Interacting Drug Possible Effect Implications
Food Interactions
Clinical Use and Dosing
CLINICAL PEARL
Amlodipine can be crushed and put down a nasogas-
tric (NG) tube, which is not possible with sustained-
release preparations. This provides the clinical
advantage of allowing amlodipine to act as if it were
sustained-release with less venous pooling, less re-
flex tachycardia, and once-daily dosing.
CLINICAL PEARL
Constipation is especially common with verapamil,
with almost 100% of patients experiencing significant
issues. Patients taking this drug should be encouraged
to increase the fiber in their diet and may need to use
a stool softener.
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313
Table 16–7 ” Dosage Schedule: Selected Calcium Channel Blockers
Drug Indication Dosage Forms Starting Dose Maintenance Dose
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314
Table 16–7 ” Dosage Schedule: Selected Calcium Channel Blockers—cont’d
Drug Indication Dosage Forms Starting Dose Maintenance Dose
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Rational Drug Selection
315
CLINICAL PEARL
The delivery system for nifedipine (Procardia XL) is
excreted in the feces as a whole orange capsule. This
does not mean that the liquid drug inside the capsule
was not absorbed. To avoid alarm, the patient should be
warned about this.
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Monitoring
Patient Education
CARDIAC GLYCOSIDES
Pharmacodynamics
Mechanical Effects on Heart Muscle
Electrical Effects on Heart Muscle
316
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Other Effects
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
317
1. Digoxin inhibits
Na+/K+ pump
2. Na+ builds
up in the cell
Cell
membrane
4. Calcium ion
increases in cell
3. Decreased gradient
for Na+ to run Na+/Ca2+
transporterK+
Na
Na
Di
go
xi
n
Ca
pump
2Napump
/K+
+
Na+
Na+
Na+ Na+
Na+ Ca2+
Ca2+
Ca2+
+
+
+
Figure 16–3. Effects of digoxin on the sodium–potassium
pump. The sodium pump is the major determinant of the
concentration of sodium in the cell. Inhibition of this pump
results in sodium buildup inside the cell. The resultant
decrease in sodium gradient reduces the sodium–calcium
transport mechanism, and calcium ions also increase in-
side the cell. The influx of sodium through voltage-gated
channels is a major determinant in cardiac action poten-
tials. This influx is reduced when the sodium gradient is
decreased. Ultimately, contraction of cardiac muscle re-
sults from the interaction of calcium with the actin–myosin
system. Reduced extracellular calcium levels decrease this
contraction.
Table 16–8 ! Pharmacokinetics: Cardiac Glycosides
Time to
Protein Oral Steady Volume of
Drug Onset Peak Duration Binding Bioavailability Half-Life State Distribution Elimination
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Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
318
3827_Ch16_295-360 01/07/15 5:26 PM Page 318

Drug Interactions
319
CLINICAL PEARL
A full neutralizing dose of Digibind is expensive (up
to 20 vials at $750 per vial). This cost should be con-
sidered in deciding to treat patients with suspected
or non–life-threatening toxicity. It should also be re-
membered that Digibind has a half-life of 2 to 6 hours,
and during that time the rhythm disturbance for which
the CG was given may recur and cannot be treated
with a CG.
Table 16–9 # Drug Interactions: Cardiac Glycosides
Drug Interacting Drug Possible Effect Implications
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Clinical Use and Dosing
320
Table 16–9 # Drug Interactions: Cardiac Glycosides—cont’d
Drug Interacting Drug Possible Effect Implications
Food Interactions
Table 16–10 ” Dosage Schedule: Cardiac Glycosides
Drug Form Indication Patient Status Digitalizing or Loading Dose Maintenance
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Rational Drug Selection
321
Table 16–10 ” Dosage Schedule: Cardiac Glycosides—cont’d
Drug Form Indication Patient Status Digitalizing or Loading Dose Maintenance
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Monitoring
Patient Education
322
CLINICAL PEARL
Heart failure treatment
1. CGs should not be used unless there is clear evi-
dence of severe chronic systolic dysfunction or atrial
fibrillation. In older adults, ankle edema is more often
due to venous insufficiency than to heart failure.
Even if it is related to heart failure, it is more often
caused by diastolic dysfunction and better treated
with diuretics or ACEIs.
2. Digoxin should not be discontinued unless a re-
versible cause of the heart failure has been com-
pletely corrected or there was no basis for the drug
in the first place.
3. ST-T wave changes on the ECG do not correlate di-
rectly with serum drug levels and should not be used
as an indication of toxicity. Serum drug levels are
needed.
3827_Ch16_295-360 01/07/15 5:26 PM Page 322

ANTIARRHYTHMICS Pharmacodynamics
323
Ph
as
e
0
M
em
br
an
e
po
te
nt
ia
l (
m
illi
vo
lts
)
Time (milliseconds)
-100
0
ERP RRP
Phase 1
Phase 2
Phase 3
Phase 4
50 100 150 200 250
-80
-60
-40
-20
0
+20
+40
ERP: effective refractory period
RRP: relative refractory period
TP: threshold potential
RP: resting potential
TP
RP
Figure 16–4. Cardiac action potential: ventricles.
3827_Ch16_295-360 01/07/15 5:26 PM Page 323

Class I
Class II
Class III
324
Table 16–11 Mechanism of Action of Selected Antiarrhythmics
Effect on Effect on Effect Sinoatrial
Sinoatrial Atrioventricular Node Effect on Effect on on QT Node
Drug Rate Refractory Period PR Interval QRS Duration Interval Automaticity
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Class IV
Pharmacokinetics
Absorption and Distribution Metabolism and Excretion
325
Table 16–12 ! Pharmacokinetics: Selected Antiarrhythmics
Protein Active
Drug Onset Peak Duration Bioavailability Binding Half-Life Metabolite Elimination
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Pharmacotherapeutics
Precautions and Contraindications
326
CLINICAL PEARL
For patients with diabetes who must take a beta
blocker, the diaphoresis associated with hypoglycemia
is not masked by these drugs, and diabetics should be
taught to recognize this indication of hypoglycemia.
3827_Ch16_295-360 01/07/15 5:26 PM Page 326

Adverse Drug Reactions Drug Interactions
327
Table 16–13 # Drug and Food Interactions: Selected Antiarrhythmics
Drug Interacting Drug/Food Possible Effect Implications
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328
Table 16–13 # Drug and Food Interactions: Selected Antiarrhythmics—cont’d
Drug Interacting Drug/Food Possible Effect Implications
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329
Table 16–13 # Drug and Food Interactions: Selected Antiarrhythmics—cont’d
Drug Interacting Drug/Food Possible Effect Implications
Clinical Use and Dosing
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Rational Drug Selection
Monitoring
330
3827_Ch16_295-360 01/07/15 5:26 PM Page 330

Patient Education
331
Table 16–14 Monitoring Parameters for Selected Antiarrhythmics
Drug Parameters Timing Comments
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332
Table 16–15 ” Dosage Schedule for Selected Outpatient Labeled Uses: Selected Antiarrhythmics
Indication/Plasma
Drug Concentration Dosage Forms Starting Dose Maintenance Dose
3827_Ch16_295-360 01/07/15 5:26 PM Page 332

NITRATES
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
333
3827_Ch16_295-360 01/07/15 5:26 PM Page 333

334
Nitrates Endothelial cells
Guanylyl cyclaseGuanylyl cyclase (activated)
cGMP
Myosin-LC
Relaxation
MLCK
(activated)
Nitric oxide
GTP
Myosin-LC
Actin
Myosin-LC-PO4
Contraction
Figure 16–5. Action of substances
that increase nitric oxide concentra-
tion in smooth muscle cells. Nitrates,
nitrites, and other substances that
increase nitric oxide concentration
in smooth muscle cells potentiate the
activation of guanylyl cyclase. Acti-
vated guanylyl cyclase then facilitates
the production of cyclic guanosine
monophosphate (cGMP). Through a
series of not clearly known interme-
diate steps, the cGMP facilitates the
dephosphorylation of the myosin light
chain, resulting in muscle relaxation.
Table 16–16 ! Pharmacokinetics: Selected Nitrates
Drug Onset Peak Duration Metabolite Half-Life Excretion
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Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
335
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336
Table 16–17 # Drug Interactions: Nitrates
Drug Interacting Drug Possible Effect Implications
Table 16–18 ” Dosage Schedule: Selected Nitrates
Clinical Use Dosage Form Starting Dose Maintenance Dose
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Rational Drug Selection
Monitoring
337
CLINICAL PEARL
Patients with migraine headaches are especially at risk
for nitrate headaches. Start them first on a beta blocker
for migraine prophylaxis, and then add the nitrate to
prevent the problem with chronic use.
3827_Ch16_295-360 01/07/15 5:26 PM Page 337

Patient Education
PERIPHERAL VASODILATORS (PADs)
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
338
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339
Table 16–19 ! Pharmacokinetics: Selected Peripheral Vasodilators
Drug Onset Peak Duration Protein Binding Bioavailability Half-Life Elimination
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Table 16–20 # Drug Interactions: Peripheral Vasodilators
Drug Interacting Drug Possible Effect Implications
3827_Ch16_295-360 01/07/15 5:26 PM Page 339

Rational Drug Selection
Monitoring
Patient Education ANTILIPIDEMICS
340
Table 16–21 ” Dosage Schedule and Available Dosage Forms: Peripheral Vasodilators
Available Dosage
Drug Indication Form Starting Dose Maintenance Dose
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341
On The
Horizon CEPTS
Cholesterol ester transfer proteins (CEPTs) facilitate turning
good HDL cholesterol into atherogenic VLDL/LDL particles.
Drugs in the pipeline inhibit this protein and it is hoped that
they will increase HDL levels. The REVEAL and ACELERATE
clinical trials will not publish until 2016.
Pharmacodynamics
Resins
Hepatocyte
Acetyl-CoA
HMG-CoA
HMG-CoA
reductase
inhibitors
LDL
VLDL
Blood
R
Niacin
Bile acids
Cholesterol
Gut
B-100
B-
10
0
Figure 16–6. Sites of action of antihyperlipidemics.
3827_Ch16_295-360 01/07/15 5:26 PM Page 341

Pharmacokinetics
Absorption and Distribution
342
On The
Horizon
PROPROTEIN CONVERTASE SUBTILISIN/
KESIN TYPE 9 INHIBITORS
A new biological drug class called proprotein convertase
subtilisin/kesin type 9 inhibitors helps clear LDL. Studies done
on statin-intolerant patients demonstrated over 50% of LDL
reduction in just 12 weeks. These monoclonal antibodies do
appear to have a neurological adverse side effect profile.
Because they are just coming to market, they are not further
covered in this chapter.
PHARMACOMETABOLICS
The new field of pharmacometabolics uses genetic and environ-
mental data to inform treatment choices. The microbiome of the
gut is being studied as the reason why some patients respond to
statins and others do not. Bacteria modify the drug into its active
metabolites. Poor responders do not have good levels of bile
acids mediated by gut flora (Kaddurah-Daouk et al, 2011).
Metabolism and Excretion
On The
Horizon
3827_Ch16_295-360 01/07/15 5:26 PM Page 342

343
Table 16–22 ! Pharmacokinetics: Selected Antilipidemics
Drug Onset Peak Duration Protein Binding Bioavailability Half-Life Elimination
Pharmacotherapeutics
Precautions and Contraindications
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344
Table 16–23 # Drug Interactions: Selected Antilipidemics
Drug Interacting Drug Possible Effect Implications
3827_Ch16_295-360 01/07/15 5:26 PM Page 344

345
Table 16–23 # Drug Interactions: Selected Antilipidemics—cont’d
Drug Interacting Drug Possible Effect Implications
Adverse Drug Reactions
3827_Ch16_295-360 01/07/15 5:26 PM Page 345

Drug Interactions
Clinical Use and Dosing
346
Table 16–24 ” Dosage Schedule: Selected Antilipidemics Labeled Uses
Drug Indication Dosage Form Starting Dose Maintenance Dose
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347
Table 16–24 ” Dosage Schedule: Selected Antilipidemics Labeled Uses—cont’d
Drug Indication Dosage Form Starting Dose Maintenance Dose
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348
Table 16–24 ” Dosage Schedule: Selected Antilipidemics Labeled Uses—cont’d
Drug Indication Dosage Form Starting Dose Maintenance Dose
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Rational Drug Selection
Monitoring
349
3827_Ch16_295-360 01/07/15 5:26 PM Page 349

Patient Education
DIURETICS
Pharmacodynamics
350
3827_Ch16_295-360 01/07/15 5:26 PM Page 350

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
351
+
Na
K2CI

Na
K2CI

PROXIMAL CONVOLUTED TUBULE DISTAL CONVOLUTED TUBULE
Na
NaCl
Amino acids
Glucose
HCO3– PO43 –
GLOMERULUS
NaCl
CORTEX
MEDULLA
Na+
PARS
RECTA
Urea
ASCENDING LIMB
ANP
sensitive
Urea DESCENDING LIMB
H2O
H2O
Urea Passive
H2O
(with ADH)
H2O
no
ADH
Na
KFurosemide sensitive
Aldosterone
sensitive
THICK
ASCENDING
LIMB
Thiazide
sensitive
COLLECTING
DUCT
H2O
H2O
(with ADH)
no
ADH
Na
Passive
NaCl
NaCI
Organic acids
+
+
+
Figure 16–7. Sites of action of diuretics.
3827_Ch16_295-360 01/07/15 5:26 PM Page 351

Pharmacotherapeutics
Precautions and Contradictions
Adverse Drug Reactions
352
Table 16–25 ! Pharmacokinetics: Selected Diuretics
Drug Onset (h) Peak (h) Duration (h) Protein Binding Bioavailability Half-Life (h) Elimination
Thiazide and Related Diuretics
Loop Diuretics
Potassium-Sparing Diuretics
3827_Ch16_295-360 01/07/15 5:26 PM Page 352

Table 16–26 # Drug Interactions: Selected Diuretics
Drug Interacting Drug Possible Effect Implications
Drug Interactions
353
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354
Table 16–26 # Drug Interactions: Selected Diuretics—cont’d
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
3827_Ch16_295-360 01/07/15 5:26 PM Page 354

355
Table 16–27 ” Dosage Schedule: Selected Diuretics Labeled Use
Drug Indication Dosage Forms Starting Dose Maintenance Dose
3827_Ch16_295-360 01/07/15 5:26 PM Page 355

Rational Drug Selection
356
Table 16–27 ” Dosage Schedule: Selected Diuretics Labeled Use—cont’d
Drug Indication Dosage Forms Starting Dose Maintenance Dose
3827_Ch16_295-360 01/07/15 5:26 PM Page 356

Monitoring
Patient Education
357
3827_Ch16_295-360 01/07/15 5:26 PM Page 357

REFERENCES
358
3827_Ch16_295-360 01/07/15 5:26 PM Page 358

359
3827_Ch16_295-360 01/07/15 5:26 PM Page 359

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361
N
BRONCHODILATORS
BETA2-RECEPTOR AGONISTS
Pharmacodynamics
CHAPTER 17
Teri Moser Woo
BRONCHODILATORS, 361
BETA2RECEPTOR AGONISTS
XANTHINE DERIVATIVES
ANTICHOLINERGICS
LEUKOTRIENE MODIFIERS
RESPIRATORY INHALANTS, 384
CORTICOSTEROIDS
INHALED ANTIINFLAMMATORY AGENTS
INHALED ANTIHISTAMINES
OXYGEN
ALLERGY MEDICATIONS, 396
ANTIHISTAMINES
COUGH AND COLD MEDICATIONS, 404
DECONGESTANTS
ANTITUSSIVES
EXPECTORANTS
3827_Ch17_361-414 02/07/15 12:11 PM Page 361

Metabolism and Excretion
362
Pharmacokinetics
Absorption and Distribution
3827_Ch17_361-414 02/07/15 12:11 PM Page 362

Pharmacotherapeutics
Precautions and Contraindications
363
Table 17–1 ! Pharmacokinetics: Selected Bronchodilators
Drug Onset Peak Duration Half-Life Metabolism Elimination
Beta2 Agonists
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364
Table 17–1 ! Pharmacokinetics: Selected Bronchodilators—cont’d
Drug Onset Peak Duration Half-Life Metabolism Elimination
Anticholinergic
Xanthine Derivatives
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Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
365
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366
Table 17–2 ” Drug Interactions: Selected Bronchodilators
Drug Interacting Drug Possible Effect Implications
Beta2 Agonists
3827_Ch17_361-414 02/07/15 12:11 PM Page 366

367
Table 17–2 ” Drug Interactions: Selected Bronchodilators—cont’d
Drug Interacting Drug Possible Effect Implications
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368
Table 17–2 ” Drug Interactions: Selected Bronchodilators—cont’d
Drug Interacting Drug Possible Effect Implications
Anticholinergics
Xanthine Derivatives
3827_Ch17_361-414 02/07/15 12:11 PM Page 368

369
3827_Ch17_361-414 02/07/15 12:11 PM Page 369

Rational Drug Selection
370
Table 17–3 # Dosage Schedule: Selected Bronchodilators
Drug Indication Dosage Form Dose Comments
Beta2 Agonists
INHALER
INHALATION
SOLUTION
ORAL
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371
Table 17–3 # Dosage Schedule: Selected Bronchodilators—cont’d
Drug Indication Dosage Form Dose Comments
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372
Table 17–3 # Dosage Schedule: Selected Bronchodilators—cont’d
Drug Indication Dosage Form Dose Comments
Anticholinergics
Combination Medications
Xanthine Derivatives
IMMEDIATE-RELEASE
3827_Ch17_361-414 02/07/15 12:11 PM Page 372

Monitoring
Patient Education
373
Table 17–3 # Dosage Schedule: Selected Bronchodilators—cont’d
Drug Indication Dosage Form Dose Comments
TIMED-RELEASE
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XANTHINE DERIVATIVES
Pharmacodynamics
374
CLINICAL PEARL
Administering a medication via a nebulizer to an infant
or toddler is, at times, a challenge. A pediatric mask
may be used if the child tolerates it. One trick is to
“blow” the nebulized medication into the patient’s face
near the nose and mouth. This is achieved by occluding
the mouthpiece end of the unit and aiming the “tail”
end toward the patient’s nose and mouth. This is espe-
cially effective if the child is sleeping and needs the
medication. Another suggestion to parents of young
children is to read a book to the child during the treat-
ment or play an appropriate short video to make the
time pass more quickly.
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Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug and Food Interactions
375
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Clinical Use and Dosing
376
3827_Ch17_361-414 02/07/15 12:11 PM Page 376

Rational Drug Selection
Monitoring
Patient Education
ANTICHOLINERGICS
377
3827_Ch17_361-414 02/07/15 12:11 PM Page 377

Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
378
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Drug Interactions
Clinical Use and Dosage
Rational Drug Selection
379
3827_Ch17_361-414 02/07/15 12:11 PM Page 379

Monitoring
Patient Education
LEUKOTRIENE MODIFIERS
Pharmacodynamics
Leukotriene-Receptor Agonists
380
3827_Ch17_361-414 02/07/15 12:11 PM Page 380

5-Lipoxygenase Pathway Inhibitors
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
381
Table 17–4 ! Pharmacokinetics: Leukotriene Modifiers
Protein
Drug Onset Peak Duration Binding Bioavailability Half-Life Metabolism Elimination
3827_Ch17_361-414 02/07/15 12:11 PM Page 381

Adverse Reactions
Drug Interactions
382
Table 17–5 ” Drug Interactions: Leukotriene Modifiers
Drug Interacting Drug Possible Effect Implications
3827_Ch17_361-414 02/07/15 12:11 PM Page 382

Clinical Use and Dosing Rational Drug Selection
Monitoring
Patient Education
383
Table 17–5 ” Drug Interactions: Leukotriene Modifiers—cont’d
Drug Interacting Drug Possible Effect Implications
Table 17–6 # Dosage Schedule: Leukotriene Modifiers
Drug Indication Dosage Form Dose Comments
3827_Ch17_361-414 02/07/15 12:11 PM Page 383

RESPIRATORY INHALANTS
CORTICOSTEROIDS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
384
3827_Ch17_361-414 02/07/15 12:11 PM Page 384

Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
385
Table 17–7 ! Pharmacokinetics: Respiratory Inhalants
Protein
Drug Onset Peak Binding Bioavailability Half-Life Metabolism Elimination
Corticosteroids
Inhaled Antihistamine
Anti-Inflammatory Agents
3827_Ch17_361-414 02/07/15 12:11 PM Page 385

Adverse Reactions
Drug Interactions
Clinical Use and Dosing
386
3827_Ch17_361-414 02/07/15 12:11 PM Page 386

387
Table 17–8 ” Drug Interactions: Respiratory Inhalants
Drug Interacting Drug Possible Effect Implications
Corticosteroids
Inhaled Antihistamines
Anti-Inflammatory Agents
Table 17–9 # Dosage Schedule: Respiratory Inhalants
Drug Indication Dosage Form Dose Comments
Corticosteroids
3827_Ch17_361-414 02/07/15 12:11 PM Page 387

388
Table 17–9 # Dosage Schedule: Respiratory Inhalants—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch17_361-414 02/07/15 12:11 PM Page 388

389
Table 17–9 # Dosage Schedule: Respiratory Inhalants—cont’d
Drug Indication Dosage Form Dose Comments
3827_Ch17_361-414 02/07/15 12:11 PM Page 389

390
Table 17–9 # Dosage Schedule: Respiratory Inhalants—cont’d
Drug Indication Dosage Form Dose Comments
Inhaled Antihistamine
Anti-Inflammatory Agents
3827_Ch17_361-414 02/07/15 12:11 PM Page 390

Rational Drug Selection
Monitoring
Patient Education
391
3827_Ch17_361-414 02/07/15 12:11 PM Page 391

INHALED ANTI-INFLAMMATORY
AGENTS
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Reactions
Drug Interactions
Clinical Use and Dosing
392
3827_Ch17_361-414 02/07/15 12:11 PM Page 392

Rational Drug Selection
Monitoring
Patient Education
INHALED ANTIHISTAMINES
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
393
3827_Ch17_361-414 02/07/15 12:11 PM Page 393

Adverse Reactions
Drug Interactions
Clinical Use and Dosing
Rational Drug Selection
Monitoring
Patient Education
OXYGEN
Pharmacodynamics
394
3827_Ch17_361-414 02/07/15 12:11 PM Page 394

Pharmacokinetics
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
395
3827_Ch17_361-414 02/07/15 12:11 PM Page 395

Monitoring
Patient Education
ALLERGY MEDICATIONS
ANTIHISTAMINES
Pharmacodynamics
396
3827_Ch17_361-414 02/07/15 12:11 PM Page 396

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
397
3827_Ch17_361-414 02/07/15 12:11 PM Page 397

398
Table 17–10 ! Pharmacokinetics: Selected Antihistamines
Protein
Drug Onset Peak Duration Binding Half-Life Metabolism Elimination
First-Generation Antihistamines
Second-Generation Antihistamines
3827_Ch17_361-414 02/07/15 12:11 PM Page 398

Adverse Drug Reactions
Drug Interactions
399
Table 17–11 ” Drug Interactions: Selected Antihistamines
Drug Interacting Drug Possible Effect Implications
First-Generation Antihistamines
3827_Ch17_361-414 02/07/15 12:11 PM Page 399

400
Table 17–11 ” Drug Interactions: Selected Antihistamines—cont’d
Drug Interacting Drug Possible Effect Implications
Second-Generation Antihistamines
3827_Ch17_361-414 02/07/15 12:11 PM Page 400

Clinical Use and Dosing
401
Table 17–11 ” Drug Interactions: Selected Antihistamines—cont’d
Drug Interacting Drug Possible Effect Implications
Table 17–12 # Dosage Schedule: Selected Antihistamines
Drug Indication Dosage Form Dose Comments
First-Generation Antihistamines
3827_Ch17_361-414 02/07/15 12:11 PM Page 401

402
Table 17–12 # Dosage Schedule: Selected Antihistamines—cont’d
Drug Indication Dosage Form Dose Comments
Second-Generation Antihistamines
3827_Ch17_361-414 02/07/15 12:11 PM Page 402

403
Table 17–12 # Dosage Schedule: Selected Antihistamines—cont’d
Drug Indication Dosage Form Dose Comments
Rational Drug Selection
3827_Ch17_361-414 02/07/15 12:11 PM Page 403

Monitoring
Patient Education
COUGH AND COLD MEDICATIONS
DECONGESTANTS
Pharmacodynamics
404
3827_Ch17_361-414 02/07/15 12:11 PM Page 404

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
405
Table 17–13 ! Pharmacokinetics: Selected Decongestants
Drug Onset Peak Duration Protein Binding Half-Life Metabolism Elimination
Systemic
Topical
3827_Ch17_361-414 02/07/15 12:11 PM Page 405

Drug Interactions
Clinical Use and Dosing
406
Table 17–14 ” Drug Interactions: Selected Decongestants
Drug Interacting Drug Possible Effect Implications
Systemic
Topical
3827_Ch17_361-414 02/07/15 12:11 PM Page 406

407
Table 17–15 # Dosage Schedule: Selected Decongestants
Drug Indication Dosage Form Dose Comments
Systemic
Topical
3827_Ch17_361-414 02/07/15 12:11 PM Page 407

Rational Drug Selection
Monitoring
Patient Education
ANTITUSSIVES
Pharmacodynamics
408
3827_Ch17_361-414 02/07/15 12:11 PM Page 408

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Drug Interactions
409
Table 17–16 ! Pharmacokinetics: Selected Cough Preparations
Drug Onset Peak Duration Protein Binding Half-Life Metabolism Elimination
Expectorants
3827_Ch17_361-414 02/07/15 12:11 PM Page 409

Clinical Use and Dosing
Rational Drug Selection
Monitoring
410
Table 17–17 ” Drug Interactions: Selected Cough Preparations
Drug Interacting Drug Possible Effect Implications
Antitussives
Expectorants
3827_Ch17_361-414 02/07/15 12:11 PM Page 410

Patient Education
EXPECTORANTS
411
Table 17–18 # Dosage Schedule: Selected Cough Preparations
Drug Indication Dosage Form Dose Comments
Antitussives
Expectorants
3827_Ch17_361-414 02/07/15 12:11 PM Page 411

Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Effects
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
REFERENCES
412
3827_Ch17_361-414 02/07/15 12:11 PM Page 412

413
3827_Ch17_361-414 02/07/15 12:11 PM Page 413

3827_Ch17_361-414 02/07/15 12:11 PM Page 414

415
CHAPTER 18
Teri Moser Woo • Kristen Osborne
ANTICOAGULANTS AND ANTIPLATELETS, 415
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
HEMATOPOIETIC GROWTH FACTORS, 430
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
IRON PREPARATIONS, 436
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
FOLIC ACID, 441
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
VITAMIN B12, 442
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
T
ANTICOAGULANTS
AND ANTIPLATELETS
3827_Ch18_415_446 01/07/15 5:30 PM Page 415

416
Pharmacodynamics
Tissue factor pathway
inhibitor (TFPI)
Factor VII (inhibited by
oral anticoagulant
drugs, i.e., warfarin)
plus tissue factor
Factor VIIa (inhibited by
heparin) minus tissue factor
Factor XIa (downregulated
by protein C act)
Factor IX (inhibited by
oral anticoagulant
drugs, i.e., warfarin)
Factor IXa
(inhibited by heparin)
Factor VIIIa (downregulated
by protein C act)
Factor X (inhibited by
oral anticoagulant drugs,
i.e., warfarin)
Factor Xa (inhibited
by heparin)
Factor Va (downregulated
by protein C act)
Factor II—Prothrombin
(inhibited by oral anticoagulant
drugs, i.e., warfarin)
Factor IIa—Thrombin
(inhibited by heparin)
Factor I—Fibrinogen Factor Ia—Fibrin clot
Figure 18–1. The clotting cascade.
On The
Horizon IDRABIOTAPARINUX
Idraparinux is an analog of fondaparinux given once a week,
but trials were discontinued due to excessive bleeding. Idra-
biotaparinux is a biotinylated version of idraparinux that
is currently being studied for treatment of pulmonary
embolism and is as effective as warfarin with less bleeding
(Büller et al. 2012). Idrabiotaparinux is also being studied
for prophylaxis treatment of DVT (Equinox Investigators,
2011).
3827_Ch18_415_446 01/07/15 5:30 PM Page 416

Pharmacokinetics
Absorption and Distribution
Metabolism and Excretion
417
3827_Ch18_415_446 01/07/15 5:30 PM Page 417

418
Table 18–1 ! Pharmacokinetics: Selected Anticoagulants and Antiplatelets
Drug
Anticoagulants
Antiplatelets
Du ration
Protein
Binding
Bioavailability/
Volume of
Distribution Half-Life EliminationPeakOnset
3827_Ch18_415_446 01/07/15 5:30 PM Page 418

Pharmacotherapeutics
Precautions and Contraindications
419
3827_Ch18_415_446 01/07/15 5:30 PM Page 419

Adverse Drug Reactions
420
3827_Ch18_415_446 01/07/15 5:30 PM Page 420

Drug Interactions
421
CLINICAL PEARL
To maintain anticoagulation in patients with allergic
reactions to warfarin, enoxaparin or fondaparinux
can be given SC long term. The usual dose is 1 mg/kg.
Table 18–2 ” Drug Interactions: Selected Anticoagulants and Antiplatelets
Drug Interacting Drug Possible Effect Implications
Anticoagulants
3827_Ch18_415_446 01/07/15 5:30 PM Page 421

422
Table 18–2 ” Drug Interactions: Selected Anticoagulants and Antiplatelets—cont’d
Drug Interacting Drug Possible Effect Implications
Antiplatelets
3827_Ch18_415_446 01/07/15 5:30 PM Page 422

423
Table 18–2 ” Drug Interactions: Selected Anticoagulants and Antiplatelets—cont’d
Drug Interacting Drug Possible Effect Implications
Clinical Use and Dosing
3827_Ch18_415_446 01/07/15 5:30 PM Page 423

424
3827_Ch18_415_446 01/07/15 5:30 PM Page 424

425
Table 18–3 # Dosage Schedule: Selected Anticoagulants and Antiplatelets
Drug Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch18_415_446 01/07/15 5:30 PM Page 425

426
Table 18–3 # Dosage Schedule: Selected Anticoagulants and Antiplatelets—cont’d
Drug Indication Dosage Form Initial Dose Maintenance Dose
3827_Ch18_415_446 01/07/15 5:30 PM Page 426

427
Table 18–4 Recommended INR Values Based on Reason for Warfarin Use
Reason for Use INR range
3827_Ch18_415_446 01/07/15 5:30 PM Page 427

Rational Drug Selection
Monitoring
428
3827_Ch18_415_446 01/07/15 5:30 PM Page 428

Patient Education: Anticoagulants
429
3827_Ch18_415_446 01/07/15 5:30 PM Page 429

Patient Education: Antiplatelets
HEMATOPOIETIC GROWTH FACTORS
Pharmacodynamics
430
3827_Ch18_415_446 01/07/15 5:30 PM Page 430

Pharmacokinetics
Absorption and Distribution
431
Myeloid stem cell
Megakaryoblast
Promegakaryocyte
Megakaryocyte
Monoblast
Promonocyte
Pronormoblast
Basophilic
normoblast
Polychromatic
normoblast
Orthochromatic
normoblast
Red
blood cell
Basophil
precursor
Mature
basophil
Monocyte
Myeloblast type I
Myeloblast
type II
Eosinophil
precursor
Promyelocyte Mature
eosinophil
Neutrophil
myelocyte
Neutrophil
metamyelocyte
Neutrophil
band
Segmented
neutrophil
Granulocyte-
macrophage colony-
stimulating factor
(GM-CSF)
Erythropoietin
Granulocyte-macrophage
colony-stimulating
factor (GM-CSF)
= Controlling factor in cell differentiation in each cell line
Thrombopoietin
(Erythropoietin)
Granulocyte colony-stimulating
factor (G-CSF)
Granulocyte-macrophage colony-
stimulating factor (GM-CSF)
Figure 18–2. Development of blood cells.
3827_Ch18_415_446 01/07/15 5:30 PM Page 431

432
Table 18–5 ! Pharmacokinetics: Hematopoietic Growth Factors
Drug Onset Peak Duration Half-Life
Metabolism and Excretion
Pharmacotherapeutics
Precautions and Contraindications
3827_Ch18_415_446 01/07/15 5:30 PM Page 432

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
433
3827_Ch18_415_446 01/07/15 5:30 PM Page 433

434
Table 18–6 ” Drug Interactions: Hematopoietic Growth Factors
Drug Interacting Drug Possible Effect Implications
Table 18–7 # Dosage Schedule: Hematopoietic Growth Factors
Drug Indication Initial Dose Maintenance Dose
3827_Ch18_415_446 01/07/15 5:30 PM Page 434

435
Rational Drug Selection
Monitoring
3827_Ch18_415_446 01/07/15 5:30 PM Page 435

Patient Education
IRON PREPARATIONS
436
Table 18–8 $ Available Dosage Forms: Hematopoietic Growth Factors
Drug Dosage Form Other Forms Cost
3827_Ch18_415_446 01/07/15 5:30 PM Page 436

Pharmacodynamics
437
Mature erythrocytes
(from the bone marrow)
Circulate in the blood-
stream (about 120 days)
Aged, damaged, or abnormal
erythrocytes (removed by the
macrophages of the mononuclear
phagocyte system [MPS])
Macrophages of the MPS in the
spleen, liver, and bone marrow
break down the erythrocytes
Hemoglobin
Heme
Iron
Iron released from the
gastrointestinal epithelial cells
Circulates with its plasma
carrier, transferrin
Returned directly to
the bloodstream
Secreted with bile
Globin
Iron reused (to synthesize new hemoglobin)
by the erythroblasts in the bone marrow
Bilirubin
Stored in the liver
Released from the liver
into the bloodstream
Stored in the spleen
Released from the spleen
into the bloodstream
Figure 18–3. The iron cycle.
On The
Horizon
INTERLEUKIN-3, STEM CELL FACTOR,
AND MONOCYTE-MACROPHAGE
COLONY–STIMULATING FACTOR
IL-3, stem cell factor, and monocyte-macrophage colony–
stimulating factor are currently in clinical trials. IL-3 would
provide broad-based therapy because it is involved in the
generation and stimulation of all progenitor cells. Stem cell
factor would provide therapy at an even earlier stage in blood
cell development. Monocyte-macrophage colony–stimulating
factor would provide a targeted approach to patients who do
not require such a broad stimulation of blood cell growth.
3827_Ch18_415_446 01/07/15 5:30 PM Page 437

Pharmacokinetics
Absorption and Distribution
Metabolism, Storage, and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
438
3827_Ch18_415_446 01/07/15 5:30 PM Page 438

Rational Drug Selection
Monitoring
Patient Education
439
Table 18–9 ” Drug Interactions: Iron
Drug Interacting Drug Possible Effect Implications
3827_Ch18_415_446 01/07/15 5:30 PM Page 439

440
Table 18–10 # Dosage Schedule: Iron
Drug Indication Dosage Form Maintenance Dose
3827_Ch18_415_446 01/07/15 5:30 PM Page 440

FOLIC ACID
Pharmacodynamics
Pharmacokinetics
Absorption and Distribution
Metabolism, Storage, and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
441
3827_Ch18_415_446 01/07/15 5:30 PM Page 441

442
Table 18–11 ” Drug Interactions: Folic Acid
Drug Interacting Drug Possible Effect Implications
Table 18–12 # Dosage Schedule: Folic Acid
Drug Indication Initial Dose Maintenance Dose
Rational Drug Selection
Monitoring
Patient Education
VITAMIN B12
Pharmacodynamics
3827_Ch18_415_446 01/07/15 5:30 PM Page 442

Pharmacokinetics
Absorption and Distribution
Metabolism, Storage, and Excretion
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
443
Table 18–13 $ Available Dosage Forms: Folic Acid
Drug Dosage Form Other Forms Cost
3827_Ch18_415_446 01/07/15 5:30 PM Page 443

444
Table 18–14 ” Drug Interactions: Vitamin B12
Drug Interacting Drug Possible Effect Implications
Table 18–15 # Dosage Schedule: Vitamin B12
Drug Indication Initial Dose Maintenance Dose
3827_Ch18_415_446 01/07/15 5:30 PM Page 444

Rational Drug Selection
Monitoring
Patient Education
445
Table 18–16 $ Available Dosage Forms: Vitamin B12
Drug Dosage Form How Supplied Cost
3827_Ch18_415_446 01/07/15 5:30 PM Page 445

REFERENCES
446
3827_Ch18_415_446 01/07/15 5:30 PM Page 446

447
CHAPTER 19
Teri Moser Woo
IMMUNIZATIONS
ATTENUATED VACCINES, 448
INFLUENZA LIVE, ATTENUATED INFLUENZA VACCINE
MEASLES, MUMPS, AND RUBELLA VACCINE
MEASLES, MUMPS, RUBELLA, AND VARICELLA VACCINE
ORAL POLIOVIRUS VACCINE
ROTAVIRUS VACCINE
VARICELLA VIRUS VACCINE
ZOSTER VACCINE
ORAL TYPHOID VACCINE
YELLOW FEVER VACCINE
BACILLUS CALMETTEGUÉRIN VACCINE
INACTIVATED VACCINES, 471
DIPHTHERIA, TETANUS, AND PERTUSSIS VACCINE
B CONJUGATE VACCINE
INACTIVATED POLIOVIRUS VACCINE
HEPATITIS B VIRUS VACCINE
HEPATITIS A VIRUS VACCINE
HUMAN PAPILLOMAVIRUS VACCINE
INFLUENZA VACCINE
PNEUMOCOCCAL VACCINE
MENINGOCOCCAL VACCINE
LYME DISEASE VACCINE
TYPHOID VACCINE
CHOLERA VACCINE
JAPANESE ENCEPHALITIS VIRUS VACCINE
PLAGUE VACCINE
RABIES VACCINE
IMMUNE GLOBULIN SERUMS
DIAGNOSTIC BIOLOGICALS, 490
TUBERCULIN PURIFIED PROTEIN DERIVATIVE
IMMUNOMODULATORS
P
3827_Ch19_447_496 02/07/15 12:05 PM Page 447

448
Pharmacokinetics
Pharmacotherapeutics
Precautions and Contraindications
Adverse Drug Reactions
Drug Interactions
IMMUNIZATIONS
ATTENUATED VACCINES
INFLUENZA LIVE, ATTENUATED
INFLUENZA VACCINE
Pharmacodynamics
3827_Ch19_447_496 02/07/15 12:05 PM Page 448

Clinical Use and Dosing
Monitoring
Patient Education
MEASLES, MUMPS, AND RUBELLA
VACCINE
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
Precautions and Contraindications
449
3827_Ch19_447_496 02/07/15 12:05 PM Page 449

Adverse Drug Reactions
Drug Interactions
Clinical Use and Dosing
Monitoring
Patient Education
450
3827_Ch19_447_496 02/07/15 12:05 PM Page 450

451
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er
se
e
ve
nt
s t
ha
t f
ol
lo
w

va
cc
in
at
io
n
sh
ou
ld
b
e
re
po
rt
ed
to
th
e
Va
cc
in
e
Ad
ve
rs
e
Ev
en
t R
ep
or
tin
g
Sy
st
em
(V
AE
RS
) o
nl
in
e
(h
tt
p:
//
w
w
w
.v
ae
rs
.h
hs
.g
ov
) o
r b
y
te
le
ph
on
e
(8
00
-8
22
-7
96
7)
. S
us
pe
ct
ed
c
as
es
o
f v
ac
ci
ne
-p
re
ve
nt
ab
le

di
se
as
es
sh
ou
ld
b
e
re
po
rt
ed
to
th
e
st
at
e
or
lo
ca
l h
ea
lth
d
ep
ar
tm
en
t.
Ad
di
tio
na
l i
nf
or
m
at
io
n,
in
cl
ud
in
g
pr
ec
au
tio
ns
a
nd
c
on
tr
ai
nd
ic
at
io
ns
fo
r v
ac
ci
na
tio
n,
is
a
va
ila
bl
e
fro
m
C
D
C
on
lin
e

(h
tt
p:
//
w
w
w
.c
dc
.g
ov
/v
ac
ci
ne
s/
re
cs
/v
ac
-a
dm
in
/c
on
tr
ai
nd
ic
at
io
ns
.h
tm
) o
r b
y
te
le
ph
on
e
(8
00
-C
D
C-
IN
FO
[8
00
-2
32
-4
63
6]
).
Th
is
sc
he
du
le
is
a
pp
ro
ve
d
by
th
e
Ad
vi
so
ry
C
om
m
itt
ee
o
n
Im
m
un
iz
at
io
n
Pr
ac
tic
es
(h
tt
p/
/w
w
w
.c
dc
.g
ov
/v
ac
ci
ne
s/
ac
ip
),
th
e
Am
er
ic
an
A
ca
de
m
y
of
P
ed
ia
tr
ic
s (
ht
tp
://
w
w
w
.a
ap
.o
rg
),
th
e
Am
er
ic
an
A
ca
de
m
y
of

Fa
m
ily
P
hy
sic
ia
ns
(h
tt
p:
//
w
w
w
.a
af
p.
or
g)
, a
nd
th
e
Am
er
ic
an
C
ol
le
ge
o
f O
bs
te
tr
ic
ia
ns
a
nd
G
yn
ec
ol
og
ist
s (
ht
tp
://
w
w
w
.a
co
g.
or
g)
.
N
ot
ro
ut
in
el
y
re
co
m
m
en
de
d
Ra
ng
e
of
re
co
m
m
en
de
d
ag
es
fo
r
ce
rt
ai
n
hi
gh
-r
isk
g
ro
up
s
Ra
ng
e
of
re
co
m
m
en
de
d
ag
es
fo
r a
ll
ch
ild
re
n
Ra
ng
e
of
re
co
m
m
en
de
d
ag
es

fo
r c
at
ch
-u
p
im
m
un
iz
at
io
n
Ra
ng
e
of
re
co
m
m
en
de
d
ag
es
d
ur
in
g
w
hi
ch
c
at
ch
-u
p
is
en
co
ur
ag
ed
a
nd
fo
r
ce
rt
ai
n
hi
gh
-r
isk
g
ro
up
s
Va
cc
in
e
Bi
rt
h
1
m
o
2
m
os
4
m
os
6
m
os
9
m
os
12
m
os
15
m
os
18
m
os
19
–2
3
m
os
2-
3
yr
s
4-
6
yr
s
7-
10
y
rs
11
-1
2
yr
s
13
–1
5
yr
s
16
–1
8
yr
s
H
ep
at
iti
s B
1 (
H
ep
B)
Ro
ta
vi
ru
s2
(R
V)
R
V1
(2
-d
os
e
se
rie
s)
; R
V5
(3
-d
os
e
se
rie
s)
D
ip
ht
he
ria
, t
et
an
us
, &
a
ce
llu
la
r
pe
rt
us
sis
3 (
DT
aP
: < 7 yr s) Te ta nu s, di ph th er ia , & a ce llu la r pe rt us sis 4 (T da p: >
7
yr
s)
ty
pe
b
5
(H
ib
)
Pn
eu
m
oc
oc
ca
l c
on
ju
ga
te
6
(P
CV
13
)
Pn
eu
m
oc
oc
ca
l p
ol
ys
ac
ch
ar
id
e6

(P
PS
V2
3)
In
ac
tiv
at
ed
p
ol
io
vi
ru
s7
(IP
V:
< 18 y rs ) 8 ( IIV ; L AI V) 2 d os es fo r so m e: S ee fo ot no te 8 M ea sle s, m um ps , r ub el la 9 ( M M R) Va ric el la 10 (V AR ) H ep at iti s A 11 (H ep A) H um an p ap ill om av iru s1 2 ( H PV 2: fe m al es o nl y; H PV 4: m al es a nd fe m al es ) M en in go co cc al 13 (H ib -M en CY >
6
w
ee
ks
; M
en
AC
W
Y-
D
>
9
m
os
;
M
en
AC
W
Y-
CR
M
≥
2
m
os
)
Bo
os
te
r
1s
t d
os
e
Se
e
fo
ot
no
te
1
3
(3
-d
os
e
se
rie
s)

An
nu
al
v
ac
ci
na
tio
n
(L
AI
V
or

IIV
) 1
o
r 2
d
os
es
An
nu
al
v
ac
ci
na
tio
n
(II
V
on
ly
) 1
o
r 2
d
os
es
(T
da
p)
Se
e
fo
ot
no
te
2
2n
d d
os
e
1s
t d
os
e
4t
h d
os
e
3r
d d
os
e
2n
d d
os
e
1s
t d
os
e
2-
do
se
se
rie
s,
Se
e
fo
ot
no
te
1
1
4t
h d
os
e
3r
d d
os
e
2n
d
do
se
1s
t d
os
e
2n
d
do
se
1s
t d
os
e
3r
d o
r 4
th
d
os
e,

Se
e
fo
ot
no
te
5
Se
e
fo
ot
no
te
5
2n
d
do
se
1s
t d
os
e
2n
d
do
se
1s
t d
os
e
5t
h d
os
e
4t
h d
os
e
3r
d d
os
e
2n
d d
os
e
1s
t d
os
e
3r
d d
os
e
2n
d d
os
e
1s
t d
os
e
An
nu
al
v
ac
ci
na
tio
n
(L
AI
V
or
II
V)

1
do
se
o
nl
y
Se
e
fo
ot
no
te
9
Ta
bl
e
19
–1
!
Re
co
m
m
en
de
d
Im
m
un
iz
at
io
n
Sc
he
du
le
fo
r P
er
so
ns
A
ge
d
0
Th
ro
ug
h1
8
Ye
ar
s—
U
ni
te
d
St
at
es
, 2
01
5
3827_Ch19_447_496 02/07/15 12:05 PM Page 451

452
Ta
bl
e
19
–1
!
Re
co
m
m
en
de
d
Im
m
un
iz
at
io
n
Sc
he
du
le
fo
r P
er
so
ns
A
ge
d
0
Th
ro
ug
h1
8
Ye
ar
s—
U
ni
te
d
St
at
es
, 2
01
5—
co
nt
’d
Fo
ot
no
te
s —
R
ec
om
m
en
de
d
im
m
un
iz
at
io
n
sc
he
du
le
fo
r p
er
so
ns
a
ge
d
0
th
ro
ug
h
18
y
ea
rs
—
U
ni
te
d
St
at
es
, 2
01
5
Fo
r f
ur
th
er
g
ui
da
nc
e
on
th
e
us
e
of
th
e
va
cc
in
es
m
en
tio
ne
d
be
lo
w
, s
ee
: h
tt
p:
//
w
w
w
.c
dc
.g
ov
/v
ac
ci
ne
s/
hc
p/
ac
ip
-re
cs
/in
de
x.
ht
m
l.

Fo
r v
ac
ci
ne
re
co
m
m
en
da
tio
ns
fo
r p
er
so
ns
1
9
ye
ar
s o
f a
ge
a
nd
o
ld
er
, s
ee
th
e
Ad
ul
t I
m
m
un
iz
at
io
n
Sc
he
du
le
.
Ad
di
tio
na
l i
nf
or
m
at
io
n
•
Fo
r c
on
tr
ai
nd
ic
at
io
ns
a
nd
p
re
ca
ut
io
ns
to
u
se
o
f a
v
ac
ci
ne
a
nd
fo
r a
dd
iti
on
al
in
fo
rm
at
io
n
re
ga
rd
in
g
th
at
v
ac
ci
ne
, v
ac
ci
na
tio
n
pr
ov
id
er
s s
ho
ul
d
c o
ns
ul
t t
he
re
le
va
nt
A
CI
P
st
at
em
en
t a
va
ila
bl
e
on
lin
e
at

ht
tp
://
w
w
w
.cd
c.g
ov
/v
ac
ci
ne
s/
hc
p/
ac
ip
-re
cs
/in
de
x.
ht
m
l.
•
Fo
r p
ur
po
se
s o
f c
al
cu
la
tin
g
in
te
rv
al
s b
et
w
ee
n
do
se
s,
4
w
ee
ks
=
2
8
da
ys
. I
nt
er
va
ls
of
4
m
on
th
s o
r g
re
at
er
a
re
d
et
er
m
in
ed
b
y
ca
le
nd
ar
m
on
th
s.
•
Va
cc
in
e
do
se
s a
dm
in
ist
er
ed
4
d
ay
s o
r l
es
s b
ef
or
e
th
e
m
in
im
um
in
te
rv
al
a
re
c
on
sid
er
ed
v
al
id
. D
os
es
o
f a
ny
v
ac
ci
ne
a
dm
in
ist
er
ed
≥
5
da
ys
e
ar
lie
r t
ha
n
th
e
m
in
im
um
in
te
rv
al
o
r m
in
im
um
a
ge
sh
ou
ld
n
ot

be
c
ou
nt
ed
a
s v
al
id
d
os
es
a
nd
sh
ou
ld
b
e
re
pe
at
ed
a
s a
ge
-a
pp
ro
pr
ia
te
. T
he
re
pe
at
d
os
e
sh
ou
ld
b
e
sp
ac
ed
a
fte
r t
he
in
va
lid
d
os
e
by
th
e
re
co
m
m
en
de
d
m
in
im
um
in
te
rv
al
. F
or
fu
rt
he
r d
et
ai
ls,
se
e M
M
W
R,

Ge
ne
ra
l R
ec
om
m
en
da
tio
ns
o
n
Im
m
un
iza
tio
n
an
d
Re
po
rt
s /
V
ol
. 6
0
/ N
o.
2
; T
ab
le
1
. R
ec
om
m
en
de
d
an
d
m
in
im
um
a
ge
s a
nd
in
te
rv
al
s b
et
w
ee
n
va
cc
in
e d
os
es
a
va
ila
bl
e
on
lin
e
at

ht
tp
://
w
w
w
.cd
c.g
ov
/m
m
w
r/
pd
f/r
r/
rr
60
02
.p
df
.
•
In
fo
rm
at
io
n
on
tr
av
el
v
ac
ci
ne
re
qu
ire
m
en
ts
a
nd
re
co
m
m
en
da
tio
ns
is
a
va
ila
bl
e
at
h
tt
p:
//
w
w
w
nc
.cd
c.g
ov
/t
ra
ve
l/d
es
tin
at
io
ns
/li
st
.
•
in
G
en
er
al
R
ec
om
m
en
da
tio
ns
o
n
Im
m
un
iza
tio
n
(A
CI
P)
, a
va
ila
bl
e
at
h
tt
p:
//
w
w
w
.cd
c.g
ov
/m
m
w
r/
pd
f/r
r/
rr
60
02
.p
df
.; a
nd
A
m
er
ic
an
A
ca
de
m
y
of
P
ed
ia
tr
ic
s.
“Im
m
un
iz
at
io
n
in
S
pe
ci
al
C
lin
ic
al
C
irc
um
st
an
ce
s ,”
in
P
ic
ke
rin
g
LK
, B
ak
er
C
J,
Ki
m
be
rli
n
D
W
, L
on
g
SS
e
ds
. R
ed
B
oo
k:
2
01
2
re
po
rt
o
f t
he
C
om
m
itt
ee
o
n
In
fe
ct
io
us
D
ise
as
es
. 2
9t
h
ed
. E
lk
G
ro
ve
V
ill
ag
e,
IL
: A
m
er
ic
an
A
ca
de
m
y
of
P
ed
ia
tr
ic
s.
1.

H
ep
at
iti
s B
(H
ep
B)
v
ac
ci
ne
. (
M
in
im
um
a
ge
: b
irt
h)
Ro
ut
in
e
va
cc
in
at
io
n:

At
b
irt
h:
•
Ad
m
in
ist
er
m
on
ov
al
en
t H
ep
B
va
cc
in
e
to
a
ll
ne
w
bo
rn
s b
ef
or
e
ho
sp
ita
l d
isc
ha
rg
e.
•
Fo
r i
nf
an
ts
b
or
n
to
h
ep
at
iti
s B
su
rfa
ce
a
nt
ig
en
(H
Bs
Ag
)-p
os
iti
ve
m
ot
he
rs
, a
dm
in
ist
er
H
ep
B
va
cc
in
e
an
d
0.
5
m
L
of
h
ep
at
iti
s B
im
m
un
e
gl
ob
ul
in
(H
BI
G
) w
ith
in
1
2
ho
ur
s o
f b
irt
h.
T
he
se
in
fa
nt
s s
ho
ul
d
be
te
st
ed

fo
r H
Bs
Ag
a
nd
a
nt
ib
od
y
to
H
Bs
Ag
(a
nt
i-H
Bs
) 1
to
2
m
on
th
s a
fte
r c
om
pl
et
io
n
of
th
e
H
ep
B
se
rie
s a
t a
ge
9

th
ro
ug
h
18
m
on
th
s (
pr
ef
er
ab
ly
a
t t
he
n
ex
t w
el
l-c
hi
ld
v
isi
t).
•
If
m
ot
he
r’s
H
Bs
Ag
st
at
us
is
u
nk
no
w
n,
w
ith
in
1
2
ho
ur
s o
f b
irt
h
ad
m
in
ist
er
H
ep
B
va
cc
in
e
re
ga
rd
le
ss
o
f b
irt
h
w
ei
gh
t.
Fo
r i
nf
an
ts
w
ei
gh
in
g
le
ss
th
an
2
,0
00
g
ra
m
s,
ad
m
in
ist
er
H
BI
G
in
a
dd
iti
on
to
H
ep
B
va
cc
in
e
w
ith
in

12
h
ou
rs
o
f b
irt
h.
D
et
er
m
in
e
m
ot
he
r’s
H
Bs
Ag
st
at
us
a
s s
oo
n
as
p
os
sib
le
a
nd
, if
m
ot
he
r i
s H
Bs
Ag
-p
os
iti
ve
,
al
so
a
dm
in
ist
er
H
BI
G
fo
r i
nf
an
ts
w
ei
gh
in
g
2,
00
0
gr
am
s o
r m
or
e
as
so
on
a
s p
os
sib
le
, b
ut
n
o
la
te
r t
ha
n
ag
e
7
da
ys
.
D
os
es
fo
llo
w
in
g
th
e
bi
rt
h
do
se
:
•
Th
e
se
co
nd
d
os
e
sh
ou
ld
b
e
ad
m
in
ist
er
ed
a
t a
ge
1
o
r 2
m
on
th
s.
M
on
ov
al
en
t H
ep
B
va
cc
in
e
sh
ou
ld
b
e
us
ed
fo
r d
os
es
a
dm
in
ist
er
ed
b
ef
or
e
ag
e
6
w
ee
ks
.
•
In
fa
nt
s w
ho
d
id
n
ot
re
ce
iv
e
a
bi
rt
h
do
se
sh
ou
ld
re
ce
iv
e
3
do
se
s o
f a
H
ep
B-
co
nt
ai
ni
ng
v
ac
ci
ne
o
n
a
sc
he
du
le
o
f 0
, 1
to
2
m
on
th
s,
an
d
6
m
on
th
s s
ta
rt
in
g
as
so
on
a
s f
ea
sib
le
. S
ee
F
ig
ur
e
2.
•
th
e
th
ird
d
os
e
at
le
as
t 8
w
ee
ks
a
fte
r t
he
se
co
nd
d
os
e
AN
D
a
t l
ea
st
1
6
w
ee
ks
a
fte
r t
he

(th
ird
o
r f
ou
rt
h)
d
os
e
in
th
e
H
ep
B
va
cc
in
e
se
rie
s s
ho
ul
d
be
a
dm
in
ist
er
ed
n
o
ea
rli
er
th
an
a
ge
2
4
w
ee
ks
.
•
Ad
m
in
ist
ra
tio
n
of
a
to
ta
l o
f 4
d
os
es
o
f H
ep
B
va
cc
in
e
is
pe
rm
itt
ed
w
he
n
a
co
m
bi
na
tio
n
va
cc
in
e
co
nt
ai
ni
ng

H
ep
B
is
ad
m
in
ist
er
ed
a
fte
r t
he
b
irt
h
do
se
.
Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
U
nv
ac
ci
na
te
d
pe
rs
on
s s
ho
ul
d
co
m
pl
et
e
a
3-
do
se
se
rie
s.
•
A
2-
do
se
se
rie
s (
do
se
s s
ep
ar
at
ed
b
y
at
le
as
t 4
m
on
th
s)
o
f a
du
lt
fo
rm
ul
at
io
n
Re
co
m
bi
va
x
H
B
is
lic
en
se
d
fo
r
us
e
in
c
hi
ld
re
n
ag
ed
1
1
th
ro
ug
h
15
y
ea
rs
.
•
Fo
r o
th
er
c
at
ch
-u
p
gu
id
an
ce
, s
ee
F
ig
ur
e
2.
2.

Ro
ta
vi
ru
s (
RV
) v
ac
ci
ne
s.
(M
in
im
um
a
ge
: 6
w
ee
ks
fo
r b
ot
h
RV
1
[R
ot
ar
ix
] a
nd

RV
5
[R
ot
aT
eq
])
Ro
ut
in
e
va
cc
in
at
io
n:
Ad
m
in
ist
er
a
se
rie
s o
f R
V
va
cc
in
e
to
a
ll
in
fa
nt
s a
s f
ol
lo
w
s:
1.
I
f R
ot
ar
ix
is
u
se
d,
a
dm
in
ist
er
a
2
-d
os
e
se
rie
s a
t 2
a
nd
4
m
on
th
s o
f a
ge
.
2.
I
f R
ot
aT
eq
is
u
se
d,
a
dm
in
ist
er
a
3
-d
os
e
se
rie
s a
t a
ge
s 2
, 4
, a
nd
6
m
on
th
s.
3.
I
f a
ny
d
os
e
in
th
e
se
rie
s w
as
R
ot
aT
eq
o
r v
ac
ci
ne
p
ro
du
ct
is
u
nk
no
w
n
fo
r a
ny
d
os
e
in
th
e
se
rie
s,
a
to
ta
l o
f
3
do
se
s o
f R
V
va
cc
in
e
sh
ou
ld
b
e
ad
m
in
ist
er
ed
.
Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
fo
r i
nf
an
ts
a
ge
d
15
w
ee
ks
, 0
d
ay
s o
r o
ld
er
.
• •
Fo
r o
th
er
c
at
ch
-u
p
gu
id
an
ce
, s
ee
F
ig
ur
e
2.
3.

D
ip
ht
he
ria
a
nd
te
ta
nu
s t
ox
oi
ds
a
nd
a
ce
llu
la
r p
er
tu
ss
is
(D
Ta
P)
v
ac
ci
ne
. (
M
in
im
um

ag
e:
6
w
ee
ks
. E
xc
ep
tio
n:
D
Ta
P-
IP
V
[K
in
rix
]:
4
ye
ar
s)
Ro
ut
in
e
va
cc
in
at
io
n:
•
Ad
m
in
ist
er
a
5
-d
os
e
se
rie
s o
f D
Ta
P
va
cc
in
e
at
a
ge
s 2
, 4
, 6
, 1
5
th
ro
ug
h
18
m
on
th
s,
an
d
4
th
ro
ug
h
6
ye
ar
s.

Th
e
fo
ur
th
d
os
e
m
ay
b
e
ad
m
in
ist
er
ed
a
s e
ar
ly
a
s a
ge
1
2
m
on
th
s,
pr
ov
id
ed
a
t l
ea
st
6
m
on
th
s h
av
e
el
ap
se
d
sin
ce
th
e
th
ird
d
os
e.
H
ow
ev
er
, t
he
fo
ur
th
d
os
e
of
D
Ta
P
ne
ed
n
ot
b
e
re
pe
at
ed
if
it
w
as
a
dm
in
ist
er
ed
a
t
le
as
t 4
m
on
th
s a
fte
r t
he
th
ird
d
os
e
of
D
Ta
P.
3.

D
ip
ht
he
ria
a
nd
te
ta
nu
s t
ox
oi
ds
a
nd
a
ce
llu
la
r p
er
tu
ss
is
(D
Ta
P)
v
ac
ci
ne
(c
on
t’d
)
Ca
tc
h-
up
v
ac
ci
na
tio
n:
• •
Fo
r o
th
er
c
at
ch
-u
p
gu
id
an
ce
, s
ee
F
ig
ur
e
2.
4.

Te
ta
nu
s a
nd
d
ip
ht
he
ria
to
xo
id
s a
nd
a
ce
llu
la
r p
er
tu
ss
is
(T
da
p)
v
ac
ci
ne
. (
M
in
im
um

ag
e:
1
0
ye
ar
s f
or
b
ot
h
Bo
os
tr
ix
a
nd
A
da
ce
l)
Ro
ut
in
e
va
cc
in
at
io
n:

•
Ad
m
in
ist
er
1
d
os
e
of
Td
ap
v
ac
ci
ne
to
a
ll
ad
ol
es
ce
nt
s a
ge
d
11
th
ro
ug
h
12
y
ea
rs
.
•
Td
ap
m
ay
b
e
ad
m
in
ist
er
ed
re
ga
rd
le
ss
o
f t
he
in
te
rv
al
si
nc
e
th
e
la
st
te
ta
nu
s a
nd
d
ip
ht
he
ria
to
xo
id
–
co
nt
ai
ni
ng
v
ac
ci
ne
.
•
Ad
m
in
ist
er
1
d
os
e
of
Td
ap
v
ac
ci
ne
to
p
re
gn
an
t a
do
le
sc
en
ts
d
ur
in
g
ea
ch
p
re
gn
an
cy
(p
re
fe
rre
d
du
rin
g
27

th
ro
ug
h
36
w
ee
ks
’ g
es
ta
tio
n)
re
ga
rd
le
ss
o
f t
im
e
sin
ce
p
rio
r T
d
or
Td
ap
v
ac
ci
na
tio
n.

Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
Pe
rs
on
s a
ge
d
7
ye
ar
s a
nd
o
ld
er
w
ho
a
re
n
ot
fu
lly
im
m
un
iz
ed
w
ith
D
Ta
P
va
cc
in
e
sh
ou
ld
re
ce
iv
e
Td
ap

va
cc
in
e.
F
or
c
hi
ld
re
n
7
th
ro
ug
h
10
y
ea
rs
w
ho
re
ce
iv
e
a
do
se
o
f T
da
p
as
p
ar
t o
f t
he
c
at
ch
-u
p
se
rie
s,
an

ad
ol
es
ce
nt
Td
ap
v
ac
ci
ne
d
os
e
at
a
ge
1
1
th
ro
ug
h
12
y
ea
rs
sh
ou
ld
N
O
T
be
a
dm
in
ist
er
ed
. T
d
sh
ou
ld
b
e
ad
m
in
ist
er
ed
in
st
ea
d
10
y
ea
rs
a
fte
r t
he
Td
ap
d
os
e.
•
Pe
rs
on
s a
ge
d
11
th
ro
ug
h
18
y
ea
rs
w
ho
h
av
e
no
t r
ec
ei
ve
d
Td
ap
v
ac
ci
ne
sh
ou
ld
re
ce
iv
e
a
do
se
fo
llo
w
ed
b
y
te
ta
nu
s a
nd
d
ip
ht
he
ria
to
xo
id
(T
d)
b
oo
st
er
d
os
es
e
ve
ry
1
0
ye
ar
s t
he
re
af
te
r.
•
In
ad
ve
rt
en
t d
os
es
o
f D
Ta
P
va
cc
in
e:
–
If
ad
m
in
ist
er
ed
in
ad
ve
rt
en
tly
to
a
c
hi
ld
a
ge
d
7
th
ro
ug
h
10
y
ea
rs
m
ay
c
ou
nt
a
s p
ar
t o
f t
he
c
at
ch
-u
p
se
rie
s.
Th
is
do
se
m
ay
c
ou
nt
a
s t
he
a
do
le
sc
en
t T
da
p
do
se
, o
r t
he
c
hi
ld
c
an
la
te
r r
ec
ei
ve
a
Td
ap
b
oo
st
er

do
se
a
t a
ge
1
1
th
ro
ug
h
12
y
ea
rs
.
–
If
ad
m
in
ist
er
ed
in
ad
ve
rt
en
tly
to
a
n
ad
ol
es
ce
nt
a
ge
d
11
th
ro
ug
h
18
y
ea
rs
, t
he
d
os
e
sh
ou
ld
b
e
co
un
te
d
as
th
e
ad
ol
es
ce
nt
Td
ap
b
oo
st
er
.
•
Fo
r o
th
er
c
at
ch
-u
p
gu
id
an
ce
, s
ee
F
ig
ur
e
2.
5.

ty
pe
b
(H
ib
) c
on
ju
ga
te
v
ac
ci
ne
. (
M
in
im
um
a
ge
: 6
w
ee
ks

fo
r P
RP
-T
[A
CT
H
IB
, D
Ta
P-
IP
V/
H
ib
(P
en
ta
ce
l)
an
d
H
ib
-M
en
CY
(M
en
H
ib
rix
)],
P
RP
-O
M
P
[P
ed
va
xH
IB
o
r C
O
M
VA
X]
, 1
2
m
on
th
s f
or
P
RP
-T
[H
ib
er
ix
])
Ro
ut
in
e
va
cc
in
at
io
n:
•
Ad
m
in
ist
er
a
2
– o
r 3
-d
os
e
H
ib
v
ac
ci
ne
p
rim
ar
y
se
rie
s a
nd
a
b
oo
st
er
d
os
e
(d
os
e
3
or
4
d
ep
en
di
ng
o
n
va
cc
in
e
us
ed
in
p
rim
ar
y
se
rie
s)
a
t a
ge
1
2
th
ro
ug
h
15
m
on
th
s t
o
co
m
pl
et
e
a
fu
ll
H
ib
v
ac
ci
ne
se
rie
s.
•
Th
e
pr
im
ar
y
se
rie
s w
ith
A
ct
H
IB
, M
en
H
ib
rix
, o
r P
en
ta
ce
l c
on
sis
ts
o
f 3
d
os
es
a
nd
sh
ou
ld
b
e
ad
m
in
ist
er
ed
a
t
2,
4
, a
nd
6
m
on
th
s o
f a
ge
. T
he
p
rim
ar
y
se
rie
s w
ith
P
ed
va
xH
ib
o
r C
O
M
VA
X
co
ns
ist
s o
f 2
d
os
es
a
nd
sh
ou
ld

be
a
dm
in
ist
er
ed
a
t 2
a
nd
4
m
on
th
s o
f a
ge
; a
d
os
e
at
a
ge
6
m
on
th
s i
s n
ot
in
di
ca
te
d.
•
O
ne
b
oo
st
er
d
os
e
(d
os
e
3
or
4
d
ep
en
di
ng
o
n
va
cc
in
e
us
ed
in
p
rim
ar
y
se
rie
s)
o
f a
ny
H
ib
v
ac
ci
ne
sh
ou
ld

be
a
dm
in
ist
er
ed
a
t a
ge
1
2
th
ro
ug
h
15
m
on
th
s.
An
e
xc
ep
tio
n
is
H
ib
er
ix
v
ac
ci
ne
. H
ib
er
ix
sh
ou
ld
o
nl
y
be

pr
io
r d
os
e
of
H
ib
-c
on
ta
in
in
g
va
cc
in
e.
•
Fo
r r
ec
om
m
en
da
tio
ns
o
n
th
e
us
e
of
M
en
H
ib
rix
in
p
at
ie
nt
s a
t i
nc
re
as
ed
ri
sk
fo
r m
en
in
go
co
cc
al
d
ise
as
e,

pl
ea
se
re
fe
r t
o
th
e
m
en
in
go
co
cc
al
v
ac
ci
ne
fo
ot
no
te
s a
nd
a
lso
to
M
M
W
R
Fe
br
ua
ry
2
8,
2
01
4
/ 6
3(
RR
01
);1
–
13
, a
va
ila
bl
e
at
h
tt
p:
//
w
w
w
.cd
c.g
ov
/m
m
w
r/
PD
F/
rr
/r
r6
30
1.
pd
f.
3827_Ch19_447_496 02/07/15 12:05 PM Page 452

453
5.
ty
pe
b
(H
ib
) c
on
ju
ga
te
v
ac
ci
ne
(c
on
t’d
)
Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
w
ee
ks
a
fte
r d
os
e
1,
re
ga
rd
le
ss
o
f H
ib
v
ac
ci
ne
u
se
d
in
th
e
pr
im
ar
y
se
rie
s.
•
th
e
se
co
nd
d
os
e.
•
w
hi
ch
ev
er
is
la
te
r.
• •
Fo
r u
nv
ac
ci
na
te
d
ch
ild
re
n
ag
ed
1
5
m
on
th
s o
r o
ld
er
, a
dm
in
ist
er
o
nl
y
1
do
se
.
•
Fo
r o
th
er
c
at
ch
-u
p
gu
id
an
ce
, s
ee
F
ig
ur
e
2.
F
or
c
at
ch
-u
p
gu
id
an
ce
re
la
te
d
to
M
en
H
ib
rix
, p
le
as
e
se
e
th
e
m
en
in
go
co
cc
al
v
ac
ci
ne
fo
ot
no
te
s a
nd
a
lso
M
M
W
R
Fe
br
ua
ry
2
8,
2
01
4
/ 6
3(
RR
01
);1
-1
3,
a
va
ila
bl
e
at

ht
tp
://
w
w
w
.cd
c.g
ov
/m
m
w
r/
PD
F/
rr
/r
r6
30
1.
pd
f.
Va
cc
in
at
io
n
of
p
er
so
ns
w
ith
h
ig
h-
ris
k
co
nd
iti
on
s:
•
Ch
ild
re
n
ag
ed
1
2
th
ro
ug
h
59
m
on
th
s w
ho
a
re
a
t i
nc
re
as
ed
ri
sk
fo
r H
ib
d
ise
as
e,
in
cl
ud
in
g
ch
em
ot
he
ra
py

re
ci
pi
en
ts
a
nd
th
os
e
w
ith
a
na
to
m
ic
o
r f
un
ct
io
na
l a
sp
le
ni
a
(in
cl
ud
in
g
sic
kl
e
ce
ll
di
se
as
e)
, h
um
an

sh
ou
ld
re
ce
iv
e
2
ad
di
tio
na
l d
os
es
o
f H
ib
v
ac
ci
ne
8
w
ee
ks
a
pa
rt
; c
hi
ld
re
n
w
ho
re
ce
iv
ed
2
o
r m
or
e
d
os
es
o
f
H
ib
v
ac
ci
ne
b
ef
or
e
12
m
on
th
s o
f a
ge
sh
ou
ld
re
ce
iv
e
1
ad
di
tio
na
l d
os
e.
•
Fo
r p
at
ie
nt
s y
ou
ng
er
th
an
5
y
ea
rs
o
f a
ge
u
nd
er
go
in
g
ch
em
ot
he
ra
py
o
r r
ad
ia
tio
n
tre
at
m
en
t w
ho
re
ce
iv
ed

a
H
ib
v
ac
ci
ne
d
os
e(
s)
w
ith
in
1
4
da
ys
o
f s
ta
rt
in
g
th
er
ap
y
or
d
ur
in
g
th
er
ap
y,
re
pe
at
th
e
do
se
(s
) a
t l
ea
st
3

m
on
th
s f
ol
lo
w
in
g
th
er
ap
y
co
m
pl
et
io
n.
•
Re
ci
pi
en
ts
o
f h
em
at
op
oi
et
ic
st
em
c
el
l t
ra
ns
pl
an
t (
H
SC
T)
sh
ou
ld
b
e
re
va
cc
in
at
ed
w
ith
a
3
-d
os
e
re
gi
m
en

of
H
ib
v
ac
ci
ne
st
ar
tin
g
6
to
1
2
m
on
th
s a
fte
r s
uc
ce
ss
fu
l t
ra
ns
pl
an
t,
re
ga
rd
le
ss
o
f v
ac
ci
na
tio
n
hi
st
or
y;
d
os
es

sh
ou
ld
b
e
ad
m
in
ist
er
ed
a
t l
ea
st
4
w
ee
ks
a
pa
rt
.
•
A
sin
gl
e
do
se
o
f a
ny
H
ib
-c
on
ta
in
in
g
va
cc
in
e
sh
ou
ld
b
e
ad
m
in
ist
er
ed
to
u
ni
m
m
un
iz
ed
* c
hi
ld
re
n
an
d
ad
ol
es
ce
nt
s 1
5
m
on
th
s o
f a
ge
a
nd
o
ld
er
u
nd
er
go
in
g
an
e
le
ct
iv
e
sp
le
ne
ct
om
y;
if
p
os
sib
le
, v
ac
ci
ne
sh
ou
ld

be
a
dm
in
ist
er
ed
a
t l
ea
st
1
4
da
ys
b
ef
or
e
pr
oc
ed
ur
e.
•
H
ib
v
ac
ci
ne
is
n
ot
ro
ut
in
el
y
re
co
m
m
en
de
d
fo
r p
at
ie
nt
s 5
y
ea
rs
o
r o
ld
er
. H
ow
ev
er
, 1
d
os
e
of
H
ib
v
ac
ci
ne

sh
ou
ld
b
e
ad
m
in
ist
er
ed
to
u
ni
m
m
un
iz
ed
* p
er
so
ns
a
ge
d
5
ye
ar
s o
r o
ld
er
w
ho
h
av
e
an
at
om
ic
o
r
fu
nc
tio
na
l a
sp
le
ni
a
(in
cl
ud
in
g
sic
kl
e
ce
ll
di
se
as
e)
a
nd
u
nv
ac
ci
na
te
d
pe
rs
on
s 5
th
ro
ug
h
18
y
ea
rs
o
f a
ge

* P
at
ie
nt
s w
ho
h
av
e n
ot
re
ce
iv
ed
a
p
rim
ar
y s
er
ie
s a
nd
b
oo
st
er
d
os
e o
r a
t l
ea
st
1
d
os
e o
f H
ib
va
cc
in
e a
fte
r 1
4
m
on
th
s o
f a
ge
a
re
co
ns
id
er
ed
u
ni
m
m
un
ize
d.

6.
Pn
eu
m
oc
oc
ca
l v
ac
ci
ne
s.
(M
in
im
um
a
ge
: 6
w
ee
ks
fo
r P
CV
13
, 2
y
ea
rs
fo
r P
PS
V2
3)
Ro
ut
in
e
va
cc
in
at
io
n
w
ith
P
CV
13
:
•
Ad
m
in
ist
er
a
4
-d
os
e
se
rie
s o
f P
CV
13
v
ac
ci
ne
a
t a
ge
s 2
, 4
, a
nd
6
m
on
th
s a
nd
a
t a
ge
1
2
th
ro
ug
h
15
m
on
th
s.
•
Fo
r c
hi
ld
re
n
ag
ed
1
4
th
ro
ug
h
59
m
on
th
s w
ho
h
av
e
re
ce
iv
ed
a
n
ag
e-
ap
pr
op
ria
te
se
rie
s o
f 7
-v
al
en
t P
CV

(P
CV
7)
, a
dm
in
ist
er
a
si
ng
le
su
pp
le
m
en
ta
l d
os
e
of
1
3-
va
le
nt
P
CV
(P
CV
13
).
Ca
tc
h-
up
v
ac
ci
na
tio
n
w
ith
P
CV
13
:
•
Ad
m
in
ist
er
1
d
os
e
of
P
CV
13
to
a
ll
he
al
th
y
ch
ild
re
n
ag
ed
2
4
th
ro
ug
h
59
m
on
th
s w
ho
a
re
n
ot
c
om
pl
et
el
y
va
cc
in
at
ed
fo
r t
he
ir
ag
e.
•
Fo
r o
th
er
c
at
ch
-u
p
gu
id
an
ce
, s
ee
F
ig
ur
e
2.

Va
cc
in
at
io
n
of
p
er
so
ns
w
ith
h
ig
h-
ris
k
co
nd
iti
on
s w
ith
P
CV
13
a
nd
P
PS
V2
3:
•
Al
l r
ec
om
m
en
de
d
PC
V1
3
do
se
s s
ho
ul
d
be
a
dm
in
ist
er
ed
p
rio
r t
o
PP
SV
23
v
ac
ci
na
tio
n
if
po
ss
ib
le
.
•
Fo
r c
hi
ld
re
n
2
th
ro
ug
h
5
ye
ar
s o
f a
ge
w
ith
a
ny
o
f t
he
fo
llo
w
in
g
co
nd
iti
on
s:
ch
ro
ni
c
he
ar
t d
ise
as
e
(p
ar
tic
ul
ar
ly
c
ya
no
tic
c
on
ge
ni
ta
l h
ea
rt
d
ise
as
e
an
d
ca
rd
ia
c
fa
ilu
re
);
ch
ro
ni
c
lu
ng
d
ise
as
e
(in
cl
ud
in
g
co
ch
le
ar
im
pl
an
t;
sic
kl
e
ce
ll
di
se
as
e
an
d
ot
he
r h
em
og
lo
bi
no
pa
th
ie
s;
an
at
om
ic
o
r f
un
ct
io
na
l a
sp
le
ni
a;

H
IV
in
fe
ct
io
n;
c
hr
on
ic
re
na
l f
ai
lu
re
; n
ep
hr
ot
ic
sy
nd
ro
m
e;
d
ise
as
es
a
ss
oc
ia
te
d
w
ith
tr
ea
tm
en
t w
ith

im
m
un
os
up
pr
es
siv
e
dr
ug
s o
r r
ad
ia
tio
n
th
er
ap
y,
in
cl
ud
in
g
m
al
ig
na
nt
n
eo
pl
as
m
s,
le
uk
em
ia
s,
ly
m
ph
om
as
,
1.
Ad
m
in
ist
er
1
d
os
e
of
P
CV
13
if
a
ny
in
co
m
pl
et
e
sc
he
du
le
o
f 3
d
os
es
o
f P
CV
(P
CV
7
an
d/
or
P
CV
13
) w
er
e
re
ce
iv
ed
p
re
vi
ou
sly
.
2.
Ad
m
in
ist
er
2
d
os
es
o
f P
CV
13
a
t l
ea
st
8
w
ee
ks
a
pa
rt
if
u
nv
ac
ci
na
te
d
or
a
ny
in
co
m
pl
et
e
sc
he
du
le
o
f f
ew
er

th
an
3
d
os
es
o
f P
CV
(P
CV
7
an
d/
or
P
CV
13
) w
er
e
re
ce
iv
ed
p
re
vi
ou
sly
.
3.
Ad
m
in
ist
er
1
su
pp
le
m
en
ta
l d
os
e
of
P
CV
13
if
4
d
os
es
o
f P
CV
7
or
o
th
er
a
ge
-a
pp
ro
pr
ia
te
c
om
pl
et
e
PC
V7

se
rie
s w
as
re
ce
iv
ed
p
re
vi
ou
sly
.
4.
Th
e
m
in
im
um
in
te
rv
al
b
et
w
ee
n
do
se
s o
f P
CV
(P
CV
7
or
P
CV
13
) i
s 8
w
ee
ks
.
5.
Fo
r c
hi
ld
re
n
w
ith
n
o
hi
st
or
y
of
P
PS
V2
3
va
cc
in
at
io
n,
a
dm
in
ist
er
P
PS
V2
3
at
le
as
t 8
w
ee
ks
a
fte
r t
he
m
os
t
re
ce
nt
d
os
e
of
P
CV
13
.
6.
Pn
eu
m
oc
oc
ca
l v
ac
ci
ne
s (
co
nt
’d
)
•
di
se
as
e
an
d
ot
he
r h
em
og
lo
bi
no
pa
th
ie
s;
an
at
om
ic
o
r f
un
ct
io
na
l a
sp
le
ni
a;
c
on
ge
ni
ta
l o
r a
cq
ui
re
d
w
ith
tr
ea
tm
en
t w
ith
im
m
un
os
up
pr
es
siv
e
dr
ug
s o
r r
ad
ia
tio
n
th
er
ap
y,
in
cl
ud
in
g
m
al
ig
na
nt
n
eo
pl
as
m
s,
le
uk
em
ia
s,
ly
m
ph
om
as
, a
nd
H
od
gk
in
’s
di
se
as
e;
g
en
er
al
iz
ed
m
al
ig
na
nc
y;
so
lid
o
rg
an
tr
an
sp
la
nt
at
io
n;
o
r
m
ul
tip
le
m
ye
lo
m
a:
1.
If
ne
ith
er
P
CV
13
n
or
P
PS
V2
3
ha
s b
ee
n
re
ce
iv
ed
p
re
vi
ou
sly
, a
dm
in
ist
er
1
d
os
e
of
P
CV
13
n
ow
a
nd
1
d
os
e
of
P
PS
V2
3
at
le
as
t 8
w
ee
ks
la
te
r.
2.
If
PC
V1
3
ha
s b
ee
n
re
ce
iv
ed
p
re
vi
ou
sly
b
ut
P
PS
V2
3
ha
s n
ot
, a
dm
in
ist
er
1
d
os
e
of
P
PS
V2
3
at
le
as
t 8
w
ee
ks

af
te
r t
he
m
os
t r
ec
en
t d
os
e
of
P
CV
13
.
3.
If
PP
SV
23
h
as
b
ee
n
re
ce
iv
ed
b
ut
P
CV
13
h
as
n
ot
, a
dm
in
ist
er
1
d
os
e
of
P
CV
13
a
t l
ea
st
8
w
ee
ks
a
fte
r t
he

m
os
t r
ec
en
t d
os
e
of
P
PS
V2
3.
•
Fo
r c
hi
ld
re
n
ag
ed
6
th
ro
ug
h
18
y
ea
rs
w
ith
c
hr
on
ic
h
ea
rt
d
ise
as
e
(p
ar
tic
ul
ar
ly
c
ya
no
tic
c
on
ge
ni
ta
l h
ea
rt

di
se
as
e
an
d
ca
rd
ia
c
fa
ilu
re
),
ch
ro
ni
c
lu
ng
d
ise
as
e
(in
cl
ud
in
g
as
th
m
a
if
tre
at
ed
w
ith
h
ig
h-
do
se
o
ra
l
co
rt
ic
os
te
ro
id
th
er
ap
y)
, d
ia
be
te
s m
el
lit
us
, a
lc
oh
ol
ism
, o
r c
hr
on
ic
li
ve
r d
ise
as
e,
w
ho
h
av
e
no
t r
ec
ei
ve
d
PP
SV
23
, a
dm
in
ist
er
1
d
os
e
of
P
PS
V2
3.
If
P
CV
13
h
as
b
ee
n
re
ce
iv
ed
p
re
vi
ou
sly
, t
he
n
PP
SV
23
sh
ou
ld
b
e
ad
m
in
ist
er
ed
a
t l
ea
st
8
w
ee
ks
a
fte
r a
ny
p
rio
r P
CV
13
d
os
e.
•
sic
kl
e
ce
ll
di
se
as
e
or
o
th
er
h
em
og
lo
bi
no
pa
th
ie
s;
an
at
om
ic
o
r f
un
ct
io
na
l a
sp
le
ni
a;
c
on
ge
ni
ta
l o
r a
cq
ui
re
d
w
ith
tr
ea
tm
en
t w
ith
im
m
un
os
up
pr
es
siv
e
dr
ug
s o
r r
ad
ia
tio
n
th
er
ap
y,
in
cl
ud
in
g
m
al
ig
na
nt
n
eo
pl
as
m
s,
le
uk
em
ia
s,
ly
m
ph
om
as
, a
nd
H
od
gk
in
’s
di
se
as
e;
g
en
er
al
iz
ed
m
al
ig
na
nc
y;
so
lid
o
rg
an
tr
an
sp
la
nt
at
io
n;
o
r
m
ul
tip
le
m
ye
lo
m
a.
7.
In
ac
tiv
at
ed
p
ol
io
vi
ru
s v
ac
ci
ne
(I
PV
).
(M
in
im
um
a
ge
: 6
w
ee
ks
)
Ro
ut
in
e
va
cc
in
at
io
n:
•
se
rie
s s
ho
ul
d
be
ad
m
in
ist
er
ed
o
n
or
af
te
r t
he
fo
ur
th
b
irt
hd
ay
an
d
at
le
as
t 6
m
on
th
s a
fte
r t
he
p
re
vi
ou
s d
os
e.
Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
of
im
m
in
en
t e
xp
os
ur
e
to
ci
rc
ul
at
in
g
po
lio
vi
ru
s (
i.e
., t
ra
ve
l t
o
a
po
lio
-e
nd
em
ic
re
gi
on
o
r d
ur
in
g
an
o
ut
br
ea
k)
.
•
If
4
or
m
or
e
do
se
s a
re
a
dm
in
ist
er
ed
b
ef
or
e
ag
e
4
ye
ar
s,
an
a
dd
iti
on
al
d
os
e
sh
ou
ld
b
e
ad
m
in
ist
er
ed
a
t a
ge
4

th
ro
ug
h
6
ye
ar
s a
nd
a
t l
ea
st
6
m
on
th
s a
fte
r t
he
p
re
vi
ou
s d
os
e.
•
A
fo
ur
th
d
os
e
is
no
t n
ec
es
sa
ry
if
th
e
th
ird
d
os
e
w
as
a
dm
in
ist
er
ed
a
t a
ge
4
ye
ar
s o
r o
ld
er
a
nd
a
t l
ea
st
6
m
on
th
s
af
te
r t
he
p
re
vi
ou
s d
os
e.
•
If
bo
th
O
PV
a
nd
IP
V
w
er
e
ad
m
in
ist
er
ed
a
s p
ar
t o
f a
se
rie
s,
a
to
ta
l o
f 4
d
os
es
sh
ou
ld
b
e
ad
m
in
ist
er
ed
, r
eg
ar
dl
es
s
of
th
e
ch
ild
’s
cu
rre
nt
a
ge
. IP
V
is
no
t r
ou
tin
el
y r
ec
om
m
en
de
d
fo
r U
.S
. r
es
id
en
ts
a
ge
d
18
ye
ar
s o
r o
ld
er
.
•
Fo
r o
th
er
ca
tc
h-
up
g
ui
da
nc
e,
se
e
Fi
gu
re
2
.
8.
In
flu
en
za
v
ac
ci
ne
s.
(M
in
im
um
a
ge
: 6
m
on
th
s f
or
in
ac
tiv
at
ed
in
flu
en
za
v
ac
ci
ne
[I
IV
],
2
ye
ar
s f
or
li
ve
, a
tt
en
ua
te
d
in
flu
en
za
v
ac
ci
ne
[L
AI
V]
)
Ro
ut
in
e
va
cc
in
at
io
n:
•
no
np
re
gn
an
t p
er
so
ns
a
ge
d
2
th
ro
ug
h
49
y
ea
rs
, e
ith
er
L
AI
V
or
II
V
m
ay
b
e
us
ed
. H
ow
ev
er
, L
AI
V
sh
ou
ld
N
O
T
be
a
dm
in
ist
er
ed
to
so
m
e
pe
rs
on
s,
in
cl
ud
in
g
1)
p
er
so
ns
w
ho
h
av
e
ex
pe
rie
nc
ed
se
ve
re
a
lle
rg
ic
re
ac
tio
ns

17
y
ea
rs
re
ce
iv
in
g
as
pi
rin
o
r a
sp
iri
n-
co
nt
ai
ni
ng
p
ro
du
ct
s;
3)
p
er
so
ns
w
ho
a
re
a
lle
rg
ic
to
e
gg
s;
4)
p
re
gn
an
t
w
om
en
; 5
) i
m
m
un
os
up
pr
es
se
d
pe
rs
on
s;
6)
c
hi
ld
re
n
2
th
ro
ug
h
4
ye
ar
s o
f a
ge
w
ith
a
st
hm
a
or
w
ho
h
ad

pr
ev
io
us
4
8
ho
ur
s.
Fo
r a
ll
ot
he
r c
on
tr
ai
nd
ic
at
io
ns
a
nd
p
re
ca
ut
io
ns
to
u
se
o
f L
AI
V,
se
e M
M
W
R
Au
gu
st
1
5,

20
14
/
63
(3
2)
;6
91
-6
97
[4
0
pa
ge
s]
a
va
ila
bl
e
at

ht
tp
://
w
w
w
.cd
c.g
ov
/m
m
w
r/
pd
f/w
k/
m
m
63
32
.p
df
.
Fo
r c
hi
ld
re
n
ag
ed
6
m
on
th
s t
hr
ou
gh
8
y
ea
rs
:
•
Fo
r t
he
2
01
4-
15
se
as
on
, a
dm
in
ist
er
2
d
os
es
(s
ep
ar
at
ed
b
y
at
le
as
t 4
w
ee
ks
) t
o
ch
ild
re
n
w
ho
a
re
re
ce
iv
in
g
va
cc
in
e
re
co
m
m
en
da
tio
ns
, M
M
W
R
Au
gu
st
1
5,
2
01
4
/ 6
3(
32
);6
91
-6
97
[4
0
pa
ge
s]
a
va
ila
bl
e
at
h
tt
p:
//
w
w
w
.
cd
c.g
ov
/m
m
w
r/
pd
f/w
k/
m
m
63
32
.p
df
.
• Fo
r p
er
so
ns
a
ge
d
9
ye
ar
s a
nd
o
ld
er
:
•
Ad
m
in
ist
er
1
d
os
e.
Fo
r f
ur
th
er
g
ui
da
nc
e
on
th
e
us
e
of
th
e
va
cc
in
es
m
en
tio
ne
d
be
lo
w
, s
ee
: h
tt
p:
//
w
w
w
.c
dc
.g
ov
/v
ac
ci
ne
s/
hc
p/
ac
ip
-re
cs
/in
de
x.
ht
m
l.
3827_Ch19_447_496 02/07/15 12:05 PM Page 453

454
Fo
r f
ur
th
er
g
ui
da
nc
e
on
th
e
us
e
of
th
e
va
cc
in
es
m
en
tio
ne
d
be
lo
w
, s
ee
: h
tt
p:
//
w
w
w
.c
dc
.g
ov
/v
ac
ci
ne
s/
hc
p/
ac
ip
-re
cs
/in
de
x.
ht
m
l.
9.

M
ea
sl
es
, m
um
ps
, a
nd
ru
be
lla
(M
M
R)
v
ac
ci
ne
. (
M
in
im
um
a
ge
: 1
2
m
on
th
s f
or
ro
ut
in
e
va
cc
in
at
io
n)
Ro
ut
in
e
va
cc
in
at
io
n:
•
Ad
m
in
ist
er
a
2
-d
os
e
se
rie
s o
f M
M
R
va
cc
in
e
at
a
ge
s 1
2
th
ro
ug
h
15
m
on
th
s a
nd
4
th
ro
ug
h
6
ye
ar
s.
Th
e
do
se
.
•
Ad
m
in
ist
er
1
d
os
e
of
M
M
R
va
cc
in
e
to
in
fa
nt
s a
ge
d
6
th
ro
ug
h
11
m
on
th
s b
ef
or
e
de
pa
rt
ur
e
fro
m
th
e
Un
ite
d
at
a
ge
1
2
th
ro
ug
h
15
m
on
th
s (
12
m
on
th
s i
f t
he
ch
ild
re
m
ai
ns
in
a
n
ar
ea
w
he
re
d
ise
as
e
ris
k
is
hi
gh
),
an
d
th
e
se
co
nd
d
os
e
at
le
as
t 4
w
ee
ks
la
te
r.
•
Ad
m
in
ist
er
2
d
os
es
o
f M
M
R
va
cc
in
e
to
ch
ild
re
n
ag
ed
1
2
m
on
th
s a
nd
o
ld
er
b
ef
or
e
de
pa
rt
ur
e
fro
m
th
e
th
e
se
co
nd
d
os
e
at
le
as
t 4
w
ee
ks
la
te
r.
Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
En
su
re
th
at
a
ll
sc
ho
ol
-a
ge
d
ch
ild
re
n
an
d
ad
ol
es
ce
nt
s h
av
e
ha
d
2
do
se
s o
f M
M
R
va
cc
in
e;
th
e
m
in
im
um

in
te
rv
al
b
et
w
ee
n
th
e
2
do
se
s i
s 4
w
ee
ks
.
10
.
Va
ric
el
la
(V
AR
) v
ac
ci
ne
. (
M
in
im
um
a
ge
: 1
2
m
on
th
s)

Ro
ut
in
e
va
cc
in
at
io
n:
•
Ad
m
in
ist
er
a
2
-d
os
e
se
rie
s o
f V
AR
v
ac
ci
ne
a
t a
ge
s 1
2
th
ro
ug
h
15
m
on
th
s a
nd
4
th
ro
ug
h
6
ye
ar
s.
Th
e
se
co
nd
d
os
e
m
ay
b
e
ad
m
in
ist
er
ed
b
ef
or
e
ag
e
4
ye
ar
s,
pr
ov
id
ed
a
t l
ea
st
3
m
on
th
s h
av
e
el
ap
se
d
sin
ce
th
e
va
lid
.
Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
En
su
re
th
at
a
ll
pe
rs
on
s a
ge
d
7
th
ro
ug
h
18
y
ea
rs
w
ith
ou
t e
vi
de
nc
e
of
im
m
un
ity
(s
ee
M
M
W
R
20
07
/
56
[N
o.

RR
-4
],
av
ai
la
bl
e
at
h
tt
p:
//
w
w
w
.cd
c.g
ov
/m
m
w
r/
pd
f/r
r/
rr
56
04
.p
df
)
ha
ve
2
d
os
es
o
f v
ar
ic
el
la
v
ac
ci
ne
. F
or

ch
ild
re
n
ag
ed
7
th
ro
ug
h
12
y
ea
rs
, t
he
re
co
m
m
en
de
d
m
in
im
um
in
te
rv
al
b
et
w
ee
n
do
se
s i
s 3
m
on
th
s (
if
pe
rs
on
s a
ge
d
13
y
ea
rs
a
nd
o
ld
er
, t
he
m
in
im
um
in
te
rv
al
b
et
w
ee
n
do
se
s i
s 4
w
ee
ks
.
11
.
H
ep
at
iti
s A
(H
ep
A)
v
ac
ci
ne
. (
M
in
im
um
a
ge
: 1
2
m
on
th
s)
Ro
ut
in
e
va
cc
in
at
io
n:
•
In
iti
at
e
th
e
2-
do
se
H
ep
A
va
cc
in
e
se
rie
s a
t 1
2
th
ro
ug
h
23
m
on
th
s;
se
pa
ra
te
th
e
2
do
se
s b
y
6
to
1
8
m
on
th
s.
•
Ch
ild
re
n
w
ho
h
av
e
re
ce
iv
ed
1
d
os
e
of
H
ep
A
va
cc
in
e
be
fo
re
a
ge
2
4
m
on
th
s s
ho
ul
d
re
ce
iv
e
a
se
co
nd
d
os
e
•
Fo
r a
ny
p
er
so
n
ag
ed
2
y
ea
rs
a
nd
o
ld
er
w
ho
h
as
n
ot
a
lre
ad
y
re
ce
iv
ed
th
e
H
ep
A
va
cc
in
e
se
rie
s,
2
do
se
s o
f
H
ep
A
va
cc
in
e
se
pa
ra
te
d
by
6
to
1
8
m
on
th
s m
ay
b
e
ad
m
in
ist
er
ed
if
im
m
un
ity
a
ga
in
st
h
ep
at
iti
s A
v
iru
s
in
fe
ct
io
n
is
de
sir
ed
.
Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
Th
e
m
in
im
um
in
te
rv
al
b
et
w
ee
n
th
e
tw
o
do
se
s i
s 6
m
on
th
s.
Sp
ec
ia
l p
op
ul
at
io
ns
:
•
Ad
m
in
ist
er
2
d
os
es
o
f H
ep
A
va
cc
in
e
at
le
as
t 6
m
on
th
s a
pa
rt
to
p
re
vi
ou
sly
u
nv
ac
ci
na
te
d
pe
rs
on
s w
ho

liv
e
in
a
re
as
w
he
re
v
ac
ci
na
tio
n
pr
og
ra
m
s t
ar
ge
t o
ld
er
c
hi
ld
re
n,
o
r w
ho
a
re
a
t i
nc
re
as
ed
ri
sk
fo
r i
nf
ec
tio
n.

Th
is
in
cl
ud
es
p
er
so
ns
tr
av
el
in
g
to
o
r w
or
ki
ng
in
c
ou
nt
rie
s t
ha
t h
av
e
hi
gh
o
r i
nt
er
m
ed
ia
te
e
nd
em
ic
ity
o
f
in
fe
ct
io
n;
m
en
h
av
in
g
se
x
w
ith
m
en
; u
se
rs
o
f i
nj
ec
tio
n
an
d
no
n-
in
je
ct
io
n
ill
ic
it
dr
ug
s;
pe
rs
on
s w
ho
w
or
k
w
ith
H
AV
-in
fe
ct
ed
p
rim
at
es
o
r w
ith
H
AV
in
a
re
se
ar
ch
la
bo
ra
to
ry
; p
er
so
ns
w
ith
c
lo
tt
in
g-
fa
ct
or
d
iso
rd
er
s;
pe
rs
on
s w
ith
c
hr
on
ic
li
ve
r d
ise
as
e;
a
nd
p
er
so
ns
w
ho
a
nt
ic
ip
at
e
cl
os
e
pe
rs
on
al
c
on
ta
ct
(e
.g
., h
ou
se
ho
ld

so
on
a
s t
he
a
do
pt
io
n
is
pl
an
ne
d,
id
ea
lly
2
o
r m
or
e
w
ee
ks
b
ef
or
e
th
e
ar
riv
al
o
f t
he
a
do
pt
ee
.
12
.
H
um
an
p
ap
ill
om
av
iru
s (
H
PV
) v
ac
ci
ne
s.
(M
in
im
um
a
ge
: 9
y
ea
rs
fo
r H
PV
2
[C
er
va
rix
]
an
d
H
PV
4
[G
ar
da
si
l])

Ro
ut
in
e
va
cc
in
at
io
n:
•
Ad
m
in
ist
er
a
3
-d
os
e
se
rie
s o
f H
PV
v
ac
ci
ne
o
n
a
sc
he
du
le
o
f 0
, 1
-2
, a
nd
6
m
on
th
s t
o
al
l a
do
le
sc
en
ts
a
ge
d
11

th
ro
ug
h
12
y
ea
rs
. E
ith
er
H
PV
4
or
H
PV
2
m
ay
b
e
us
ed
fo
r f
em
al
es
, a
nd
o
nl
y
H
PV
4
m
ay
b
e
us
ed
fo
r m
al
es
.
•
Th
e
va
cc
in
e
se
rie
s m
ay
b
e
st
ar
te
d
at
a
ge
9
y
ea
rs
.
• Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
Ad
m
in
ist
er
th
e
va
cc
in
e
se
rie
s t
o
fe
m
al
es
(e
ith
er
H
PV
2
or
H
PV
4)
a
nd
m
al
es
(H
PV
4)
a
t a
ge
1
3
th
ro
ug
h
18

ye
ar
s i
f n
ot
p
re
vi
ou
sly
v
ac
ci
na
te
d.
•
U
se
re
co
m
m
en
de
d
ro
ut
in
e
do
sin
g
in
te
rv
al
s (
se
e
Ro
ut
in
e
va
cc
in
at
io
n
ab
ov
e)
fo
r v
ac
ci
ne
se
rie
s c
at
ch
-u
p.

13
.
M
en
in
go
co
cc
al
co
nj
ug
at
e
va
cc
in
es
. (
M
in
im
um
a
ge
: 6
w
ee
ks
fo
r H
ib
-M
en
CY

[M
en
H
ib
rix
],
9
m
on
th
s f
or
M
en
AC
W
Y-
D
[M
en
ac
tr
a]
, 2
m
on
th
s f
or
M
en
AC
W
Y-
CR
M

[M
en
ve
o]
)
Ro
ut
in
e
va
cc
in
at
io
n:
•
Ad
m
in
ist
er
a
si
ng
le
d
os
e
of
M
en
ac
tr
a
or
M
en
ve
o
va
cc
in
e
at
a
ge
1
1
th
ro
ug
h
12
y
ea
rs
, w
ith
a
b
oo
st
er
d
os
e
at
a
ge
1
6
ye
ar
s.
•
re
ce
iv
e
a
2-
do
se
p
rim
ar
y
se
rie
s o
f M
en
ac
tr
a
or
M
en
ve
o
w
ith
a
t l
ea
st
8
w
ee
ks
b
et
w
ee
n
do
se
s.
•
Fo
r c
hi
ld
re
n
ag
ed
2
m
on
th
s t
hr
ou
gh
1
8
ye
ar
s w
ith
h
ig
h-
ris
k
co
nd
iti
on
s,
se
e
be
lo
w
.
Ca
tc
h-
up
v
ac
ci
na
tio
n:
•
Ad
m
in
ist
er
M
en
ac
tr
a
or
M
en
ve
o
va
cc
in
e
at
a
ge
1
3
th
ro
ug
h
18
y
ea
rs
if
n
ot
p
re
vi
ou
sly
v
ac
ci
na
te
d.
•
16
th
ro
ug
h
18
y
ea
rs
w
ith
a
m
in
im
um
in
te
rv
al
o
f a
t l
ea
st
8
w
ee
ks
b
et
w
ee
n
do
se
s.
• •
Fo
r o
th
er
c
at
ch
-u
p
gu
id
an
ce
, s
ee
F
ig
ur
e
2.
Va
cc
in
at
io
n
of
p
er
so
ns
w
ith
h
ig
h-
ris
k
co
nd
iti
on
s a
nd
o
th
er
p
er
so
ns
a
t i
nc
re
as
ed
ri
sk
o
f d
is
ea
se
:
•
Ch
ild
re
n
w
ith
a
na
to
m
ic
o
r f
un
ct
io
na
l a
sp
le
ni
a
(in
cl
ud
in
g
sic
kl
e
ce
ll
di
se
as
e)
:
1.
M
en
ve
o

o
Ch
ild
re
n
w
ho
in
iti
at
e v
ac
cin
at
io
n
at
8
w
ee
ks
th
ro
ug
h
6 m
on
th
s: A
dm
in
ist
er
d
os
es
at
2
, 4
, 6
, a
nd
1
2
m
on
th
s
of
a
ge
.
o
Un
va
cc
in
at
ed
ch
ild
re
n
7 t
hr
ou
gh
23
m
on
th
s:
Ad
m
in
ist
er
2
d
os
es
, w
ith
th
e
se
co
nd
d
os
e
at
le
as
t 1
2
w
ee
ks

o
Ch
ild
re
n
24
m
on
th
s a
nd
o
ld
er
w
ho
h
av
e
no
t r
ec
ei
ve
d
a
co
m
pl
et
e
se
rie
s:
Ad
m
in
ist
er
2
p
rim
ar
y
do
se
s a
t
le
as
t 8
w
ee
ks
a
pa
rt
.
2.
M
en
H
ib
rix
o
Ch
ild
re
n
6
w
ee
ks
th
ro
ug
h
18
m
on
th
s:
Ad
m
in
ist
er
d
os
es
a
t 2
, 4
, 6
, a
nd
1
2
th
ro
ug
h
15
m
on
th
s o
f a
ge
.
o
at
le
as
t 8
w
ee
ks
a
pa
rt
to
e
ns
ur
e
pr
ot
ec
tio
n
ag
ai
ns
t s
er
og
ro
up
s C
a
nd
Y
m
en
in
go
co
cc
al
d
ise
as
e.
3.
M
en
ac
tr
a
o
Ch
ild
re
n
24
m
on
th
s a
nd
o
ld
er
w
ho
h
av
e
no
t r
ec
ei
ve
d
a
co
m
pl
et
e
se
rie
s:
Ad
m
in
ist
er
2
p
rim
ar
y
do
se
s a
t
le
as
t 8
w
ee
ks
a
pa
rt
. If
M
en
ac
tr
a
is
ad
m
in
ist
er
ed
to
a
ch
ild
w
ith
a
sp
le
ni
a
(in
cl
ud
in
g
sic
kl
e
ce
ll
di
se
as
e)
,
do
n
ot
a
dm
in
ist
er
M
en
ac
tr
a
un
til
2
ye
ar
s o
f a
ge
a
nd
a
t l
ea
st
4
w
ee
ks
a
fte
r t
he
co
m
pl
et
io
n
of
a
ll P
CV
13

do
se
s.
•
1.
M
en
ve
o
o
Ch
ild
re
n
w
ho
in
iti
at
e v
ac
cin
at
io
n
at
8
w
ee
ks
th
ro
ug
h
6 m
on
th
s:
Ad
m
in
ist
er
d
os
es
at
2
, 4
, 6
, a
nd
1
2
m
on
th
s
of
a
ge
.
o
Un
va
cc
in
at
ed
ch
ild
re
n
7 t
hr
ou
gh
23
m
on
th
s:
Ad
m
in
ist
er
2
d
os
es
, w
ith
th
e
se
co
nd
d
os
e
at
le
as
t 1
2
w
ee
ks

o
Ch
ild
re
n
24
m
on
th
s a
nd
o
ld
er
w
ho
h
av
e
no
t r
ec
ei
ve
d
a
co
m
pl
et
e
se
rie
s:
Ad
m
in
ist
er
2
p
rim
ar
y
do
se
s a
t
le
as
t 8
w
ee
ks
a
pa
rt
.
2.
M
en
H
ib
rix
o
Ch
ild
re
n
6
w
ee
ks
th
ro
ug
h
18
m
on
th
s:
Ad
m
in
ist
er
d
os
es
a
t 2
, 4
, 6
, a
nd
1
2
th
ro
ug
h
15
m
on
th
s o
f a
ge
.
o
at
le
as
t 8
w
ee
ks
a
pa
rt
to
e
ns
ur
e
pr
ot
ec
tio
n
ag
ai
ns
t s
er
og
ro
up
s C
a
nd
Y
m
en
in
go
co
cc
al
d
ise
as
e.
3.
M
en
ac
tr
a
o
Ch
ild
re
n
9
th
ro
ug
h
23
m
on
th
s:
Ad
m
in
ist
er
2
p
rim
ar
y
do
se
s a
t l
ea
st
1
2
w
ee
ks
a
pa
rt
.
o
Ch
ild
re
n
24
m
on
th
s a
nd
o
ld
er
w
ho
h
av
e
no
t r
ec
ei
ve
d
a
co
m
pl
et
e
se
rie
s:
Ad
m
in
ist
er
2
p
rim
ar
y
do
se
s a
t
le
as
t 8
w
ee
ks
a
pa
rt
.
•
Fo
r c
hi
ld
re
n
w
ho
tr
av
el
to
o
r r
es
id
e
in
c
ou
nt
rie
s i
n
w
hi
ch
m
en
in
go
co
cc
al
d
ise
as
e
is
hy
pe
re
nd
em
ic
o
r
ep
id
em
ic
, in
cl
ud
in
g
co
un
tr
ie
s i
n
th
e
Af
ric
an
m
en
in
gi
tis
b
el
t o
r t
he
H
aj
j, a
dm
in
ist
er
a
n
ag
e-
ap
pr
op
ria
te

fo
rm
ul
at
io
n
an
d
se
rie
s o
f M
en
ac
tr
a
or
M
en
ve
o
fo
r p
ro
te
ct
io
n
ag
ai
ns
t s
er
og
ro
up
s A
a
nd
W
m
en
in
go
co
cc
al

be
ca
us
e
it
do
es
n
ot
c
on
ta
in
se
ro
gr
ou
ps
A
o
r W
.
•
Fo
r c
hi
ld
re
n
at
ri
sk
d
ur
in
g
a
co
m
m
un
ity
o
ut
br
ea
k
at
tr
ib
ut
ab
le
to
a
v
ac
ci
ne
se
ro
gr
ou
p,
a
dm
in
ist
er
o
r
co
m
pl
et
e
an
a
ge
– a
nd
fo
rm
ul
at
io
n-
ap
pr
op
ria
te
se
rie
s o
f M
en
H
ib
rix
, M
en
ac
tr
a,
o
r M
en
ve
o.
•
Fo
r b
oo
st
er
d
os
es
a
m
on
g
pe
rs
on
s w
ith
h
ig
h-
ris
k
co
nd
iti
on
s,
re
fe
r t
o
M
M
W
R
20
13
/
62
(R
R0
2)
;1
-2
2,

av
ai
la
bl
e
at
h
tt
p:
//
w
w
w
.cd
c.g
ov
/m
m
w
r/
pr
ev
ie
w
/m
m
w
rh
tm
l/r
r6
20
2a
1.
ht
m
.
Fo
r o
th
er
c
at
ch
-u
p
re
co
m
m
en
da
tio
ns
fo
r t
he
se
p
er
so
ns
, a
nd
c
om
pl
et
e
in
fo
rm
at
io
n
on
u
se
o
f
m
en
in
go
co
cc
al
v
ac
ci
ne
s,
in
cl
ud
in
g
gu
id
an
ce
re
la
te
d
to
v
ac
ci
na
tio
n
of
p
er
so
ns
a
t i
nc
re
as
ed
ri
sk
o
f i
nf
ec
tio
n,

se
e
M
M
W
R
M
ar
ch
2
2,
2
01
3
/ 6
2(
RR
02
);1
-2
2,
a
va
ila
bl
e
at
h
tt
p:
//
w
w
w
.cd
c.g
ov
/m
m
w
r/
pd
f/r
r/
rr
62
02
.p
df
.
CS
2
44
08
3-
B
Ta
bl
e
19
–1
!
Re
co
m
m
en
de
d
Im
m
un
iz
at
io
n
Sc
he
du
le
fo
r P
er
so
ns
A
ge
d
0
Th
ro
ug
h1
8
Ye
ar
s—
U
ni
te
d
St
at
es
, 2
01
5—
co
nt
’d
3827_Ch19_447_496 02/07/15 12:05 PM Page 454

455
Ta
bl
e
19
–2
!
Ca
tc
h-
U
p
Im
m
un
iz
at
io
n
Sc
he
du
le
fo
r P
er
so
ns
A
ge
d
4
M
on
th
s
Th
ro
ug
h
18
Y
ea
rs
W
ho
S
ta
rt
L
at
e
or
W
ho
A
re
M
or
e
Th
an
1
M
on
th
B
eh
in
d
–
U
ni
te
d
St
at
es
, 2
01
5
FI
G
U
RE
2
. C
at
ch
-u
p
im
m
un
iz
at
io
n
sc
he
du
le
fo
r p
er
so
ns
a
ge
d
4
m
on
th
s t
hr
ou
gh
1
8
ye
ar
s w
ho
st
ar
t l
at
e
or
w
ho
a
re
m
or
e
th
an
1
m
on
th
b
eh
in
d
—
U
ni
te
d
St
at
es
, 2
01
5.
ap
pr
op
ria
te
fo
r t
he
c
hi
ld
’s
ag
e.
A
lw
ay
s u
se
th
is
ta
bl
e
in
c
on
ju
nc
tio
n
w
ith
F
ig
ur
e
1
an
d
th
e
fo
ot
no
te
s t
ha
t f
ol
lo
w
.
Ch
ild
re
n
ag
e
4
m
on
th
s t
hr
ou
gh
6
y
ea
rs
Va
cc
in
e
M
in
im
um

Ag
e
fo
r
D
os
e
1
M
in
im
um
In
te
rv
al
B
et
w
ee
n
D
os
es
D
os
e
1
to
D
os
e
2
D
os
e
2
to
D
os
e
3
D
os
e
3
to
D
os
e
4
D
os
e
4
to
D
os
e
5
H
ep
at
iti
s B
1
Bi
rt
h
4
w
ee
ks
8
w
ee
ks

an
d
.
Ro
ta
vi
ru
s2
6
w
ee
ks
4
w
ee
ks
4
w
ee
ks
2
D
ip
ht
he
ria
, t
et
an
us
, a
nd
a
ce
l-
lu
la
r p
er
tu
ss
is3
6
w
ee
ks
4
w
ee
ks
4
w
ee
ks
6
m
on
th
s
6
m
on
th
s3

ty
pe
b
5
6
w
ee
ks
4
w
ee
ks

st
b
irt
hd
ay
.

N
o
fu
rt
he
r d
os
es
n
ee
de
d
m
on
th
s o
r o
ld
er
.
4
w
ee
ks
5
if
cu
rr
en
t a
ge
is
y
ou
ng
er
th
an
1
2
m
on
th
s a
nd
yo
un
ge
r t
ha
n
ag
e
7
m
on
th
s,
an
d
at
le
as
t 1
p
re
vi
ou
s d
os
e
w
as
P
RP
-T
(A
ct
H
ib
,
Pe
nt
ac
el
) o
r u
nk
no
w
n.
8
w
ee
ks

an
d
5
•
if
cu
rr
en
t a
ge
is
y
ou
ng
er
th
an
1
2
m
on
th
s
an
d

O
R
•
if
cu
rr
en
t a
ge
is
1
2
th
ro
ug
h
59
m
on
th
s
an
d
st
b
irt
hd
ay
, a
nd
se
co
nd
d
os
e
ad
m
in
ist
er
ed
a
t y
ou
ng
er
th
an
1
5
m
on
th
s;

O
R
•
if
bo
th
d
os
es
w
er
e
PR
P-
O
M
P
(P
ed
va
xH
IB
; C
om
va
x)

an
d
w
er
e
ad
m
in
ist
er
ed
b
ef
or
e
th
e
1s
t b
irt
hd
ay
.
N
o
fu
rt
he
r d
os
es
n
ee
de
d
if
pr
ev
io
us
d
os
e
w
as
a
dm
in
ist
er
ed
a
t a
ge
1
5
m
on
th
s o
r o
ld
er
.
Th
is
do
se
o
nl
y
ne
ce
ss
ar
y
fo
r c
hi
ld
re
n
ag
e
12
th
ro
ug
h
59
m
on
th
s
w
ho
re
ce
iv
ed
3
d
os
es
b
ef
or
e
th
e
1s
t b
irt
hd
ay
.
Pn
eu
m
oc
oc
ca
l6
6
w
ee
ks
4
w
ee
ks

st
b
irt
hd
ay
.
st
b
irt
hd
ay
o
r a
fte
r.
N
o
fu
rt
he
r d
os
es
n
ee
de
d
ol
de
r.
4
w
ee
ks

if
cu
rre
nt
a
ge
is
y
ou
ng
er
th
an
1
2
m
on
th
s a
nd
p
re
vi
ou
s d
os
e
gi
ve
n
at
< 7m on th s ol d. if pr ev io us d os e gi ve n be tw ee n 7- 11 m on th s ( w ai t u nt il at le as t 1 2 m on th s o ld ); O R if cu rr en t a ge is 1 2 m on th s o r o ld er a nd a t l ea st 1 d os e w as g iv en b ef or e ag e 12 m on th s. N o fu rt he r d os es n ee de d fo r h ea lth y ch ild re n if pr ev io us d os e ad m in ist er ed a t ag e 24 m on th s o r o ld er . Th is do se o nl y ne ce ss ar y fo r c hi ld re n ag ed 1 2 th ro ug h 59 m on th s w ho re ce iv ed 3 d os es b ef or e ag e 12 m on th s o r f or c hi ld re n at h ig h ris k w ho re ce iv ed 3 d os es a t a ny a ge . In ac tiv at ed p ol io vi ru s7 6 w ee ks 4 w ee ks 7 4 w ee ks 7 6 m on th s7 M en in go co cc al 13 6 w ee ks 8 w ee ks 13 Se e fo ot no te 1 3 Se e fo ot no te 1 3 M ea sle s, m um ps , r ub el la 9 12 m on th s 4 w ee ks Va ric el la 10 12 m on th s 3 m on th s H ep at iti s A 11 12 m on th s 6 m on th s Ch ild re n an d ad ol es ce nt s a ge 7 th ro ug h 18 y ea rs Te ta nu s, di ph th er ia ; t et an us , di ph th er ia , a nd a ce llu la r pe rt us sis 4 7 ye ar s4 4 w ee ks 4 w ee ks st b irt hd ay . st b irt hd ay . 6 m on th s st bi rt hd ay . H um an p ap ill om av iru s1 2 9 ye ar s Ro ut in e do sin g in te rv al s a re re co m m en de d. 12 H ep at iti s A 11 N ot ap pl ic ab le (N /A ) 6 m on th s H ep at iti s B 1 N /A 4 w ee ks 8 w ee ks a nd In ac tiv at ed p ol io vi ru s7 N /A 4 w ee ks 4 w ee ks 7 6 m on th s7 M en in go co cc al 13 N /A 8 w ee ks 13 M ea sl es , m um ps , r ub el la 9 N /A 4 w ee ks Va ric el la 10 N /A 3 m on th s i f y ou ng er th an a ge 1 3 ye ar s. 4 w ee ks if a ge 1 3 ye ar s o r o ld er . N O TE : T he a bo ve re co m m en da tio ns m us t b e re ad a lo ng w ith th e fo ot no te s o f t hi s s ch ed ul e. 3827_Ch19_447_496 02/07/15 12:05 PM Page 455 456 Ta bl e 19 –2 ! Ca tc h- U p Im m un iz at io n Sc he du le fo r P er so ns A ge d 4 M on th s Th ro ug h 18 Y ea rs W ho S ta rt L at e or W ho A re M or e Th an 1 M on th B eh in d – U ni te d St at es , 2 01 5— co nt ’d Fo ot no te s — R ec om m en de d im m un iz at io n sc he du le fo r p er so ns a ge d 0 th ro ug h 18 y ea rs — U ni te d St at es , 2 01 5 Fo r f ur th er g ui da nc e on th e us e of th e va cc in es m en tio ne d be lo w , s ee : h tt p: // w w w .c dc .g ov /v ac ci ne s/ hc p/ ac ip -re cs /in de x. ht m l. Fo r v ac ci ne re co m m en da tio ns fo r p er so ns 1 9 ye ar s o f a ge a nd o ld er , s ee th e Ad ul t I m m un iz at io n Sc he du le . Ad di tio na l i nf or m at io n • Fo r c on tr ai nd ic at io ns a nd p re ca ut io ns to u se o f a v ac ci ne a nd fo r a dd iti on al in fo rm at io n re ga rd in g th at v ac ci ne , v ac ci na tio n pr ov id er s s ho ul d co ns ul t t he re le va nt A CI P st at em en t a va ila bl e on lin e at ht tp :// w w w .cd c.g ov /v ac ci ne s/ hc p/ ac ip -re cs /in de x. ht m l. • Fo r p ur po se s o f c al cu la tin g in t e rv al s b et w ee n do se s, 4 w ee ks = 2 8 da ys . I nt er va ls of 4 m on th s o r g re at er a re d et er m in ed b y ca le nd ar m on th s. • Va cc in e do se s a dm in ist er ed 4 d ay s o r l es s b ef or e th e m in im um in te rv al a re c on sid er ed v al id . D os es o f a ny v ac ci ne a dm in ist er ed ≥ 5 da ys e ar lie r t ha n th e m in im um in te rv al o r m in im um a ge sh ou ld n ot be c ou nt ed a s v al id d os es a nd sh ou ld b e re pe at ed a s a ge -a pp ro pr ia te . T he re pe at d os e sh ou ld b e sp ac ed a fte r t he in va lid d os e by th e re co m m en de d m in im um in te rv al . F or fu rt he r d et ai ls, se e M M W R, Ge ne ra l R ec om m en da tio ns o n Im m un iza tio n an d Re po rt s / V ol . 6 0 / N o. 2 ; T ab le 1 . R ec om m en de d an d m in im um a ge s a nd in te rv al s b et w ee n va cc in e d os es a va ila bl e on lin e at ht tp :// w w w .cd c.g ov /m m w r/ pd f/r r/ rr 60 02 .p df . • In f o rm at io n on tr av el v ac ci ne re qu ire m en ts a nd re co m m en da tio ns is a va ila bl e at h tt p: // w w w nc .cd c.g ov /t ra ve l/d es tin at io ns /li st . • in G en er al R ec om m en da tio ns o n Im m un iza tio n (A CI P) , a va ila bl e at h tt p: // w w w .cd c.g ov /m m w r/ pd f/r r/ rr 60 02 .p df .; a nd A m er ic an A ca de m y of P ed ia tr ic s. “Im m un iz at io n in S pe ci al C lin ic al C irc um st an ce s,” in P ic ke rin g LK , B ak er C J, Ki m be rli n D W , L on g SS e ds . R ed B oo k: 2 01 2 re po rt o f t he C om m itt ee o n In fe ct io us D ise as es . 2 9t h ed . E lk G ro ve V ill ag e, IL : A m er ic an A ca de m y of P ed ia tr ic s. 1. H ep at iti s B (H ep B) v ac ci ne . ( M in im um a ge : b irt h) Ro ut in e va cc in at io n: At b irt h: • Ad m in ist er m on ov al en t H ep B va cc in e to a ll ne w bo rn s b ef or e ho sp ita l d isc ha rg e. • Fo r i nf an ts b or n to h ep at iti s B su rfa ce a nt ig en (H Bs Ag )-p os iti ve m ot he rs , a dm in ist er H ep B va cc in e an d 0. 5 m L of h ep at iti s B im m un e gl ob ul in (H BI G ) w ith in 1 2 ho ur s o f b irt h. T he se in fa nt s s ho ul d be te st ed fo r H Bs Ag a nd a nt ib od y to H Bs Ag (a nt i-H Bs ) 1 to 2 m on th s a fte r c om pl et io n of th e H ep B se rie s a t a ge 9 th ro ug h 18 m on th s ( pr ef er ab ly a t t he n ex t w el l-c hi ld v isi t). • If m ot he r’s H Bs Ag st at us is u nk no w n, w ith in 1 2 ho ur s o f b irt h ad m in ist er H ep B va cc in e re ga rd le ss o f b irt h w ei gh t. Fo r i nf an ts w ei gh in g le ss th an 2 ,0 00 g ra m s, ad m in ist er H BI G in a dd iti on to H ep B va cc in e w ith in 12 h ou rs o f b irt h. D et er m in e m ot he r’s H Bs Ag st at us a s s oo n as p os sib le a nd , if m ot he r i s H Bs Ag -p os iti ve , al so a dm in ist er H BI G fo r i nf an ts w ei gh in g 2, 00 0 gr am s o r m or e as so on a s p os sib le , b ut n o la te r t ha n ag e 7 da ys . D os es fo llo w in g th e bi rt h do se : • Th e se co nd d os e sh ou ld b e ad m in ist er ed a t a ge 1 o r 2 m on th s. M on ov al en t H ep B va cc in e sh ou ld b e us ed fo r d os es a dm in ist er ed b ef or e ag e 6 w ee ks . • In fa nt s w ho d id n ot re ce iv e a bi rt h do se sh ou ld re ce iv e 3 do se s o f a H ep B- co nt ai ni ng v ac ci ne o n a sc he du le o f 0 , 1 to 2 m on th s, an d 6 m on th s s ta rt in g as so on a s f ea sib le . S ee F ig ur e 2. • th e th ird d os e at le as t 8 w ee ks a fte r t he se co nd d os e AN D a t l ea st 1 6 w ee ks a fte r t he (th ird o r f ou rt h) d os e in th e H ep B va cc in e se rie s s ho ul d be a dm in ist er ed n o ea rli er th an a ge 2 4 w ee ks . • Ad m in ist ra tio n of a to ta l o f 4 d os es o f H ep B va cc in e is pe rm itt ed w he n a co m bi na tio n va cc in e co nt ai ni ng H ep B is ad m in ist er ed a fte r t he b irt h do se . Ca tc h- up v ac ci na tio n: • U nv ac ci na te d pe rs on s s ho ul d co m pl et e a 3- do se se rie s. • A 2- do se se rie s ( do se s s ep ar at ed b y at le as t 4 m on th s) o f a du lt fo rm ul at io n Re co m bi va x H B is lic en se d fo r us e in c hi ld re n ag ed 1 1 th ro ug h 15 y ea rs . • Fo r o th er c at ch -u p gu id an ce , s ee F ig ur e 2. 2. Ro ta vi ru s ( RV ) v ac ci ne s. (M in im um a ge : 6 w ee ks fo r b ot h RV 1 [R ot ar ix ] a nd RV 5 [R ot aT eq ]) Ro ut in e va cc in at io n: Ad m in ist er a se rie s o f R V va cc in e to a ll in fa nt s a s f ol lo w s: 1. I f R ot ar ix is u se d, a dm in ist er a 2 -d os e se rie s a t 2 a nd 4 m on th s o f a ge . 2. I f R ot aT eq is u se d, a dm in ist er a 3 -d os e se rie s a t a ge s 2 , 4 , a nd 6 m on th s. 3. I f a ny d os e in th e se rie s w as R ot aT eq o r v ac ci ne p ro du ct is u nk no w n fo r a ny d os e in th e se rie s, a to ta l o f 3 do se s o f R V va cc in e sh ou ld b e ad m in ist er ed . Ca tc h- up v ac ci na tio n: • fo r i nf an ts a ge d 15 w ee ks , 0 d ay s o r o ld er . • • Fo r o th er c at ch -u p gu id an ce , s ee F ig ur e 2. 3. D ip ht he ria a nd te ta nu s t ox oi ds a nd a ce llu la r p er tu ss is (D Ta P) v ac ci ne . ( M in im um ag e: 6 w ee ks . E xc ep tio n: D Ta P- IP V [K in rix ]: 4 ye ar s) Ro ut in e va cc in at io n: • Ad m in ist er a 5 -d os e se rie s o f D Ta P va cc in e at a ge s 2 , 4 , 6 , 1 5 th ro ug h 18 m on th s, an d 4 th ro ug h 6 ye ar s. Th e fo ur th d os e m ay b e ad m in ist er ed a s e ar ly a s a ge 1 2 m on th s, pr ov id ed a t l ea st 6 m on th s h av e el ap se d sin ce th e th ird d os e. H ow ev er , t he fo ur th d os e of D Ta P ne ed n ot b e re pe at ed if it w as a dm in ist er ed a t le as t 4 m on th s a fte r t he th ird d os e of D Ta P. 3. D ip ht he ria a nd te ta nu s t ox oi ds a nd a ce llu la r p er tu ss is (D Ta P) v ac ci ne (c on t’d ) Ca tc h- up v ac ci na tio n: • • Fo r o th er c at ch -u p gu id an ce , s ee F ig ur e 2. 4. Te ta nu s a nd d ip ht he ria to xo id s a nd a ce llu la r p er tu ss is (T da p) v ac ci ne . ( M in im um ag e: 1 0 ye ar s f or b ot h Bo os tr ix a nd A da ce l) Ro ut in e va cc in at io n: • Ad m in ist er 1 d os e of Td ap v ac ci ne to a ll ad ol es ce nt s a ge d 11 th ro ug h 12 y ea rs . • Td ap m ay b e ad m in ist er ed re ga rd le ss o f t he in te rv al si nc e th e la st te ta nu s a nd d ip ht he ria to xo id - co nt ai ni ng v ac ci ne . • Ad m in ist er 1 d os e of Td ap v ac ci ne to p re gn an t a do le sc en ts d ur in g ea ch p re gn an cy (p re fe rre d du rin g 27 th ro ug h 36 w ee ks ’ g es ta tio n) re ga rd le ss o f t im e sin ce p rio r T d or Td ap v ac ci na tio n. Ca tc h- up v ac ci na tio n: • Pe rs on s a ge d 7 ye ar s a nd o ld er w ho a re n ot fu lly im m un iz ed w ith D Ta P va cc in e sh ou ld re ce iv e Td ap va cc in e. F or c hi ld re n 7 th ro ug h 10 y ea rs w ho re ce iv e a do se o f T da p as p ar t o f t he c at ch -u p se rie s, an ad ol es ce nt Td ap v ac ci ne d os e at a ge 1 1 th ro ug h 12 y ea rs sh ou ld N O T be a dm in ist er ed . T d sh ou ld b e ad m in ist er ed in st ea d 10 y ea rs a fte r t he Td ap d os e. • Pe rs on s a ge d 11 th ro ug h 18 y ea rs w ho h av e no t r ec ei ve d Td ap v ac ci ne sh ou ld re ce iv e a do se fo llo w ed b y te ta nu s a nd d ip ht he ria to xo id (T d) b oo st er d os es e ve ry 1 0 ye ar s t he re af te r. • In ad ve rt en t d os es o f D Ta P va cc in e: - If ad m in ist er ed in ad ve rt en tly to a c hi ld a ge d 7 th ro ug h 10 y ea rs m ay c ou nt a s p ar t o f t he c at ch -u p se rie s. Th is do se m ay c ou nt a s t he a do le sc en t T da p do se , o r t he c hi ld c an la te r r ec ei ve a Td ap b oo st er do se a t a ge 1 1 th ro ug h 12 y ea rs . - If ad m in ist er ed in ad ve rt en tly to a n ad ol es ce nt a ge d 11 th ro ug h 18 y ea rs , t he d os e sh ou ld b e co un te d as th e ad ol es ce nt Td ap b oo st er . • Fo r o th er c at ch -u p gu id an ce , s ee F ig ur e 2. 5. ty pe b (H ib ) c on ju ga te v ac ci ne . ( M in im um a ge : 6 w ee ks fo r P RP -T [A CT H IB , D Ta P- IP V/ H ib (P en ta ce l) an d H ib -M en CY (M en H ib rix )], P RP -O M P [P ed va xH IB o r C O M VA X] , 1 2 m on th s f or P RP -T [H ib er ix ]) Ro ut in e va cc in at io n: • Ad m in ist er a 2 - o r 3 -d os e H ib v ac ci ne p rim ar y se rie s a nd a b oo st er d os e (d os e 3 or 4 d ep en di ng o n va cc in e us ed in p rim ar y se rie s) a t a ge 1 2 th ro ug h 15 m on th s t o co m pl et e a fu ll H ib v ac ci ne se rie s. • Th e pr im ar y se rie s w ith A ct H IB , M en H ib rix , o r P en ta ce l c on sis ts o f 3 d os es a nd sh ou ld b e ad m in ist er ed a t 2, 4 , a nd 6 m on th s o f a ge . T he p rim ar y se rie s w ith P ed va xH ib o r C O M VA X co ns ist s o f 2 d os es a nd sh ou ld be a dm in ist er ed a t 2 a nd 4 m on th s o f a ge ; a d os e at a ge 6 m on th s i s n ot in di ca te d. • O ne b oo st er d os e (d os e 3 or 4 d ep en di ng o n va cc in e us ed in p rim ar y se rie s) o f a ny H ib v ac ci ne sh ou ld be a dm in ist er ed a t a ge 1 2 th ro ug h 15 m on th s. An e xc ep tio n is H ib er ix v ac ci ne . H ib er ix sh ou ld o nl y be pr io r d os e of H ib -c on ta in in g va cc in e. • Fo r r ec om m en da tio ns o n th e us e of M en H ib rix in p at ie nt s a t i nc re as ed ri sk fo r m en in go co cc al d ise as e, pl ea se re fe r t o th e m en in go co cc al v ac ci ne fo ot no te s a nd a lso to M M W R Fe br ua ry 2 8, 2 01 4 / 6 3( RR 01 );1 - 13 , a va ila bl e at h tt p: // w w w .cd c.g ov /m m w r/ PD F/ rr /r r6 30 1. pd f. 3827_Ch19_447_496 02/07/15 12:05 PM Page 456 457 5. ty pe b (H ib ) c on ju ga te v ac ci ne (c on t’d ) Ca tc h- up v ac ci na tio n: • w ee ks a fte r d os e 1, re ga rd le ss o f H ib v ac ci ne u se d in th e pr im ar y se rie s. • th e se co nd d os e. • w hi ch ev er is la te r. • • Fo r u nv ac ci na te d ch ild re n ag ed 1 5 m on th s o r o ld er , a dm in ist er o nl y 1 do se . • Fo r o th er c at ch -u p gu id an ce , s ee F ig ur e 2. F or c at ch -u p gu id an ce re la te d to M en H ib rix , p le as e se e th e m en in go co cc al v ac ci ne fo ot no te s a nd a lso M M W R Fe br ua ry 2 8, 2 01 4 / 6 3( RR 01 );1 -1 3, a va ila bl e at ht tp :// w w w .cd c.g ov /m m w r/ PD F/ rr /r r6 30 1. pd f. Va c c in at io n of p er so ns w ith h ig h- ris k co nd iti on s: • Ch ild re n ag ed 1 2 th ro ug h 59 m on th s w ho a re a t i nc re as ed ri sk fo r H ib d ise as e, in cl ud in g ch em ot he ra py re ci pi en ts a nd th os e w ith a na to m ic o r f un ct io na l a sp le ni a (in cl ud in g sic kl e ce ll di se as e) , h um an sh ou ld re ce iv e 2 ad di tio na l d os es o f H ib v ac ci ne 8 w ee ks a pa rt ; c hi ld re n w ho re ce iv ed 2 o r m or e d os es o f H ib v ac ci ne b ef or e 12 m on th s o f a ge sh ou ld re ce iv e 1 ad di tio na l d os e. • Fo r p at ie nt s y ou ng er th an 5 y ea rs o f a ge u nd er go in g ch em ot he ra py o r r ad ia tio n tre at m en t w ho re ce iv ed a H ib v ac ci ne d os e( s) w ith in 1 4 da ys o f s ta rt in g th er ap y or d ur in g th er ap y, re pe at th e do se (s ) a t l ea st 3 m on th s f ol lo w in g th er ap y co m pl et io n. • Re ci pi en ts o f h em at op oi et ic st em c el l t ra ns pl an t ( H SC T) sh ou ld b e re va cc in at ed w ith a 3 -d os e re gi m en of H ib v ac ci ne st ar tin g 6 to 1 2 m on th s a fte r s uc ce ss fu l t ra ns pl an t, re ga rd le ss o f v ac ci na tio n hi st or y; d os es sh ou ld b e ad m in ist er ed a t l ea st 4 w ee ks a pa rt . • A sin gl e do se o f a ny H ib -c on ta in in g va cc in e sh ou ld b e ad m in ist er ed to u ni m m un iz ed * c hi ld re n an d ad ol es ce nt s 1 5 m on th s o f a ge a nd o ld er u nd er go in g an e le ct iv e sp le ne ct om y; if p os sib le , v ac ci ne sh ou ld be a dm in ist er ed a t l ea st 1 4 da ys b ef or e pr oc ed ur e. • H ib v ac ci ne is n ot ro ut in el y re co m m en de d fo r p at ie nt s 5 y ea rs o r o ld er . H ow ev er , 1 d os e of H ib v ac ci ne sh ou ld b e ad m in ist er ed to u ni m m un iz ed * p er so ns a ge d 5 ye ar s o r o ld er w ho h av e an at om ic o r fu nc tio na l a sp le ni a (in cl ud in g sic kl e ce ll di se as e) a nd u nv ac ci na te d pe rs on s 5 th ro ug h 18 y ea rs o f a ge * P at ie nt s w ho h av e n ot re ce iv ed a p rim ar y s er ie s a nd b oo st er d os e o r a t l ea st 1 d os e o f H ib va cc in e a fte r 1 4 m on th s o f a ge a re co ns id er ed u ni m m un ize d. 6. Pn eu m oc oc ca l v ac ci ne s. (M in im um a ge : 6 w ee ks fo r P CV 13 , 2 y ea rs fo r P PS V2 3) Ro ut in e va cc in at io n w ith P CV 13 : • Ad m in ist er a 4 -d os e se rie s o f P CV 13 v ac ci ne a t a ge s 2 , 4 , a nd 6 m on th s a nd a t a ge 1 2 th ro ug h 15 m on th s. • Fo r c hi ld re n ag ed 1 4 th ro ug h 59 m on th s w ho h av e re ce iv ed a n ag e- ap pr op ria te se rie s o f 7 -v al en t P CV (P CV 7) , a dm in ist er a si ng le su pp le m en ta l d os e of 1 3- va le nt P CV (P CV 13 ). Ca tc h- up v ac ci na tio n w ith P CV 13 : • Ad m in ist er 1 d os e of P CV 13 to a ll he al th y ch ild re n ag ed 2 4 th ro ug h 59 m on th s w ho a re n ot c om pl et el y va cc in at ed fo r t he ir ag e. • Fo r o th er c at ch -u p gu id an ce , s ee F ig ur e 2. Va cc in at io n of p er so ns w ith h ig h- ris k co nd iti on s w ith P CV 13 a nd P PS V2 3: • Al l r ec om m en de d PC V1 3 do se s s ho ul d be a dm in ist er ed p rio r t o PP SV 23 v ac ci na tio n if po ss ib le . • Fo r c hi ld re n 2 th ro ug h 5 ye ar s o f a ge w ith a ny o f t he fo llo w in g co nd iti on s: ch ro ni c he ar t d ise as e (p ar tic ul ar ly c ya no tic c on ge ni ta l h ea rt d ise as e an d ca rd ia c fa ilu re ); ch ro ni c lu ng d ise as e (in cl ud in g co ch le ar im pl an t; sic kl e ce ll di se as e an d ot he r h em og lo bi no pa th ie s; an at om ic o r f un ct io na l a sp le ni a; H IV in fe ct io n; c hr on ic re na l f ai lu re ; n ep hr ot ic sy nd ro m e; d ise as es a ss oc ia te d w ith tr ea tm en t w ith im m un os up pr es siv e dr ug s o r r ad ia tio n th er ap y, in cl ud in g m al ig na nt n eo pl as m s, le uk em ia s, ly m ph om as , 1. A dm in ist er 1 d os e of P CV 13 if a ny in co m pl et e sc he du le o f 3 d os es o f P CV (P CV 7 an d/ or P CV 13 ) w er e re ce iv ed p re vi ou sly . 2. A dm in ist er 2 d os es o f P CV 13 a t l ea st 8 w ee ks a pa rt if u nv ac ci na te d or a ny in co m pl et e sc he du le o f f ew er th an 3 d os es o f P CV (P CV 7 an d/ or P CV 13 ) w er e re ce iv ed p re vi ou sly . 3. A dm in ist er 1 su pp le m en ta l d os e of P CV 13 if 4 d os es o f P CV 7 or o th er a ge -a pp ro pr ia te c om pl et e PC V7 se rie s w as re ce iv ed p re vi ou sly . 4. T he m in im um in te rv al b et w ee n do se s o f P CV (P CV 7 or P CV 13 ) i s 8 w ee ks . 5. F or c hi ld re n w ith n o hi st or y of P PS V2 3 va cc in at io n, a dm in ist er P PS V2 3 at le as t 8 w ee ks a fte r t he m os t re ce nt d os e of P CV 13 . 6. Pn eu m oc oc ca l v ac ci ne s ( co nt ’d ) • di se as e an d ot he r h em og lo bi no pa th ie s; an at om ic o r f un ct io na l a sp le ni a; c on ge ni ta l o r a cq ui re d w ith tr ea tm en t w ith im m un os up pr es siv e dr ug s o r r ad ia tio n th er ap y, in cl ud in g m al ig na nt n eo pl as m s, le uk em ia s, ly m ph om as , a nd H od gk in ’s di se as e; g en er al iz ed m al ig na nc y; so lid o rg an tr an sp la nt at io n; o r m ul tip le m ye lo m a: 1. I f n ei th er P CV 13 n or P PS V2 3 ha s b ee n re ce iv ed p re vi ou sly , a dm in ist er 1 d os e of P CV 13 n ow a nd 1 d os e of P PS V2 3 at le as t 8 w ee ks la te r. 2. I f P CV 13 h as b ee n re ce iv ed p re vi ou sly b ut P PS V2 3 ha s n ot , a dm in ist er 1 d os e of P PS V2 3 at le as t 8 w ee ks af te r t he m os t r ec en t d os e of P CV 13 . 3. I f P PS V2 3 ha s b ee n re ce iv ed b ut P CV 13 h as n ot , a dm in ist er 1 d os e of P CV 13 a t l ea st 8 w ee ks a fte r t he m os t r ec en t d os e of P PS V2 3. • Fo r c hi ld re n ag ed 6 th ro ug h 18 y ea rs w ith c hr on ic h ea rt d ise as e (p ar tic ul ar ly c ya no tic c on ge ni ta l h ea rt di se as e an d ca rd ia c fa ilu re ), ch ro ni c lu ng d ise as e (in cl ud in g as th m a if tre at ed w ith h ig h- do se o ra l co rt ic os te ro id th er ap y) , d ia be te s m el lit us , a lc oh ol ism , o r c hr on ic li ve r d ise as e, w ho h av e no t r ec ei ve d PP SV 23 , a dm in ist er 1 d os e of P PS V2 3. If P CV 13 h as b ee n re ce iv ed p re vi ou sly , t he n PP SV 23 sh ou ld b e ad m in ist er ed a t l ea st 8 w ee ks a fte r a ny p rio r P CV 13 d os e. • sic kl e ce ll di se as e or o th er h em og lo bi no pa th ie s; an at om ic o r f un ct io na l a sp le ni a; c on ge ni ta l o r a cq ui re d w ith tr ea tm en t w ith im m un os up pr es siv e dr ug s o r r ad ia tio n th er ap y, in cl ud in g m al ig na nt n eo pl as m s, le uk em ia s, ly m ph om as , a nd H od gk in ’s di se as e; g en er al iz ed m al ig na nc y; so lid o rg an tr an sp la nt at io n; o r m ul tip le m ye lo m a. 7. In ac tiv at ed p ol io vi ru s v ac ci ne (I PV ). (M in im um a ge : 6 w ee ks ) Ro ut in e va cc in at io n: • se rie s s ho ul d be ad m in ist er ed o n or af te r t he fo ur th b irt hd ay an d at le as t 6 m on th s a fte r t he p re vi ou s d os e. Ca tc h- up v ac ci na tio n: • of im m in en t e xp os ur e to ci rc ul at in g po lio vi ru s ( i.e ., t ra ve l t o a po lio -e nd em ic re gi on o r d ur in g an o ut br ea k) . • If 4 or m or e do se s a re a dm in ist er ed b ef or e ag e 4 ye ar s, an a dd iti on al d os e sh ou ld b e ad m in ist er ed a t a ge 4 th ro ug h 6 ye ar s a nd a t l ea st 6 m on th s a fte r t he p re vi ou s d os e. • A fo ur th d os e is no t n ec es sa ry if th e th ird d os e w as a dm in ist er ed a t a ge 4 ye ar s o r o ld er a nd a t l ea st 6 m on th s af te r t he p re vi ou s d os e. • If bo th O PV a nd IP V w er e ad m in ist er ed a s p ar t o f a se rie s, a to ta l o f 4 d os es sh ou ld b e ad m in ist er ed , r eg ar dl es s of th e ch ild ’s cu rre nt a ge . IP V is no t r ou tin el y r ec om m en de d fo r U .S . r es id en ts a ge d 18 ye ar s o r o ld er . • Fo r o th er ca tc h- up g ui da nc e, se e Fi gu re 2 . 8. In flu en za v ac ci ne s. (M in im um a ge : 6 m on th s f or in ac tiv at ed in flu en za v ac ci ne [I IV ], 2 ye ar s f or li ve , a tt en ua te d in flu en za v ac ci ne [L AI V] ) Ro ut in e va cc in at io n: • no np re gn an t p er so ns a ge d 2 th ro ug h 49 y ea rs , e ith er L AI V or II V m ay b e us ed . H ow ev er , L AI V sh ou ld N O T be a dm in ist er ed to so m e pe rs on s, in cl ud in g 1) p er so ns w ho h av e ex pe rie nc ed se ve re a lle rg ic re ac tio ns 17 y ea rs re ce iv in g as pi rin o r a sp iri n- co nt ai ni ng p ro du ct s; 3) p er so ns w ho a re a lle rg ic to e gg s; 4) p re gn an t w om en ; 5 ) i m m un os up pr es se d pe rs on s; 6) c hi ld re n 2 th ro ug h 4 ye ar s o f a ge w ith a st hm a or w ho h ad pr ev io us 4 8 ho ur s. Fo r a ll ot he r c on tr ai nd ic at io ns a nd p re ca ut io ns to u se o f L AI V, se e M M W R Au gu st 1 5, 20 14 / 63 (3 2) ;6 91 -6 97 [4 0 pa ge s] a va ila bl e at ht tp :// w w w .cd c.g ov /m m w r/ pd f/w k/ m m 63 32 .p df . F o r c hi ld re n ag ed 6 m on th s t hr ou gh 8 y ea rs : • Fo r t he 2 01 4- 15 se as on , a dm in ist er 2 d os es (s ep ar at ed b y at le as t 4 w ee ks ) t o ch ild re n w ho a re re ce iv in g va cc in e re co m m en da tio ns , M M W R Au gu st 1 5, 2 01 4 / 6 3( 32 );6 91 -6 97 [4 0 pa ge s] a va ila bl e at h tt p: // w w w . cd c.g ov /m m w r/ pd f/w k/ m m 63 32 .p df . • Fo r p er so ns a ge d 9 ye ar s a nd o ld er : • Ad m in ist er 1 d os e. Fo r f ur th er g ui da nc e on th e us e of th e va cc in es m en tio ne d be lo w , s ee : h tt p: // w w w .c dc .g ov /v ac ci ne s/ hc p/ ac ip -re cs /in de x. ht m l. 3827_Ch19_447_496 02/07/15 12:05 PM Page 457 458 Fo r f ur th er g ui da nc e on th e us e of th e va cc in es m en tio ne d be lo w , s ee : h tt p: // w w w .c dc .g ov /v ac ci ne s/ hc p/ ac ip -re cs /in de x. ht m l. 9. M ea sl es , m um ps , a nd ru be lla (M M R) v ac ci ne . ( M in im um a ge : 1 2 m on th s f or ro ut in e va cc in at io n) Ro ut in e va cc in at io n: • Ad m in ist er a 2 -d os e se rie s o f M M R va cc in e at a ge s 1 2 th ro ug h 15 m on th s a nd 4 th ro ug h 6 ye ar s. Th e do se . • Ad m in ist er 1 d os e of M M R va cc in e to in fa nt s a ge d 6 th ro ug h 11 m on th s b ef or e de pa rt ur e fro m th e Un ite d at a ge 1 2 th ro ug h 15 m on th s ( 12 m on th s i f t he ch ild re m ai ns in a n ar ea w he re d ise as e ris k is hi gh ), an d th e se co nd d os e at le as t 4 w ee ks la te r. • Ad m in ist er 2 d os es o f M M R va cc in e to ch ild re n ag ed 1 2 m on th s a nd o ld er b ef or e de pa rt ur e fro m th e th e se co nd d os e at le as t 4 w ee ks la te r. Ca tc h- up v ac ci na tio n: • En su re th at a ll sc ho ol -a ge d ch ild re n an d ad ol es ce nt s h av e ha d 2 do se s o f M M R va cc in e; th e m in im um in te rv al b et w ee n th e 2 do se s i s 4 w ee ks . 10 . Va ric el la (V AR ) v ac ci ne . ( M in im um a ge : 1 2 m on th s) Ro ut in e va cc in at io n: • Ad m in ist er a 2 -d os e se rie s o f V AR v ac ci ne a t a ge s 1 2 th ro ug h 15 m on th s a nd 4 th ro ug h 6 ye ar s. Th e se co nd d os e m ay b e ad m in ist er ed b ef or e ag e 4 ye ar s, pr ov id ed a t l ea st 3 m on th s h av e el ap se d sin ce th e va lid . Ca tc h- up v ac ci na tio n: • En su re th at a ll pe rs on s a ge d 7 th ro ug h 18 y ea rs w ith ou t e vi de nc e of im m un ity (s ee M M W R 20 07 / 56 [N o. RR -4 ], av ai la bl e at h tt p: // w w w .cd c.g ov /m m w r/ pd f/r r/ rr 56 04 .p df ) ha ve 2 d os es o f v ar ic el la v ac ci ne . F or ch ild r e n ag ed 7 th ro ug h 12 y ea rs , t he re co m m en de d m in im um in te rv al b et w ee n do se s i s 3 m on th s ( if pe rs on s a ge d 13 y ea rs a nd o ld er , t he m in im um in te rv al b et w ee n do se s i s 4 w ee ks . 11 . H ep at iti s A (H ep A) v ac ci ne . ( M in im um a ge : 1 2 m on th s) Ro ut in e va cc in at io n: • In iti at e th e 2- do se H ep A va cc in e se rie s a t 1 2 th ro ug h 23 m on th s; se pa ra te th e 2 do se s b y 6 to 1 8 m on th s. • Ch ild re n w ho h av e re ce iv ed 1 d os e of H ep A va cc in e be fo re a ge 2 4 m on th s s ho ul d re ce iv e a se co nd d os e • Fo r a ny p er so n ag ed 2 y ea rs a nd o ld er w ho h as n ot a lre ad y re ce iv ed th e H ep A va cc in e se rie s, 2 do se s o f H ep A va cc in e se pa ra te d by 6 to 1 8 m on th s m ay b e ad m in ist er ed if im m un ity a ga in st h ep at iti s A v iru s in fe ct io n is de sir ed . Ca tc h- up v ac ci na tio n: • Th e m in im um in te rv al b et w ee n th e tw o do se s i s 6 m on th s. Sp ec ia l p op ul at io ns : • Ad m in ist er 2 d os es o f H ep A va cc in e at le as t 6 m on th s a pa rt to p re vi ou sly u nv ac ci na te d pe rs on s w ho liv e in a re as w he re v ac ci na tio n pr og ra m s t ar ge t o ld er c hi ld re n, o r w ho a re a t i nc re as ed ri sk fo r i nf ec tio n. Th is in cl ud es p er so ns tr av el in g to o r w or ki ng in c ou nt rie s t ha t h av e hi gh o r i nt er m ed ia te e nd em ic ity o f in fe ct io n; m en h av in g se x w ith m en ; u se rs o f i nj ec tio n an d no n- in je ct io n ill ic it dr ug s; pe rs on s w ho w or k w ith H AV -in fe ct ed p rim at es o r w ith H AV in a re se ar ch la bo ra to ry ; p er so ns w ith c lo tt in g- fa ct or d iso rd er s; pe rs on s w ith c hr on ic li ve r d ise as e; a nd p er so ns w ho a nt ic ip at e cl os e pe rs on al c on ta ct (e .g ., h ou se ho ld so on a s t he a do pt io n is pl an ne d, id ea lly 2 o r m or e w ee ks b ef or e th e ar riv al o f t he a do pt ee . 12 . H um an p ap ill om av iru s ( H PV ) v ac ci ne s. (M in im um a ge : 9 y ea rs fo r H PV 2 [C er va rix ] an d H PV 4 [G ar da si l]) Ro ut in e va cc in at io n: • Ad m in ist er a 3 -d os e se rie s o f H PV v ac ci ne o n a sc he du le o f 0 , 1 -2 , a nd 6 m on th s t o al l a do le sc en ts a ge d 11 th ro ug h 12 y ea rs . E ith er H PV 4 or H PV 2 m ay b e us ed fo r f em al es , a nd o nl y H PV 4 m ay b e us ed fo r m al es . • Th e va cc in e se rie s m ay b e st ar te d at a ge 9 y ea rs . • Ca tc h- up v ac ci na tio n: • Ad m in ist er th e va cc in e se rie s t o fe m al es (e ith er H PV 2 or H PV 4) a nd m al es (H PV 4) a t a ge 1 3 th ro ug h 18 ye ar s i f n ot p re vi ou sly v ac ci na te d. • U se re co m m en de d ro ut in e do sin g in te rv al s ( se e Ro ut in e va cc in at io n ab ov e) fo r v ac ci ne se rie s c at ch -u p. 13 . M en in go co cc al co nj ug at e va cc in es . ( M in im um a ge : 6 w ee ks fo r H ib -M en CY [M en H ib rix ], 9 m on th s f or M en AC W Y- D [M en ac tr a] , 2 m on th s f or M en AC W Y- CR M [M en ve o] ) Ro ut in e va cc in at io n: • Ad m in ist er a si ng le d os e of M en ac tr a or M en ve o va cc in e at a ge 1 1 th ro ug h 12 y ea rs , w ith a b oo st er d os e at a ge 1 6 ye ar s. • re ce iv e a 2- do se p rim ar y se rie s o f M en ac tr a or M en ve o w ith a t l ea st 8 w ee ks b et w ee n do se s. • Fo r c hi ld re n ag ed 2 m on th s t hr ou gh 1 8 ye ar s w ith h ig h- ris k co nd iti on s, se e be lo w . Ca tc h- up v ac ci na tio n: • Ad m in ist er M en ac tr a or M en ve o va cc in e at a ge 1 3 th ro ug h 18 y ea rs if n ot p re vi ou sly v ac ci na te d. • 16 th ro ug h 18 y ea rs w ith a m in im um in te rv al o f a t l ea st 8 w ee ks b et w ee n do se s. • • Fo r o th er c at ch -u p gu id an ce , s ee F ig ur e 2. Va cc in at io n of p er so ns w ith h ig h- ris k co nd iti on s a nd o th er p er so ns a t i nc re as ed ri sk o f d is ea se : • Ch ild re n w ith a na to m ic o r f un ct io na l a sp le ni a (in cl ud in g sic kl e ce ll di se as e) : 1. M en ve o o Ch ild re n w ho in iti at e v ac cin at io n at 8 w ee ks th ro ug h 6 m on th s: A dm in ist er d os es at 2 , 4 , 6 , a nd 1 2 m on th s of a ge . o Un va cc in at ed ch ild re n 7 t hr ou gh 23 m on th s: Ad m in ist er 2 d os es , w ith th e se co nd d os e at le as t 1 2 w ee ks o Ch ild re n 24 m on th s a nd o ld er w ho h av e no t r ec ei ve d a co m pl et e se rie s: Ad m in ist er 2 p rim ar y do se s a t le as t 8 w ee ks a pa rt . 2. M en H ib rix o Ch ild re n 6 w ee ks th ro ug h 18 m on th s: Ad m in ist er d os es a t 2 , 4 , 6 , a nd 1 2 th ro ug h 15 m on th s o f a ge . o at le as t 8 w ee ks a pa rt to e ns ur e pr ot ec tio n ag ai ns t s er og ro up s C a nd Y m en in go co cc al d ise as e. 3. M en ac tr a o Ch ild re n 24 m on th s a nd o ld er w ho h av e no t r ec ei ve d a co m pl et e se rie s: Ad m in ist er 2 p rim ar y do se s a t le as t 8 w ee ks a pa rt . If M en ac tr a is ad m in ist er ed to a ch ild w ith a sp le ni a (in cl ud in g sic kl e ce ll di se as e) , do n ot a dm in ist er M en ac tr a un til 2 ye ar s o f a ge a nd a t l ea st 4 w ee ks a fte r t he co m pl et io n of a ll P CV 13 do se s. • 1. M en ve o o Ch ild re n w ho in iti at e v ac cin at io n at 8 w ee ks th ro ug h 6 m on th s: Ad m in ist er d os es at 2 , 4 , 6 , a nd 1 2 m on th s of a ge . o Un va cc in at ed ch ild re n 7 t hr ou gh 23 m on th s: Ad m in ist er 2 d os es , w ith th e se co nd d os e at le as t 1 2 w ee ks o Ch ild re n 24 m on th s a nd o ld er w ho h av e no t r ec ei ve d a co m pl et e se rie s: Ad m in ist er 2 p rim ar y do se s a t le as t 8 w ee ks a pa rt . 2. M en H ib rix o Ch ild re n 6 w ee ks th ro ug h 18 m on th s: Ad m in ist er d os es a t 2 , 4 , 6 , a nd 1 2 th ro ug h 15 m on th s o f a ge . o at le as t 8 w ee ks a pa rt to e ns ur e pr ot ec tio n ag ai ns t s er og ro up s C a nd Y m en in go co cc al d ise as e. 3. M en ac tr a o Ch ild re n 9 th ro ug h 23 m on th s: Ad m in ist er 2 p rim ar y do se s a t l ea st 1 2 w ee ks a pa rt . o Ch ild re n 24 m on th s a nd o ld er w ho h av e no t r ec ei ve d a co m pl et e se rie s: Ad m in ist er 2 p rim ar y do se s a t le as t 8 w ee ks a pa rt . • Fo r c hi ld re n w ho tr av el to o r r es id e in c ou nt rie s i n w hi ch m en in go co cc al d ise as e is hy pe re nd em ic o r ep id em ic , in cl ud in g co un tr ie s i n th e Af ric an m en in gi tis b el t o r t he H aj j, a dm in ist er a n ag e- ap pr op ria te fo rm ul at io n an d se rie s o f M en ac tr a or M en ve o fo r p ro te ct io n ag ai ns t s er og ro up s A a nd W m en in go co cc al be ca us e it do es n ot c on ta in se ro gr ou ps A o r W . • Fo r c hi ld re n at ri sk d ur in g a co m m un ity o ut br ea k at tr ib ut ab le to a v ac ci ne se ro gr ou p, a dm in ist er o r co m pl et e an a ge - a nd fo rm ul at io n- ap pr op ria te se rie s o f M en H ib rix , M en ac tr a, o r M en ve o. • Fo r b oo st er d os es a m on g pe rs on s w ith h ig h- ris k co nd iti on s, re fe r t o M M W R 20 13 / 62 (R R0 2) ;1 -2 2, av ai la bl e at h tt p: // w w w .cd c.g ov /m m w r/ pr ev ie w /m m w rh tm l/r r6 20 2a 1. ht m . Fo r o th er c at c h -u p re co m m en da tio ns fo r t he se p er so ns , a nd c om pl et e in fo rm at io n on u se o f m en in go co cc al v ac ci ne s, in cl ud in g gu id an ce re la te d to v ac ci na tio n of p er so ns a t i nc re as ed ri sk o f i nf ec tio n, se e M M W R M ar ch 2 2, 2 01 3 / 6 2( RR 02 );1 -2 2, a va ila bl e at h tt p: // w w w .cd c.g ov /m m w r/ pd f/r r/ rr 62 02 .p df . CS 2 44 08 3- B Ta bl e 19 –2 ! Ca tc h- U p Im m un iz at io n Sc he du le fo r P er so ns A ge d 4 M on th s Th ro ug h 18 Y ea rs W ho S ta rt L at e or W ho A re M or e Th an 1 M on th B eh in d – U ni te d St at es , 2 01 5— co nt ’d 3827_Ch19_447_496 02/07/15 12:05 PM Page 458 459 Table 19–3 Vaccine Information Statements MEASLES, MUMPS, RUBELLA, AND VARICELLA VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 3827_Ch19_447_496 02/07/15 12:05 PM Page 459 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Patient Education ORAL POLIOVIRUS VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 460 3827_Ch19_447_496 02/07/15 12:05 PM Page 460 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Patient Education ROTAVIRUS VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 461 3827_Ch19_447_496 02/07/15 12:05 PM Page 461 Drug Interactions Clinical Use and Dosing Patient Education VARICELLA VIRUS VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 462 3827_Ch19_447_496 02/07/15 12:05 PM Page 462 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 463 3827_Ch19_447_496 02/07/15 12:05 PM Page 463 Monitoring Patient Education ZOSTER VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 464 CLINICAL PEARL Administering Multiple Vaccines Currently a child from age 12 to 18 months should re- ceive six possible injections. This can be traumatic for patient and parent. Most public health officials recom- mend giving all the recommended vaccines at one visit; therefore, the child who is 15 months old could be getting as many as all six injections at that visit. Using combined vaccines is best (Pediarix, Pentacel) to decrease the number of injections or spread the administration of the vaccines over two or three visits. If it is necessary to give all the vaccines in one visit, as in the case of upcoming international travel or a history of unreliable attendance at well-child examinations, two people can administer the vaccines simultane- ously. Giving the vaccines simultaneously makes the process faster and simpler for the patient and the per- son administering the vaccine. The CDC guidelines for administering multiple injections to infants are located in Appendix D of the Pink Book at www.cdc.gov/ vaccines/pubs/pinkbook/index.html. 3827_Ch19_447_496 02/07/15 12:05 PM Page 464 Drug Interactions Clinical Use and Dosing Monitoring Patient Education ORAL TYPHOID VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 465 3827_Ch19_447_496 02/07/15 12:05 PM Page 465 466 *Covered by the Vaccine Injury Compensation Program For all persons in this category who meet the age requirements and who lack documentation of vaccination or have no evidence of previous infection; zoster vaccine recommended regardless of prior episode of zoster Recommended if some other risk factor is present (e.g., on the basis of medical, occupational, lifestyle, or other indication) No recommendation Recommended Adult Immunization Schedule—United States - 2015 Note: These recommendations must be read with the footnotes that follow containing number of doses, intervals between doses, and other important information. Figure 1. Recommended adult immunization schedule, by vaccine and age group1 report are available at www.vaers.hhs.gov or by telephone, 800-822-7967. www.hrsa.gov/vaccinecompensation claim for vaccine injury, contact the U.S. Court of Federal Claims, 717 Madison Place, N.W., Washington, D.C. 20005; telephone, 202-357-6400. Additional information about the vaccines in this schedule, extent of available data, and contraindications for vaccination is also available at www.cdc.gov/vaccines or from the CDC-INFO Contact Center at 800-CDC-INFO (800-232-4636) in English and Spanish, 8:00 a.m. - 8:00 p.m. Eastern Time, Monday - Friday, excluding holidays. The recommendations in this schedule were approved by the Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP), the American Academy of Family Physicians (AAFP), the America College of Physicians (ACP), American College of Obstetricians and Gynecologists (ACOG) and American College of Nurse-Midwives (ACNM). Figure 2. Vaccines that might be indicated for adults based on medical and other indications1 VACCINE AGE GROUP 19-21 years 22-26 years 27-49 years 50-59 years 60-64 years ≥ 65 years 3 doses 1 or 3 doses 2 doses 1 or more doses 1 dose1 or 2 doses 1 or 2 doses 1 dose 3 doses 2 doses Substitute 1-time dose of Tdap for Td booster; then boost with Td every 10 yrs 1 dose annually VACCINE INDICATION Pregnancy Immuno- compromising conditions (excluding human virus [HIV]) 4,6,7,8,13 HIV infection CD4+ T lymphocyte count 4,6,7,8,13 Men who have sex with men (MSM) Kidney failure, end-stage renal disease, receipt of hemodialysis Heart disease, chronic lung disease, chronic alcoholism Asplenia (including elective splenectomy and persistent complement component 8,12 Chronic liver disease Diabetes Healthcare personnel < 200 cells/ L ≥ 200 cells/ L These schedules indicate the recommended age groups and medical indications for which administration of currently licensed vaccines is commonly recommended for adults ages 19 years and older, as of February 1, 2015. For all vaccines being recommended on the Adult Immunization Schedule: a vaccine series does not need to be restarted, regardless of the time that has elapsed between doses. Licensed combination vaccines may be used whenever any components of the combination are indicated and when the vaccine’s other components are not contraindicated. For detailed recommendations on all vaccines, including those used primarily for travelers or that are issued during the year, consult the manufacturers’ package inserts and the complete statements from the Advisory Committee on Immunization Practices (www.cdc.gov/vaccines/hcp/acip-recs/index.html imply endorsement by the U.S. Department of Health and Human Services. 3 doses 1 or 3 doses 2 doses 1 or more doses 1 dose 1 or 2 doses 1 or 2 dosesContraindicated 1 doseContraindicated 3 doses through age 21 yrs3 doses through age 26 yrs 3 doses through age 26 yrs3 doses through age 26 yrs 2 dosesContraindicated Substitute 1-time dose of Tdap for Td booster; then boost with Td every 10 yrs 1 does IIV or LAIV annually1 dose IIV annually 1 dose IIV or LAIV annually 1 dose Tdap each pregnancy 1 dose IIV annually post-HSCT recipients only For all persons in this category who meet the age requirements and who lack documentation of vaccination or have no evidence of previous infection; zoster vaccine recommended regardless of prior episode of zoster Recommended if some other risk factor is present (e.g., on the basis of medical, occupational, lifestyle, or other indications) No recommendation*Covered by the Vaccine Injury Compensation Program 3 doses 1-time dose Table 19–4 ! Recommended Adult Immunization Schedule – United States, 2015 3827_Ch19_447_496 02/07/15 12:05 PM Page 466 467 Table 19–4 ! Recommended Adult Immunization Schedule – United States, 2015—cont’d 1. Additional information • Additional guidance for the use of the vaccines described in this supplement is available at www.cdc.gov/vaccines/hcp/acip-recs/index.html. • Information on vaccination recommendations when vaccination status is unknown and other general immunization information can be found in the General Recommendations on Immunization at www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm. • Information on travel vaccine requirements and recommendations (e.g., for hepatitis A and B, meningococcal, and other vaccines) is available at wwwnc.cdc.gov/travel/destinations/list. • Additional information and resources regarding vaccination of pregnant women can be found at www.cdc.gov/vaccines/adults/rec-vac/pregnant.html. 2. Influenza vaccination • months or older. • Persons aged 6 months or older, including pregnant women and persons with age-appropriate IIV formulation should be used. • (RIV) (FluBlok). RIV does not contain any egg protein and can be given to age- appropriate persons with egg allergy of any severity. • Healthy, nonpregnant persons aged 2 to 49 years without high-risk medical conditions can receive either intranasally administered live, attenuated • Health care personnel who care for severely immunocompromised persons who require care in a protected environment should receive IIV or RIV; health care personnel who receive LAIV should avoid providing care for severely immunosuppressed persons for 7 days after vaccination. • The intramuscularly or intradermally administered IIV are options for adults aged 18 through 64 years. • Adults aged 65 years or older can receive the standard-dose IIV or the high- dose IIV (Fluzone High-Dose). • . 3. Tetanus, diphtheria, and acellular pertussis (Td/Tdap) vaccination • Administer 1 dose of Tdap vaccine to pregnant women during each pregnancy (preferably during 27 to 36 weeks’ gestation) regardless of interval since prior Td or Tdap vaccination. • Persons aged 11 years or older who have not received Tdap vaccine or for whom vaccine status is unknown should receive a dose of Tdap followed by tetanus and diphtheria toxoids (Td) booster doses every 10 years thereafter. Tdap can be administered regardless of interval since the most recent tetanus or diphtheria-toxoid containing vaccine. • Adults with an unknown or incomplete history of completing a 3-dose primary vaccination series with Td-containing vaccines should begin or complete a primary vaccination series including a Tdap dose. • the third dose 6 to 12 months after the second. • For incompletely vaccinated (i.e., less than 3 doses) adults, administer remaining doses. • Refer to the ACIP statement for recommendations for administering Td/Tdap as prophylaxis in wound management (see footnote 1). 4. Varicella vaccination • receive 2 doses of single-antigen varicella vaccine or a second dose if they have received only 1 dose. • Vaccination should be emphasized for those who have close contact with persons at high risk for severe disease (e.g., health care personnel and family contacts of persons with immunocompromising conditions) or are at high risk for exposure or transmission (e.g., teachers; child care employees; institutions; college students; military personnel; adolescents and adults living in households with children; nonpregnant women of childbearing age; and international travelers). • Pregnant women should be assessed for evidence of varicella immunity. of varicella vaccine upon completion or termination of pregnancy and before discharge from the health care facility. The second dose should be administered • Evidence of immunity to varicella in adults includes any of the following: documentation of 2 doses of varicella vaccine at least 4 weeks apart; U.S.-born before 1980, except health care personnel and pregnant women; a health care provider; disease by a health care provider; or 5. Human papillomavirus (HPV) vaccination • Two vaccines are licensed for use in females, bivalent HPV vaccine (HPV2) and quadrivalent HPV vaccine (HPV4), and one HPV vaccine for use in males (HPV4). • For females, either HPV4 or HPV2 is recommended in a 3-dose series for routine vaccination at age 11 or 12 years and for those aged 13 through 26 years, if not previously vaccinated. • For males, HPV4 is recommended in a 3-dose series for routine vaccination at age 11 or 12 years and for those aged 13 through 21 years, if not previously vaccinated. Males aged 22 through 26 years may be vaccinated. • HPV4 is recommended for men who have sex with men through age 26 years for those who did not get any or all doses when they were younger. • Vaccination is recommended for immunocompromised persons (including those with HIV infection) through age 26 years for those who did not get any or all doses when they were younger. • A complete series for either HPV4 or HPV2 consists of 3 doses. The second dose should be administered 4 to 8 weeks (minimum interval of 4 weeks) after the and 16 weeks after the second dose (minimum interval of at least 12 weeks). • HPV vaccines are not recommended for use in pregnant women. However, pregnancy testing is not needed before vaccination. If a woman is found to be pregnant after initiating the vaccination series, no intervention is needed; the remainder of the 3-dose series should be delayed until completion or termination of pregnancy. 6. Zoster vaccination • A single dose of zoster vaccine is recommended for adults aged 60 years or older regardless of whether they report a prior episode of herpes zoster. Although the vaccine is licensed by the U.S. Food and Drug Administration for use among and can be administered to persons aged 50 years or older, ACIP recommends that vaccination begin at age 60 years. • Persons aged 60 years or older with chronic medical conditions may be vaccinated unless their condition constitutes a contraindication, such as 7. Measles, mumps, rubella (MMR) vaccination • Adults born before 1957 are generally considered immune to measles and mumps. All adults born in 1957 or later should have documentation of 1 or more doses of MMR vaccine unless they have a medical contraindication to the vaccine or laboratory evidence of immunity to each of the three diseases. Documentation of provider-diagnosed disease is not considered acceptable evidence of immunity for measles, mumps, or rubella. Measles component: • A routine second dose of MMR vaccine, administered a minimum of 28 days are students in postsecondary educational institutions, work in a health care facility, or plan to travel internationally. • Persons who received inactivated (killed) measles vaccine or measles vaccine of unknown type during 1963–1967 should be revaccinated with 2 doses of MMR vaccine. Mumps component: • A routine second dose of MMR vaccine, administered a minimum of 28 days are students in a postsecondary educational institution, work in a health care facility, or plan to travel internationally. • Persons vaccinated before 1979 with either killed mumps vaccine or mumps vaccine of unknown type who are at high risk for mumps infection (e.g., persons who are working in a health care facility) should be considered for revaccination with 2 doses of MMR vaccine. Rubella component: • For women of childbearing age, regardless of birth year, rubella immunity should be determined. If there is no evidence of immunity, women who are not pregnant should be vaccinated. Pregnant women who do not have evidence of immunity should receive MMR vaccine upon completion or termination of pregnancy and before discharge from the health care facility. Health care personnel born before 1957: • For unvaccinated health care personnel born before 1957 who lack laboratory evidence of measles, mumps, and/or rubella immunity or laboratory personnel with 2 doses of MMR vaccine at the appropriate interval for measles and mumps or 1 dose of MMR vaccine for rubella. 8. Pneumococcal (13-valent pneumococcal conjugate vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPSV23]) vaccination • General information When indicated, only a single dose of PCV13 is recommended for adults. No additional dose of PPSV23 is indicated for adults vaccinated with PPSV23 at or after age 65 years. When both PCV13 and PPSV23 are indicated, PCV13 should be the same visit. When indicated, PCV13 and PPSV23 should be administered to adults whose pneumococcal vaccination history is incomplete or unknown. • Adults aged 65 years or older who Have not received PCV13 or PPSV23: Administer PCV13 followed by PPSV23 in 6 to 12 months. Have not received PCV13 but have received a dose of PPSV23 at age 65 years or older: Administer PCV13 at least 1 year after the dose of PPSV23 received at age 65 years or older. Footnotes—Recommended Immunization Schedule for Adults Aged 19 Years or Older: United States, 2015 3827_Ch19_447_496 02/07/15 12:05 PM Page 467 468 Table 19–4 ! Recommended Adult Immunization Schedule – United States, 2015—cont’d 8. Pneumococcal vaccination (continued) Have not received PCV13 but have received 1 or more doses of PPSV23 before age 65: Administer PCV13 at least 1 year after the most recent dose of PPSV23; administer a dose of PPSV23 6 to 12 months after PCV13, or as soon as possible if this time window has passed, and at least 5 years after the most recent dose of PPSV23. Have received PCV13 but not PPSV23 before age 65 years: Administer PPSV23 6 to 12 months after PCV13 or as soon as possible if this time window has passed. Have received PCV13 and 1 or more doses of PPSV23 before age 65 years: Administer PPSV23 6 to 12 months after PCV13, or as soon as possible if this time window has passed, and at least 5 years after the most recent dose of PPSV23. • Adults aged 19 through 64 years with immunocompromising conditions or Have not received PCV13 or PPSV23: Administer PCV13 followed by PPSV23 at least 8 weeks after PCV13; administer a second dose of PPSV23 at least 5 Have not received PCV13 but have received 1 dose of PPSV23: Administer PCV13 at least 1 year after the PPSV23; administer a second dose of PPSV23 PPSV23. Have not received PCV13 but have received 2 doses of PPSV23: Administer PCV13 at least 1 year after the most recent dose of PPSV23. Have received PCV13 but not PPSV23: Administer PPSV23 at least 8 weeks after PCV13; administer a second dose of PPSV23 at least 5 years after the Have received PCV13 and 1 dose of PPSV23: Administer a second dose of • implants: Administer PCV13 followed by PPSV23 at least 8 weeks after PCV13. • Adults aged 19 through 64 years with chronic heart disease (including congestive heart failure and cardiomyopathies, excluding hypertension), chronic lung disease (including chronic obstructive lung disease, emphysema, and asthma), chronic liver disease (including cirrhosis), alcoholism, or diabetes mellitus: Administer PPSV23. • Adults aged 19 through 64 years who smoke cigarettes or reside in nursing home or long-term care facilities: Administer PPSV23. • Routine pneumococcal vaccination is not recommended for American Indian/ Alaska Native or other adults unless they have the indications as above; however, public health authorities may consider recommending the use of pneumococcal vaccines for American Indians/Alaska Natives or other adults who live in areas with increased risk for invasive pneumococcal disease. • Immunocompromising conditions that are indications for pneumococcal excluding chronic granulomatous disease), HIV infection, chronic renal failure, nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized malignancy, multiple myeloma, solid organ transplant, and iatrogenic immunosuppression (including long-term systemic corticosteroids and radiation therapy). • Anatomical or functional asplenia that are indications for pneumococcal vaccination are: Sickle cell disease and other hemoglobinopathies, congenital or acquired asplenia, splenic dysfunction, and splenectomy. Administer pneumococcal vaccines at least 2 weeks before immunosuppressive therapy or an elective splenectomy, and as soon as possible to adults who are newly diagnosed with asymptomatic or symptomatic HIV infection. 9. Meningococcal vaccination • Administer 2 doses of quadrivalent meningococcal conjugate vaccine (MenACWY [Menactra, Menveo]) at least 2 months apart to adults of all ages with anatomical or functional asplenia or persistent complement component MenACWY. If an HIV-infected person of any age is vaccinated, 2 doses of MenACWY should be administered at least 2 months apart. • Administer a single dose of meningococcal vaccine to microbiologists routinely exposed to isolates of Neisseria meningitidis, military recruits, persons at risk during an outbreak attributable to a vaccine serogroup, and persons who travel to or live in countries in which meningococcal disease is hyperendemic or epidemic. • First-year college students up through age 21 years who are living in residence halls should be vaccinated if they have not received a dose on or after their 16th birthday. • MenACWY is preferred for adults with any of the preceding indications who are aged 55 years or younger as well as for adults aged 56 years or older who a) were vaccinated previously with MenACWY and are recommended for revaccination, or b) for whom multiple doses are anticipated. Meningococcal polysaccharide vaccine (MPSV4 [Menomune]) is preferred for adults aged 56 years or older who have not received MenACWY previously and who require a single dose only (e.g., travelers). • Revaccination with MenACWY every 5 years is recommended for adults previously vaccinated with MenACWY or MPSV4 who remain at increased risk for infection (e.g., adults with anatomical or functional asplenia, persistent 10. Hepatitis A vaccination • Vaccinate any person seeking protection from hepatitis A virus (HAV) infection and persons with any of the following indications: men who have sex with men and persons who use injection or noninjection illicit drugs; persons working with HAV-infected primates or with HAV in a research laboratory setting; persons with chronic liver disease and persons who receive clotting factor concentrates; persons traveling to or working in countries that have high or intermediate endemicity of hepatitis A; and unvaccinated persons who anticipate close personal contact (e.g., household or regular babysitting) with an international adoptee during or intermediate endemicity. (See footnote 1 for more information on travel should be administered as soon as adoption is planned, ideally 2 or more weeks before the arrival of the adoptee. • Single-antigen vaccine formulations should be administered in a 2-dose schedule at either 0 and 6 to 12 months (Havrix), or 0 and 6 to 18 months (Vaqta). If the combined hepatitis A and hepatitis B vaccine (Twinrix) is used, administer 3 doses at 0, 1, and 6 months; alternatively, a 4-dose schedule may be used, administered on days 0, 7, and 21 to 30 followed by a booster dose at month 12. 11. Hepatitis B vaccination • Vaccinate persons with any of the following indications and any person seeking protection from hepatitis B virus (HBV) infection: sexually active persons who are not in a long-term, mutually monogamous relationship (e.g., persons with more than 1 sex partner during the previous 6 months); persons seeking evaluation or treatment for a sexually transmitted disease (STD); current or recent injection drug users; and men who have sex with men; health care personnel and public safety workers who are potentially persons with diabetes who are younger than age 60 years as soon as feasible after diagnosis; persons with diabetes who are age 60 years or older at the discretion of the treating clinician based on the likelihood of acquiring HBV infection, including the risk posed by an increased need for assisted blood glucose monitoring in long-term care facilities, the likelihood of experiencing chronic sequelae if infected with HBV, and the likelihood of immune response to vaccination; persons with end-stage renal disease, including patients receiving hemodialysis, persons with HIV infection, and persons with chronic liver disease; household contacts and sex partners of hepatitis B surface antigen– developmental disabilities, and international travelers to countries with high or intermediate prevalence of chronic HBV infection; and all adults in the following settings: STD treatment facilities, HIV testing and treatment facilities, facilities providing drug abuse treatment and prevention services, health care settings targeting services to injection drug users or men who have sex with men, correctional facilities, end-stage renal disease programs and facilities for chronic hemodialysis patients, and institutions and nonresidential day care facilities for persons with developmental disabilities. • Administer missing doses to complete a 3-dose series of hepatitis B vaccine to those persons not vaccinated or not completely vaccinated. The second dose given at least 2 months after the second dose (and at least 4 months after the give 3 doses at 0, 1, and 6 months; alternatively, a 4-dose Twinrix schedule, administered on days 0, 7, and 21 to 30 followed by a booster dose at month 12 may be used. • Adult patients receiving hemodialysis or with other immunocompromising conditions should receive 1 dose of 40 mcg/mL (Recombivax HB) administered on a 3-dose schedule at 0, 1, and 6 months or 2 doses of 20 mcg/mL (Engerix-B) administered simultaneously on a 4-dose schedule at 0, 1, 2, and 6 months. 12. type b (Hib) vaccination • One dose of Hib vaccine should be administered to persons who have anatomical or functional asplenia or sickle cell disease or are undergoing elective splenectomy if they have not previously received Hib vaccine. Hib vaccination 14 or more days before splenectomy is suggested. • Recipients of a hematopoietic stem cell transplant (HSCT) should be vaccinated with a 3-dose regimen 6 to 12 months after a successful transplant, regardless of vaccination history; at least 4 weeks should separate doses. • Hib vaccine is not recommended for adults with HIV infection since their risk for Hib infection is low. 13. Immunocompromising conditions • Inactivated vaccines generally are acceptable (e.g., pneumococcal, www.cdc.gov/vaccines/hcp/acip-recs/index.html. Footnotes—Recommended Immunization Schedule for Adults Aged 19 Years or Older: United States, 2015 3827_Ch19_447_496 02/07/15 12:05 PM Page 468 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education YELLOW FEVER VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 469 3827_Ch19_447_496 02/07/15 12:05 PM Page 469 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education BACILLUS CALMETTEGUÉRIN VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 470 3827_Ch19_447_496 02/07/15 12:05 PM Page 470 Drug Interactions Clinical Use and Dosing Monitoring Patient Education INACTIVATED VACCINES DIPHTHERIA, TETANUS, AND PERTUSSIS VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 471 3827_Ch19_447_496 02/07/15 12:05 PM Page 471 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 472 3827_Ch19_447_496 02/07/15 12:05 PM Page 472 Monitoring Patient Education B CONJUGATE VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education INACTIVATED POLIOVIRUS VACCINE Pharmacodynamics 473 CLINICAL PEARL Patients With Shot Phobia In older children and adults who have a true phobia of injections, use EMLA cream to anesthetize the injection area. Have the patient apply the disk or cream 1 hour prior to the scheduled administration time, or the cream can be applied in the clinic and the injection adminis- tered after 1 hour. 3827_Ch19_447_496 02/07/15 12:05 PM Page 473 Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education HEPATITIS B VIRUS VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 474 3827_Ch19_447_496 02/07/15 12:05 PM Page 474 475 CLINICAL PEARL Administering Injections A technique to help older children, adolescents, or adults who are anxious about receiving injections is to encourage them to take slow, deep breaths. Younger children (5-year-olds) can be told to pretend they are blowing up a balloon. Have the patient inhale and ex- hale two or three times, and then, on the third or fourth exhalation, administer the injection. Table 19–5 ! Recommended Doses of Currently Licensed Formulations of Hepatitis B Vaccine by Age Group and Vaccine Type Single-Antigen Combination Vaccine Vaccine x§ Volume Dose Volume Dose Volume Dose Volume Dose Volume Age Group Dose (mcg) (mL) (mcg) (mL) (mcg) (mL) (mcg) (mL) (mcg) (mL) Adolescents Hemodialysis Patients and Other Immunocompromised Persons 3827_Ch19_447_496 02/07/15 12:05 PM Page 475 Monitoring Patient Education HEPATITIS A VIRUS VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 476 3827_Ch19_447_496 02/07/15 12:05 PM Page 476 Patient Education HUMAN PAPILLOMAVIRUS VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 477 CLINICAL PEARL Bioterrorism Providers need to have a basic understanding of vaccines available against possible biological weapons. The CDC Web site has an area dedicated to bioterrorism located at www.bt.cdc.gov/bioterrorism/. There are vaccines available for anthrax and smallpox, although this chapter does not discuss them because they are not currently recommended. Full prescribing information for both the anthrax and the smallpox vaccines are available at the CDC National Immunization Web site at www.cdc.gov/ nip/publications/acip-list.htm. Monitoring 3827_Ch19_447_496 02/07/15 12:05 PM Page 477 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education INFLUENZA VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 478 3827_Ch19_447_496 02/07/15 12:05 PM Page 478 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education PNEUMOCOCCAL VACCINE Pharmacodynamics 479 3827_Ch19_447_496 02/07/15 12:05 PM Page 479 Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 480 3827_Ch19_447_496 02/07/15 12:05 PM Page 480 Monitoring Patient Education MENINGOCOCCAL VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 481 3827_Ch19_447_496 02/07/15 12:05 PM Page 481 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education LYME DISEASE VACCINE Pharmacodynamics 482 3827_Ch19_447_496 02/07/15 12:05 PM Page 482 TYPHOID VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education CHOLERA VACCINE Pharmacodynamics JAPANESE ENCEPHALITIS VIRUS VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications 483 3827_Ch19_447_496 02/07/15 12:05 PM Page 483 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education PLAGUE VACCINE Pharmacodynamics RABIES VACCINE Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions 484 3827_Ch19_447_496 02/07/15 12:05 PM Page 484 Clinical Use and Dosing Monitoring Patient Education 485 Table 19–6 Issues in Immunization Childhood Immunization Standards for Child and Adolescent Immunization Practices (National Vaccine Advisory Committee, 2009) AVAILABILITY OF VACCINES ASSESSMENT OF VACCINATION STATUS EFFECTIVE COMMUNICATION ABOUT VACCINE BENEFITS AND RISKS PROPER STORAGE AND ADMINISTRATION OF VACCINES AND DOCUMENTATION OF VACCINATIONS IMPLEMENTATION OF STRATEGIES TO IMPROVE VACCINATION COVERAGE 3827_Ch19_447_496 02/07/15 12:05 PM Page 485 486 Table 19–6 Issues in Immunization—cont’d Standards for Adult Immunization Practices (National Vaccine Advisory Committee, 2013) MAKE VACCINATIONS AVAILABLE. ASSESS PATIENTS’ VACCINATION STANDARDS. COMMUNICATE EFFECTIVELY WITH PATIENTS. ADMINISTER AND DOCUMENT VACCINATIONS PROPERLY. IMPLEMENT STRATEGIES TO IMPROVE VACCINATION RATES. PARTNER WITH THE COMMUNITY. Immunization in Special Populations PREGNANT PATIENTS May Be Given Contraindicated During Vaccine if Indicated Pregnancy Comments Routine 3827_Ch19_447_496 02/07/15 12:05 PM Page 486 487 Table 19–6 Issues in Immunization—cont’d Travel and Others Immunocompromised Patients Travel Immunization May Be Given Contraindicated Vaccine if Indicated During Pregnancy Comments 3827_Ch19_447_496 02/07/15 12:05 PM Page 487 IMMUNE GLOBULIN SERUMS Pharmacodynamics Pharmacokinetics 488 3827_Ch19_447_496 02/07/15 12:05 PM Page 488 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 489 Table 19–7 ! Dosage Schedule: Immune Globulins Drug Indication Dose Comments 3827_Ch19_447_496 02/07/15 12:05 PM Page 489 490 Table 19–7 ! Dosage Schedule: Immune Globulins—cont’d Drug Indication Dose Comments Monitoring Patient Education DIAGNOSTIC BIOLOGICALS TUBERCULIN PURIFIED PROTEIN DERIVATIVE Pharmacodynamics Pharmacotherapeutics Precautions and Contraindications 3827_Ch19_447_496 02/07/15 12:05 PM Page 490 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education IMMUNOMODULATORS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion 491 3827_Ch19_447_496 02/07/15 12:05 PM Page 491 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 492 Table 19–8 " Drug Interactions: Immunomodulators Drug Interacting Drug Possible Effect Implications 3827_Ch19_447_496 02/07/15 12:05 PM Page 492 493 Table 19–8 " Drug Interactions: Immunomodulators—cont’d Drug Interacting Drug Possible Effect Implications Monitoring Patient Education REFERENCES 3827_Ch19_447_496 02/07/15 12:05 PM Page 493 494 3827_Ch19_447_496 02/07/15 12:05 PM Page 494 495 3827_Ch19_447_496 02/07/15 12:05 PM Page 495 3827_Ch19_447_496 02/07/15 12:05 PM Page 496 497 CHAPTER 20 Teri Moser Woo HISTAMINE2 RECEPTOR ANTAGONISTS, 519 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics PROKINETICS, 524 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics PROTON PUMP INHIBITORS, 528 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics LAXATIVES, 533 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics T ANTACIDS ANTACIDS, 497 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ANTIDIARRHEALS, 502 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics CYTOPROTECTIVE AGENTS, 508 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ANTIEMETICS, 510 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics EMETICS, 519 3827_Ch20_497-540 01/07/15 1:30 PM Page 497 Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 498 Table 20–1 ! Pharmacokinetics: Selected Antacids Drug Acid-Neutralizing Capacity (ANC)Onset Peak Duration Half-Life Elimination 3827_Ch20_497-540 01/07/15 1:30 PM Page 498 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 499 Table 20–2 " Drug Interactions: Selected Antacids Drug Interacting Drug Possible Effect Implications 3827_Ch20_497-540 01/07/15 1:30 PM Page 499 500 Table 20–2 " Drug Interactions: Selected Antacids—cont’d Drug Interacting Drug Possible Effect Implications Table 20–3 # Dosage Schedule: Selected Antacids Drug Indication Dosage Form Dosage Schedule 3827_Ch20_497-540 01/07/15 1:30 PM Page 500 501 Table 20–3 # Dosage Schedule: Selected Antacids—cont’d Drug Indication Dosage Form Dosage Schedule Rational Drug Selection 3827_Ch20_497-540 01/07/15 1:30 PM Page 501 Monitoring Patient Education ANTIDIARRHEALS Pharmacodynamics 502 3827_Ch20_497-540 01/07/15 1:30 PM Page 502 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 503 DurationOnset Peak Half-Life Elimination Table 20–4 ! Pharmacokinetics: Selected Antidiarrheals Drug 3827_Ch20_497-540 01/07/15 1:30 PM Page 503 Drug Interactions Clinical Use and Dosing Adverse Drug Reactions 504 3827_Ch20_497-540 01/07/15 1:30 PM Page 504 505 Table 20–5 " Drug Interactions: Selected Antidiarrheals Drug Interacting Drug Possible Effect Implications CLINICAL PEARL Oral Rehydration Therapy Evaluation of the effectiveness of oral rehydration is based on at least three wet diapers per 24 hours in in- fants. For children older than 1 year, avoid all fruit juices and other drinks that contain fructose because they usually make the diarrhea worse. If the infant or child is drinking milk or lactose-based formula, try withholding milk or lactose products. Probiotics may decrease the duration of diarrhea. Resolution of the diarrhea suggests lactose intolerance. 3827_Ch20_497-540 01/07/15 1:30 PM Page 505 Rational Drug Selection 506 Table 20–6 # Dosage Schedule: Selected Antidiarrheals Drug Indication Dosage Form Initial Dose Additional Doses 3827_Ch20_497-540 01/07/15 1:30 PM Page 506 Patient Education 507 Table 20–6 # Dosage Schedule: Selected Antidiarrheals—cont’d Drug Indication Dosage Form Initial Dose Additional Doses 3827_Ch20_497-540 01/07/15 1:30 PM Page 507 CYTOPROTECTIVE AGENTS Pharmacodynamics Pharmacokinetics Absorption and Distribution 508 Table 20–7 ! Pharmacokinetics: Cytoprotective Agents Drug Onset Peak Duration Protein Binding Half-Life Elimination 3827_Ch20_497-540 01/07/15 1:30 PM Page 508 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 509 Table 20–8 " Drug Interactions: Cytoprotective Agents Drug Interacting Drug Possible Effect Implications 3827_Ch20_497-540 01/07/15 1:30 PM Page 509 Rational Drug Selection Monitoring Patient Education ANTIEMETICS 510 Table 20–9 # Dosage Schedule: Cytoprotective Agents Drug Indication Dosage Forms Dosage Schedule 3827_Ch20_497-540 01/07/15 1:30 PM Page 510 Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 511 3827_Ch20_497-540 01/07/15 1:30 PM Page 511 512 Table 20–10 ! Pharmacokinetics: Selected Antiemetics Drug Onset Peak Duration Protein Binding Half-Life Elimination 3827_Ch20_497-540 01/07/15 1:30 PM Page 512 513 Table 20–11 " Drug Interactions: Selected Antiemetics Drug Interacting Drug Possible Effect Implications 3827_Ch20_497-540 01/07/15 1:30 PM Page 513 514 Table 20–11 " Drug Interactions: Selected Antiemetics—cont’d Drug Interacting Drug Possible Effect Implications 3827_Ch20_497-540 01/07/15 1:30 PM Page 514 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Rational Drug Selection 515 3827_Ch20_497-540 01/07/15 1:30 PM Page 515 516 Table 20–12 # Dosage Schedule: Selected Antiemetics Drug Indications Dosage Form Dosage Schedule Notes 3827_Ch20_497-540 01/07/15 1:30 PM Page 516 517 Table 20–12 # Dosage Schedule: Selected Antiemetics—cont’d Drug Indications Dosage Form Dosage Schedule Notes 3827_Ch20_497-540 01/07/15 1:30 PM Page 517 518 Table 20–12 # Dosage Schedule: Selected Antiemetics—cont’d Drug Indications Dosage Form Dosage Schedule Notes ! ! ! Monitoring Patient Education 3827_Ch20_497-540 01/07/15 1:30 PM Page 518 EMETICS HISTAMINE2 RECEPTOR ANTAGONISTS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion 519 3827_Ch20_497-540 01/07/15 1:30 PM Page 519 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 520 Table 20–13 ! Pharmacokinetics: Histamine2 Blockers Drug Onset Peak Duration Protein Binding Bioavailability Half-Life Metabolized Elimination 3827_Ch20_497-540 01/07/15 1:30 PM Page 520 521 Table 20–14 " Drug Interactions: Histamine2 Blockers Drug Interacting Drug Possible Effect Implications 3827_Ch20_497-540 01/07/15 1:30 PM Page 521 522 Table 20–15 # Dosage Schedule: Histamine2 Blockers Drug Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch20_497-540 01/07/15 1:30 PM Page 522 523 Table 20–15 # Dosage Schedule: Histamine2 Blockers—cont’d Drug Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch20_497-540 01/07/15 1:30 PM Page 523 Rational Drug Selection Monitoring Patient Education PROKINETICS 524 3827_Ch20_497-540 01/07/15 1:30 PM Page 524 Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 525 Table 20–16 ! Pharmacokinetics: Prokinetic Agents Onset Peak Duration Protein Binding Bioavailability Half-Life Elimination 3827_Ch20_497-540 01/07/15 1:30 PM Page 525 Drug Interactions Clinical Use and Dosing 526 Table 20–17 " Drug Interactions: Prokinetic Agents Drug Interacting Drug Possible Effect Implications 3827_Ch20_497-540 01/07/15 1:30 PM Page 526 Rational Drug Selection Monitoring Patient Education 527 Table 20–18 # Dosage Schedule: Prokinetic Agents Drug Indication Available Dosage Dosage Schedule Notes 3827_Ch20_497-540 01/07/15 1:30 PM Page 527 PROTON PUMP INHIBITORS Pharmacodynamics Pharmacokinetics Absorption and Distribution 528 On The Horizon ILAPRAZOLE Ilaprazole is a proton pump inhibitor developed by Il-Yang Pharmaceutical (Korea) and is approved for use in Korea and China. It has completed phase II trials in the United States. Onset Table 20–19 ! Pharmacokinetics: Proton Pump Inhibitors Drug Peak Duration Protein Binding Bioavailability Half-Life Elimination 3827_Ch20_497-540 01/07/15 1:30 PM Page 528 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 529 3827_Ch20_497-540 01/07/15 1:30 PM Page 529 Drug Interactions Clinical Use and Dosing 530 Table 20–20 " Drug Interactions: Proton Pump Inhibitors Drug Interacting Drug Possible Effect Implications 3827_Ch20_497-540 01/07/15 1:30 PM Page 530 531 Table 20–21 # Dosage Schedule: Proton Pump Inhibitors Drug Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch20_497-540 01/07/15 1:30 PM Page 531 532 Table 20–21 # Dosage Schedule: Proton Pump Inhibitors—cont’d Drug Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch20_497-540 01/07/15 1:30 PM Page 532 Rational Drug Selection Monitoring Patient Education LAXATIVES 533 3827_Ch20_497-540 01/07/15 1:30 PM Page 533 Pharmacodynamics Stimulants Osmotics Bulk-Producing Laxatives Lubricants Surfactants Hyperosmolar Laxatives Chloride Channel Activators Opioid-Receptor Antagonists Pharmacokinetics Absorption and Distribution 534 3827_Ch20_497-540 01/07/15 1:30 PM Page 534 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 535 Table 20–22 ! Pharmacokinetics: Selected Laxatives Drug Class Onset Peak Site of Action Elimination 3827_Ch20_497-540 01/07/15 1:30 PM Page 535 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Rational Drug Selection 536 3827_Ch20_497-540 01/07/15 1:30 PM Page 536 537 Table 20–23 " Drug Interactions: Selected Laxatives Drug Interacting Drug Possible Effect Implications Table 20–24 # Dosage Schedule: Selected Laxatives Drug Indication Dosage Form Dose Notes 3827_Ch20_497-540 01/07/15 1:30 PM Page 537 538 Table 20–24 # Dosage Schedule: Selected Laxatives—cont’d Drug Indication Dosage Form Dose Notes 3827_Ch20_497-540 01/07/15 1:30 PM Page 538 REFERENCES 539 CLINICAL PEARL Polyethylene Glycol/Electrolyte Solution The taste of polyethylene glycol/electrolyte solution is quite salty, and many patients find it difficult to con- sume the required volume in the required amount of time. Place the container of solution in ice in a basin. Do not pour it over ice, which will melt and increase the volume the patient must consume. Have the patient drink 240 mL of fluid each 10 minutes and give a Tic-Tac or similar small mint-flavored hard candy to suck on between glasses of the drug. This reduces the salty taste in the mouth and makes the drug more palatable. Monitoring Patient Education 3827_Ch20_497-540 01/07/15 1:30 PM Page 539 540 3827_Ch20_497-540 01/07/15 1:30 PM Page 540 541 CHAPTER 21 Marylou Robinson • Kathy Shaw BISPHOSPHONATES, 542 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics HYPOTHALAMIC AND PITUITARY HORMONES, 549 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics EXOCRINE PANCREATIC ENZYMES, 553 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ENDOCRINE PANCREATIC HORMONES INSULIN, 557 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ORAL DIABETIC AGENTS, 567 BIGUANIDES, 567 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics SULFONYLUREAS, 573 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ALPHAGLUCOSIDASE INHIBITORS, 578 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics THIAZOLIDINEDIONES , 580 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics MEGLITINIDES, 583 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics DIPEPTIDYL PEPTIDASE4 INHIBITORS , 586 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics SELECTIVE SODIUM GLUCOSE COTRANSPORTER 2 SGLT2 INHIBITORS, 589 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics AMYLIN AGONISTS, 592 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics GLUCAGONLIKE PEPTIDE AGONISTS, 595 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics GLUCAGON, 598 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics 3827_Ch21_541-614 01/07/15 5:40 PM Page 541 BISPHOSPHONATES Pharmacodynamics 542 THYROID AGENTS, 599 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ANTITHYROID AGENTS, 605 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics AROMATASE INHIBITORS, 609 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics 3827_Ch21_541-614 01/07/15 5:40 PM Page 542 Pharmacokinetics Absorption and Distribution 543 Bone is damaged by trauma or aging process. Osteoclasts adhere to damaged surface and secrete acids and enzymes. Bone is dissolved, leaving resorption pit. Osteoblasts adhere to resorption pit and build new bone. Osteoclasts leave area. Figure 21–1. Bone remodeling. Damaged bone sections are re- moved by osteoclasts that use pseudopods to attach to bone surface. Bone is dissolved, leaving a resorption pit. The osteoclasts then leave the site of damage. Osteoblasts enter the resorption pit and build new bone. The process takes 4 to 5 months. 3827_Ch21_541-614 01/07/15 5:40 PM Page 543 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 544 Table 21–1 ! Pharmacokinetics: Bisphosphonates Bioavailability Steady-State Half-Life Onset of (With/Without Vd Exclusive Normal Renal Drug Effect Peak Duration Food) of Bone (Function) Elimination 3827_Ch21_541-614 01/07/15 5:40 PM Page 544 Drug Interactions Clinical Use and Dosing 545 Table 21–2 " Drug and Food Interactions: Bisphosphonates Drug Interacting Drugs and Food Possible Effect Implications 3827_Ch21_541-614 01/07/15 5:40 PM Page 545 546 Table 21–3 # Dosage Schedule: Selected Bisphosphonates Drug Indication Dosage Forms Initial Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:40 PM Page 546 547 Table 21–3 # Dosage Schedule: Selected Bisphosphonates—cont’d Drug Indication Dosage Forms Initial Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:40 PM Page 547 Rational Drug Selection Monitoring Patient Education 548 3827_Ch21_541-614 01/07/15 5:40 PM Page 548 HYPOTHALAMIC AND PITUITARY HORMONES Pharmacodynamics 549 HypothalamusStimulation Secretes growth hormone– releasing hormone Anterior pituitary Secretes growth hormone Decreased glucose Increased glucose Inhibition Increased protein synthesis Increased lipolysis Increased cell growth Retention of sodium, potassium, phosphorus Figure 21–2. Hypothalamus-pituitary–growth hormone axis. 3827_Ch21_541-614 01/07/15 5:40 PM Page 549 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 550 Table 21–4 ! Pharmacokinetics: Growth Hormones Onset of Peak Duration Half-Life (Normal Drug Effect (Drug in Plasma) (Drugin Plasma) Bioavailability Renal Function) Elimination 3827_Ch21_541-614 01/07/15 5:40 PM Page 550 551 Table 21–5 # Dosage Schedule: Selected Growth Hormones Drug* Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:40 PM Page 551 Rational Drug Selection Monitoring Patient Education 552 Table 21–5 # Dosage Schedule: Selected Growth Hormones—cont’d Drug* Indication Dosage Form Initial Dose Maintenance Dose The average expected growth with hormone therapy can be estimated. For girls, subtract 13 cm from the father’s height and average this number with the mother’s height. For boys, add 13 cm to the mother’s height and average the sum with the father’s height (Albert, 2012). Conversion from inches to cm is achieved by using the formula 1 in. = 2.54 cm. A mother who is 65 in. tall would be 165.1 cm. A father who is 68 in. tall would be 172.72 cm. For their daughter, the calculation would be 172.72 – 13 cm, or 159.72, which averaged with the mother’s 165.1 cm would yield a 162.41 cm expected height. BOX 21–1 CALCULATING TARGET HEIGHT GOAL 3827_Ch21_541-614 01/07/15 5:40 PM Page 552 EXOCRINE PANCREATIC ENZYMES Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 553 On The Horizon GROWTH HORMONE There are multiple studies currently in progress studying the short- and long-term effects of growth horomone in children and adults. Sustained, related, once-weekly injections of growth hormone currently in clinical trials portend sustained growth without impaired bone maturation. 3827_Ch21_541-614 01/07/15 5:41 PM Page 553 Adverse Drug Reactions Drug and Food Interactions Clinical Use and Dosing 554 Table 21–6 " Drug and Food Interactions: Pancreatic Enzymes Drug Interacting Drug Possible Effect Implications Table 21–7 # Dosage Schedule: Pancreatic Enzymes Drug Indication Dosage in USP Units Initial Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 554 Rational Drug Selection 555 Table 21–7 # Dosage Schedule: Pancreatic Enzymes—cont’d Drug Indication Dosage in USP Units Initial Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 555 Monitoring Patient Education ENDOCRINE PANCREATIC HORMONES (INSULIN) 556 3827_Ch21_541-614 01/07/15 5:41 PM Page 556 Pharmacodynamics Action on Glucose Transporters Action on the Liver Action on Muscle Cells Action on Adipose Tissue Pharmacokinetics Absorption and Distribution 557 3827_Ch21_541-614 01/07/15 5:41 PM Page 557 558 Increased serum glucose levels Increased ATP production Potassium channels close Depolarization of the pancreatic beta cell Voltage-gated calcium channels open Increased intracellular calcium Increased insulin secretion Insulin attaches to insulin receptor on body cells Opens channels in plasma membrane Potassium enters cell Pancreatic beta cell repolarizes Voltage-gated calcium channels close Decreased intracellular calcium Decreased insulin secretion Glycogen Lipids Pyruvate Glucose enters cell Mg2+ and PO3 enter cell Amino acids enter cell Generation of insulin substrate (IRS-1) by autophosphorylation CO2 Opens Glut-4 transport protein channel Protein synthesis Figure 21–3. Mechanism of insulin release from beta cells. 3827_Ch21_541-614 01/07/15 5:41 PM Page 558 559 Table 21–8 ! Pharmacokinetics: Insulins Onset (m) Peak (h) Duration (h)* Elimination Compatibility Short-Acting Intermediate-Acting Long-Acting Inhaled On The Horizon INSULIN DEGLUDEC The ultra–long-acting basal insulin analogue degludec (Tresiba) has been placed on a more extended roll-out by Novo-Nordisk in the United States. It is used for both type 1 and type 2 patients, especially those who need to overcome nocturnal hypoglycemia. The 42 hour action time may allow a staggered administration plan. Due to limited post-marketing experience, it is not fully described in this edition. 3827_Ch21_541-614 01/07/15 5:41 PM Page 559 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 560 On The Horizon PIPELINE DRUGS There are many drugs currently in the pipeline to treat DM. Insulin degludec (Tresiba) has a longer duration of action than insulin glargine. Insulin degludec/liraglutide (Xultopy) is an insulin/GLP-1 agonist combination in phase 3 trials. Other dia- betes drugs in phase III trials include exenatice subcutaneous implant (ITCA 650, Intarcia Therapeutics); semaglutide (Novo Nordisk) is a once-weekly GLP-1 analog; omariglipin (Merck) is a once-weekly DPP-4 inhibitor similar to once daily Januvia; Oral-Lyn (Generex) is an investigational liquid regular recom- binant human insulin that is delivered to the buccal mucosa using a trademarked RapidMist device; and insulin peglispro (Eli Lilly) is a new long-acting basal insulin. Lixisenatide (Lyxumia), a once-daily prandial GLP-1 recep- tor agonist approved in Europe, was denied FDA approval in June 2014 due to pronounced after meal hypoglycemia. 3827_Ch21_541-614 01/07/15 5:41 PM Page 560 Drug Interactions Clinical Use and Dosing 561 Table 21–9 " Drug Interactions With Insulin Interacting Drug Possible Effects Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 561 562 Table 21–10 # Dosage Schedule: Insulin Drug Dosage Form Schedule Initial Dose Comments 3827_Ch21_541-614 01/07/15 5:41 PM Page 562 563 Table 21–10 # Dosage Schedule: Insulin—cont’d Drug Dosage Form Schedule Initial Dose Comments 3827_Ch21_541-614 01/07/15 5:41 PM Page 563 Rational Drug Selection 564 CLINICAL PEARL For patients on insulin pumps, be attentive to daylight saving time changes. Many pump computers are not GPS enabled or time zone adjusting. This is not an issue with basal insulin provision, but could be significant for rapid-acting forms. Verify date and time settings during appointments (Aldasouqui & Reed, 2014). 3827_Ch21_541-614 01/07/15 5:41 PM Page 564 Monitoring 565 3827_Ch21_541-614 01/07/15 5:41 PM Page 565 Patient Education 566 3827_Ch21_541-614 01/07/15 5:41 PM Page 566 ORAL AGENTS BIGUANIDES Pharmacodynamics 567 3827_Ch21_541-614 01/07/15 5:41 PM Page 567 Pharmacokinetics Absorption and Distribution 568 Table 21–11 ! Pharmacokinetics: Selected Antihyperglycemic Agents Protein Drug Onset* Peak* Duration* Binding Bioavailability Half-Life Excretion 3827_Ch21_541-614 01/07/15 5:41 PM Page 568 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 569 Table 21–11 ! Pharmacokinetics: Selected Antihyperglycemic Agents—cont’d Protein Drug Onset* Peak* Duration* Binding Bioavailability Half-Life Excretion 3827_Ch21_541-614 01/07/15 5:41 PM Page 569 Adverse Drug Reactions Drug Interactions 570 Table 21–12 " Drug Interactions With Metformin Interacting Drug Possible Effects Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 570 Clinical Use and Dosing 571 Table 21–13 # Dosage Schedule: Selected Metformin Formulations Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose Extended-Release Combination Drugs 3827_Ch21_541-614 01/07/15 5:41 PM Page 571 572 3827_Ch21_541-614 01/07/15 5:41 PM Page 572 Monitoring SULFONYLUREAS Pharmacodynamics Pharmacokinetics Absorption and Distribution 573 CLINICAL PEARL When metformin is added to a sulfonylurea, the increased sensitivity to insulin caused by metformin results in less need for the insulin secretion generated by the sulfonylurea. If the BG level drops too much, the dose of the sulfonylurea should be reduced. Patient Education 3827_Ch21_541-614 01/07/15 5:41 PM Page 573 574 Table 21–14 ! Pharmacokinetics: Sulfonylureas Protein Drug Onset (h) Peak (h) Duration (h) Binding Half-Life (h) Metabolism Elimination First-Generation Second-Generation Metabolism and Excretion 3827_Ch21_541-614 01/07/15 5:41 PM Page 574 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions 575 3827_Ch21_541-614 01/07/15 5:41 PM Page 575 Clinical Use and Dosing 576 Table 21–15 " Drug Interactions: Sulfonylureas Drug Interacting Drug Possible Effect Implications Table 21–16 # Dosage Schedule: Sulfonylureas Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose First-Generation 3827_Ch21_541-614 01/07/15 5:41 PM Page 576 Rational Drug Selection Monitoring Patient Education 577 Table 21–16 # Dosage Schedule: Sulfonylureas—cont’d Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose Second-Generation Glyburide CLINICAL PEARL Tolazamide has the added advantage that it may be crushed and put down a nasogastric tube or sprinkled on applesauce or other soft food for patients who have difficulty in swallowing tablets. 3827_Ch21_541-614 01/07/15 5:41 PM Page 577 ALPHA-GLUCOSIDASE INHIBITORS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 578 3827_Ch21_541-614 01/07/15 5:41 PM Page 578 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 579 CLINICAL PEARL Starting the alpha-glucosidase inhibitor at 25 mg daily for 1 week and increasing the dose to 25 mg twice daily for 1 week and then to 25 mg 3 times daily for 1 week decreases the incidence of GI-adverse responses. Table 21–17 " Drug Interactions: Alpha-Glucosidase Inhibitors Drug Interacting Drug Possible Effect Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 579 Rational Drug Selection Monitoring Patient Education 580 CLINICAL PEARL The delayed absorption of carbohydrates caused by alpha-glucosidase inhibitors results in less need for the insulin secretion generated by a sulfonylurea. If the BG level drops too much, the dose of the sulfonyl - urea should be reduced. Table 21–18 # Dosage Schedule: Alpha-Glucosidase Inhibitors Drug Dosage Form Initial Dose Maintenance Dose Maximum Dose THIAZOLIDINEDIONES 3827_Ch21_541-614 01/07/15 5:41 PM Page 580 Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion 581 CLINICAL PEARL When thiazolidinediones are added to a sulfonylurea in a diabetic regimen, the increased sensitivity to insulin caused by the thiazolidinedione results in less need for the insulin secretion generated by the sulfonyl - urea. If the BG level drops too much, the dose of the sulfonylurea should be reduced. Pharmacotherapeutics Precautions and Contraindications 3827_Ch21_541-614 01/07/15 5:41 PM Page 581 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 582 Table 21–19 " Drug Interactions With Thiazolidinediones Drug Interacting Drug Possible Effect Implications Table 21–20 # Dosage Schedule: Thiazolidinediones Drug Initial Dose Dosage Form Maximum Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 582 Monitoring Patient Education MEGLITINIDES 583 3827_Ch21_541-614 01/07/15 5:41 PM Page 583 Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions 584 Table 21–21 " Drug Interactions With Meglitinides and Repaglinide Interacting Drug Possible Effect Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 584 Clinical Use and Dosing Monitoring Patient Education 585 Table 21–22 # Dosage Schedule: Meglitinides Drug Initial Dose Dosage Form Maximum Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 585 DIPEPTIDYL PEPTIDASE-4 INHIBITORS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 586 3827_Ch21_541-614 01/07/15 5:41 PM Page 586 Drug Interactions Clinical Use and Dosing 587 Table 21–23 " Drug Interactions With Dipeptidyl Peptidase-4 Inhibitors (Gliptins) Drug Interacting Drug Possible Outcomes Implications Table 21–24 # Dosage Schedule for Dipeptidyl Peptidase-4 Inhibitors (Gliptins) Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 587 Rational Drug Selection 588 Table 21–24 # Dosage Schedule for Dipeptidyl Peptidase-4 Inhibitors (Gliptins)—cont’d Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 588 Monitoring Patient Education SELECTIVE SODIUM GLUCOSE CO-TRANSPORTER 2 (SGLT-2) INHIBITORS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 589 3827_Ch21_541-614 01/07/15 5:41 PM Page 589 Adverse Drug Reactions Drug Interactions 590 3827_Ch21_541-614 01/07/15 5:41 PM Page 590 Clinical Use and Dosing Monitoring 591 Table 21–25 " Drug Interactions With SGLT-2 Drugs Drug Interacting Drug Possible Outcomes Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 591 Patient Education AMYLIN AGONISTS Pharmacodynamics Pharmacokinetics Absorption and Distribution 592 Table 21–26 # Dosing Schedule for SGLT2 Drugs Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 592 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions 593 Table 21–27 " Drug Interactions With GLP-1 and Amylin Agonists Drug Interacting Drug Possible Outcomes Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 593 Clinical Use and Dosing Monitoring Patient Education 594 Table 21–27 " Drug Interactions With GLP-1 and Amylin Agonists—cont’d Drug Interacting Drug Possible Outcomes Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 594 GLUCAGON-LIKE PEPTIDE AGONISTS 595 Table 21–28 # Dosage Schedule GLP-1 and Amylin Agonists Drug Initial Dose Dosage Form Maintenance Dose Maximum Dose Pramlintide Dose in Micrograms Amount to Draw Up in a U-100 Insulin Syringe 15 30 45 60 120 2.5 5 7.5 10 20 Figure 21–4. Conversion of mcg to units for injecting pramlintide. 3827_Ch21_541-614 01/07/15 5:41 PM Page 595 Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 596 3827_Ch21_541-614 01/07/15 5:41 PM Page 596 Drug Interactions Clinical Use and Dosing Rational Drug Selection Monitoring Patient Education 597 3827_Ch21_541-614 01/07/15 5:41 PM Page 597 GLUCAGON Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 598 3827_Ch21_541-614 01/07/15 5:41 PM Page 598 Monitoring Patient Education THYROID AGENTS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 599 Table 21–29 # Dosage Schedule: Glucagon Drug Initial Dose Dosage Form Maximum Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 599 600 HypothalamusStimulation Secretes TRHCold, stress, decreased thyroxine Iodine Inhibition Anterior pituitary Secretes TSH Thyroid gland Excess thyroxine Synthesizes and secretes tri-iodothyronine and thyroxine Increases: —Metabolic rate in tissues —Oxygen consumption —Body temperature —Heart rate —Respiratory rate —Blood volume —Rate of fat metabolism —Rate of protein metabolism —Rate of carbohydrate metabolism —Enzyme system activity —Growth, differentiation, and maturation of tissues Figure 21–5. Hypothalamus- pituitary-thyroid hormone axis. Table 21–30 ! Pharmacokinetics: Oral Thyroid Hormones Drug Onset* Peak* Duration* Biological Potency Half-Life Excretion 3827_Ch21_541-614 01/07/15 5:41 PM Page 600 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 601 Table 21–31 " Drug Interactions With Thyroid Hormones Interacting Drug Possible Outcomes Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 601 602 Table 21–32 # Dosage Schedule: Thyroid Hormones Drug Indication Dose Form Initial Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 602 603 Table 21–32 # Dosage Schedule: Thyroid Hormones—cont’d Drug Indication Dosage Form Maintenance Dose Initial Dose CLINICAL PEARL Thyroid Hormone Replacement During Pregnancy Increasing the dose by 25% usually results in adequate coverage during pregnancy. Recheck TSH levels in 4 weeks to determine any dosage adjustment. 3827_Ch21_541-614 01/07/15 5:41 PM Page 603 Inappropriate Use of Thyroid Hormones 604 CLINICAL PEARL Levothyroxine tablets can be crushed and suspended in a small amount of formula or water for infants who cannot swallow whole tablets. For children who cannot swallow the intact tablet, it may be crushed and sprin- kled over a small amount of food such as cooked cereal or applesauce. The suspension cannot be stored for any period of time. The tablet should be crushed, mixed to form a suspension, and given immediately. Rational Drug Selection 3827_Ch21_541-614 01/07/15 5:41 PM Page 604 Monitoring Patient Education ANTITHYROID AGENTS 605 3827_Ch21_541-614 01/07/15 5:41 PM Page 605 Pharmacodynamics Pharmacokinetics Absorption and Distribution 606 Table 21–33 ! Pharmacokinetics: Antithyroid Drugs Placental Transport and Protein Breast Milk Drug Onset* Peak* Duration* Bioavailability Binding Levels Half-Life Excretion 3827_Ch21_541-614 01/07/15 5:41 PM Page 606 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions 607 Table 21–34 " Drug Interactions With Antithyroid Drugs Drug Interacting Drug Possible Effect Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 607 Clinical Use and Dosing Rational Drug Selection Monitoring 608 Table 21–35 # Dosage Schedule of Antithyroid Drugs Drug Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 608 Patient Education AROMATASE INHIBITORS Pharmacodynamics Pharmacokinetics Pharmacotherapeutics 609 3827_Ch21_541-614 01/07/15 5:41 PM Page 609 Adverse Drug Reactions Drug Interactions Education and Lifestyle Management 610 Table 21–36 ! Pharmacokinetics of Aromatase Inhibitors Drug Site of Metabolism Peak Protein Binding Half-Life (in hours) Elimination Table 21–37 # Dosing and Indications Aromatase Inhibitors Drug Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch21_541-614 01/07/15 5:41 PM Page 610 REFERENCES 611 Table 21–38 " Drug interactions of Aromatase Inhibitors Drug Interacting Drug Possible Effect Implications 3827_Ch21_541-614 01/07/15 5:41 PM Page 611 612 3827_Ch21_541-614 01/07/15 5:41 PM Page 612 613 3827_Ch21_541-614 01/07/15 5:41 PM Page 613 3827_Ch21_541-614 01/07/15 5:41 PM Page 614 615 CHAPTER 22 Diana L Dewel ANDROGENS AND ANTIANDROGENS, 615 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ESTROGENS AND ANTIESTROGENS, 623 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics PROGESTERONES AND PROGESTERONE ANTAGONISTS, 635 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics OTHER DRUGS AFFECTING THE REPRODUCTIVE SYSTEM, 642 Drugs Commonly Used in Fertility Clinics Lactation Inhibitors Drugs Used in Erectile Dysfunction T ANDROGENS AND ANTIANDROGENS 3827_Ch22_615-646 01/07/15 5:42 PM Page 615 616 BOX 22–1 COMPOUNDS WITH ANTIANDROGENIC PROPERTIES The problems of reduced potency in the oral form and the virilizing side effects of androgens led investigators to develop drugs that inhibit synthesis and block sex hormone production receptors. This approach of countering the effects of undesir- able androgen excess has enabled therapy at higher dosages. Dihydrotestosterone is the essential androgen in the prostate. The effect of androgens can be reduced by inhibiting 5-alpha-reductase in its target tissues. PSA levels and digital prostate examination are required monitoring for men on these agents. Users of alpha1-adrenergic antagonists may experience hypotension, syncopy, impotence, and decreased libido. Caution is advised with concurrent use of agents that potentiate the alpha1-adrenergic blocking and agents that increase the risk of hypotension. Finasteride (Propecia, Proscar) Finasteride, a steroid-like drug, inhibits 5-alpha-reductase, an intracellular enzyme that converts testosterone to 5-alpha- dihydrotestosterone (DHT). It has a 100-fold selectivity for 5-alpha-reductase type 2, the isoenzyme found primarily in the prostate, seminal vesicles, epididymides, and hair follicles. It is well absorbed orally, and the reduction in DHT begins within 8 hours of administration and lasts for about 24 hours. Finasteride undergoes extensive hepatic metabolism, with 39% being excreted in the urine and 57% in feces. Approximately 90% is bound to plasma proteins. The FDA approved doses of 5 mg per day to treat benign prostatic hyperplasia (BPH). Although early improvement may be seen, 6 to 12 months of therapy may be needed to determine if a beneficial response has been achieved. Most patients experience a rapid regression in prostate gland size, and about 50% experience an increase in urinary flow and improvement in BPH symptoms (Drug Facts and Comparisons, 2005). In 1998, the FDA approved a 1 mg dose for treating male pattern baldness. Three months of therapy are usually required to demonstrate benefits. Stopping the drugs reverses the effect within 12 months. The main undesirable adverse effects are decreased libido and impotence, which occur with both doses. Dutasteride (Avodart) Like finasteride, dutasteride inhibits 5-alpha-reductase, an intracellular enzyme that converts testosterone to 5-alpha- dihydrotesterone (DHT). It inhibits both type 1 and type 2 forms of the isoenzyme. It does not bind to the human androgen receptor. It is absorbed well after oral administration and reaches peak serum concentration within 2 to 3 hours. However, peak clinical effect does not occur until 6 to 12 months of therapy have been completed. Heavily bound to plasma protein (99%), it is extensively metabolized by the liver, utilizing the CYP450 3A4/5 substrate. The drug and its metabolites are ex- creted mainly in feces (45%). Only trace amounts are found in the urine. This drug is approved for the treatment of BPH. BPH patients treated with this drug had a decrease of 94% of DHT after 1 year. Because of its long half-life, serum concentrations remain detectable for up to 6 months after discontinuance of treatment. Dutasteride is absorbed through the skin, so women who are pregnant or may become pregnant should not handle dutasteride capsules due to the potential risk of fetal anomaly to a male fetus. The main undesirable adverse effects are decreased libido and impotence. 3827_Ch22_615-646 01/07/15 5:42 PM Page 616 617 BOX 22–1 COMPOUNDS WITH ANTIANDROGENIC PROPERTIES—cont’d Leuprolide Acetate (Lupron) Leuprolide is a luteinizing hormone–releasing agonist. This drug produces gonadal suppression when blood levels are continuous in the treatment of prostate cancer. It may be given in a dose of 1 mg SC daily or IM every 3 months in the depot formulation. Mean plasma levels are achieved in 4 hours and are maintained after an initial drop in concentration. It has even greater suppression when used with flutamide. In pediatric patients, its use is to treat central precocious puberty. In gynecol- ogy, its use is in reducing uterine fibroids, endometriosis, and polycystic ovary syndrome. Approximately 90% of women with unstaged endometriosis have relief of pain, and 50% regain fertility with leuprolide. Flutamide (Eulexin, Euflex) Flutamide behaves like a competitive antagonist at the androgen receptor site, although it is truly a nonsteroidal agent. It has been used with leuprolide for the treatment of advanced prostate cancer and with female androgen excess syndrome. The adverse effects in men are gynecomastia and reversible liver toxicity. Flutamide is rapidly absorbed orally. It is metabo- lized into six compounds and bound 97% to plasma proteins, reaching a steady state by the fourth dose. Flutamide is excreted in the urine but has not required changes in dose unless renal function is less than 29 mL/min. There is a Black-Box Warning regarding hepatic failure, hepatic encephalopathy, and death with this agent. Most of these events have occurred within the first 3 months of therapy. Baseline and monthly liver function testing is necessary for the first 4 months of therapy and then periodically. Medication should be discontinued if any symptoms of hepatic injury or jaundice develop. Spironolactone (Aldactone) Spironolactone is another competitive inhibitor of the dihydrotestosterone, aldosterone, and interferes with the androgen receptors in the prostate. It also reduces 17-alpha-hydroxylase activity, lowering plasma levels of testosterone and androstenedione. Refer to Chapter 16 for its uses as a diuretic. Spironolactone is absorbed orally, reaches peak levels in 2 hours, and is metabolized by the liver and excreted through the portal system. Spironolactone has short-term use for primary hyperaldosteronism in patients preoperatively. It is used long-term for those patients who are not good candidates for surgery or those with idiopathic hyperaldosteronism. There are also edematous conditions that require potassium conser- vation, such as congestive heart failure and cirrhosis of the liver associated with ascites. An off-labeled use is in females with androgen excess for the treatment of hirsutism and acne in dosages of 50 to 200 mg/day. Adverse reactions are usually dose- related and reversible when the drug is discontinued. The most common adverse reactions are GI upset, drowsiness, gyneco- mastia, impotence, cutaneous eruptions, and urticaria. Early animal chronic toxicity studies demonstrated tumorigenicity. Therefore, use should be balanced against risk (there is a Black-Box Warning regarding this concern). This drug is contraindi- cated in pregnancy, yet the American Academy of Physicians has stated that it is compatible with breastfeeding. Although this drug is classified as a diuretic, its use in premenstrual syndrome is probably effective because of its antiandrogen effect, even at low doses (25 to 50 mg daily). Pharmacodynamics 3827_Ch22_615-646 01/07/15 5:42 PM Page 617 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Onset, Peak, and Duration 618 Table 22–1 ! Pharmacokinetics: Androgens and Anti-Androgens Protein Drug Onset Peak Duration Binding (in %) Half-Life Elimination Androgens 3827_Ch22_615-646 01/07/15 5:42 PM Page 618 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 619 Table 22–1 ! Pharmacokinetics: Androgens and Anti-Androgens—cont’d Protein Drug Onset Peak Duration Binding (in %) Half-Life Elimination Anti-Androgens 3827_Ch22_615-646 01/07/15 5:42 PM Page 619 Drug Interactions Clinical Use and Dosing 620 Table 22–2 " Common Drug Interactions: Androgens and Anti-Androgens Drug Interacting Drug Possible Effect Implications Androgens Anti-Androgens 3827_Ch22_615-646 01/07/15 5:42 PM Page 620 Rational Drug Selection 621 Table 22–3 # Dosage Schedule: Androgens and Anti-Androgens Drug Indication Dosage Form Initial Dose Maintenance Dose Androgens 3827_Ch22_615-646 01/07/15 5:42 PM Page 621 622 Table 22–3 # Dosage Schedule: Androgens and Anti-Androgens—cont’d Drug Indication Dosage Form Initial Dose Maintenance Dose Anti-Androgens Cost Monitoring 3827_Ch22_615-646 01/07/15 5:42 PM Page 622 PATIENT EDUCATION ESTROGENS AND ANTIESTROGENS 623 3827_Ch22_615-646 01/07/15 5:42 PM Page 623 624 BOX 22–2 ANTIESTROGENS Although naturally occurring hormones such as progesterone and testosterone may modify the action of estrogen, the following discussion focuses on the synthetic estrogen antagonists. Drugs in this class may have limited use by most practitioners in primary care. Clomiphene is used for ovulation stimulation by infertility clinics. Danazol is primarily used for endometriosis by gynecologists, and tamoxifen is used for female cancers by oncologists. Monitoring by primary care providers is essential. Clomiphene (Clomid) Clomiphene was the first chemical used to initiate ovulation in normogonadotropic, normoprolactinemic, and anovulatory patients. It has also been used as a component in the management of luteal-phase dysfunction, oligo-ovulation, artificial insemination, unexplained infertility, and in vitro fertilization. Although clomiphene has been used for 30 years, it is still a drug that remains in a specialized practice setting. The list of adverse side effects are hot flashes, multiple gestation, visual symptoms, cervical mucus abnormalities, luteal-phase defect, luteinized unruptured follicle syndrome, ovarian cancer, teratogenicity, enlargement of ovarian cysts, and liver disease. The agonist–antagonist characteristics of clomiphene depend on the hormone climate. Clomiphene initiates ovulation in the presence of high estrogen levels in anovulatory females. It does this as long as other endogenous mechanisms trigger an LH surge and follicle rupture. Clomiphene blocks endogenous estrogen-negative feedback at the level of the hypothalamus. It also elevates estrogen and progesterone levels higher than normal. Its function may even affect the ovary and pituitary glands. Clomiphene also decreases serum insulin-like growth factors and increases SHBG, which assists those infertile women with polycystic ovary (PCO) disease. It has direct antiestrogenic effects on the endometrium and cervical mucus- producing glands. Elevated estrogen levels of women in the reproductive years can override the direct antiestrogen effects on the endometrium and cervical mucus. This compound is active when taken orally, but little is known about its metabolism. Half of the compound is excreted in the feces within 5 days of administration. The hypothesis is that it is excreted through a slow enterohepatic pathway. Danazol (Danocrine) Although the major use of danazol has been to treat endometriosis, it has been employed in severe fibrocystic breast changes, hematological disorders, and idiopathic thrombocytopenic purpura. Danazol must be used with great caution in hepatic dysfunction and carries a Black-Box Warning for this and for the risk of thromboembolism. The list of adverse effects is long, which is, in part, why this drug is not indicated for most primary care settings. Danazol suppresses the pituitary-ovarian axis, inhibiting the midcycle surge of LH and FSH to suppress ovarian function. It has weak progestational and androgenic properties, as does its major metabolite, ethisterone. Danazol binds to androgen, progesterone, and glucocorticoid receptors and alters androgen metabolism. It does not inhibit aromatase, the enzyme required for estrogen synthesis. It also increases the clearance rate of progesterone by competing with the hormone for binding proteins. Danazol is taken orally and is slowly metabolized by the liver (CYP450 3A4 inhibitor), being excreted primarily in the urine after a 24 hour half-life. Tamoxifen (Nolvadex) Tamoxifen is the first agent in the selective estrogen receptor modulator (SERM) class of medications used to treat conditions that respond to adding or withdrawing estrogens. As the class name implies, these agents target selective estrogen receptors, while not stimulating others. It is used primarily as part of adjuvant therapy for breast cancer in patients with estro- gen receptor (ER)–positive tumors. Recent studies have demonstrated a reduction in breast cancer in those individuals at high risk for developing the disease within 5 years. In the Gail model, age, family history, medical history of premalignant biopsies, and age at first live birth calculate the patient’s absolute risk. An antiestrogen in mammary tissue, tamoxifen blunts the effect of estrogen and has direct antigrowth activity of its own in the absence of estrogen. The mechanism may be that it blocks estradiol-induced cancer cell growth by altering the local production of growth factors and/or inhibiting the development of the tumor’s blood supply. Tamoxifen con- tinues to stimulate estrogen receptors in the endometrial tissue and causes hyperplasia in the postmenopausal woman’s endometrium and vagina. Several large-scale, longitudinal trials are under way to evaluate its effectiveness in preventing disease in high-risk women. The results will try to address its potential benefits on bone and lipids while reducing the risk on breast tissue. This is a nonsteroidal agent that is given orally. Peak plasma levels are reached in a few hours with an initial half-life of 7 to 14 hours. The liver extensively metabolizes tamoxifen, and 65% of the drug is excreted through the gut within 2 weeks. Raloxifene (Evista) Raloxifene is also a SERM. Indications initially were for osteoporosis prevention in women who cannot or will not take hormone replacement therapy. Post-marketing studies have shown a positive lipid effect, which may improve cardiovascular disease risk. Results from the recent MORE randomized trial demonstrated a 76% reduced risk of invasive breast cancer 3827_Ch22_615-646 01/07/15 5:42 PM Page 624 625 BOX 22–2 ANTIESTROGENS—cont’d among the women taking raloxifene for osteoporosis. This was attributed to the effect of the drug on ER-positive tumors. This drug can be used only in women past menopause who have never had thromboembolic problems. Raloxifene is a selective estrogen receptor modulator similar to tamoxifen with different degrees of estrogen agonist or antagonist activity in different tissues. It is an estrogen agonist on bone and an antagonist on breast and uterus. Unlike tamoxifen, it appears to be neutral on the vaginal tissues. A comparison of the beneficial effect on bone mineral density is slightly less than that of estrogen. Whether this bone effect will decrease the incidence of fractures has yet to be proved. Raloxifene is taken orally without regard to meals, with a 60% absorption rate, but is extensively glucuronidated, and only 2% is bioavailable. It is excreted though the GI tract with a half-life of 32.5 hours. Raloxifene is not indicated for pediatric patients or for premenopausal women. Concomitant hormone replacement ther- apy is not recommended. The primary reasons sited by patients for discontinuing therapy were hot flashes and leg cramps. One reported that these symptoms may have lasted up to 6 months. Raloxifene is highly bound (95%) to plasma proteins. Close monitoring or alternative treatments should be considered for patients using bile acid sequestrants, thyroid hormones, and warfarin. One short-term trial indicated that it might be effective for prevention of postmenopausal bone loss without the risk for breast or uterine cancer. It may also have a beneficial effect on lipid metabolism. More studies are needed to validate that the effect on lipids actually confers a cardio-protective effect. This drug may be useful for advance practice nurses in primary care practices, but at this time, the long-term safety effects are not known. Like estrogens, there is some increase in thromboem- bolic disease, and it is teratogenic. Patients on concurrent anticoagulant therapy will require frequent INR levels initially during therapy, and dose adjust- ments of anticoagulants may be needed. Women should also be advised to continue with supplemental calcium and vitamin D for bone health. Raloxifene can be administered orally without regard to food. Patients need to know that hot flashes can sometimes occur at the beginning of therapy, even in postmenopausal women. The risk of thromboembolic disease (1%) is the same as it is for estrogen users. Individuals on raloxifene should discon- tinue use 72 hours prior to surgery to decrease risk of thrombosis and embolism. When traveling, patients should get up and move around every hour to avoid long periods of inactivity. Pharmacodynamics 3827_Ch22_615-646 01/07/15 5:42 PM Page 625 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Onset, Peak, and Duration Pharmacotherapeutics Precautions and Contraindications 626 3827_Ch22_615-646 01/07/15 5:42 PM Page 626 627 Table 22–4 ! Pharmacokinetics: Estrogens and Antiestrogens Half-Life (in hours by formulation and metabolites in Site of individuals with Drug Metabolism Active Metabolism normal renal function) Elimination Estrogens Antiestrogens 3827_Ch22_615-646 01/07/15 5:42 PM Page 627 Adverse Drug Reactions Drug Interactions 628 Table 22–5 " Common Drug Interactions: Estrogens and Antiestrogens Drug Interacting Drug Possible Effect Implications Estrogens 3827_Ch22_615-646 01/07/15 5:42 PM Page 628 629 Table 22–5 " Common Drug Interactions: Estrogens and Antiestrogens—cont’d Drug Interacting Drug Possible Effect Implications Antiestrogens Clinical Use and Dosing 3827_Ch22_615-646 01/07/15 5:42 PM Page 629 630 3827_Ch22_615-646 01/07/15 5:42 PM Page 630 Rational Drug Selection 631 3827_Ch22_615-646 01/07/15 5:42 PM Page 631 632 Table 22–6 # Dosage Schedule: Estrogens and Antiestrogens Drug Indication Dosage Form Initial Dose Maintenance Dose Estrogens 3827_Ch22_615-646 01/07/15 5:42 PM Page 632 633 Table 22–6 # Dosage Schedule: Estrogens and Antiestrogens—cont’d Drug Indication Dosage Form Initial Dose Maintenance Dose Antiestrogens 3827_Ch22_615-646 01/07/15 5:42 PM Page 633 634 Table 22–6 # Dosage Schedule: Estrogens and Antiestrogens—cont’d Drug Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch22_615-646 01/07/15 5:42 PM Page 634 Monitoring PATIENT EDUCATION 635 3827_Ch22_615-646 01/07/15 5:42 PM Page 635 PROGESTERONES AND PROGESTERONE ANTAGONISTS 636 Pharmacodynamics BOX 22–3 PROGESTERONE ANTAGONISTS Mifepristone (Mifeprex) Mifepristone was approved by the FDA on September 28, 2000, for termination of intrauterine pregnancy. It has a long half- life (18 h) and may prolong the follicular phase of the subsequent cycle. It is strongly bound to plasma proteins (98%). This binding is saturable and the drug has nonlinear pharmacokinetics with relation to plasma concentration and clearance. The antiprogestational activity results from competitive interaction with progesterone at progesterone receptor sites. The drug inhibits the activity of both endogenous and exogenous progesterone. When there is no progesterone to maintain a preg- nancy, termination results. In 85% of women, mifepristone will act as an abortifacient when used in conjunction with miso- prostol during the first 7 weeks of pregnancy. Women should expect to experience bleeding or spotting for an average of 9 to 16 days. Persistent heavy or moderate bleeding for more than 30 days could indicate an incomplete abortion. There are very specific requirements associated with administration of this drug, and it is best done in clinics that can meet these requirements. The drug is available only from the manufacturer and not through licensed pharmacies. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. Off-labeled uses in the treatment of endometriosis, Cushing’s syndrome, and uterine leiomyomata are under study. 3827_Ch22_615-646 01/07/15 5:42 PM Page 636 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Onset, Peak, and Duration 637 Table 22–7 ! Pharmacokinetics: Progesterones and Progesterone Antagonists Drug Peak Active Metabolite Half-Life Elimination Progesterones Progesterone Antagonists 3827_Ch22_615-646 01/07/15 5:42 PM Page 637 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 638 Table 22–8 " Common Drug Interactions: Progesterones and Progesterone Antagonists Drug Interacting Drug Possible Effect Implications Progesterones Progesterone Antagonists 3827_Ch22_615-646 01/07/15 5:42 PM Page 638 639 Table 22–9 # Dosage Schedule: Progesterones and Progesterone Antagonists Drug Indication Dosage form Initial Dose Maintenance Dose Progesterones 3827_Ch22_615-646 01/07/15 5:42 PM Page 639 640 Table 22–9 # Dosage Schedule: Progesterones and Progesterone Antagonists—cont’d Drug Indication Dosage form Initial Dose Maintenance Dose Progesterone Antagonists 3827_Ch22_615-646 01/07/15 5:42 PM Page 640 641 Table 22–9 # Dosage Schedule: Progesterones and Progesterone Antagonists—cont’d Drug Indication Dosage form Initial Dose Maintenance Dose Rational Drug Selection 3827_Ch22_615-646 01/07/15 5:42 PM Page 641 Monitoring Patient Education OTHER DRUGS AFFECTING THE REPRODUCTIVE SYSTEM Drugs Commonly Used in Fertility Clinics Gonadotropin-Releasing Hormone 642 3827_Ch22_615-646 01/07/15 5:42 PM Page 642 Follicle-Stimulating Hormone/Gonadotropins Luteinizing Hormone and Human Chorionic Gonadotropin Lactation Inhibitors Bromocriptine Drugs Used for Erectile Dysfunction Phosphodiesterase Type 5 Inhibitors 643 3827_Ch22_615-646 01/07/15 5:42 PM Page 643 REFERENCES 644 3827_Ch22_615-646 01/07/15 5:42 PM Page 644 645 3827_Ch22_615-646 01/07/15 5:42 PM Page 645 3827_Ch22_615-646 01/07/15 5:42 PM Page 646 647 CHAPTER 23 Cally Bartley ANTIINFECTIVES, 648 TOPICAL ANTIBACTERIALS, 648 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ANTIFUNGALS, 651 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics TOPICAL ANTIVIRALS, 658 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics AGENTS USED TO TREAT ACNE, 659 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics TOPICAL CORTICOSTEROIDS, 666 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics TOPICAL IMMUNOMODULATORS, 671 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics TOPICAL ANTIPSORIASIS AGENTS, 672 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics TOPICAL ANTISEBORRHEIC MEDICATIONS, 675 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics TOPICAL ANTIHISTAMINES AND ANTIPRURITICS, 677 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics MOISTURIZERS, EMOLLIENTS, AND LUBRICANTS, 679 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics AGENTS USED IN THE TREATMENT OF BURNS, 680 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics SCABICIDES AND PEDICULICIDES, 681 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics CAUTERIZING AND DESTRUCTIVE AGENTS, 684 Pharmacodynamics Pharmacotherapeutics KERATOLYTICS, 685 Pharmacodynamics Pharmacotherapeutics TOPICAL ANESTHETICS, 685 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics MINOXIDIL, 687 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics MISCELLANEOUS TOPICAL MEDICATIONS, 688 Bath Dermatologicals Astringents Hair-Growth Retardants Sunscreens 3827_Ch23_647-690 02/07/15 11:46 AM Page 647 T ANTI-INFECTIVES TOPICAL ANTIBACTERIALS 648 Table 23–1 ! Dosage Schedule: Selected Anti-Infectives Used to Treat Skin Disorders Drug Indication Available Dosage Forms Dosage Antibacterial Antifungals 3827_Ch23_647-690 02/07/15 11:46 AM Page 648 649 Table 23–1 ! Dosage Schedule: Selected Anti-Infectives Used to Treat Skin Disorders–cont’d Drug Indication Available Dosage Forms Dosage Antivirals 3827_Ch23_647-690 02/07/15 11:46 AM Page 649 Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Clinical Use and Dosing ! 650 3827_Ch23_647-690 02/07/15 11:46 AM Page 650 Rational Drug Selection Monitoring Patient Education ANTIFUNGALS 651 3827_Ch23_647-690 02/07/15 11:46 AM Page 651 Pharmacodynamics Topical Antifungals Systemic Antifungals 652 3827_Ch23_647-690 02/07/15 11:46 AM Page 652 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 653 3827_Ch23_647-690 02/07/15 11:46 AM Page 653 Adverse Drug Reactions Drug Interactions 654 3827_Ch23_647-690 02/07/15 11:46 AM Page 654 Clinical Use and Dosing 655 3827_Ch23_647-690 02/07/15 11:46 AM Page 655 656 3827_Ch23_647-690 02/07/15 11:46 AM Page 656 Rational Drug Selection 657 Monitoring Metholated ointment (Vicks VapoRub) is a common lay treatment for onychomycosis. A small study (n = 18) of the use of daily topical mentholated ointment showed a positive treatment effect (83%), with myco- logical cure in 27.8% of study subjects and partial cure in 55.6% (Derby, Rohal, Jackson, Beutler, & Olsen, 2011). 3827_Ch23_647-690 02/07/15 11:46 AM Page 657 Pharmacodynamics Pharmacokinetics Absorption and Distribution Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 658 Patient Education TOPICAL ANTIVIRALS 3827_Ch23_647-690 02/07/15 11:46 AM Page 658 Drug Interactions Clinical Use and Dosing Rational Drug Selection Monitoring Patient Education AGENTS USED TO TREAT ACNE Pharmacodynamics Topical Retinoids 659 3827_Ch23_647-690 02/07/15 11:46 AM Page 659 Topical Antibiotics Systemic Retinoids Pharmacokinetics Absorption and Distribution Metabolism and Excretion 660 3827_Ch23_647-690 02/07/15 11:46 AM Page 660 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 661 3827_Ch23_647-690 02/07/15 11:46 AM Page 661 Drug Interactions 662 Table 23–2 " Drug Interactions: Selected Acne Medications Drug Interacting Drug Possible Effect Implications Topical Acne Medications Topical Antibiotics 3827_Ch23_647-690 02/07/15 11:46 AM Page 662 Clinical Use and Dosing 663 Table 23–2 " Drug Interactions: Selected Acne Medications—cont’d Drug Interacting Drug Possible Effect Implications Systemic Acne Medication 3827_Ch23_647-690 02/07/15 11:46 AM Page 663 664 Table 23–3 ! Dosage Schedule: Selected Acne Medications Drug Available Dosage Forms Dosage Notes Retinoids Topical Antibiotics Acne Medication 3827_Ch23_647-690 02/07/15 11:46 AM Page 664 Rational Drug Selection Monitoring Patient Education 665 3827_Ch23_647-690 02/07/15 11:46 AM Page 665 666 Table 23–4 # Available Dosage Forms: Topical Corticosteroids Drug Potency Dosage Form Rx Required Clobetasol Desonide Desoximetasone Fluocinonide TOPICAL CORTICOSTEROIDS Pharmacodynamics 3827_Ch23_647-690 02/07/15 11:46 AM Page 666 667 Table 23–4 # Available Dosage Forms: Topical Corticosteroids—cont’d Drug Potency Dosage Form Rx Required Fluocinolone Acetonide Flurandrenolide Halcinonide Halobetasol Proprionate Hydrocortisone Mometasone Furoate Triamcinolone Acetonide Pharmacokinetics Absorption and Distribution 3827_Ch23_647-690 02/07/15 11:46 AM Page 667 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 668 3827_Ch23_647-690 02/07/15 11:46 AM Page 668 669 Table 23–5 ! Dosage Schedule: Selected Topical Corticosteroids Drug Dosage Comments Least Potent (group 7) Mild Potency (group 6) Lower Mid-Strength Potency (group 5) Mid-Strength Potency (group 4) Upper Mid-Strength Potency (group 3) High Potency (group 2) Super High Potency (group 1) 3827_Ch23_647-690 02/07/15 11:46 AM Page 669 Rational Drug Selection Monitoring Patient Education 670 3827_Ch23_647-690 02/07/15 11:46 AM Page 670 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 671 TOPICAL IMMUNOMODULATORS Pharmacodynamics Pharmacokinetics Absorption and Distribution 3827_Ch23_647-690 02/07/15 11:46 AM Page 671 Rational Drug Selection Monitoring Patient Education TOPICAL ANTIPSORIASIS AGENTS Pharmacodynamics Pharmacokinetics Absorption and Distribution 672 3827_Ch23_647-690 02/07/15 11:46 AM Page 672 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 673 3827_Ch23_647-690 02/07/15 11:46 AM Page 673 674 Table 23–6 " Drug Interactions: Selected Psoriasis Medications Drug Interacting Drug Possible Effect Implications Table 23–7 ! Dosage Schedule: Topical Psoriasis Medications Drug Available Dosage Forms Dosage Notes 3827_Ch23_647-690 02/07/15 11:46 AM Page 674 Rational Drug Selection Monitoring Patient Education TOPICAL ANTISEBORRHEIC MEDICATIONS Pharmacodynamics 675 3827_Ch23_647-690 02/07/15 11:46 AM Page 675 676 Table 23–8 ! Dosage Schedule: Topical Antiseborrheic Medications Available Drug Indication Dosage Forms Dosage Notes Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 3827_Ch23_647-690 02/07/15 11:46 AM Page 676 Rational Drug Selection Monitoring Patient Education TOPICAL ANTIHISTAMINES AND ANTIPRURITICS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 677 3827_Ch23_647-690 02/07/15 11:46 AM Page 677 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Rational Drug Selection 678 Table 23–9 " Drug Interactions: Topical Antihistamine and Antipruritic Medications Drug Interacting Drug Possible Effect Implications Table 23–10 ! Dosage Schedule: Topical Antihistamine and Antipruritic Medications Available Drug Indication Dosage Form Dosage Comments 3827_Ch23_647-690 02/07/15 11:46 AM Page 678 Monitoring Patient Education MOISTURIZERS, EMOLLIENTS, AND LUBRICANTS Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Rational Drug Selection Monitoring Patient Education 679 3827_Ch23_647-690 02/07/15 11:46 AM Page 679 AGENTS USED IN THE TREATMENT OF BURNS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Clinical Use and Dosing Monitoring Patient Education 680 3827_Ch23_647-690 02/07/15 11:46 AM Page 680 SCABICIDES AND PEDICULICIDES Pharmacodynamics 681 Table 23–11 ! Dosage Schedule: Ectoparasiticides Available Drug Indication Dosage Forms Dosage Comments 3827_Ch23_647-690 02/07/15 11:46 AM Page 681 Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 682 3827_Ch23_647-690 02/07/15 11:46 AM Page 682 Clinical Use and Dosing 683 3827_Ch23_647-690 02/07/15 11:46 AM Page 683 Rational Drug Selection Monitoring Patient Education CAUTERIZING AND DESTRUCTIVE AGENTS Pharmacodynamics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Use and Dosing 684 3827_Ch23_647-690 02/07/15 11:46 AM Page 684 KERATOLYTICS Pharmacodynamics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Clinical Use and Dosing Patient Education TOPICAL ANESTHETICS Pharmacodynamics 685 3827_Ch23_647-690 02/07/15 11:46 AM Page 685 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education 686 3827_Ch23_647-690 02/07/15 11:46 AM Page 686 687 Table 23–12 " Drug Interactions: Miscellaneous Topical Medications Drug Interacting Drug Possible Effect Implications Table 23–13 ! Dosage Schedule: Miscellaneous Topical Medications Drug Indication Dosage Comments Pharmacodynamics MINOXIDIL 3827_Ch23_647-690 02/07/15 11:46 AM Page 687 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education MISCELLANEOUS TOPICAL MEDICATIONS Bath Dermatologicals Astringents 688 3827_Ch23_647-690 02/07/15 11:46 AM Page 688 Hair-Growth Retardants Sunscreens REFERENCES 689 3827_Ch23_647-690 02/07/15 11:46 AM Page 689 690 3827_Ch23_647-690 02/07/15 11:46 AM Page 690 691 CHAPTER 24 Jennifer Jordan • R. Brigg Turner • Teri Moser Woo ANTIMICROBIAL RESISTANCE, 692 ANTIBIOTICS: BETALACTAMS, 693 PENICILLINS, 693 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics CEPHALOSPORINS, 707 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics FLUOROQUINOLONES, 719 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics LINCOSAMIDES, 726 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics MACROLIDES, AZALIDES, AND KETOLIDES, 729 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics FIDAXOMICIN, 740 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics OXAZOLIDINONES, 741 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics SULFONAMIDES, TRIMETHOPRIM, NITROFURANTOIN, AND FOSFOMYCIN, 744 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics TETRACYCLINES, 751 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics GLYCOPEPTIDES, 757 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ANTIMYCOBACTERIALS, 760 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ANTIVIRALS, 770 NUCLEOSIDE ANALOGUES, 770 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ANTIVIRALS FOR INFLUENZA, 775 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics 3827_Ch24_691-800 01/07/15 5:45 PM Page 691 SYSTEMIC AZOLES AND OTHER ANTIFUNGALS, 778 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ANTHELMINTICS, 787 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics METRONIDAZOLE, NITAZOXANIDE, AND TINIDAZOLE, 790 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics 692 I ANTIMICROBIAL RESISTANCE 3827_Ch24_691-800 01/07/15 5:45 PM Page 692 ANTIBIOTICS: BETA-LACTAMS PENICILLINS Pharmacodynamics Penicillin Aminopenicillins 693 3827_Ch24_691-800 01/07/15 5:45 PM Page 693 Penicillinase-Resistant Penicillins Anti-Pseudomonal Penicillins Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion 694 3827_Ch24_691-800 01/07/15 5:45 PM Page 694 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 695 3827_Ch24_691-800 01/07/15 5:45 PM Page 695 696 Ta bl e 24 –1 ! Ph ar m ac ok in et ic s: P en ic ill in s D ru g O ns et Pe ak D ur at io n Pr ot ei n Bi nd in g Bi oa va ila bi lit y H al f- Li fe Pe ni ci lli na se Re si st an ce A ci d St ab ili ty El im in at io n 3827_Ch24_691-800 01/07/15 5:45 PM Page 696 Drug Interactions Clinical Use and Dosing 697 Table 24–2 " Drug Interactions: Penicillins Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 697 698 3827_Ch24_691-800 01/07/15 5:45 PM Page 698 699 3827_Ch24_691-800 01/07/15 5:45 PM Page 699 700 3827_Ch24_691-800 01/07/15 5:45 PM Page 700 Rational Drug Selection 701 Table 24–3 # Dosage Schedule: Penicillins Maximal Dose and Drug Indications Dosage Forms Initial Dose Maintanence Dose 3827_Ch24_691-800 01/07/15 5:45 PM Page 701 702 Table 24–3 # Dosage Schedule: Penicillins—cont’d Maximal Dose and Drug Indications Dosage Forms Initial Dose Maintanence Dose 3827_Ch24_691-800 01/07/15 5:45 PM Page 702 703 Table 24–3 # Dosage Schedule: Penicillins—cont’d Maximal Dose and Drug Indications Dosage Forms Initial Dose Maintanence Dose 3827_Ch24_691-800 01/07/15 5:45 PM Page 703 704 Table 24–3 # Dosage Schedule: Penicillins—cont’d Maximal Dose and Drug Indications Dosage Forms Initial Dose Maintanence Dose 3827_Ch24_691-800 01/07/15 5:45 PM Page 704 705 Table 24–4 Steps in Antimicrobial Drug Selection 3827_Ch24_691-800 01/07/15 5:45 PM Page 705 Monitoring Patient Education 706 3827_Ch24_691-800 01/07/15 5:45 PM Page 706 CEPHALOSPORINS Pharmacodynamics Spectrum of Activity First-Generation Cephalosporins Second-Generation Cephalosporins and Cephamycins Third-Generation Cephalosporins 707 3827_Ch24_691-800 01/07/15 5:45 PM Page 707 Fourth-Generation Cephalosporin Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion Changes Related to Pregnancy and in Children 708 BOX 24–1 ANTI-MRSA CEPHALOSPORINS Ceftaroline (Teflaro) is an injectable cephalosporin ap- proved for complicated skin and soft tissue infections and CAP. Ceftaroline inhibits cell wall synthesis by bind- ing to the modified PBP sites expressed by MRSA and penicillin-resistant S. pneumoniae. Gram-negative activ- ity is similar to third-generation cephalosporins but does not include Pseudomonas. Ceftobiprole is an in- jectable cephalosporin that has activity against MRSA and pseudomonal species. Ceftobiprole was rejected by the FDA in 2009; however, clinical investigations continue. 3827_Ch24_691-800 01/07/15 5:45 PM Page 708 Pharmacotherapeutics Precautions and Contraindications 709 Table 24–5 ! Pharmacokinetics: Cephalosporins Drug Onset Peak Bioavailability Half-Life NRF/ESRD*Duration Protein Binding Elimination (% unchanged in urine) 3827_Ch24_691-800 01/07/15 5:45 PM Page 709 Adverse Drug Reactions Drug Interactions 710 Table 24–6 " Drug Interactions: Cephalosporins Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 710 Clinical Use and Dosing 711 Table 24–7 # Dosage Schedule Cephalosporins Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 711 712 Table 24–7 # Dosage Schedule Cephalosporins—cont’d Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 712 713 Table 24–7 # Dosage Schedule Cephalosporins—cont’d Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 713 714 Table 24–7 # Dosage Schedule Cephalosporins—cont’d Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 714 715 Table 24–7 # Dosage Schedule Cephalosporins—cont’d Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 715 716 Table 24–7 # Dosage Schedule Cephalosporins—cont’d Maximal Dose Drug Indications Dosage Forms Initial Dose and Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 716 Rational Drug Selection 717 On The Horizon CEFTOBIPROLE Ceftobiprole is a new fifth-generation cephalosporin active against MRSA, DRSP, and Pseudomonas aeruginosa. It is in- tended for use with skin and skin structure infection and for nosocomial pneumonia. It was originally submitted to the FDA in May 2007 for the treatment of complicated skin and skin structure infections. In 2010, the FDA requested further infor- mation and studies before approving ceftobiprole. 3827_Ch24_691-800 01/07/15 5:45 PM Page 717 Monitoring Patient Education 718 3827_Ch24_691-800 01/07/15 5:45 PM Page 718 FLUOROQUINOLONES Pharmacodynamics Spectrum of Activity Resistance 719 3827_Ch24_691-800 01/07/15 5:45 PM Page 719 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 720 Table 24–8 ! Pharmacokinetics: Fluoroquinolones Drug Onset Half-Life*Peak Duration Protein Binding Bioavailability Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 720 Adverse Drug Reactions Drug Interactions 721 3827_Ch24_691-800 01/07/15 5:45 PM Page 721 722 Table 24–9 " Drug Interactions: Fluoroquinolones Drug Interacting Drug Possible Effect Implications Clinical Use and Dosing 3827_Ch24_691-800 01/07/15 5:45 PM Page 722 723 Table 24–10 # Dosage Schedule: Fluoroquinolones Drug Indications Dosage Forms Initial Adult Dose Maintanence Dose 3827_Ch24_691-800 01/07/15 5:45 PM Page 723 724 Table 24–10 # Dosage Schedule: Fluoroquinolones—cont’d Drug Indications Dosage Forms Initial Adult Dose Maintanence Dose 3827_Ch24_691-800 01/07/15 5:45 PM Page 724 Rational Drug Selection 725 3827_Ch24_691-800 01/07/15 5:45 PM Page 725 Monitoring Patient Education LINCOSAMIDES Pharmacodynamics Spectrum of Activity 726 3827_Ch24_691-800 01/07/15 5:45 PM Page 726 Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 727 Table 24–11 ! Pharmacokinetics: Lincosamides Drug Onset Peak Duration Protein Binding Bioavailability Half-Life Elimination Table 24–12 " Drug Interactions: Lincosamides Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 727 Rational Drug Selection 728 Table 24–13 # Dosage Schedule: Lincosamides Drug Indication Dosage Forms Initial Dose Maintanence Dose 3827_Ch24_691-800 01/07/15 5:45 PM Page 728 Monitoring Patient Education MACROLIDES, AZALIDES, AND KETOLIDES Pharmacodynamics Spectrum of Activity 729 3827_Ch24_691-800 01/07/15 5:45 PM Page 729 Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 730 Table 24–14 ! Pharmacokinetics: Macrolides, Azalides, and Ketolides Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 730 Adverse Drug Reactions 731 3827_Ch24_691-800 01/07/15 5:45 PM Page 731 Drug Interactions Clinical Use and Dosing 732 Table 24–15 " Drug Interactions: Macrolides and Azalides Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 732 733 Table 24–15 " Drug Interactions: Macrolides and Azalides—cont’d Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 733 734 Table 24–16 # Dosage Schedule: Macrolides, Azalides, and Ketolides Drug Indication Dosage Form Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 734 735 Table 24–16 # Dosage Schedule: Macrolides, Azalides, and Ketolides—cont’d Drug Indication Dosage Form Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 735 736 Table 24–16 # Dosage Schedule: Macrolides, Azalides, and Ketolides—cont’d Drug Indication Dosage Form Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 736 737 Table 24–16 # Dosage Schedule: Macrolides, Azalides, and Ketolides—cont’d Drug Indication Dosage Form Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 737 738 3827_Ch24_691-800 01/07/15 5:45 PM Page 738 Rational Drug Selection Monitoring Patient Education 739 3827_Ch24_691-800 01/07/15 5:45 PM Page 739 FIDAXOMICIN Pharmacodynamics Spectrum of Activity Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Rational Drug Selection Monitoring Patient Education 740 3827_Ch24_691-800 01/07/15 5:45 PM Page 740 OXAZOLIDINONES Pharmacodynamics Spectrum of Activity Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 741 Table 24–17 ! Pharmacokinetics: Oxazolidinones Drug Onset (h) Peak (h) Duration (h) Protein Binding Bioavailability Half-Life (h) Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 741 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 742 Table 24–18 " Drug Interactions: Oxazolidinones Drug Interacting Drug FOOD INTERACTIONS Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 742 Rational Drug Selection Monitoring Patient Education 743 Table 24–19 # Dosage Schedules: Oxazolidinones Drug Indication DoseAvailable Dosage Forms Comments On The Horizon TEDIZOLID Tedizolid is a next-generation oxazolidinone in development. It has greater potency than linezolid and a similar antimicrobial spectrum, including but not limited to MRSA, VRE, streptococci, and M. tuberculosis. Clinical trials with up to 21 days of therapy have not demonstrated myelosuppression. Preliminary testing suggests that tedizolid has lower potential than linezolid for MAOI drug and food interactions (Flanagan, Bartizal, Minassian, Fang, & Prokocimer, 2013). Like linezolid, tedizolid has excellent oral bioavailability and tissue penetration (Urbina et al, 2013). 3827_Ch24_691-800 01/07/15 5:45 PM Page 743 SULFONAMIDES, TRIMETHOPRIM, NITROFURANTOIN, AND FOSFOMYCIN Pharmacodynamics Sulfonamides Trimethoprim Nitrofurantoin 744 3827_Ch24_691-800 01/07/15 5:45 PM Page 744 Fosfomycin Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 745 3827_Ch24_691-800 01/07/15 5:45 PM Page 745 746 Table 24–20 ! Pharmacokinetics: Sulfonamides, Trimethoprim, Nitrofurantoin, and Fosfomycin Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 746 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 747 3827_Ch24_691-800 01/07/15 5:45 PM Page 747 Rational Drug Selection 748 Table 24–21 " Drug Interactions: Sulfonamides, Trimethoprim, Nitrofurantoin, and Fosfomycin Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 748 749 Table 24–22 # Dosage Schedule: Sulfonamides, Trimethoprim, Nitrofurantoin, and Fosfomycin Drug Indication Available Dosage Forms Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 749 750 Table 24–22 # Dosage Schedule: Sulfonamides, Trimethoprim, Nitrofurantoin, and Fosfomycin—cont’d Drug Indication Available Dosage Forms Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 750 Monitoring Patient Education Adverse Reactions TETRACYCLINES Pharmacodynamics 751 3827_Ch24_691-800 01/07/15 5:45 PM Page 751 Spectrum of Activity Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion 752 Table 24–23 ! Pharmacokinetics: Tetracyclines Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 752 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 753 3827_Ch24_691-800 01/07/15 5:45 PM Page 753 754 Table 24–24 " Drug Interactions: Tetracyclines Drug Interacting Drug Possible Effects Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 754 Rational Drug Selection 755 Table 24–25 # Dosage Schedule: Tetracyclines Drug Indication Dosage Form Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 755 756 Table 24–25 # Dosage Schedule: Tetracyclines—cont’d Drug Indication Dosage Form Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 756 Monitoring Patient Education GLYCOPEPTIDES 757 3827_Ch24_691-800 01/07/15 5:45 PM Page 757 Pharmacodynamics Spectrum of Activity Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 758 On The Horizon DALBAVANCIN A new glycopeptide antibiotic, dalbavancin (Zeven), is in phase III trials. The only other drug structurally related to dalbavancin is vancomycin. This once-weekly antibiotic is effective against MRSA and MRSE. In 2008, Pfizer withdrew its global applications to conduct further studies on dalbavancin. In 2010, Pfizer out-licensed dalbavancin to Durata Therapeu- tics, which will continue phase III trials. 3827_Ch24_691-800 01/07/15 5:45 PM Page 758 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education 759 3827_Ch24_691-800 01/07/15 5:45 PM Page 759 ANTIMYCOBACTERIALS Pharmacodynamics Spectrum of Activity 760 3827_Ch24_691-800 01/07/15 5:45 PM Page 760 Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion 761 3827_Ch24_691-800 01/07/15 5:45 PM Page 761 Pharmacotherapeutics Precautions and Contraindications 762 Table 24–26 ! Pharmacokinetics: Selected Antimycobacterials Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 762 763 Table 24–27 " Drug Interactions: Selected Antimycobacterials Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 763 Adverse Drug Reactions 764 Table 24–27 " Drug Interactions: Selected Antimycobacterials—cont’d Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 764 Drug Interactions Clinical Use and Dosing Rational Drug Selection 765 3827_Ch24_691-800 01/07/15 5:45 PM Page 765 766 Table 24–28 # Dosage Schedule: Selected Antimycobacterials Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 766 767 Table 24–28 # Dosage Schedule: Selected Antimycobacterials—cont’d Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 767 768 Table 24–28 # Dosage Schedule: Selected Antimycobacterials—cont’d Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 768 769 Table 24–28 # Dosage Schedule: Selected Antimycobacterials—cont’d Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 769 Patient Education ANTIVIRALS NUCLEOSIDE ANALOGUES Pharmacodynamics 770 3827_Ch24_691-800 01/07/15 5:45 PM Page 770 Spectrum of Activity Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 771 Table 24–29 ! Pharmacokinetics: Nucleoside Analogues for Herpes Virus Infections Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 771 Drug Interactions Clinical Use and Dosing 772 Table 24–30 " Drug Interactions: Nucleoside Analogues Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 772 Rational Drug Selection 773 Table 24–31 # Dosage Schedule: Nucleoside Analogues for Herpes Virus Infections Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 773 774 Table 24–31 # Dosage Schedule: Nucleoside Analogues for Herpes Virus Infections—cont’d Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 774 Monitoring Patient Education ANTIVIRALS FOR INFLUENZA 775 Table 24–31 # Dosage Schedule: Nucleoside Analogues for Herpes Virus Infections—cont’d Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 775 Pharmacodynamics Mechanism of Action Resistance Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions 776 CLINICAL PEARL CDC Influenza Antiviral Recommendations The CDC tracks influenza worldwide to determine circu- lating and emerging strains. Weekly updates on flu activ- ity and surveillance provide information on what strains are circulating in each state. The CDC also provides rec- ommendations for the use of antivirals during influenza season, including updates as resistance patterns emerge. Providers can refer to “Information for Health Profession- als,” accessible at http://www.cdc.gov/flu, for the latest information. 3827_Ch24_691-800 01/07/15 5:45 PM Page 776 Clinical Use and Dosing 777 Table 24–32 ! Pharmacokinetics: Antivirals for Influenza Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination Table 24–33 # Dosage Schedule: Antivirals for Influenza Drug Indications Initial DoseDosage Form Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 777 Rational Drug Selection Monitoring Patient Education SYSTEMIC AZOLES AND OTHER ANTIFUNGALS Pharmacodynamics ! 778 On The Horizon ISAVUCONAZOLE Isavaconazole is a novel, broad-spectrum azole intended to treat most yeasts and molds, including fluconazole-resistant Candida strains, Aspergillus, and Zygomyces. It is currently in phase III trials. 3827_Ch24_691-800 01/07/15 5:45 PM Page 778 Spectrum of Activity Resistance Pharmacokinetics Absorption and Distribution 779 Table 24–34 ! Pharmacokinetics: Systemic Antifungal Agents Drug Onset Half-LifePeak Duration Protein Binding Bioavailability Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 779 Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 780 3827_Ch24_691-800 01/07/15 5:45 PM Page 780 Adverse Drug Reactions Drug Interactions 781 Table 24–35 " Drug Interactions: Selected Systemic Antifungal Agents Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 781 782 Table 24–35 " Drug Interactions: Selected Systemic Antifungal Agents—cont’d Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 782 Clinical Use and Dosing Rational Drug Selection Monitoring Patient Education 783 Table 24–36 # Dosage Schedule: Selected Systemic Antifungal Agents Drug Indication Dosage Form Initial and Maintenance Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 783 784 Table 24–36 # Dosage Schedule: Selected Systemic Antifungal Agents—cont’d Drug Indication Dosage Form Initial and Maintenance Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 784 785 Table 24–36 # Dosage Schedule: Selected Systemic Antifungal Agents—cont’d Drug Indication Dosage Form Initial and Maintenance Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 785 786 Table 24–36 # Dosage Schedule: Selected Systemic Antifungal Agents—cont’d Drug Indication Dosage Form Initial and Maintenance Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 786 ANTHELMINTICS Pharmacodynamics Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 787 3827_Ch24_691-800 01/07/15 5:45 PM Page 787 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 788 Table 24–37 ! Pharmacokinetics: Selected Anthelmintics Drug Onset Half-LifePeak Protein Binding Bioavailability Elimination Table 24–38 " Drug Interactions: Selected Anthelmintics Drug Interacting Drug Possible Effect Implications 3827_Ch24_691-800 01/07/15 5:45 PM Page 788 789 Table 24–39 # Dosage Schedule: Selected Anthelmintics Drug Indication Initial DoseDosage Form Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 789 Rational Drug Selection Monitoring Patient Education METRONIDAZOLE, NITAZOXANIDE, AND TINIDAZOLE Pharmacodynamics 790 3827_Ch24_691-800 01/07/15 5:45 PM Page 790 Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 791 Table 24–40 ! Pharmacokinetics: Metronidazole, Nitazoxanide, and Tinidazole Drug Onset (h) Half-LifePeak (h) Duration (h) Protein Binding Bioavailability Elimination 3827_Ch24_691-800 01/07/15 5:45 PM Page 791 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 792 3827_Ch24_691-800 01/07/15 5:45 PM Page 792 793 Table 24–41 # Dosage Schedule: Metronidazole, Nitazoxanide, and Tinidazole Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 793 794 Table 24–41 # Dosage Schedule: Metronidazole, Nitazoxanide, and Tinidazole—cont’d Drug Indication Dosage Form Initial Dose Comments 3827_Ch24_691-800 01/07/15 5:45 PM Page 794 Rational Drug Selection Monitoring Patient Education 795 3827_Ch24_691-800 01/07/15 5:45 PM Page 795 REFERENCES 796 3827_Ch24_691-800 01/07/15 5:45 PM Page 796 797 3827_Ch24_691-800 01/07/15 5:45 PM Page 797 798 3827_Ch24_691-800 01/07/15 5:45 PM Page 798 799 3827_Ch24_691-800 01/07/15 5:45 PM Page 799 3827_Ch24_691-800 01/07/15 5:45 PM Page 800 801 CHAPTER 25 Teri Moser Woo ANTIGOUT AND URICOSURIC AGENTS, 801 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics CORTICOSTEROIDS, 808 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics NONSTEROIDAL ANTIINFLAMMATORY DRUGS NSAIDS, 816 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics ASPIRIN AND NONACETYLATED SALICYLATES, 828 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics I ANTIGOUT AND URICOSURIC AGENTS 3827_Ch25_801-836 01/07/15 5:46 PM Page 801 802 Pharmacodynamics Antigout Drugs Uricosuric Drugs Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 3827_Ch25_801-836 01/07/15 5:46 PM Page 802 Adverse Drug Reactions 803 Table 25–1 ! Pharmacokinetics: Antigout and Uricosuric Agents Drug Onset Peak (in plasma) Duration Protein Binding Half-Life Elimination 3827_Ch25_801-836 01/07/15 5:46 PM Page 803 Drug Interactions 804 Table 25–2 " Drug Interactions: Antigout and Uricosuric Agents Drug Interacting Drug Possible Effect Implications 3827_Ch25_801-836 01/07/15 5:46 PM Page 804 805 Table 25–2 " Drug Interactions: Antigout and Uricosuric Agents—cont’d Drug Interacting Drug Possible Effect Implications Clinical Use and Dosing 3827_Ch25_801-836 01/07/15 5:47 PM Page 805 806 Table 25–3 # Dosage Schedule: Antigout and Uricosuric Agents Drug Indication Dosage Form Initial Dose Maintenance Dose 3827_Ch25_801-836 01/07/15 5:47 PM Page 806 Rational Drug Selection Monitoring 807 3827_Ch25_801-836 01/07/15 5:47 PM Page 807 808 Patient Education CORTICOSTEROIDS Pharmacodynamics 3827_Ch25_801-836 01/07/15 5:47 PM Page 808 809 Hypothalamus Stress Corticotropin-releasing factor (CRF) Hypoxia Hypoglycemia Hyperthermia Exercise Cortisol insufficiency Somatostatin Hypothalamic lesions Diurnal rhythms Anterior pituitary Adrenocorticotropic hormone (ACTH) Adrenal cortex Glucocorticoids • Decreased peripheral uptake of glucose; glucogenesis in liver • Decreased protein synthesis in muscle, lymphoid tissue, skin, bone • Lipolysis in adipose tissue in extremities; lipogenesis in face and trunk • Decreased circulating eosinophils, lymphocytes, monocytes; increased PMNs • Decreased leukocytes at inflammation sites • Decrease in all lymphoid tissues; inhibits production of IL-1 and IL-2 • Blocks generation of fever • Promotes gastric acid secretion; enhances urinary excretion • Decreased proliferation of fibroblasts in connective tissue; delayed healing • Maintains normal contractility of skeletal and cardiac muscle • Increases osteoclastic activity; decreases osteoblastic activity • Maintains normal blood pressure; increases response of arterioles to NE • Modulates emotional and perceptual function; essential for normal arousal (+) (+) (+) (–) (–) (–) (–) (–) Figure 25–1. Hypothalamus- pituitary-adrenal axis and feedback control of cortisol. 3827_Ch25_801-836 01/07/15 5:47 PM Page 809 Pharmacokinetics Absorption and Distribution Metabolism and Excretion 810 Table 25–4 ! Pharmacokinetics: Selected Corticosteroids Onset Peak Duration Protein Drug (hours) (hours) (days) Binding Half-Life RAP RMP Elimination 3827_Ch25_801-836 01/07/15 5:47 PM Page 810 Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 811 3827_Ch25_801-836 01/07/15 5:47 PM Page 811 Drug Interactions Clinical Use and Dosing 812 3827_Ch25_801-836 01/07/15 5:47 PM Page 812 813 Table 25–5 " Drug Interactions: Selected Corticosteroids Drug Interacting Drug Possible Effect Implications 3827_Ch25_801-836 01/07/15 5:47 PM Page 813 814 Table 25–6 # Dosage Schedule: Selected Corticosteroids Drug Indication Dosage Form Dose Notes 3827_Ch25_801-836 01/07/15 5:47 PM Page 814 815 Table 25–6 # Dosage Schedule: Selected Corticosteroids—cont’d Drug Indication Dosage Form Dose Notes 3827_Ch25_801-836 01/07/15 5:47 PM Page 815 Rational Drug Selection Monitoring Patient Education 816 3827_Ch25_801-836 01/07/15 5:47 PM Page 816 NONSTEROIDAL ANTI- INFLAMMATORY DRUGS (NSAIDS) Pharmacodynamics 817 3827_Ch25_801-836 01/07/15 5:47 PM Page 817 818 Cell membrane destruction Prostaglandin E Prostacyclin Thromboxane Prostaglandin FInflammation Bronchospasm CyclooxygenaseLipoxygenase Vasodilation Edema Bronchodilation Pain sensitization Vasodilation Inhibits platelets Vasoconstriction Platelet aggregation Vasoconstriction Arachidonic acid Leukotrienes Prostaglandins Figure 25–2. Sequence of events in inflammatory response. The sequence of events is the same, regardless of the source of injury. Pharmacokinetics Absorption and Distribution Metabolism and Excretion 3827_Ch25_801-836 01/07/15 5:47 PM Page 818 819 Table 25–7 ! Pharmacokinetics: Selected NSAIDs and Acetaminophen Onset Peak Duration Anal/ Anal/ Anal/ Protein Drug AntiR AntiR AntiR Binding Bioavailability Half-Life Elimination 3827_Ch25_801-836 01/07/15 5:47 PM Page 819 Pharmacotherapeutics Precautions and Contraindications 820 Table 25–7 ! Pharmacokinetics: Selected NSAIDs and Acetaminophen—cont’d Onset Peak Duration Anal/ Anal/ Anal/ Protein Drug AntiR AntiR AntiR Binding Bioavailability Half-Life Elimination 3827_Ch25_801-836 01/07/15 5:47 PM Page 820 Adverse Drug Reactions Drug Interactions 821 3827_Ch25_801-836 01/07/15 5:47 PM Page 821 822 Table 25–8 " Drug Interactions: Selected NSAIDs and Acetaminophen Drug Interacting Drug Possible Effect Implications Clinical Use and Dosing 3827_Ch25_801-836 01/07/15 5:47 PM Page 822 823 Table 25–9 # Dosage Schedule: Selected NSAIDs and Acetaminophen Drug Indication Dosage Forms Dosage Schedule Comments ORAL DOSES SUPPOSITORIES 3827_Ch25_801-836 01/07/15 5:47 PM Page 823 824 Table 25–9 # Dosage Schedule: Selected NSAIDs and Acetaminophen—cont’d Drug Indication Dosage Forms Dosage Schedule Comments 3827_Ch25_801-836 01/07/15 5:47 PM Page 824 825 Table 25–9 # Dosage Schedule: Selected NSAIDs and Acetaminophen—cont’d Drug Indication Dosage Forms Dosage Schedule Comments 3827_Ch25_801-836 01/07/15 5:47 PM Page 825 826 Table 25–9 # Dosage Schedule: Selected NSAIDs and Acetaminophen—cont’d Drug Indication Dosage Forms Dosage Schedule Comments 3827_Ch25_801-836 01/07/15 5:47 PM Page 826 827 3827_Ch25_801-836 01/07/15 5:47 PM Page 827 ASPIRIN AND NONACETYLATED SALICYLATES Pharmacodynamics 828 Rational Drug Selection Monitoring Patient Education 3827_Ch25_801-836 01/07/15 5:47 PM Page 828 829 Table 25–10 ! Pharmacokinetics: Salicylates Drug Onset Peak Duration Protein Binding Half-Life Elimination Pharmacokinetics Absorption and Distribution Metabolism and Excretion Pharmacotherapeutics Precautions and Contraindications 3827_Ch25_801-836 01/07/15 5:47 PM Page 829 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 830 3827_Ch25_801-836 01/07/15 5:47 PM Page 830 831 Table 25–11 " Drug Interactions: Salicylates Drug Interacting Drug Possible Effect Implications 3827_Ch25_801-836 01/07/15 5:47 PM Page 831 832 Table 25–12 # Dosage Schedule: Salicylates Drug Indication Dosage Forms Dose Comments 3827_Ch25_801-836 01/07/15 5:47 PM Page 832 Rational Drug Selection Monitoring 833 3827_Ch25_801-836 01/07/15 5:47 PM Page 833 Patient Education REFERENCES 834 3827_Ch25_801-836 01/07/15 5:47 PM Page 834 835 3827_Ch25_801-836 01/07/15 5:47 PM Page 835 3827_Ch25_801-836 01/07/15 5:47 PM Page 836 837 CHAPTER 26 Teri Moser Woo DRUGS USED IN TREATING EYE DISORDERS, 837 OPHTHALMIC ANTIINFECTIVES ANTIGLAUCOMA AGENTS OCULAR ANTIALLERGIC AND ANTIINFLAMMATORY AGENTS OCULAR LUBRICANTS OPHTHALMIC VASOCONSTRICTORS OPHTHALMIC DIAGNOSTIC PRODUCTS DRUGS USED IN TREATING EAR DISORDERS, 857 OTIC ANTIINFECTIVES OTIC ANALGESICS CERUMINOLYTICS T DRUGS USED IN TREATING EYE DISORDERS OPHTHALMIC ANTIINFECTIVES Pharmacodynamics 3827_Ch26_837-862 02/07/15 12:00 PM Page 837 Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions 838 3827_Ch26_837-862 02/07/15 12:00 PM Page 838 Drug Interactions 839 Table 26–1 ! Drug Interactions: Ophthalmic Anti-Infectives Drug Interacting Drug Possible Effect Implications 3827_Ch26_837-862 02/07/15 12:00 PM Page 839 Clinical Use and Dosing 840 Table 26–2 Clinical and Laboratory Features of Conjunctivitis Type Common Patient Group Common Pathogens Clinical Features 3827_Ch26_837-862 02/07/15 12:00 PM Page 840 841 Table 26–3 " Dosage Schedule: Ophthalmic Anti-Infectives Drug Indication Dosage Form Dose Comments 3827_Ch26_837-862 02/07/15 12:00 PM Page 841 842 Table 26–3 " Dosage Schedule: Ophthalmic Anti-Infectives—cont’d Drug Indication Dosage Form Dose Comments 3827_Ch26_837-862 02/07/15 12:00 PM Page 842 Rational Drug Selection Monitoring Patient Education 843 CLINICAL PEARL Proper Instillation of Eyedrops • Wash hands before administering eyedrops. • Tilt head back or lie on back. • Gently pull down lower eyelid to form a “pocket” to place the drop of medication into. • Squeeze the medication onto the eye without touch- ing eye with the dropper. • Close eye. Do not rub. Try not to blink. • To prevent cross-contamination, do not use medica- tion labeled for another patient. • Wait at least 5 minutes between administrations if administering more than one eye medication. Proper Instillation of Eye Ointment • Wash hands prior to administering eye medications. • Warm the ointment by holding it in the hand for 1 to 2 minutes. • With first use of a new tube, squeeze out and discard the first 0.25 in. of medication. • Angle head back or lie on back. • Gently pull down lower eyelid to form a “pocket” to place the drop of medication into. • Squeeze 0.25 to 0.5 in. of medication onto the eye without touching eye with tip of tube. • Close eye for 1 to 2 minutes. Do not rub. • Wipe excess medication from around the eye with a tissue. • To prevent cross-contamination, do not use medica- tion labeled for another patient. • Wait at least 10 minutes between administrations if administering more than one eye medication. • Temporary blurred vision is typical after administration of ophthalmic ointment. 3827_Ch26_837-862 02/07/15 12:00 PM Page 843 ANTIGLAUCOMA AGENTS Pharmacodynamics 844 CLINICAL PEARL Tips for Administering Eye Medications to a Child If only one adult is available to administer eyedrops, then the adult can sit on the floor with the child be- tween his or her legs, with the child’s legs in the same direction as the adult’s. The child’s head can be immo- bilized between the adult’s thighs and the arms held firmly down under the adult’s thighs. This leaves the adult’s hands free to instill the medication. The child may kick, but this will not affect the administration of the medication. Although this method may sound dras- tic, trying to administer eye medication to a squirming toddler or preschooler can be almost impossible, and with this method, the eyedrops can be effectively administered in less than 1 minute. 3827_Ch26_837-862 02/07/15 12:00 PM Page 844 Pharmacokinetics 845 Table 26–4 # Pharmacokinetics: Antiglaucoma Agents Drug Duration Beta Blockers Miotics Carbonic Anhydrase Inhibitors Sympathomimetics Alpha-Adrenergic Agonists Prostaglandin Analogues 3827_Ch26_837-862 02/07/15 12:00 PM Page 845 Pharmacotherapeutics Precautions and Contraindications 846 3827_Ch26_837-862 02/07/15 12:00 PM Page 846 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 847 3827_Ch26_837-862 02/07/15 12:00 PM Page 847 848 Table 26–5 ! Drug Interactions: Antiglaucoma Agents Drug Interacting Drug Possible Effect Implications Beta Blockers Miotics Carbonic Anhydrase Inhibitors 3827_Ch26_837-862 02/07/15 12:00 PM Page 848 849 Patient Education OCULAR ANTIALLERGIC AND ANTIINFLAMMATORY AGENTS Table 26–5 ! Drug Interactions: Antiglaucoma Agents—cont’d Drug Interacting Drug Possible Effect Implications Sympathomimetics Alpha-Adrenergic Agonists Prostaglandin Analogues 3827_Ch26_837-862 02/07/15 12:00 PM Page 849 850 Table 26–6 $ Available Dosage Forms: Antiglaucoma Agents Drug Dosage Form How Supplied Beta Blockers BETAXOLOL CARTEOLOL LEVOBUNOLOL METIPRANOLOL TIMOLOL COMBINATION PRODUCTS Miotics CARBACHOL PILOCARPINE ECHOTHIOPHATE Carbonic Anhydrase Inhibitors ACETAZOLAMIDE BRINZOLAMIDE DORZOLAMIDE METHAZOLAMIDE 3827_Ch26_837-862 02/07/15 12:00 PM Page 850 851 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Table 26–6 $ Available Dosage Forms: Antiglaucoma Agents—cont’d Drug Dosage Form How Supplied Sympathathomimetics EPINEPHRINE DIPIVEFRIN Alpha-Adrenergic Agonists APRACLONIDINE BRIMONIDINE Prostaglandin Analogues LATANOPROST UNOPROSTONE TRAVOPROST 3827_Ch26_837-862 02/07/15 12:00 PM Page 851 Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 852 3827_Ch26_837-862 02/07/15 12:00 PM Page 852 853 Table 26–7 " Dosage Schedule: Selected Ocular Antiallergic and Anti-Inflammatory Agents Drug Indication Dosage Form Dose Notes Mast Cell Stabilizers Antihistamines 3827_Ch26_837-862 02/07/15 12:00 PM Page 853 854 Table 26–7 " Dosage Schedule: Selected Ocular Antiallergic and Anti-Inflammatory Agents—cont’d Drug Indication Dosage Form Dose Notes NSAIDs Rational Drug Selection Monitoring Patient Education OCULAR LUBRICANTS 3827_Ch26_837-862 02/07/15 12:00 PM Page 854 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 855 Table 26–8 " Dosage Schedule: Miscellaneous Ophthalmic Products Drug Indication Dosage Forms Dose Comments Ocular Lubricants Ophthalmic Vasoconstrictors 3827_Ch26_837-862 02/07/15 12:00 PM Page 855 856 Table 26–8 " Dosage Schedule: Miscellaneous Ophthalmic Products—cont’d Drug Indication Dosage Forms Dose Comments Ophthalmic Diagnostic Products Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing Monitoring Patient Education OPHTHALMIC VASOCONSTRICTORS Pharmacodynamics Pharmacokinetics 3827_Ch26_837-862 02/07/15 12:00 PM Page 856 857 Rational Drug Selection Patient Education OPHTHALMIC DIAGNOSTIC PRODUCTS Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Patient Education DRUGS USED IN TREATING EAR DISORDERS OTIC ANTIINFECTIVES 3827_Ch26_837-862 02/07/15 12:00 PM Page 857 Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Precautions and Contraindications Adverse Drug Reactions Drug Interactions Clinical Use and Dosing 858 3827_Ch26_837-862 02/07/15 12:00 PM Page 858 859 Table 26–9 " Dosage Schedule: Drugs Used in Treating Ear Disorders Drug Indication Dosage Forms Dose Comments Otic Anti-Infectives Otic Anti-Infective- Steroid Combination 3827_Ch26_837-862 02/07/15 12:00 PM Page 859 860 Table 26–9 " Dosage Schedule: Drugs Used in Treating Ear Disorders—cont’d Drug Indication Dosage Forms Dose Comments Acid–Alcohol Solutions Otic Analgesics Ceruminolytics Monitoring Patient Education 3827_Ch26_837-862 02/07/15 12:00 PM Page 860 OTIC ANALGESICS CERUMINOLYTICS REFERENCES 861 3827_Ch26_837-862 02/07/15 12:00 PM Page 861 3827_Ch26_837-862 02/07/15 12:00 PM Page 862 UNIT III 3827_Ch27_863-880 01/07/15 6:19 PM Page 863 3827_Ch27_863-880 01/07/15 6:19 PM Page 864 865 A PATHOPHYSIOLOGY COMMON TO ALL ANEMIAS CHAPTER 27 Teri Moser Woo • Kristen Osborn PATHOPHYSIOLOGY COMMON TO ALL ANEMIAS, 865 Iron Deficiency Anemia Folic Acid Deficiency Anemia Pernicious Anemia Anemia of Chronic Disease Sickle Cell Anemia GOALS OF TREATMENT, 870 RATIONAL DRUG SELECTION, 870 Iron Deficiency Anemia Folic Acid Deficiency Anemia Pernicious Anemia Anemia of Chronic Disease Sickle Cell Anemia 3827_Ch27_863-880 01/07/15 6:19 PM Page 865 866 Table 27–1 Normal Blood Values by Age and Gender Mean Corpuscle Mean Corpuscle Volume (mcg3) Hemoglobin RBC Hemoglobin RBC Count Concentration Concentration Distribution Age/Gender (g/100 mL) Hematocrit (million/mm3) (pg/cell) (pg/cell) Width Iron Deficiency Anemia (IDA) 3827_Ch27_863-880 01/07/15 6:19 PM Page 866 867 Disease process erythropoiesis, blood loss, or RBC destruction Compensatory mechanisms Renal Heart rate DPG in cells Heart angina Erythropoietin Stroke volume Hyperdynamic circulation High-output heart failureCardiac murmurs Cardiovascular Fatty changes in liver and kidneyIschemia Hypoxia Release of O2 from Hb to tissues RBCs, Hb anemia Claudication (muscles) Stimulates bone marrow Weakness and fatigue Respiratory rate, depth, and exertional dyspnea Dizziness and syncope Myocardial oxygen demand Capillary dilation Pale skin and mucosa Renin-angiotensin-aldosterone response Na+ and H2O retention ECF volume Figure 27–1. Progression and manifestations of anemia. Table 27–2 Laboratory Findings in Selected Anemias Folic Acid Iron Deficiency Deficiency Pernicious Anemia of Sickle Test Anemia Anemia Anemia Chronic Disease Cell Anemia 3827_Ch27_863-880 01/07/15 6:19 PM Page 867 Folic Acid Deficiency Anemia (FOA) Pernicious Anemia (PA) 868 3827_Ch27_863-880 01/07/15 6:19 PM Page 868 Anemia of Chronic Disease (ACD) Sickle Cell Anemia (SCD) 869 3827_Ch27_863-880 01/07/15 6:19 PM Page 869 GOALS OF TREATMENT RATIONAL DRUG SELECTION Iron Deficiency Anemia (IDA) Risk Stratification and Screening 870 3827_Ch27_863-880 01/07/15 6:19 PM Page 870 Prevention of IDA Drug Therapy 871 Table 27–3 Iron Intake Recommendations for the Prevention and Treatment of Iron Deficiency Anemia Risk Group Prevention Treatment 3827_Ch27_863-880 01/07/15 6:19 PM Page 871 Monitoring Outcome Evaluation 872 Poor utilization? Evaluate and treat for: chronic inflammation, lead poisoning Trial of oral ferrous sulfate for 4–6 weeks Hemoglobin and hematocrit at 4 weeks If severe anemia, reticulocyte count after 5–10 days Adequate response Inadequate response Continue oral iron for 6–12 months to replenish iron stores Hemoglobin, hematocrit, and ferritin levels at 3 months Inadequate dose? Increase dose and recheck hemoglobin and hematocrit Consult/refer Adherence? Explore reasons Patient education Hemoglobin less than 7 mg/dL Unable to determine reason for inadequate response Malabsorption of iron? Evaluate for gastroenteropathy Figure 27–2. Drug treatment algorithm for iron deficiency anemia. 3827_Ch27_863-880 01/07/15 6:19 PM Page 872 Lifestyle Modifications Drug Therapy 873 PATIENT EDUCATION PA TIENT EDUCATION Patient education related to IDA should focus on: 1. Understanding the pathophysiology of IDA and its potential long-term effects. 2. Recognizing the importance of prevention and the role of diet and energy conservation. 3. Understanding the necessity of adherence to the treatment regimen. 4. Understanding the need for follow-up visits with the primary care provider because IDA can recur. Stress to the patient that a diet with sufficient amounts of iron-rich foods may avoid the need for sup- plemental iron therapy but only after the IDA has been resolved. When diet alone is inadequate or when iron needs are very high, as in pregnancy, drug therapy is initiated. Patient education specific to drug therapy includes the following: 1. The reason for taking iron. 2. Doses and schedules for the drug. 3. Potential drug interactions and the need to in- form other providers that they are taking iron. 4. Possible adverse reactions and ways to reduce them. The most common adverse reactions that lead to nonadherence are GI problems such as nausea and constipation. Taking iron with food reduces the total amount absorbed but can also reduce the nausea. Adequate fluids and fiber can prevent constipation. Stool softeners may be needed to treat constipation associated with iron therapy. Additional patient education related to iron therapy is presented in Chapter 18. Folic Acid Deficiency Anemia Risk Groups 3827_Ch27_863-880 01/07/15 6:19 PM Page 873 Monitoring Pernicious Anemia (PA) Risk Groups Lifestyle Modifications Drug Therapy 874 PATIENT EDUCATION PA TIENT EDUCATION Patient education for folic acid deficiency anemia focuses on prevention as well as treatment. Diet and appropriate cooking methods are central to prevention, especially for strict vegetarians. The need for folic acid supplementation should be discussed with women of childbearing age. When diet alone is inadequate or folate needs are very high, as in pregnancy, drug therapy is initiated. Patient education specific to drug therapy includes the following: 1. The reason for taking folic acid. 2. The doses and schedule for the drug. 3. The fact that some drugs may potentially inter- fere with folate metabolism. 4. The need to inform their providers that they are taking supplemental folic acid. More specific discussion of patient education is found in Chapter 18. 3827_Ch27_863-880 01/07/15 6:19 PM Page 874 Monitoring Anemia of Chronic Disease Risk Stratification and Screening Treatment of ACD 875 PATIENT EDUCATION PA TIENT EDUCATION Patient education related to pernicious anemia (PA) should focus on: 1. Understanding the pathophysiology of PA and its potential long-term effects. 2. The importance of adherence to the treatment regimen. 3. The need for follow-up visits with the primary care provider in that PA and its symptoms can recur, even with continuing therapy. Patient education specific to the drug therapy in- cludes the following: 1. The reason for taking vitamin B12. 2. The fact that the oral vitamin B12 found in multi- vitamin tablets is not sufficient to treat the problem. 3. The doses and schedule for the drug. 4. The fact that patients need to take the drug for the rest of their lives. 3827_Ch27_863-880 01/07/15 6:19 PM Page 875 Sickle Cell Anemia Prevention Dietary Counseling Drug Therapy 876 3827_Ch27_863-880 01/07/15 6:19 PM Page 876 877 PATIENT EDUCATION PA TIENT EDUCATION Patient and parental information related to sickle cell anemia should focus on the following: 1. Understanding the pathophysiology of SCD and the organs commonly damaged. 2. Recognizing the importance of prevention, especially the central role of prevention of infection and avoidance of precipitants of sickling. 3. Learning how to administer prophylactic antibiotics and other drugs. 4. Understanding the necessity of adherence to the treatment regimen. 5. Recognizing the need for regular follow-up visits with a primary care provider to manage this chronic disease. 6. Understanding the role of genetic counseling. Prevention of sickling requires the parents and the patient to learn specific assessment skills. Any sign of illness in a child with SCD can be serious. Patient education related to the administration of penicillin is discussed in Chapter 24. Measures to minimize the risk of vaso-occlusive events beyond prevention of infection were discussed previously. The hazards of cigarette smoking and excessive alcohol intake and the benefits of a well-planned exercise program should be included. Although IDA is not common for patients with SCD, prevention of IDA with a diet that includes sufficient amounts of iron-rich foods should be discussed. When iron is required, follow the patient education instructions for IDA. Patient education specific to the use of hydroxyurea includes the following: 1. Take the drug exactly as prescribed, even if nausea, vomiting, or diarrhea occurs. 2. If a dose is missed, do not take it at all; do not double dose. 3. Notify the health-care provider of fever; chills; sore throat; loss of appetite; nausea; vomiting; diarrhea; bleeding gums; bruising; petechiae; or blood in the urine, stool, or emesis. 4. Avoid alcoholic beverages, aspirin, and NSAIDs, which may increase the risk of bleeding. 5. Inspect oral mucosa for erythema and ulceration. If it occurs, use a sponge brush and rinse mouth with water after eating and drinking. If mouth pain interferes with eating, contact the health-care provider for lidocaine-based mouthwash. 6. Encourage fluid intake of 2,000 to 3,000 mL of noncaffeinated fluid daily. 7. Review the need for contraception during therapy because of the teratogenic potential of this drug. Patient education related to the other drugs used in treatment of SCD and its complications is presented in the Unit II chapters that include these drugs. Patient education related to the other complications of SCD is detailed in the NIH publi- cations in the References section. Transfusions 3827_Ch27_863-880 01/07/15 6:19 PM Page 877 Monitoring Outcome Evaluation REFERENCES 878 3827_Ch27_863-880 01/07/15 6:19 PM Page 878 879 3827_Ch27_863-880 01/07/15 6:19 PM Page 879 3827_Ch27_863-880 01/07/15 6:19 PM Page 880 881 CHAPTER 28 Laura D. Rosenthal PATHOPHYSIOLOGY, 881 PHARMACODYNAMICS, 883 GOALS OF TREATMENT, 884 RATIONAL DRUG SELECTION, 884 Risk Stratification Treatment Algorithms Lifestyle Modification Drug Therapy Additional Patient Variables Cost MONITORING, 893 OUTCOME EVALUATION, 893 PATIENT EDUCATION, 895 A PATHOPHYSIOLOGY 3827_Ch28_881-896 01/07/15 6:15 PM Page 881 882 Decreased oxygen transport to myocardium ATP formation Glycolysis Na+ pump Glycogen Lactate pH Mitochondrial oxygenation Myocardial ischemia Release of lysosomal enzymes Adrenergic stimulation Cellular autodigestion Mitochondrial contraction Mitochondrial swelling Ca2+ influx and uptake in mitochondria Peripheral vasoconstriction Pump failure Fall in cardiac output Fall in arterial output SNS stimulation Na+/K+, Ca2+/Mg++ Release of CPK and AST enzymes ECF volume Afterload Increased oxygen demand Decreased oxygen supply Myocardial injury and death Peripheral vasoconstriction Heart rate Contractility H2O Figure 28–1. Pathophysiology of myocardial ischemia. 3827_Ch28_881-896 01/07/15 6:15 PM Page 882 PHARMACODYNAMICS 883 3827_Ch28_881-896 01/07/15 6:15 PM Page 883 GOALS OF TREATMENT RATIONAL DRUG SELECTION Risk Stratification Major Risk Factors 884 3827_Ch28_881-896 01/07/15 6:15 PM Page 884 Noncardiac Factors Classification System for Grading Angina Treatment Algorithms 885 Table 28–1 Grading of Angina by the New York Heart Association and the Canadian Cardiovascular Society Class New York Heart Association Canadian Cardiovascular Society 3827_Ch28_881-896 01/07/15 6:15 PM Page 885 886 Table 28–2 Risk Profiles Associated With Angina Risk Lifestyle Risk Physiological Risk Table 28–3 American College of Cardiology/American Heart Association Risk Stratification in Patients With Chronic Stable Angina Class Description Lifestyle Modification 3827_Ch28_881-896 01/07/15 6:15 PM Page 886 Drug Therapy Initial Therapy for Symptomatic Patients 887 Table 28–4 Lifestyle Modifications Attain Ideal Body Weight. Increase Aerobic Physical Activity Within the Limitations of Angina. Reduce Daily Sodium Intake to No More Than 1,500 mg. Maintain Adequate Intake of Dietary Potassium (Approximately 60 mEq/d). Reduce Intake of Dietary Saturated Fats and Cholesterol. Stop Smoking. Limit Alcohol Intake. 3827_Ch28_881-896 01/07/15 6:15 PM Page 887 888 Table 28–5 Drug Choice Based on Concomitant Disease States Drug Choice Favorable Effects Unfavorable Effects Nitrates Beta-Adrenergic Blockers ACE Inhibitors Direct Renin Inhibitors HMG-CoA Reductase Inhibitors (Statins) Calcium Channel Blockers 3827_Ch28_881-896 01/07/15 6:15 PM Page 888 Multidrug Therapy 889 3827_Ch28_881-896 01/07/15 6:15 PM Page 889 Drug Therapies That Are Not Helpful and/or Are to Be Avoided Additional Patient Variables Older Adults Women Concomitant Diseases 890 3827_Ch28_881-896 01/07/15 6:15 PM Page 890 891 3827_Ch28_881-896 01/07/15 6:15 PM Page 891 Cost 892 Table 28–6 Drugs Commonly Used: Angina Drug Brand Name ACE Inhibitors Direct Renin Inhibitors Beta-Adrenergic Blockers Calcium Channel Blockers Nitrates 3827_Ch28_881-896 01/07/15 6:15 PM Page 892 MONITORING OUTCOME EVALUATION 893 3827_Ch28_881-896 01/07/15 6:15 PM Page 893 894 Treat any concomitant diseases Begin lifestyle modifications Start patient on aspirin 81–325 mg/day Angina not under control or grade not reduced Angina still not under control or grade not reduced Angina still not under control or grade not reduced Angina still not under control or grade not reduced Add drugs for patient with concomitant disease or therapies if not already taking (see Table 28–5) or increase dose of one or more of initial drugs Add beta blocker for all patients with or without previous MI† Add ACE inhibitor for all patients with LV dysfunction‡ Add statin for all patients with LDL >100 mg/dL
Add sublingual or spray nitroglycerine (NTG)
for symptom management*
Initial drug choices
Consider referral to cardiology specialist§
* If patient nitrate intolerant, may use calcium channel blocker for symptom relief.
† If beta blocker contraindicated or has unacceptable side effects, may use calcium channel
blocker or long-acting nitrate.
‡ ACC/AHA recommends ACE inhibitors for diabetics and patients with LV dysfunction;
American College of Physicians recommends for all with no restrictions.
§ ACC/AHA class I patients may require initial referral to cardiology specialist; consultation
should occur whenever needed in planning care for all classes.
Figure 28–2. Drug treatment protocol for
chronic stable angina and low-risk unstable
angina.
3827_Ch28_881-896 01/07/15 6:15 PM Page 894

PATIENT EDUCATION
REFERENCES
895
PATIENT EDUCATION: ANGINA PA
TIENT
EDUCATION
Related to the Overall Treatment Plan/Disease Process
■■ Pathophysiology of angina and its prognosis
■■ Role of lifestyle modifications in improving prognosis and keeping down the number and cost of required drugs
■■ Importance of adherence to the treatment regimen
■■ Indications of complications that need to be reported and the need for regular follow-up visits with the primary care
provider
Specific to the Drug Therapy
■■ Reason for taking the drug(s) and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drugs
■■ Possible adverse reactions and what to do when they occur
■■ Interactions between lifestyle modification and these drugs
Reasons for Taking the Drug(s)
Specific information related to angina includes reasons for the drugs being given. Antianginal drugs are given to reduce
cardiovascular morbidity (especially MI) and mortality. Some drugs do both of these things; most do either one or the other.
The expectation should be clear about what these drugs can and cannot do. Stable angina is a chronic condition that re-
quires lifelong treatment, and so the regimen should be incorporated into the daily life of the patient. Even well-managed
angina can become unstable and may require urgent management. Knowledge of when and how to use sublingual or
translingual nitroglycerin is important.
Drugs as Part of the Total Treatment Regimen
Angina therapy is based on lifestyle modification. These modifications are not always easy to maintain, but they are equally
as important as drugs in successful control of symptoms and prevention of complications. Among the lifestyle modifica-
tions is sodium restriction to reduce extracellular fluid volume, decrease afterload, and reduce MOD. Care should be taken
not to reduce salt and fluid too quickly, which may result in fluid volume deficit, leading to hypotension and a reduction in
MOS. Patients should be taught signs and symptoms of fluid volume deficit to report. None of the antianginal drugs directly
reduces fluid volume, but all except aspirin have vasodilating actions that may make fluid volume deficit worse. Sodium
reduction may also lead some patients to seek salt substitutes that have potassium as part of their contents. Changes in
potassium levels can significantly affect myocardial functioning, so these substitutes should be used sparingly. Use of
nonsalt herbal seasoning is encouraged.
Another central lifestyle modification is regular aerobic exercise, such as walking or cycling. The amount and type of
exercise must be carefully monitored and targeted to anginal symptoms. Patients can be referred to a cardiac rehabilitation
program at the start of their exercise program so that their response can be monitored. Later, they can monitor their own
response and determine the pace and amount of exercise that works for them. The key is gradually increasing regular
aerobic exercise. Several of the antianginal drugs, especially the nitrates, have the potential to cause orthostatic hypoten-
sion. Exercise should be timed to avoid this adverse reaction, and adequate fluids should be taken while exercising.
3827_Ch28_881-896 01/07/15 6:15 PM Page 895

896
3827_Ch28_881-896 01/07/15 6:15 PM Page 896

897
CHAPTER 29
Mary Weber • Krista Estes
ASSESSMENT AND SCREENING, 898
NEUROBIOLOGY, 899
EVIDENCEDBASED TREATMENTS OF MAJOR
DEPRESSIVE DISORDER AND ANXIETY
DISORDERS, 900
CLASSES OF MEDICATIONS, 901
Nonselective Norepinephrine-Serotonin Reuptake
Inhibitors
Serotonin-Selective Reuptake Inhibitors (SSRI)
Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
Norepinephrine-Dopamine Reuptake Inhibitors
Serotonin Agonist Reuptake Inhibitors (SARI)
Norepinephrine- and Serotonin-Specific Agonist (NaSSA)
Monoamine Oxidase Inhibitors (MAOI)
Benzodiazepines/GABA-ergics (BZDs)
ADVERSE DRUG REACTIONS, 905
RATIONAL DRUG SELECTION, 905
General Principles in Selecting an Initial Antidepressant
Anxiety
Post-traumatic Stress Disorder
Obsessive-Compulsive Disorder
MONITORING AND PATIENT EDUCATION, 906
COMORBIDITY OF MEDICAL AND PSYCHIATRIC
DISORDERS, 908
SPECIAL POPULATIONS, 908
OUTCOME EVALUATION, 909
CONCLUSIONS, 910
A
3827_Ch29_897-912 01/07/15 6:12 PM Page 897

ASSESSMENT AND SCREENING
898
3827_Ch29_897-912 01/07/15 6:12 PM Page 898

NEUROBIOLOGY
899
Table 29–1 SAFE-T Assessment of Suicide Risk
Suicide Assessment Five-Step Evaluation and Triage
3827_Ch29_897-912 01/07/15 6:12 PM Page 899

EVIDENCE-BASED TREATMENTS
OF MAJOR DEPRESSIVE DISORDER
AND ANXIETY DISORDERS
900
3827_Ch29_897-912 01/07/15 6:12 PM Page 900

CLASSES OF MEDICATIONS
901
Evaluate for comorbidity, suicidality,
medical reasons for insomnia, substance
abuse, noncompliance, childbearing
potential, elderly patient, and
cultural issues.
General Algorithim for the Treatment of Depression
Based on STAR*D Effectiveness Research
Start SSRI #1
and refer to
mental health provider
for therapy.
Lack of Remission or
Poor Response?
Refer to
psychiatric provider.
SSRI #2 NDRI SNRI + NDRI + 5HT1A
Switch options Augmentation options
Figure 29–1. General algorithm for the treat-
ment of depression based on the STAR*D
effectiveness research.
General Algorithim for the Treatment
of Adults With Anxiety Disorders
Screen for medical,
psychiatric, and
substance comorbidities.
Start an SSRI or SNRI
and refer to mental health
provider for therapy.
Lack of Remission or
Poor Response?
Refer to
psychiatric provider.
Screen for anxiety disorders.
Figure 29–2. General algorithm for the treatment of anxiety
disorders.
3827_Ch29_897-912 01/07/15 6:12 PM Page 901

Nonselective Norepinephrine-Serotonin
Reuptake Inhibitors Serotonin-Selective Reuptake Inhibitors
902
Table 29–2 ! Four Cytochrome P-450 Isoenzymes and Potential Drug Interactions
Isoenzyme Substrates Inhibitors
3827_Ch29_897-912 01/07/15 6:12 PM Page 902

Serotonin-Norepinephrine Reuptake
Inhibitors
Norepinephrine-Dopamine Reuptake
Inhibitors
903
3827_Ch29_897-912 01/07/15 6:12 PM Page 903

Serotonin Agonist Reuptake Inhibitors
Norepinephrine- and Serotonin-Specific
Agonist
Monoamine Oxidase Inhibitors (MAOI) Benzodiazepines/GABA-ergics (BZDs)
904
On The
Horizon PSYCHOPHARMACOLOGY RESEARCH
What to look for during the next 5 years in psychopharmacology:
• New mechanisms of action, especially targeting
glutamate/GABA interaction
• Targeting antagonism of the glutamate receptor to treat
depression
• Development of drugs targeting the second messenger
system for faster response rates and possibly neuro-
protective qualities in preventing further depression
• Corticotropin-releasing factor antagonists to mediate
effects of stress on the pathophysiology of depression
3827_Ch29_897-912 01/07/15 6:12 PM Page 904

ADVERSE DRUG REACTIONS
RATIONAL DRUG SELECTION
General Principles in Selecting
an Initial Antidepressant
905
3827_Ch29_897-912 01/07/15 6:12 PM Page 905

Anxiety
Post-Traumatic Stress Disorder
Obsessive-Compulsive Disorder
MONITORING AND PATIENT
EDUCATION
906
3827_Ch29_897-912 01/07/15 6:12 PM Page 906

907
Table 29–3 When to Refer
3827_Ch29_897-912 01/07/15 6:12 PM Page 907

COMORBIDITY OF MEDICAL
AND PSYCHIATRIC DISORDERS
SPECIAL POPULATIONS
908
3827_Ch29_897-912 01/07/15 6:12 PM Page 908

OUTCOME EVALUATION
909
3827_Ch29_897-912 01/07/15 6:12 PM Page 909

REFERENCES
910
CLINICAL PEARLS
Treatment and Monitoring of Patients with
Anxiety and Depression
1. Always evaluate a patient for hypomania or mania
before starting an antidepressant because these
conditions can worsen bipolar symptoms.
2. When there is any anxiety disorder, consider start-
ing all antidepressants low and going slow.
3. Start low and go slow when treating older adults
with depression and/or anxiety.
4. Always monitor for suicidal thoughts throughout
the entire treatment.
5. Always discuss the risks of fetal damage with a
woman of childbearing potential who is taking an
antidepressant BEFORE she gets pregnant so that
she knows the risks and benefits of treatment.
6. Always monitor for signs and symptoms of
serotonin syndrome, especially asking about new
medications prescribed or any over-the-counter
medications taken.
7. Taper off antidepressants slowly; most have dis-
continuation side effects.
8. Withdrawal or discontinuation symptoms include
dizziness, nausea, diarrhea, sweating, irritability,
and increased anxiety. If these occur, raise the dose
to stop symptoms and taper even more slowly.
9. Do not start monoamine oxidase inhibitors (MAOIs)
within 14 days of stopping other antidepressants;
do not start another antidepressant until 14 days
after stopping an MAOI.
10. It is tempting for both the patient and primary care
provider to attribute success to the medications,
but to do so invalidates the power and capacity of
patients.
11. Medications can only help the brain return to its nor-
mal functioning. It is the whole person who makes
the changes necessary for recovery to mental health.
CONCLUSIONS
3827_Ch29_897-912 01/07/15 6:12 PM Page 910

911
3827_Ch29_897-912 01/07/15 6:12 PM Page 911

912
3827_Ch29_897-912 01/07/15 6:12 PM Page 912

913
CHAPTER 30
Benjamin J. Miller
ASTHMA, 913
Pathophysiology
Goals of Therapy
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
CHRONIC OBSTRUCTIVE PULMONARY DISEASE, 935
Pathophysiology
Goals of Therapy
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
A
ASTHMA
Pathophysiology
3827_Ch30_913-942 01/07/15 6:11 PM Page 913

914
Chronic Inflammation
Airway Hyperresponsiveness
Neutrophil
Mast cell
IL-3, IL-4,
IL-13, IL-9
Eosinophil
IL-3, IL-5
GM-CSF
IgE
I n
f la
m
a t
i o
n
Th2/Th1
cytokines (e.g.,
B lymphocyte T lymphocyte
Acute inflammation
Environmental factors
Airw
ay m
icroenvironm
ent
Initiation
Amplification
Propagation
Blood vessels
Smooth muscle
Pro-inflammatory mediators
m
IL-13, TNF-!)
Airway Effects
Bronchospasm
Acute inflammation
Persistent inflammation
RemodelingTNF-!
Dendritic cell
(myo) fibroblasts
Environmental factors and
inflammatory products
Mucus
Persistent inflammation and
development of remodeling
Figure 30–1. Factors limiting airflow in acute and persistent asthma. Key: GM-CSF, granulocyte-macrophage colony-stimulating factor; IgE,
immunoglobulin E; IL-3, interleukin 3 (and similar); TNF-!, tumor necrosis factor-alpha. (Source: Holgate, S. T., & Polosa, R. [2006]. The mecha-
nisms, diagnosis, and management of severe asthma in adults. The Lancet, 368, 780–793.)
3827_Ch30_913-942 01/07/15 6:11 PM Page 914

Airflow Obstruction
Classification of Asthma
915
3827_Ch30_913-942 01/07/15 6:11 PM Page 915

916
Goals of Therapy
Reduce Impairment
Reduce Risk
Table 30–1 Classification of Asthma Severity 12 Years of Age
Components of Severity
Impairment
Normal FEV1/FVC:
Risk
Recommended Step for Initiating Treatment.
(See ”Stepwise Approach for Managing
Asthma” for treatment steps.)
Classification of Asthma Severity 12 years of age
Intermittent Mild Moderate Severe
3827_Ch30_913-942 01/07/15 6:11 PM Page 916

917
SY
M
P
TO
M
S
Ag
es
0
–4
Ag
es
0
–4
Ag
es
0
–4
Ta
bl
e
30
–2

Cl
as
si
fic
at
io
n
of
A
st
hm
a
Se
ve
ri
ty
a
nd
In
it
ia
l T
he
ra
py
in
C
hi
ld
re
n C
la
ss
if
yi
ng
A
st
hm
a
Se
ve
ri
ty
a
nd
In
it
ia
ti
ng
T
he
ra
py
in
C
hi
ld
re
n
Co
m
po
ne
nt
s
of
S
ev
er
it
y
Im
pa
ir
m
en
t
Ri
sk
Re
co
m
m
en
de
d
St
ep
fo
r I
ni
ti
at
in
g
Th
er
ap
y.
(S
ee
“
St
ep
w
is
e
A
pp
ro
ac
h
fo
r M
an
ag
in
g
A
st
hm
a”
fo
r t
re
at
m
en
t
st
ep
s.
)
In
te
rm
itt
en
t
M
ild
M
od
er
at
e
Se
ve
re
Ag
es
0
–4
3827_Ch30_913-942 01/07/15 6:11 PM Page 917

Rational Drug Selection
Asthma Step Therapy
Initiating Control of Asthma
918
3827_Ch30_913-942 01/07/15 6:11 PM Page 918

919
Table 30–3 Assessing Asthma Control and Adjusting Therapy in Youths 12 Years and Adults
Classification of Asthma Control ( 12 years of age)
Components of Control
Impairment
Risk
Recommended Action for Treatment
SYMPTOMS
3827_Ch30_913-942 01/07/15 6:11 PM Page 919

920
Table 30–4 Assessing Asthma Control and Adjusting Therapy in Children
Assessing Asthma Control and Adjusting Therapy in Children
Components of Control
Impairment
Risk
Recommended Action for Treatment
(See “Stepwise Approach for Managing
Asthma” for treatment steps.)
Ages 0–4 Ages 0–4 Ages 0–4
SYMPTOMS
3827_Ch30_913-942 01/07/15 6:11 PM Page 920

921
Table 30–5 Stepwise Approach for Managing Asthma in Youths >12 Years and Adults
Intermittent
Asthma
Persistent Asthma: Daily Medication
Consult with asthma specialist if step 4 or higher is required.
Consider consultation at step 3.
Step 1
Preferred:
SABA PRN
Step 2
Preferred:
Low-dose ICS
Alternative:
Cromolyn,
LTRA,
Nedocromil, or
Theophylline
Step 3
Preferred:
Low-dose
ICS + LABA
or
Medium-dose
ICS
Alternative:
Low-dose
ICS + either
LTRA,
Theophylline,
or Zileuton
Step 4
Preferred:
Medium-dose
ICS + LABA
Alternative:
Medium-dose
ICS + either
LTRA,
Theophylline,
or Zileuton
Step 5
Preferred:
High-dose ICS
+ LABA
and
Consider
Omalizumab
for patients
who have
allergies
Step 6
Preferred:
High-dose
ICS + LABA
+ oral
corticosteroid
and
Consider
Omalizumab
for patients
who have
allergies
Quick-Relief Medication for All Patients
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms:
up to 3 treatments at 20-minute intervals as needed. Short course of oral systemic corticosteroids
may be needed.
• Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates
inadequate control and the need to step up treatment.
Key: Alphabetical order is usually more than one treatment option listed within either preferred
or alternative therapy. ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist, LTRA,
leukotriene receptor antagonist; SABA, inhaled short-acting beta2-agonist.
Notes:
• The stepwise approach is meant to assist, not replace, the clinical decision making required to
meet individual patient needs.
• If alternative treatment is used and response is inadequate, discontinue it and use the preferred
treatment before stepping up.
• Zileuton is a less desirable alternative due to limited studies as adjunctive therapy and the need
to monitor liver function. Theophylline requires monitoring of serum concentration levels.
• In step 6, before oral corticosteroids are introduced, a trial of high-dose ICS + LABA + either
LTRA, theophylline, or zileuton may be considered, although this approach has not been studied
in clinical trials.
• Step 1, 2, and 3 preferred therapies are based on Evidence A; step 3 alternative therapy is based
on Evidence A for LTRA, Evidence B for theophylline, and Evidence D for zileuton. Step 4 preferred
therapy is based on Evidence B, and alternative therapy is based on Evidence B for LTRA and
theophylline and Evidence D zileuton. Step 5 preferred therapy is based on Evidence B. Step 6
preferred therapy is based on (EPR—2 1997) and Evidence B for omalizumab.
• Immunotherapy for steps 2–4 is based on Evidence B for house-dust mites, animal danders,
and pollens; evidence is weak or lacking for molds and cockroaches. Evidence is strongest
for immunotherapy with single allergens. The role of allergy in asthma is greater in children than
in adults.
• Clinicians who administer immunotherapy or omalizumab should be prepared and equipped to
identify and treat anaphylaxis that may occur.
Step up if
needed
(first, check
adherence,
environmental
control, and
comorbid
conditions)
Step down
if possible
(and asthma
is well
controlled
at least 3
months)
Assess
control
Each step: Patient education, environmental control, and management of comorbidities
Steps 2–4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma
(see notes).
Stepwide Approach for Managing Asthma in Youths 12 Years of Age and Adults
3827_Ch30_913-942 01/07/15 6:11 PM Page 921

922
Table 30–6 Stepwise Approach for Managing Asthma Long Term in Children
Intermittent
Asthma
Persistent Asthma: Daily Medication
Consult with asthma specialist if step 4 or higher is required. Consider consultation at step 3. • The stepwise approach is meant to assist, not replace, the clinical
decision making required to meet individual patient needs.
• If alternative treatment is used and response is inadequate, discontinue it
and use the preferred treatment before stepping up.
• If clear benefit is not observed within 4–6 weeks, and patient’s/family’s
medication technique and adherence are satisfactory, consider adjusting
therapy or an alternative diagnosis.
• Studies on children 0–4 years of age are limited. Step 2 preferred therapy
is based on Evidence A. All other recommendations are based on expert
opinion and extrapolation from studies in older children.
• Clinicians who administer immunotherapy or omalizumab should be
prepared and equipped to identify and treat anaphylaxis that may occur.
Key: Alphabetical order is usually more than one treatment option
listed within either preferred or alternative therapy. ICS, inhaled
corticosteroid; LABA, inhaled long-acting beta2-agonist, LTRA, leukotriene
receptor antagonist; SABA, inhaled short-acting beta2-agonist.
• The stepwise approach is meant to assist, not replace, the clinical
decision making required to meet individual patient needs.
• If alternative treatment is used and response is inadequate, discontinue
it and use the preferred treatment before stepping up.
• Theophylline is a less desirable alternative due to the need to monitor
serum concentration levels.
• Steps 1 and 2 medications are based on Evidence A. Step 3 ICS and ICS
plus adjunctive therapy are based on Evidence B for efficacy of each
treatment and extrapolation from comparator trials in older children and
adults—comparator trials are not available for this age group: steps 4–6
are based on expert opinion and extrapolation from studies in older
children and adults.
• Immunotherapy for steps 2–4 is based on Evidence B for house-dust
mites, animal danders, and pollens: evidence is weak or lacking for molds
and cockroaches. Evidence is strongest for immunotherapy with single
allergens. The role of allergy in asthma is greater in children than adults.
• Clinicians who administer immunotherapy or omalizumab should be
prepared and equipped to identify and treat anaphylaxis that may occur.
Key: Alphabetical order is usually more than one treatment option
listed within either preferred or alternative therapy. ICS, inhaled
corticosteroid; LABA, inhaled long-acting beta2-agonist, LTRA, leukotriene
receptor antagonist; SABA, inhaled short-acting beta2-agonist.
Step up if needed (first, check adherence, environmental control, and comorbid conditions)
Step down if possible (and asthma is well controlled at least 3 months)
Assess control
Stepwide Approach for Managing Asthma Long Term in Children 0–4 Years and 5–11 Years of Age
NotesStep 1
Step 2
Step 3
Step 4
Step 5
Step 6
SABA PRN
Each step: Patient education and environmental control
Preferred
Alternative
Low-dose ICS
Cromolyn or
Montelukast
Medium-dose
ICS
Medium-dose
ICS
+
LABA or
Montelukast
High-dose ICS
+
LABA or
Montelukast
High-dose ICS
+
LABA or
Montelukast
+
Oral corticosteriods
ICS
Intermittent
Asthma
Persistent Asthma: Daily Medication
Consult with asthma specialist if step 4 or higher is required. Consider consultation at step 3.
SABA PRNPreferred
Alternative
Low-dose ICS
Cromolyn, LTRA,
Nedocromil, or
Theophylline
Low-dose ICS
+
LABA, LTRA, or
Theophylline
or
Medium-dose
ICS
Medium-dose
ICS
+
LABA
High-dose ICS
+ LTRA or
Theophylline
High-dose ICS
+ LTRA or
Theophylline
+
Oral corticosteriods
Medium-dose
ICS + LTRA or
Theophylline
High-dose ICS
+
LABA
High-dose ICS
+
LABA
+
Oral corticosteriods
Quick-Relief
Medication
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms.
• With viral respiratory symptoms: SABA q 4–6 hours up to 24 hours (longer with physician consult). Consider
short course of oral systemic corticosteroids if exacerbation is severe or patient has history of previous severe
exacerbations.
Caution: Frequent use of SABA may indicate the need to step up treatment See text for recommendations on
initiating dairy long-term-control therapy.
Each step: Patient education, environmental control, and management of comorbidities
Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have
persistent, allergic asthma.
Quick-Relief
Medication
• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at
20-minute intervals as needed. Short course of oral systemic corticosteroids may be needed.
Caution: Increasing use of SABA or use >2 days a week for symptom relief (not prevention of EIB) generally
indicates inadequate control and the need to step up treatment.
C
hi
ld
re
n
0–
4
Ye
ar
s
of
A
ge
C
hi
ld
re
n
5–
11
Y
ea
rs
o
f A
ge
Table 30–7 Drugs Commonly Used: Asthma and COPD
Drug Dosage How Supplied Comments
Short-Acting Bronchodilators
3827_Ch30_913-942 01/07/15 6:11 PM Page 922

923
Table 30–7 Drugs Commonly Used: Asthma and COPD—cont’d
Drug Dosage How Supplied Comments
Long-Acting Bronchodilator
3827_Ch30_913-942 01/07/15 6:11 PM Page 923

924
Table 30–7 Drugs Commonly Used: Asthma and COPD—cont’d
Drug Dosage How Supplied Comments
Anticholinergic Agents
Combination Inhaled Medications
3827_Ch30_913-942 01/07/15 6:11 PM Page 924

925
Table 30–7 Drugs Commonly Used: Asthma and COPD—cont’d
Drug Dosage How Supplied Comments
Systemic Corticosteroids
Inhaled Anti-Inflammatory Agents
Inhaled Corticosteroids
3827_Ch30_913-942 01/07/15 6:11 PM Page 925

926
Table 30–7 Drugs Commonly Used: Asthma and COPD—cont’d
Drug Dosage How Supplied Comments
Leukotriene Modifiers
3827_Ch30_913-942 01/07/15 6:11 PM Page 926

927
Ta
bl
e
30
–8

Co
m
pa
ra
ti
ve
D
ai
ly
D
os
ag
es
fo
r I
nh
al
ed
C
or
ti
co
st
er
oi
ds
Lo
w
D
ai
ly
D
os
e
M
ed
iu
m
D
ai
ly
D
os
e
H
ig
h
D
ai
ly
D
os
e
D
ru
g
Be
cl
om
et
ha
so
ne

H
FA
Bu
de
so
ni
de

D
PI
Bu
de
so
ni
de

In
ha
le
d
Fl
un
is
ol
id
e
Fl
un
is
ol
id
e
H
FA
Fl
ut
ic
as
on
e
H
FA
/M
D
I:
D
PI
:
M
om
et
as
on
e
D
PI
Tr
ia
m
ci
no
lo
ne

ac
et
on
id
e
3827_Ch30_913-942 01/07/15 6:11 PM Page 927

Emerging Therapies
Monitoring Control
928
3827_Ch30_913-942 01/07/15 6:11 PM Page 928

Managing Exacerbations
Maintaining Control of Asthma
Home Management of Exacerbations of Asthma
Patient Variables
929
3827_Ch30_913-942 01/07/15 6:11 PM Page 929

930
Assess Severity
Patients at high risk for a fatal attack require immediate medical attention after initial treatment.
Symptoms and signs suggestive of a more serious exacerbation, such as marked breathlessness,
inability to speak more than short phrases, use of accessory muscles, or drowsiness, should
result in initial treatment while immediately consulting with a clinician.
Less severe signs and symptoms can be treated initially with assessment of response to therapy
and further steps as listed below.
If available, measure PEF—values of 50%–79% predicted or personal best indicate the need for
quick-relief medication. Depending on the response to treatment, contact with a clinician may also
be indicated. Values below 50% indicate the need for immediate medical care.
Initial Treatment
Inhaled SABA: Up to two treatments 20 minutes apart of 2–6 puffs
by metered-dose inhaler (MDI) or nebulizer treatments
Note: Medication delivery is highly variable. Children and
individuals who have exacerbations of lesser severity may need
fewer puffs than suggested above.
Good Response
No wheezing or dyspnea
(assess tachypnea in young
children)
PEF “80% predicted or
personal best
Contact clinician for
follow-up instructions and
further management.
May continue inhaled
SABA every 3–4 hours for
24–48 hours.
Consider short course of
oral systemic
corticosteroids.
Incomplete Response
Persistent wheezing and
dyspnea (tachypnea)
PEF 50%–79% predicted or
personal best
Add oral systemic
corticosteroid.
Continue inhaled SABA.
Contact clinician urgently
(this day) for further
instruction.
Poor Response
Marked wheezing and dyspnea
PEF <50% predicted or personal best Add oral systemic corticosteroid. Repeat inhaled SABA immediately. If distress is severe and nonresponsive to initial treatment: —Call your doctor AND —PROCEED TO ED; —Consider calling 9–1–1 (ambulance transport). To ED Figure 30–2. Management of asthma exacerbations: Home treatment. Key: ED, emergency department; MDI, metered-dose inhaler; PEF, peak expiratory flow; SABA, short-acting beta2 agonist (quick-relief inhaler). (Source: From National Asthma Education and Prevention Program [NAEPP]. [2007]. The Expert Panel Report 3: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute, National Institutes of Health.) 3827_Ch30_913-942 01/07/15 6:11 PM Page 930 931 3827_Ch30_913-942 01/07/15 6:11 PM Page 931 Special Situations 932 3827_Ch30_913-942 01/07/15 6:11 PM Page 932 Monitoring Monitoring Signs and Symptoms of Asthma Monitoring Pulmonary Function Monitoring Quality of Life and Functional Status 933 3827_Ch30_913-942 01/07/15 6:11 PM Page 933 Monitoring History of Asthma Exacerbations Monitoring Pharmacotherapy Monitoring Patient–Provider Communication and Patient Satisfaction Outcome Evaluation Patient Education 934 PATIENT EDUCATION PA TIENT EDUCATION Asthma RELATED TO THE OVERALL TREATMENT PLAN AND DISEASE PROCESS BASIC FACTS ABOUT ASTHMA Use a variety of teaching methods such as illustrations, videos, written pamphlets or books, and models. Repeat key facts at every visit until the patient and/or family demonstrates an understanding of asthma. An example would to be to show the patient a drawing of a normal airway and an airway affected by asthma. The provider can then demonstrate how different medications act on different components of asthma (bronchodilator relaxes smooth muscle, anti-inflammatory decreases inflammation, etc.). This information can be repeated when reviewing medications at each visit until a clear understanding is demonstrated. MEDICATION SKILLS This includes proper inhaler use, spacer use if appropriate, when to take quick-relief medications, and nebulizer use if appropriate. SELF-MONITORING SKILLS This includes self-assessment of symptoms, peak flow monitoring, and how to record symptoms and peak expiratory flow (PEF) on a self-assessment diary. Recognizing early signs of declining lung function is essential knowledge for the patient and family. Environmental control and avoidance strategies will enable the patient and family to avoid possible asthma triggers. Discussion of how environmental exposure to allergens and irritants can worsen asthma symptoms and how to avoid trig- gers at home, work, and school will assist patients in learning self-management. 3827_Ch30_913-942 01/07/15 6:11 PM Page 934 935 CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENT EDUCATIONcont’d PA TIENT EDUCATION SPECIFIC TO THE DRUG THERAPY Reason for the drug being given and its anticipated action in the disease process. Doses and schedules for taking the drug. Coping mechanisms for complex and costly drug regimens. Interactions between other treatment modalities and these drugs. REASONS FOR THE DRUG(S) BEING TAKEN Patient education about specific drugs is provided in Chapter 17. DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN Information should be provided concerning drugs as part of the total treatment regimen and individualized to the patient’s age and asthma severity. Many educational resources are available, the best of which are from the National Institutes of Health (NIH) and the Global Initiative for Asthma. These documents include the following: National Asthma Education Prevention Program (2007). The Expert Panel Report 3: Guidelines for Management of Asthma. Includes copy-ready patient handouts on use of peak flow meter, inhalers, and asthma action plans. Global Initiative for Asthma (2009). Global strategy for asthma management and prevention. http://www.ginasthma.org. Includes a patient guide to asthma and interactive learning modules on asthma in adults and children. INTERNET-BASED PATIENT EDUCATION RESOURCES ON ASTHMA The Expert Panel Report 3: Guidelines can be found at http://www.nhlbi.nih.gov/guidelines/asthma/index.htm and the NIH/WHO Global Initiative for Asthma documents can be found at http:/www.ginasthma.com Other resources include the following: Allergy and Asthma Network, Mothers of Asthmatics. http://www.aanma.org/ American Academy of Allergy, Asthma, and Immunology. http://www.aaaai.org Asthma and Allergy Foundation of America. http://www.aafa.org Canadian Network for Respiratory Care. http://www.cnrchome.net/ National Asthma Education and Prevention Program. NHLBI http://www.nhlbi.nih.gov/health/public/lung/index .htm#asthma National Institutes of Health National Heart Lung and Blood Institute. Asthma. http://www.nhlbi.nih.gov/health/dci/ Diseases/Asthma/Asthma_WhatIs.html 3827_Ch30_913-942 01/07/15 6:11 PM Page 935 Pathophysiology Emphysema 936 Table 30–9 Stages of COPD Classification Definition by Spirometry At Risk Mild Moderate Severe Very Severe Table 30–10 Clinical Features of Chronic Bronchitis and Emphysema Characteristic Chronic Bronchitis Emphysema Age at onset of symptoms Primary symptoms Sputum Chest x-ray Weight Total lung capacity Chest examination Cor pulmonale with heart failure 3827_Ch30_913-942 01/07/15 6:11 PM Page 936 Chronic Bronchitis Goals of Therapy Rational Drug Selection Bronchodilators 937 3827_Ch30_913-942 01/07/15 6:11 PM Page 937 Corticosteroids Oxygen 938 3827_Ch30_913-942 01/07/15 6:11 PM Page 938 Antibiotics Leukotrienes Alpha-Trypsin Augmentation Therapy Immunizations Smoking Cessation Monitoring 939 CLINICAL PEARL Oxygen Therapy One note of caution in providing oxygen therapy to some patients with COPD who have poor ventilatory ca- pacity: These patients, known as “carbon dioxide retain- ers,” no longer rely on rises in PaCO2 as the primary drive to breathe. If these patients receive too much oxy- gen, raising their PaO2 above their normal baseline, hy- poventilation may occur. This results in CO2 retention and the somnolence, lethargy, and coma that occur with carbon dioxide narcosis. Monitoring arterial blood gases is essential in all patients receiving oxygen therapy. 3827_Ch30_913-942 01/07/15 6:11 PM Page 939 Outcome Evaluation Patient Education 940 PATIENT EDUCATION PA TIENT EDUCATION Chronic Obstructive Pulmonary Disease RELATED TO THE OVERALL TREATMENT PLAN AND DISEASE PROCESS The patient needs to be taught the following areas of self-management: SMOKING CESSATION This is a difficult area of education because of the physical and psychological addiction to cigarettes. Many patients have attempted to quit smoking previously and need to be encouraged to try again, using some of the pharmacological interventions available to aid in tobacco cessation. PATHOPHYSIOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE A basic understanding of the changes in the pulmonary system that occur with COPD will assist the patient in understanding the role that the different medications play in the treatment regimen. MEDICATION SKILLS Patients with COPD often have other chronic illnesses that require routine medications. Administering a complex regimen of multiple medications can be overwhelming, especially to older patients. Written schedules (in large print) and divided pill boxes are two strategies for medication management. Providing the patient with the generic and trade names of med- ications will decrease medication confusion. Having the patient bring all medications in for review will prevent medication errors. Often, the patient may be seeing other providers, including specialists who may also be prescribing medications. It is the role of the primary care provider to coordinate between specialty providers and monitor medications the patient is tak- ing. Encourage patients to use a magnifying glass to read the generic names on the meter dose inhaler (MDI) canisters, as the canister color may change with different brands of the same medication. SPECIFIC TO THE DRUG THERAPY Reason for the drug being given and its anticipated action in the disease process. Doses and schedules for taking the drug. Coping mechanisms for complex and costly drug regimens. Interactions between other treatment modalities and these drugs. CLINICAL PEARL Influenza Vaccine Reminders The health-care provider should keep an electronic “tickler file” of chronic respiratory patients (those with asthma and COPD) so they can remind patients each fall to get their influenza vaccine. 3827_Ch30_913-942 01/07/15 6:11 PM Page 940 REFERENCES " 941 PATIENT EDUCATIONcont’d PA TIENT EDUCATION REASONS FOR THE DRUG(S) BEING TAKEN Patient education about specific drugs should be provided, including how to use inhalers appropriately. DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN The total treatment regimen also includes teaching self-monitoring skills, including, if indicated, proper use of a peak flow meter. Infection control measures are also taught. Patients with COPD are at high risk for respiratory infections. They need to be taught the importance of annual influenza vaccine and the need for a pneumococcal pneumonia vaccine every 6 years. They need to avoid crowds and people, especially children, with respiratory infections. ADHERENCE ISSUES Health-care providers should be aware of the potential problem of nonadherence with the treatment regimen and should discuss the importance of adherence with the patient and family members. 3827_Ch30_913-942 01/07/15 6:11 PM Page 941 942 3827_Ch30_913-942 01/07/15 6:11 PM Page 942 943 CHAPTER 31 Teral Gerlt PHYSIOLOGY OF THE NORMAL MENSTRUAL CYCLE, 943 PHARMACODYNAMICS, 945 Mechanism of Pregnancy Prevention GOALS OF TREATMENT, 945 Safety Tolerance Effectiveness RATIONAL DRUG SELECTION, 946 Guidelines Cost Patient Variables Drug Variables Dosing Regimens Emergency Contraception MONITORING, 954 OUTCOME EVALUATION, 954 C PHYSIOLOGY OF THE NORMAL MENSTRUAL CYCLE 3827_Ch31_943-956 01/07/15 6:09 PM Page 943 944 Table 31–1 Contraceptive Options Perfect Use Typical Use Method Advantages Disadvantages Efficacy Efficacy 3827_Ch31_943-956 01/07/15 6:09 PM Page 944 PHARMACODYNAMICS Mechanism of Pregnancy Prevention GOALS OF TREATMENT 945 3827_Ch31_943-956 01/07/15 6:09 PM Page 945 Safety Tolerance Effectiveness RATIONAL DRUG SELECTION Guidelines 946 On The Horizon NEW OCS In the last few years most of the research on new OCs has in- volved changing the type of estrogen and/or progestin in the formulations and the dosing pattern to decrease side effects and enhance ease of use (Sitruk-Ware, Nath, & Mishell, 2013). Natazia was released in 2010 and is the only four-phasic oral contracep- tive on the market. It is the first OC to contain estradiol valerate, a synthetic prodrug of 17ß-estradiol and a new progestin, dienogest, which displays properties of 19-nortestosterone derivatives as well as properties associated with progesterone derivatives. The only chewable OC on the market, Generess, combines 0.8 mg norethindrone and 0.025 mg ethinyl estradiol with four 75 mg ferrous fumarate placebo tablets. The 24/4 regimen is intended to decrease breakthrough bleeding and provide short, light, predictable periods (Shrader & Dickerson, 2008). A combination OC, Zoely, utilizing natural estrogen (17β estradiol), and a new progestin (nomegesterol acetate), manufactured by Merck have been approved in the United Kingdom and several European and Latin American coun- tries (Bahamondes & Bahamondes, 2014). The estrogen component, 17β estradiol, is structurally identical to endoge- nous 17β estradiol (Merck, 2014). Nomegesterol acetate has a 46-hour half-life, which increases efficacy (Merck, 2014). It has not received U.S. approval yet. 3827_Ch31_943-956 01/07/15 6:09 PM Page 946 947 Table 31–2 Oral Contraceptives Brand Name Estrogen Dose (mcg) Progestin Dose (mg) 3827_Ch31_943-956 01/07/15 6:09 PM Page 947 948 Table 31–2 Oral Contraceptives—cont’d Brand Name Estrogen Dose (mcg) Progestin Dose (mg) 3827_Ch31_943-956 01/07/15 6:09 PM Page 948 949 Table 31–2 Oral Contraceptives—cont’d Brand Name Estrogen Dose (mcg) Progestin Dose (mg) Cost Patient Variables Drug Variables Drug Interactions 3827_Ch31_943-956 01/07/15 6:09 PM Page 949 950 Table 31–3 WHO Contraindications to Initiation of Combined Contraception with 35 mcg EE or Less Risk Contraindication 3827_Ch31_943-956 01/07/15 6:09 PM Page 950 Adverse Effects/Contraindications Dosing Regimens Combined Contraceptives 951 CLINICAL PEARL Multiphasic Pills Triphasic pill packs with pills of various colors may be confusing to some patients. If confusion is a concern, start with a monophasic OC for simple instructions. Dosing Options 3827_Ch31_943-956 01/07/15 6:09 PM Page 951 Topical Patch Vaginal Rings 952 Table 31–4 Instructions for Missed Oral Contraceptives Missed 1 active pill Missed 2–4 active pills Missed 5 or more active pills CLINICAL PEARL LMP Notation Last menstrual period (LMP) should be considered a vital notation to be displayed at the top of each chart note in a female patient’s medical record. 3827_Ch31_943-956 01/07/15 6:09 PM Page 952 Progesterone-Only Contraceptives 953 3827_Ch31_943-956 01/07/15 6:09 PM Page 953 Emergency Contraception MONITORING 954 CLINICAL PEARL Depo-Provera and Osteoporosis Counsel patients using Depo-Provera to increase di- etary calcium intake and weight-bearing exercise. These interventions along with stopping smoking will mitigate bone mineral density changes. CLINICAL PEARL Emergency Contraception During each office visit, provide patients under 17 with an emergency contraception prescription and instruc- tions for use in case their primary contraception method fails. OUTCOME EVALUATION 3827_Ch31_943-956 01/07/15 6:09 PM Page 954 955 CLINICAL PEARL Report of Bleeding Patient reports of irregular or abnormal bleeding should be quantified with a menstrual calendar; have the pa- tient differentiate between days on which spotting oc- curs and days on which bleeding is as heavy as her menses. Keeping a count of sanitary napkins or tam- pons used per day of bleeding may help further quantify bleeding. Bleeding may be excessive if a patient is using tampons and pads together and experiencing bleeding accidents. Serial hematocrit measurement several days or a week apart may assist in evaluating excessive bleeding. Excessive bleeding should be evaluated for underlying etiology, such as uterine cancer or polyps, thyroid disorders, or bleeding dyscrasias (Hatcher et al, 2011). PATIENT EDUCATION PA TIENT EDUCATION Overall Treatment Plan/Physiological Process ■■ Physiology of normal menstrual cycle. ■■ Need for follow-up visits: BP monitoring 3 months after initiation of methods containing estrogen, then annually. Breast and pelvic examinations, per national standards of care with client’s age, history, and risk factors taken into consideration. ■■ Breast self-awareness education. ■■ Safe-sex practices, including male or female condom use in conjunction with hormonal contraception for STI prevention. ■■ Emergency contraception access and use, which can be used with failures of all methods. SPECIFIC TO THE DRUG THERAPY ■■ How contraceptives prevent pregnancy through suppression of ovulation in the hypothalamic-pituitary-ovarian axis or endometrial and cervical changes. ■■ Doses and schedules for taking the drug. Specifically start method, active versus inactive pills, when to expect menses, what to do if pills are missed, suggestions for optimizing compliance with dosing schedule. ■■ Anticipated menstrual changes because of method use, such as lighter or shorter menses, amenorrhea, or irregular bleeding patterns. ■■ Common side effects with method use, such as breakthrough bleeding in first few cycles of OC use, breast tenderness, nausea, possible weight changes. ■■ Serious side effects, their symptoms, and how to access care in an emergency. ■■ Interactions between hormonal contraception and other treatment modalities or lifestyle habits. Emphasize the dangers of smoking with combined hormonal contraception at any age and the increased risk in women over age 35. Also advise patients to stop combined hormonal contraception 4 weeks before and 2 weeks after major surgery to prevent thrombus formation. ■■ Review time frame for return to fertility after discontinuation for specific method. REASONS FOR TAKING THE DRUG(S) Hormonal contraception offers very high efficacy; this may be particularly important for women between 15 and 35 years of age when fertility is highest. Methods can be used for long- or short-term deferment of childbearing, allowing control over timing and spacing of pregnancies. DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN ■■ Women who use hormonal contraception may also enjoy noncontraceptive benefits, such as less menstrual discomfort or lighter flow and the ability to predict or manipulate timing of menses for vacation or other social events. ■■ Use of hormonal contraception also confers protection against uterine and ovarian cancer (Speroff & Darney, 2011). Continued 3827_Ch31_943-956 01/07/15 6:09 PM Page 955 956 PATIENT EDUCATIONcont’d PA TIENT EDUCATION ADHERENCE ISSUES ■■ Access to clinic appointments and prescription refills is one of the reasons for gaps in OC use. If medically indicated, give the patient a full year of refills. ■■ Counseling, education, and use of written materials can increase a patient’s success with any method. Thorough patient education is the cornerstone of contraceptive success. ■■ The following are most important for patients taking OCs—they should take a pill every day in the correct order, and they should never just stop. If there are questions or concerns, they should always call the clinic first. REFERENCES 3827_Ch31_943-956 01/07/15 6:09 PM Page 956 957 CHAPTER 32 Teri Moser Woo DERMATITIS, 958 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education PSORIASIS, 966 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education ACNE AND ACNE ROSACEA, 969 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education SKIN INFECTIONS, 974 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education SKIN INFESTATIONS, 983 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education ALOPECIA ANDROGENETICA MALE PATTERN BALDNESS, 988 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education T 3827_Ch32_957-990 01/07/15 6:35 PM Page 957 DERMATITIS Pathophysiology Eczema Contact Dermatitis Diaper Dermatitis Seborrheic Dermatitis 958 3827_Ch32_957-990 01/07/15 6:35 PM Page 958 Goals of Treatment Rational Drug Selection Eczema 959 Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis Drug Indication Strengths Available Dose Comments Low Potency Intermediate Potency 3827_Ch32_957-990 01/07/15 6:35 PM Page 959 960 Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis—cont’d Drug Indication Strengths Available Dose Comments High Potency Super-High Potency 3827_Ch32_957-990 01/07/15 6:35 PM Page 960 961 Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis—cont’d Drug Indication Strengths Available Dose Comments 3827_Ch32_957-990 01/07/15 6:35 PM Page 961 962 Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis—cont’d Drug Indication Strengths Available Dose Comments 3827_Ch32_957-990 01/07/15 6:35 PM Page 962 963 Table 32–1 Drugs Commonly Used: Dermatitis and Psoriasis—cont’d Drug Indication Strengths Available Dose Comments 3827_Ch32_957-990 01/07/15 6:35 PM Page 963 964 3827_Ch32_957-990 01/07/15 6:35 PM Page 964 Contact Dermatitis Diaper Dermatitis 965 CLINICAL PEARL Dermatitis • Occluding the surface with plastic wrap will increase penetration of the topical corticosteroid. Do not do this in children, as it will increase the systemic ab- sorption of the steroid. • For contact dermatitis, caution the patient using bath oils against slipping in the tub. Children should be su- pervised at all times when using bath dermatologi- cals, which can all cause the tub to be slippery. Older adults should also be monitored. • For the patient with hand dermatitis, wearing cotton gloves overnight after applying a thick layer of emol- lient will increase absorption, and the patient will often see a significant improvement overnight. 3827_Ch32_957-990 01/07/15 6:35 PM Page 965 Seborrheic Dermatitis Monitoring Outcome Evaluation Patient Education PSORIASIS Pathophysiology Goals of Treatment 966 3827_Ch32_957-990 01/07/15 6:35 PM Page 966 967 PATIENT EDUCATION PA TIENT EDUCATION Dermatitis RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS ■■ Pathophysiology ■■ Role of preventive and nonpharmacological measures if appropriate ■■ Importance of adherence to the treatment regimen ■■ Self-monitoring of symptoms ■■ What to do when symptoms worsen ■■ Need for follow-up visits with the primary care provider SPECIFIC TO THE DRUG THERAPY ■■ Reason for taking the drug and its anticipated action on the disease process ■■ Doses and schedules for taking the drug ■■ Possible adverse effects and what to do if they occur ■■ Interactions between other treatment modalities and these drugs REASONS FOR TAKING THE DRUG(S) ■■ Patient education about specific drugs is provided in the appropriate chapter SPECIFICALLY FOR ECZEMA ■■ Pathophysiology of eczema, that it is a chronic disorder requiring ongoing care, and that there is an itch-scratch-itch cycle that needs to be addressed, but that it is a recurring disease that can be controlled ■■ Avoidance of offending agents that cause exacerbations ■■ Appropriate use of topical corticosteroids should be demonstrated. With a sample, the provider can demonstrate how far a pea-sized amount of topical medication can be spread. The patient or caregiver applying the medication should be aware of the adverse effects of overuse of topical corticosteroids. ■■ Avoidance of irritants or agents that cause exacerbation of the eczema should be taught, with a written list of common ir- ritants provided to the patient ■■ Long-term therapy (skin hydration and emollient use) versus acute therapy SPECIFICALLY FOR CONTACT DERMATITIS ■■ Pathophysiology ■■ Appropriate application of topical corticosteroids should be demonstrated ■■ Appropriate use of antipruritic medication SPECIFICALLY FOR DIAPER DERMATITIS ■■ The parent or patient should be educated about the underlying pathophysiology of diaper dermatitis, in that it is usually an irritant dermatitis caused by chemical irritation from urine or feces, complicated by mechanical irritation of the diaper or undergarment rubbing and chafing the skin. ■■ Describing the characteristics of a secondary infection with Candida will assist with early identification and treatment of this common complication in diaper dermatitis. ■■ Nonpharmacological management such as sitz baths, air drying, and frequent diaper changes should be discussed. ■■ If properly treated, the skin should return to normal in the area in 3 to 4 days. If the patient is not responding to treatment in 48 hours, then a reevaluation is necessary. SPECIFICALLY FOR SEBORRHEIC DERMATITIS ■■ The patient should know that seborrheic dermatitis cannot be cured and can only be controlled and that treatment will probably need to be continued long-term in adolescents and adults. In infants with cradle cap, it will usually resolve around age 6 months. ■■ The patient should contact the health-care provider if signs and symptoms of a secondary infection occur. DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN ■■ The total treatment regimen includes pharmacological and nonpharmacological measures. Be sure the patient and/or family members are aware of the specific measures to be taken. ADHERENCE ISSUES ■■ Health-care providers should be aware of the potential problem of nonadherence and should discuss the importance of completing the entire treatment regimen with the patient and/or family members. 3827_Ch32_957-990 01/07/15 6:35 PM Page 967 Rational Drug Selection 968 CLINICAL PEARL Psoriasis Psoriasis may affect a patient’s self-esteem and may exacerbate depression. The patient’s mood should be monitored. Referral to a support group or an organization such as the National Psoriasis Foundation (http://www .psoriasis.org) may be helpful. Topical Therapy 3827_Ch32_957-990 01/07/15 6:35 PM Page 968 Phototherapy Systemic Medications Monitoring Outcome Evaluation Patient Education ACNE AND ACNE ROSACEA Pathophysiology Goals of Treatment 969 3827_Ch32_957-990 01/07/15 6:35 PM Page 969 Rational Drug Selection Topical Agents 970 Mild acne No improvement Benzoyl peroxide (OTC) No improvement in 4–6 wk Add oral antibiotic (tetracycline) No improvement in 6–8 wk No response in 6–8 wk Positive response Treat as moderate acne Add topical: combined topical antibiotic or retinoid Topical: combined topical antibiotic product or topical retinoid plus topical antibiotic Moderate acne Change antibiotic to minocycline No improvement in 4–6 wk No response: refer to dermatologist Benzoyl peroxide (OTC) Maintenance dose of oral or topical antibiotics Refer to dermatologist Severe, nodular, or recalcitrant acne Figure 32–1. Algorithm: Pharmacological management of acne. 3827_Ch32_957-990 01/07/15 6:35 PM Page 970 971 Table 32–2 Drugs Commonly Used: Acne Drug Indication Strengths Available Dose Comments Topical Retinoids Topical Antibiotics 3827_Ch32_957-990 01/07/15 6:35 PM Page 971 972 Table 32–2 Drugs Commonly Used: Acne—cont’d Drug Indication Strengths Available Dose Comments Oral Antibiotics 3827_Ch32_957-990 01/07/15 6:35 PM Page 972 973 Table 32–2 Drugs Commonly Used: Acne—cont’d Drug Indication Strengths Available Dose Comments Oral Agents CLINICAL PEARL Acne Tell patients using benzoyl peroxide products that ben- zoyl peroxide can bleach clothes and towels. Advise them to use an old or white pillowcase on their bed and an old or white towel to dry their hands after using these agents. 3827_Ch32_957-990 01/07/15 6:35 PM Page 973 Acne Rosacea 974 PATIENT EDUCATION PA TIENT EDUCATION Acne RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS ■■ Pathophysiology ■■ Role of preventive and nonpharmacological measures if appropriate ■■ Importance of adherence to the treatment regimen ■■ Self-monitoring of symptoms ■■ What to do when symptoms worsen ■■ Need for follow-up visits with the primary care provider SPECIFIC TO THE DRUG THERAPY ■■ Reason for the drug’s being given and its anticipated action on the disease process ■■ Doses and schedules for taking the drug ■■ Possible adverse effects and what to do if they occur ■■ Interactions between other treatment modalities and these drugs REASONS FOR TAKING THE DRUG(S) ■■ Patient education about specific drugs is provided in the appropriate chapter. SPECIFICALLY FOR ACNE ■■ The patient should understand that it will take at least 6 weeks to determine if treatment is effective. Tying this into the explanation of normal skin growth will help the patient understand why it takes so long for the medication to work. ■■ Whatever level of treatment the patient is started on, the patient needs to understand what alternatives there are if the chosen treatment is not effective. DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN ■■ The total treatment regimen includes pharmacological and nonpharmacological measures. Be sure the patient and/or family members are aware of the specific measures to be taken. ADHERENCE ISSUES ■■ Health-care providers should be aware of the potential problem of nonadherence and should discuss the importance of completing the entire treatment regimen with the patient and/or family members. 3827_Ch32_957-990 01/07/15 6:35 PM Page 974 975 Monitoring Outcome Evaluation Patient Education SKIN INFECTIONS Pathophysiology Bacterial Skin Infections Viral Skin Infections Fungal Skin Infections 3827_Ch32_957-990 01/07/15 6:35 PM Page 975 Goals of Treatment Rational Drug Selection Bacterial Skin Infections Viral Skin Infections 976 3827_Ch32_957-990 01/07/15 6:35 PM Page 976 977 Table 32–3 Drugs Commonly Used: Skin Infections Drug Indication Strengths Available Dose Comments Topical Antibiotics Systemic Oral Antibiotics 3827_Ch32_957-990 01/07/15 6:35 PM Page 977 978 Table 32–3 Drugs Commonly Used: Skin Infections—cont’d Drug Indication Strengths Available Dose Comments Antivirals 3827_Ch32_957-990 01/07/15 6:35 PM Page 978 979 Table 32–3 Drugs Commonly Used: Skin Infections—cont’d Drug Indication Strengths Available Dose Comments Antifungals 3827_Ch32_957-990 01/07/15 6:35 PM Page 979 980 Table 32–3 Drugs Commonly Used: Skin Infections—cont’d Drug Indication Strengths Available Dose Comments 3827_Ch32_957-990 01/07/15 6:35 PM Page 980 981 Table 32–3 Drugs Commonly Used: Skin Infections—cont’d Drug Indication Strengths Available Dose Comments 3827_Ch32_957-990 01/07/15 6:35 PM Page 981 982 Table 32–3 Drugs Commonly Used: Skin Infections—cont’d Drug Indication Strengths Available Dose Comments Fungal Skin Infections CLINICAL PEARL Thrush Infants (and some older or very ill patients) are unable to hold nystatin suspension in their mouth. To achieve better results with nystatin administration, instruct the parents or caregivers to dip a clean cotton-tipped appli- cator into the nystatin solution, then rub the medication into the areas of thrush on the inner cheeks. Use a clean swab for each side and do not redip the applicator into the nystatin. After swabbing on the nystatin, the parent or caregiver can then administer 1 to 2 mL to each cheek. 3827_Ch32_957-990 01/07/15 6:35 PM Page 982 Monitoring Outcome Evaluation Patient Education SKIN INFESTATIONS Pathophysiology Lice 983 3827_Ch32_957-990 01/07/15 6:35 PM Page 983 984 PATIENT EDUCATION PA TIENT EDUCATION Skin Infections RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS ■■ Pathophysiology ■■ Role of preventive and nonpharmacological measures if appropriate ■■ Importance of adherence to the treatment regimen ■■ Self-monitoring of symptoms ■■ What to do when symptoms worsen ■■ Need for follow-up visits with the primary care provider SPECIFIC TO THE DRUG THERAPY ■■ Reason for taking the drug and its anticipated action on the disease process ■■ Doses and schedules for taking the drug ■■ Possible adverse effects and what to do if they occur ■■ Interactions between other treatment modalities and these drugs REASONS FOR TAKING THE DRUG(S) ■■ Patient education about specific drugs is provided in the appropriate chapter. SPECIFICALLY FOR BACTERIAL SKIN INFECTIONS ■■ Explanation regarding the suspected cause of the infection and the rationale for the antibiotic treatment chosen ■■ Hand washing should be stressed to prevent spread of the skin infection to the patient or others. ■■ Give clear guidelines regarding notifying the practitioner if the infection is getting worse. ■■ Improvement should be noted in 24 to 48 hours; if not, a change in therapy may be indicated. SPECIFICALLY FOR VIRAL INFECTIONS Expectations of the medication. The healthy patient will have resolution of the vesicular lesions even without pharmacolog- ical intervention. Effective antiviral therapy decreases the time to scabbing and healing of lesions and decreases viral shed- ding time. In immunocompromised patients, the medication will help decrease the severity of the outbreak. ■■ Explain how the virus can become dormant and recur at a later time, even many years later. ■■ Patients using topical antivirals need to be instructed to use a glove or finger cot to apply the ointment to prevent getting the virus on their hands and spreading it; also, the patient may experience a transient burning when the medication is applied. ■■ It should be stressed to the patient and/or family members that the patient is contagious until the lesions are healed or scabbed over, even if antiviral agents are being taken; the patient should avoid contact with immunocompromised indi- viduals and avoid sexual intercourse if the patient has genital herpes lesions. SPECIFICALLY FOR FUNGAL INFECTIONS ■■ The patient and/or family members should understand how the fungal infection is spread and how contagious the infection is. ■■ Family members and pets should be checked for signs of infection and treated if indicated. ■■ The provider should stress the possibility of relapse if the medication regimen is not followed correctly and for the full treatment time. DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN ■■ The total treatment regimen includes pharmacological and nonpharmacological measures. Be sure the patient and/or family members are aware of the specific measures to be taken. ADHERENCE ISSUES ■■ Health-care providers should be aware of the potential problem of nonadherence and should discuss the importance of completing the entire treatment regimen with the patient and/or family members. 3827_Ch32_957-990 01/07/15 6:35 PM Page 984 Scabies Goals of Treatment Rational Drug Selection Head Lice 985 3827_Ch32_957-990 01/07/15 6:35 PM Page 985 Body Lice Pubic Lice 986 3827_Ch32_957-990 01/07/15 6:35 PM Page 986 Scabies Monitoring Outcome Evaluation Patient Education 987 3827_Ch32_957-990 01/07/15 6:35 PM Page 987 ALOPECIA ANDROGENETICA (MALE PATTERN BALDNESS) Pathophysiology Goals of Treatment Rational Drug Selection Minoxidil Finasteride Monitoring 988 3827_Ch32_957-990 01/07/15 6:35 PM Page 988 Outcome Evaluation Patient Education REFERENCES 989 3827_Ch32_957-990 01/07/15 6:35 PM Page 989 3827_Ch32_957-990 01/07/15 6:35 PM Page 990 991 CHAPTER 33 Kathy Shaw • Marylou Robinson PATHOPHYSIOLOGY, 992 Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Complications Prediabetes Diagnosis and Screening PHARMACODYNAMICS, 997 General Diabetes Management and Glycemic Control Insulin Oral Agents Other Injectable Drugs GOALS OF TREATMENT, 1000 APPROPRIATE TREATMENT, 1001 Initial Assessment Setting a Glycemic Target Lifestyle Modifications Pharmacologic Management PREVENTION AND MANAGEMENT OF COMPLICATIONS IN DIABETES, 1010 Obesity Coronary Heart Disease and Heart Failure Hyperlipidemia Hypertension Nephropathy Neuropathy Retinopathy Thyroid Function Autoimmune Disorders ASSESSING GLYCEMIC CONTROL, 1016 Hb A1c Self-Monitoring of Blood Glucose (SMBG) OUTCOME EVALUATION, 1017 PATIENT EDUCATION, 1017 D 3827_Ch33_991-1020 01/07/15 2:46 PM Page 991 PATHOPHYSIOLOGY Type 1 Diabetes Mellitus 992 Table 33–1 Comparison of Type 1 and Type 2 Diabetes Mellitus Characteristic Type 1 Type 2 3827_Ch33_991-1020 01/07/15 2:46 PM Page 992 Type 2 Diabetes Mellitus 993 On The Horizon CURE FOR TYPE I DM? Two recent research endeavors are exploring the use of older non-diabetic medications to intervene in early cases of DM I. Mice given verapamil essentially eradicated a protein that causes the death of beta cells. Trials funded by the Juvenile Diabetes Foundation with humans are planned to test this “cure” of type 1 DM (Shalev, 2014). Other researchers at Massachusetts General are exploring an interesting positive effect on pancreas recovery after administration of the old BCG vaccine originally developed to assist with TB care (Faustman et al, 2012). 3827_Ch33_991-1020 01/07/15 2:46 PM Page 993 994 Polyuria InfectionsGlycosuria Dilutional hypo-NA+ Hyperglycemia No insulin HLA DR3/5 viral exposure beta cell destruction Cardiac dysrhythmia Decreased O2 trans Intracellular dehydration Intracellular starvation Altered protein metabolism Altered fat metabolism AcidosisRenal threshold exceeded Hyper-K+ Circulatory overload Polydipsia Weight loss Polyphagia Poor wound healing Impaired immune system Figure 33–1. Pathophysiology of type 1 diabetes. 3827_Ch33_991-1020 01/07/15 2:46 PM Page 994 Complications Pre-Diabetes Diagnosis and Screening Diagnostic Criteria for Diabetes and Pre-Diabetes 995 Table 33–2 Diagnostic Criteria for Diabetes Mellitus and Pre-Diabetes Diagnostic Category Diagnostic Criteria Diabetes mellitus Pre-diabetes 3827_Ch33_991-1020 01/07/15 2:46 PM Page 995 Diagnostic Criteria for Pregnant Women Screening Criteria for Children 996 Table 33–3 Criteria for Testing Asymptomatic Adults for Diabetes 3827_Ch33_991-1020 01/07/15 2:46 PM Page 996 PHARMACODYNAMICS General Diabetes Management and Glycemic Control Insulin 997 Table 33–4 Common Insulin Types, Onset, Peak, and Duration Type Insulin Onset Peak Duration Rapid-Acting Short-Acting Intermediate-Acting Long-Acting Fixed Combination 3827_Ch33_991-1020 01/07/15 2:46 PM Page 997 Oral Agents Biguanides 998 On The Horizon ULTRA-LONG-ACTING INSULIN An ultra-long-acting basal insulin analogue, insulin degludec, has just been approved. Duration of action nears 42 hours, so it might have an irregular dosing schedule. It is thought to have lower rates of nocturnal hypoglycemia compared to glargine. Its higher cost will be an issue. There are concerns about adverse CV effects. CLINICAL PEARL Rules for Fine-Tuning Insulin Doses • The correction factor (CF) and insulin: carbohydrate ratio (I:C) for patients with either type 1 or 2 taking insulin. • The rule of 1,500 enables the provider to find the CF or how much 1 unit of insulin will drop blood sugar for high blood glucose levels (usually greater than 140 to 150). First, calculate the total daily dose (TDD) of insulin as basal + bolus—about 50% of each. Then divide 1,500 by the TDD. For example, 1,500 divided by 30 units per day of insulin equals 50. One unit of rapid-acting insulin will drop glucose 50 points. • The rule of 500 enables the provider to find the I:C ratio. Divide 500 by TDD. For example, 500 divided by 30 units per day of insulin equals 16.7. One unit will cover 16 to 17 g of carbohydrate (CHO). For ease of use, round down to 1 unit:15 g. 3827_Ch33_991-1020 01/07/15 2:46 PM Page 998 Sulfonylureas Alpha-Glucosidase Inhibitors Thiazolidinediones Meglitinides Selective Sodium Glucose Co-transporter 2 (SGLT-2) 999 3827_Ch33_991-1020 01/07/15 2:46 PM Page 999 Incretin Therapy Dipeptidyl Peptidase-4 Inhibitors Glucagon-Like Peptide-1 Receptor Agonists (GLP-1s) Other Injectable Drugs GOALS OF TREATMENT 1000 3827_Ch33_991-1020 01/07/15 2:46 PM Page 1000 APPROPRIATE TREATMENT Initial Assessment Setting a Glycemic Target 1001 Table 33–5 American Diabetes Association Treatment Targets for Persons With Diabetes Hb A1c Preprandial Plasma Glucose 2-hour Postprandial Plasma Glucose Blood Pressure LDL Triglycerides HDL Excess Urinary Albumin Excretion 3827_Ch33_991-1020 01/07/15 2:46 PM Page 1001 Lifestyle Modifications 1002 Table 33–6 Correlation Between Hb A1c Level and Mean Plasma Glucose Level Hemoglobin A1c Levels Mean Plasma Glucose (mg/dL) 3827_Ch33_991-1020 01/07/15 2:46 PM Page 1002 Immunizations 1003 Table 33–7 Lifestyle Modifications for Patients With Diabetes Nutrition Exercise Weight Loss 3827_Ch33_991-1020 01/07/15 2:46 PM Page 1003 Considerations in Special Populations 1004 3827_Ch33_991-1020 01/07/15 2:46 PM Page 1004 Race and Ethnic Groups 1005 3827_Ch33_991-1020 01/07/15 2:46 PM Page 1005 Pharmacological Management Type 1 Diabetes 1006 Table 33–8 Basal Bolus Insulin Rapid-Acting (RAI) Short-Acting (SAI) Intermediate-Acting (IAI) Long-Acting (LAI) Mix 3827_Ch33_991-1020 01/07/15 2:46 PM Page 1006 1007 Establish glycemic target Adults without severe complications who are willing and able to use individualized algorithm, take up to 4 injections/day and test BG at least 4!/day. Tight control/intensive therapy: —FPG and premeal 90–130 mg/dL —Postprandial <180 mg/dL —HbA1c <7% Children Plasma blood glucose goal (mg/dL) Patients who are at high risk for hypoglycemia; older adults; patients w/ late disease or advanced, severe complications; not motivated to follow complex regimen. Conventional therapy: —FPG 120–150 mg/dL —Bedtime glucose 120–160 mg/dL —HbA1c 7%–8% Age 0–6 7–12 13–19 Before meals 100–180 90–180 90–130 Bedtime 110–200 100–180 90–150 HbA1c 7.5%–8.5% <8% <7.5% Lifestyle modifications (see Table 33-7) Plus insulin 1. Start w/ total daily dose 0.2–0.4 units/kg; usual 0.4–0.8 units/kg 2. 50% basal give once or twice daily (glargine, detemir preferred, or NPH) 3. 50% prandial—rapid acting preferred (aspart, lispro, glulisine, or R) a. Start with 1 unit/15 g carbohydrate OR b. Divide into equal doses if consistent carbohydrate OR c. Divide into 3 doses based on meal size 4. Correction dosing to be used in addition to meal dose for blood sugars >150
More advanced methods may be used as patient comfort increases. See text.
Hypoglycemia (<70) Treat before addressing hyperglycemia —Fasting: decrease basal dose —Preprandial: decrease dose of rapid acting at preceding meal Hyperglycemia —Fasting: >130 increase long-acting dose
—Preprandial: >150 increase dose at
previous meal
—Titrate both q 3 days
Contact by e-mail or phone 1–2!/wk initially by NP, RN, or CDE
FU visit at 1 month
—Review blood sugar patterns, activity,
hypoglycemic episodes
—Continue dose adjustment as needed
Contact as needed by NP, RN, or CDE
FU visit at 3 mo
—Review as above
—HbA1c
Glycemic targets met?
NoYes
—Continue regimen
—May advance to pump therapy or advanced
carbohydrate counting. See Clinical Pearls.
—Review lifestyle, insulin regimen, and adherence
—Consider confounding variables
—Adjust insulin based on patterns
HbA1c and visit every 3 mo
Most Type 1 patients should be followed by a multidisciplinary endocrinology team.
Figure 33–2. Treatment algorithm for type 1 diabetes.
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1008
CLINICAL PEARL
Type I Diabetes Treatment
• Most patients should see an endocrinologist and di-
abetes treatment team; treatment can be challenging
and a team approach works best. Consultation with
a Certified Diabetes Educator is a must.
• Make small changes gradually with close follow-up
(every 1 to 2 wk) until adequate control is achieved.
• Ongoing follow-up has been shown to be very bene-
ficial; this can be done by phone or electronically.
• It is normal to have wide variability in BGL even with
adherence to the treatment plan. Variability does not
necessarily mean nonadherence.
• Consistency in mealtimes, injection sites, and timing
and frequency of exercise is vital.
• The treatment plan must be individualized with
adjustments preplanned for anticipated sudden
increases in physical activity such as summer sports
camps or ski vacations.
Type 2 Diabetes
Table 33–9 ! Commonly Used Insulin Regimens
Insulin Therapy
Type Insulin Schedule Advantages Disadvantages
Intensive Insulin Therapy
Split-Mix Insulin
Therapy—3 injections
Split-Mix Insulin
Therapy—2 injections
Basal = IAI
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1008

1009
a. Consider beginning at this stage in patients with very high HbA1c (e.g., > 9%).
b. Consider rapid-acting, nonsulfonylurea secretagogues (meglitinides) in patients with irregular meal
schedules or who develop late postprandial hypoglycemia on sulfonylureas.
c. See (…)[text] for additional potential adverse effects and risks(…).
d. Usually a basal insulin (NPH, glargine, detemir) in combination with noninsulin agents
e. Certain noninsulin agents may be continued with insulin (see text).. Consider beginning at this stage if
patient presents with severe hyperglycemia (>16.7–19.4 mmol/L [300–350 mg/dL]; Hb A1c >10.0–12.0%)
with or without catabolic features (weight loss, ketosis, etc.).
Figure 33–3. General recommendations for antihyperglycemic therapy in type 2 diabetes. Inzucchi et al (2012). Management of hyperglycemia
in type 2 diabetes: A patient centered approach. Position Statement of the American Diabetes Association (ADA) and the European Association
for the Study of Diabetes (EASD). Diabetes Care, 35(6), 1364–1379.
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1009

Severe Insulin Resistance Therapy: U-500 Insulin
PREVENTION AND MANAGEMENT
OF COMPLICATIONS IN DIABETES
Obesity
1010
On The
Horizon U-300 INSULIN
The FDA has just approved a U-300 insulin (Toujeo), which is a
long-acting basal insulin with a lower glucose lowering effect
per unit than glargine, but lower risks of hypoglycemia. Lower-
volume injections will be beneficial. The precautions about
mixing solutions in a syringe also pertain. This insulin uses
units per dose like glargine; this is unlike the U-500 insulins,
which are volume based.
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1010

Coronary Artery Disease and Heart Failure
Hyperlipidemia
1011
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1011

1012
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1012

Hypertension
1013
On The
Horizon RENAL INSUFFICIENCY
Metformin and other medications are curtailed when creati-
nine values rise. Several recent calls to continue with drug use
if monitoring for lactic acidosis is not yet FDA-approved.
Nephropathy
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1013

Neuropathy
1014
Table 33–10 Major Clinical Manifestations of Diabetic
Autonomic Neuropathy
Body System Manifestations
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1014

Retinopathy
1015
CLINICAL PEARL
Pumps and Daylight Savings Time
Some pumps may not automatically adjust for changes
in daylight savings time. This will not impact basal in-
sulin rates, but bolus doses can be impacted. Time-zone
travel can also impact timing of doses if the pump is
not GPS-enabled.
Thyroid Function
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1015

Autoimmune Disorders
ASSESSMENT OF GLYCEMIC
CONTROL
Hb A1c
Self-Monitoring of Blood Glucose (SMBG)
1016
Table 33–11 Situations Where Hb A1c May
Be Unreliable
Disease or Impact on
Situation Hb A1c Value
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1016

OUTCOME EVALUATION PATIENT EDUCATION
1017
DIABETES MELLITUS PA
TIENT
EDUCATION
Related to the Overall Treatment Plan/Disease Process
■■ Pathophysiology of diabetes and the long-term effects of inadequate management on target organs
■■ Role of lifestyle modification, especially dietary therapy, in improving outcomes and keeping the number and cost of
required drugs down
■■ Importance of adherence to the treatment regimen
■■ Need for regular follow-up visits with the primary care provider and other specialists
SPECIFIC TO THE DRUG THERAPY
■■ Reason for taking the drug(s) and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drugs
■■ Possible adverse reactions (especially hypoglycemia, DKA, and hyperosmolar hyperglycemic non-ketotic coma), how to
prevent them, and what to do if they occur
■■ Interactions between lifestyle modifications and these drugs
REASONS FOR TAKING THE DRUG(S)
Patient education about specific drugs is provided in Chapter 21. Specific information related to diabetes includes the
following: glycemic control and management of hypertension and hyperlipidemia are central to reducing morbidity
and mortality from cardiovascular disease and preventing retinopathy and end-stage renal disease. The risks of these
complications while maintaining the potential for a good quality of life with appropriate treatment must be discussed.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
Expectations should be clear about what the drugs can and cannot do. Dietary and other lifestyle modifications comple-
ment drug therapy and are equally important. Diabetes is a chronic, progressive disease. Self-management requires incor-
porating a combination of medications, healthy eating, exercise, stress management, and SMBG into the everyday life of
the patient with diabetes.
ADHERENCE ISSUES
Nonadherence to the treatment regimen may result in increased risk for complications and reduced life expectancy. Health-
care providers should be aware of potential problems with nonadherence, discuss the importance of adherence at each
follow-up visit, and assist patients in removing barriers to adherence such as lack of social support and cost of the treat-
ment regimen. A team approach with the patient as an active partner should be maximized. Ways to deal with nonadher-
ence are discussed in Chapter 6. Patient education booklets are available from the ADA, which can be accessed on the
Internet at www.diabetes.org.
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1017

REFERENCES
1018
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1018

1019
3827_Ch33_991-1020 01/07/15 2:46 PM Page 1019

3827_Ch33_991-1020 01/07/15 2:46 PM Page 1020

1021
CHAPTER 34
Teri Moser Woo
GASTROESOPHAGEAL REFLUX DISEASE, 1021
Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
PEPTIC ULCER DISEASE, 1028
Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
P
GASTROESOPHAGEAL REFLUX
DISEASE
Pathophysiology
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1021

Signs and Symptoms
1022
Table 34–1 Foods and Drugs That Influence GERD
Foods and Drugs Action on LES Tone
Foods
Drugs
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1022

Diagnosis
Pharmacodynamics
Drugs to Improve Lower Esophageal Sphincter Tone
Drugs to Reduce the Amount of Acid
1023
Table 34–2 Signs and Symptoms of GERD and Potential Complications
Signs and Potential Suggestive of
Symptoms Common Unusual Extra-esophageal Complication Cancer (Alarm)
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1023

Drugs to Improve Peristalsis
Drugs to Decrease Mucosal Exposure
1024
K+
Parietal cell with
proton pump
Antibiotic Antacid
+ HCL water + salt
Parietal cell with
H2-receptor
Acid secretion
Ulcer with H. pylori
Proton pump inhibitors bind to the
enzyme H+, K+-ATPase and prevent
acid from being secreted.
Antibiotics eradicate H. pylori,
the primary cause of peptic ulcers.
Alkaline antacids chemically combine
with acids to lower stomach pH.
H2-receptor antagonists occupy
the histamine receptors and
prevent acid secretions.
Proton pump
Proton pump
inhibitors
H2-receptor
H2-receptor
blockers
Figure 34–1. Sites of action of drugs used to treat GERD and PUD.
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1024

Goals of Treatment
Rational Drug Selection
Algorithm
Lifestyle Modifications
Drug Therapy
Patient Variables
1025
Dyspepsia or mild
GERD symptoms
No erosive disease
OTC antacids or
H2RAs to control
symptoms
Moderate to severe
GERD or erosive
disease
Lifestyle modification and
proton pump inhibitors (PPI)
Continue therapy for 8 weeks
Reassess every 6–12 months.
Consider referral to
gastroenterology specialist.
Symptoms Relieved
Wean off PPI.
Erosive esophagitis or
Barrett’s esophagitis
NO response
to PPI
Symptoms
recur.
Restart
PPI.
Continue
on PPI.
Refer to
Gl specialist.
Figure 34–2. Algorithm for gastro –
esophageal reflux disease (GERD).
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1025

1026
BOX 34–1 LIFESTYLE MODIFICATIONS
IN GERD MANAGEMENT FOR
ADULTS
Antireflux Maneuvers
• Sleep with the head of the bed elevated 6 to
8 inches with bed blocks or wedges or by using
a hospital bed.
• Avoid the recumbent position within 3 hours after
eating.
• Avoid bending over within 3 hours after eating.
• Avoid exercise, especially strenuous exercise,
within 3 hours after eating.
• Attain and maintain appropriate body weight.
DIETARY CONSIDERATIONS
• Avoid spicy, acidic, tomato-based, or fatty foods.
• Avoid chocolate, peppermint, onions, and citrus
fruits and juices.
• Limit your intake of coffee, tea, alcohol, and
colas.
• Eat moderate amounts of food at each meal. Do
not gorge yourself.
• Avoid eating meals or bedtime snacks within
3 hours of going to bed.
• Reserve fluid intake for after or between meals.
SMOKING CESSATION
• Stop smoking. Smoking both lowers LES tone and
increases the secretion of gastric acid.
• Smoking cessation is a high priority.
WEIGHT LOSS
• Weight loss may improve symptoms
Table 34–3 Lifestyle Modifications in GERD
Management for Infants and Children
Antireflux Maneuvers Dietary Considerations
Infants
Children
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1026

Monitoring
1027
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1027

Outcome Evaluation
Patient Education
PEPTIC ULCER DISEASE
Pathophysiology
Gastric Ulcer Disease
1028
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1028

1029
PATIENT EDUCATION PA
TIENT
EDUCATION
Gastroesophageal Reflux Disease
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Pathophysiology of gastroesophageal reflux and its long-term risks for permanent esophageal damage and cancer of the
esophagus
■■ Central role of lifestyle modifications in improving prognosis and keeping the number and cost of required drugs down
■■ Importance of adherence to the treatment regimen
■■ Need for follow-up visits with the primary care provider if the symptoms do not resolve or if they recur
SPECIFIC TO THE DRUG THERAPY
■■ Reason for the drug(s) being given and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse reactions and what to do when they occur
■■ Coping mechanisms for complex and costly drug regimens
■■ Interaction between lifestyle modifications and these drugs
REASONS FOR TAKING THE DRUG(S)
Patient education about specific drugs is provided in Chapter 20. Specific information related to GERD: drugs used to treat
GERD are given to reduce symptoms, heal any esophageal ulcers, reduce the risk for permanent esophageal damage or
cancer, and prevent relapse of symptoms. Different drugs have different roles with each of these. The expectations should
be clear about what the drugs can and cannot do. Drugs alone will not correct the disorder.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
Lifestyle modification is equally important in disease management. GERD is a chronic condition. Patients with GERD must
understand the lifelong nature of the disorder and the need to incorporate the treatment regimen into their everyday lives.
ADHERENCE ISSUES
Any disease process where lifestyle modifications are central to management is prone to problems with adherence. Health-
care providers should be aware of the potential problem of nonadherence, discuss the importance of adherence at each
follow-up visit, and assist patients in removing barriers to adherence, such as the complexity and cost of the treatment
regimen and the presence of adverse reactions.
Table 34–4 Comparison of Gastric and Duodenal Ulcer Disease
Characteristic Gastric Ulcer Duodenal Ulcer
Pathophysiology
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1029

Duodenal Ulcer Disease
Diagnosis
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Algorithm
1030
BOX 34–2 SUBSTANCES THAT CAN
DISRUPT THE GASTRIC
MUCOSAL BARRIER
Drugs
Alcohol
Aspirin
Caffeine
Corticosteroids
NSAIDs
Tobacco
Other Causes
H. pylori infection
Bile and pancreatic secretions
Physiological and psychological stress
Salmonella
Spicy, irritating foods*
Staphylococcus organisms
Uremia associated with renal failure
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1030

1031
Step 1
Lifestyle modification and antacids
Refer to gastroenterologist
for endoscopy.
PPI
Continue for 8–12 weeks
until healing complete.
Repeat endoscopy
in 12 weeks to
determine healing.
Complicated (bleeding)
High risk*
Consider chronic suppressive
therapy with PPI or H2RA.
(*smokers, !60 yr, COPD, CAD,
hx of bleeding or perforated
ulcer, patients on NSAIDs)
Step 2
H. pylori testing and
proton pump inhibitor (PPI)
Step 3
Treatment for H. pylori with
antibiotics and PPI
Low risk
No ongoing
therapy
Treatment for H. pylori
Uncomplicated
Figure 34–3. Stepped-approach algo-
rithm for peptic ulcer disease.
Table 34–5 Invasive and Noninvasive Diagnostic Tests for
Test Sensitivity Specificity Comments
Noninvasive
Invasive
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Lifestyle Modifications
Drug Therapy
Adverse Drug Reactions for the Total Regimen
Antimicrobial Resistance
1032
Table 34–6 ! Drug Treatment Protocols for Eradication
Drug 1 Drug 2 Drug 3 Drug 4 Comments
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1032

Patient Variables
Monitoring
Outcome Evaluation
1033
PATIENT EDUCATION PA
TIENT
EDUCATION
Peptic Ulcer Disease
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Understanding the pathophysiology of ulcer forma-
tion and its long-term risks for bleeding and cancer
of the stomach
■■ Role of lifestyle modifications in total treatment
regimen
■■ Importance of adherence to the treatment regimen,
especially in light of antimicrobial resistance
■■ Need for follow-up visits with the primary care
provider if the symptoms recur or do not resolve
SPECIFIC TO THE DRUG THERAPY
■■ Reason for the drug(s) being given and the antici-
pated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse reactions and what to do when they
occur
■■ Coping mechanisms for complex and costly drug
regimens
■■ Interactions between lifestyle modifications and
these drugs
REASONS FOR TAKING THE DRUG(S)
Patient education about specific drugs is provided in
Chapters 20 and 24. Specific information related to PUD
includes the following: drugs used to treat PUD are
given to treat H. pylori, reduce symptoms, heal any ul-
cers, reduce the risk for complications, and prevent re-
lapse of symptoms. Different drugs have different roles
with each of these.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
Lifestyle modification is important in disease manage-
ment. PUD is often a chronic condition, requiring
lifelong maintenance therapy.
ADHERENCE ISSUES
Any disease process in which lifestyle modifications are
required or in which a complex regimen of three or four
drugs over a period of weeks is required is likely to have
problems with adherence. Health-care providers should
be aware of the potential problem of nonadherence,
discuss the importance of adherence, and assist pa-
tients in removing barriers to adherence, such as the
complexity and cost of the treatment regimen and the
presence of adverse reactions.
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1033

Patient Education
REFERENCES
1034
3827_Ch34_1021-1034 01/07/15 2:44 PM Page 1034

1035
CHAPTER 35
Theresa Mallick-Searle
MIGRAINE, 1036
Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
TENSIONTYPE HEADACHES, 1053
Pathophysiology
Goals of Therapy
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
CHRONIC DAILY HEADACHES, 1054
Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
CLUSTER HEADACHES, 1056
Pathophysiology
Goals of Treatment
Rational Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
MEDICATIONOVERUSE HEADACHES, 1057
Pathophysiology
Goals of Therapy
Rational Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
POSTTRAUMATIC POSTCONCUSSIVE
HEADACHES, 1058
Pathophysiology
Goals of Therapy
Rational Drug Therapy
Monitoring
Patient Education
H
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1035

MIGRAINE
Pathophysiology
Goals of Treatment
Rational Drug Selection
Acute Therapy
1036
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1036

1037
Table 35–1 Common Migraine Triggers
Factor Triggers
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1037

1038
Yes
No
Yes
Yes
No
Yes
No
No
Patient has a migraine
Determine severity
Early and mild
(0–4 h)
Simple analgesics
(OTC “headache” preparation,
aspirin, ibuprofen,
naproxen sodium)
Nonpharmacologic
measures (darkened room,
lying down, ice to head)
Moderate to severe
(0–4 h)
Ultrasevere or
lasting >72 h
Antiemetic, if needed for
nausea (metoclopramide)
Unresponsive to treatment
Treat as per moderate or severe
Simple analgesics
plus antiemetic or
analgesic/opioid
combination
Coronary artery disease or
uncontrolled hypertension?
Pregnant?
Taking MAOIs or SSRIs?
DHE given IM or IV
Headache pain accompanied
by nausea/vomiting?
Ergotamine suppository plus
antiemetic or sumatriptan SC
or nasal spray or DHE nasal spray
Oral triptan or
ergotamine suppository
Limit use of any medication
to 2 to 3 times per week
Poor response?
Unacceptable adverse effects?
Recurrence of migraine after use?
Switch to another drug
New drug effective?
Reevaluate treatment
Combination drug (if indicated)
(Midrin or butalbital-containing drug)
(use with caution)
Figure 35–1. Treatment algorithm for acute migraine headache.
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1038

1039
Table 35–2 Drugs Commonly Used: Headaches
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
Nonnarcotic Analgesics
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1039

1040
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
Combination Analgesics
Narcotic Analgesics
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1040

1041
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
Ergot Derivatives
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1041

1042
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
Serotonin Receptor Agonists
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1042

1043
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1043

1044
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
Alpha Agonist, Central
Antiemetics
Beta Blockers
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1044

1045
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
Tricyclic Antidepressants
Anticonvulsants
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1045

1046
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
NSAIDs
Calcium Channel Blockers
Serotonin Antagonist
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1046

1047
Table 35–2 Drugs Commonly Used: Headaches—cont’d
Strengths Rebound
Drug Initial Dose Maximum Dose Available Potential Comments
Antispasmodic/Neurotoxin (inhibits acetylcholin release from nerve endings)
Nutraceuticals
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1047

1048
CLINICAL PEARL
Ergotamine Suppositories
Ergotamine suppositories can provide relief if taken at
the beginning of a migraine attack. If a patient has not
used ergotamine before, instruct the patient to use
one-third of a 2 mg suppository initially and repeat in
30 to 60 minutes. Refrigeration makes the suppository
easier to slice.
CLINICAL PEARL
Triptans
It is advisable to administer the first dose of any of the
triptans under direct supervision to monitor for unrec-
ognized coronary disease. The patient should receive
the first dose in the clinic (or urgent care center) and be
monitored for any adverse cardiovascular effects.
Sumatriptan is effective in decreasing the severity of
headache in 54% to 80% of patients.
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1048

Preventive Therapy
1049
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1049

1050
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1050

Nonpharmacological Management of Migraine
1051
On The
Horizon MIGRAINES
A number of medications are in the pipeline for treatment
of migraines. An inhaled form of dihydroergotamine
(Semprana) will be reviewed by the FDA in 2015. Two
monoclonal antibody preparations that target calcitonin
gene-related peptide (CGRP) are in experimental trials.
CGRP is a protein that is thought to trigger migraines.
ALD403 (Alder Biopharmaceuticals) and LY2951742 (Lilly)
have both demonstrated reduction in migraines com-
pared to placebo. Boehringer Ingelheim Pharmaceuticals’
olcegepant, a CGRP antagonist, is undergoing phase II trials
in Europe.
Monitoring
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1051

Outcome Evaluation
Patient Education
1052
PATIENT EDUCATION PA
TIENT
EDUCATION
Headaches
RELATED TO THE OVERALL TREATMENT PLAN/DISEASE PROCESS
■■ Pathophysiology of headache
■■ Role of lifestyle modifications
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of symptoms and associated
symptoms
■■ What to do when symptoms and associated
symptoms worsen
■■ Need for regular follow-up visits with the primary
care provider
SPECIFIC TO THE DRUG THERAPY
■■ Reason for taking the drug and its anticipated action
in the disease process
■■ Doses (including maximum dosage) and schedules
for taking the drug
■■ Possible adverse effects and what to do if they
occur
■■ Interactions between other treatment modalities and
these drugs
■■ Potential for medication-overuse headache
REASONS FOR TAKING THE DRUG(S)
Patient education about specific drugs is provided in
the appropriate chapters. Specific reasons for taking
the drug(s) should be discussed on an individual basis,
depending on the diagnosis and nature of the headache.
Medication overuse should also be discussed at the
beginning of treatment.
DRUGS AS PART OF THE TOTAL TREATMENT REGIMEN
The total treatment regimen includes pharmacologi-
cal and nonpharmacological measures, as well as
the headache diary. A realistic expectation and goals
of the individualized treatment plan should be
presented.
ADHERENCE ISSUES
Nonadherence with the treatment regimen may affect
functional status. Health-care providers should be
aware of the potential problem of nonadherence and
discuss the importance of adherence with the patient
and family.
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1052

TENSION-TYPE HEADACHES
Pathophysiology
Goals of Therapy
Rational Drug Selection
Acute Therapy
1053
BOX 35–1 HEADACHE RESOURCES FOR
PATIENTS AND HEALTH-CARE
PROVIDERS
American Headache Society

Home

The American Headache Society (AHS) is a professional
society of health-care providers dedicated to the study
and treatment of headache and face pain. Founded in
1959, AHS brings together physicians and other health-
care providers from various fields and specialties to
share concepts and developments about headache and
related conditions.
American Council for Headache Education
http://www.achenet.org
This site is geared for patients and is connected with the
American Headache Society. There is patient information
on headaches in general, migraines, and prevention and
treatment of headaches, as well as a discussion forum
for patients. There are specific sections for children and
women.
National Headache Foundation
www.headaches.org
Nonprofit organization dedicated to educating headache
sufferers and health-care professionals about headache
causes and treatments.
International Headache Society
www.ihs-headache.org
The International Headache Society (IHS) is an interna-
tional professional organization working with others for
the benefit of people affected by headache disorders.
The purpose of IHS is to advance headache science,
education, and management, and to promote headache
awareness worldwide. Note: The Web site asks about
membership but nonmembers can access all guidelines.
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1053

Preventive Therapy
Monitoring
Outcome Evaluation
Patient Education
CHRONIC DAILY HEADACHES
1054
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1054

Pathophysiology
Goals of Treatment
Rational Drug Selection
Chronic Migraine
Hemicrania Continua
Monitoring
Outcome Evaluation
Patient Education
1055
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1055

CLUSTER HEADACHES
Pathophysiology
Goals of Treatment
Rational Drug Therapy
Acute Therapy
Preventive Therapy
Monitoring
Outcome Evaluation
1056
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1056

Patient Education
MEDICATION-OVERUSE HEADACHES
Pathophysiology
Goals of Therapy
Rational Drug Therapy
1057
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1057

Monitoring
Outcome Evaluation
Patient Education
POST-TRAUMATIC (POST-
CONCUSSIVE) HEADACHES
Pathophysiology
1058
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1058

Goals of Therapy
Rational Drug Therapy
1059
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1059

Monitoring
Patient Education
1060
On The
Horizon
DRUGS THAT MAY PROVIDE
NEUROPROTECTION FOR TBI
Magnesium has demonstrated neuroprotective properties in nu-
merous TBI models. Magnesium has been shown to have many
beneficial effects, including noncompetitive NMDA receptor
blockade, inhibition of presynaptic excitatory neurotransmitter
release, blockade of voltage-gated calcium channels, and reduc-
tion in inflammatory cascades (Burd, Breen, Friedman, Cha, &
Elovitz, 2010). Unfortunately, the data are lacking in specific and
safe recommendations for the use of magnesium in this popula-
tion. Additional studies should help clarify the clinical utility of
magnesium supplementation following TBI (Maas & Murray, 2007).
Progesterone is an agent that appears to provide neuro-
protection by multiple mechanisms. After TBI, progesterone
has been shown to decrease oxidative stress by reducing
membrane lipid peroxidation, reduce BBB disruption, and
ameliorate the brain’s inflammatory response. A phase III clini-
cal trial, the Progesterone for the Treatment of Traumatic Brain
Injury (ProTECT III), is currently underway to further assess the
clinical efficacy of progesterone (Vink & Nimmo, 2009).
Erythropoietin has been identified as a neuroprotective
agent that appears to ameliorate TBI by multiple avenues. The
Erythropoietin in Traumatic Brain Injury (EPO-TBI) trial is currently
underway to assess whether erythropoietin can improve neuro-
logical outcome in severe TBI patients (Vink & Nimmo, 2009).
Minocycline has been extensively studied in mice and has
been shown to be an effective antioxidant and attenuator of
the inflammatory sequelae of TBI. The study, A Safety and
Feasibility of Minocycline in the Treatment of Traumatic Brain
Injury, is currently underway, which will likely lead to additional
clinical investigation of this drug (Schouten, 2007).
Cyclosporin is another multifactorial compound that has
neuroprotective effects, including improving mitochondrial
functioning, blocking free radical production, and inhibiting
calcium accumulation. The animal data have been compelling
that cyclosporin A (CsA) has therapeutic benefits in TBI models.
However, the variability of study designs from the clinical stud-
ies has made the outcome data difficult to interpret. The safety
of CsA use in TBI has been demonstrated, but additional investi-
gation is needed to clarify the efficacy of the drug (Lulic, Burn,
Bae, van Loveren, & Borlongan, 2011).
Numerous other vitamins, minerals, and antioxidant agents
are being investigated as potential therapeutic modalities. These
include nicotinamide, a soluble B-group vitamin. Animal TBI
models have demonstrated beneficial effects, including reduced
cortical damage, inflammation, and behavioral disruption in
animals receiving infusions (Goffus, Anderson, & Hoane, 2010).
Omega-3 essential fatty acids (EFAs) have been shown in
experimental TBI models to improve the blood flow, reduce
the toxic effects of glutamate, and stabilize membranes. Ani-
mal models have shown that specific fatty acids can be sup-
plemented in the diet and provide a protective function for
the brain, especially in regard to seizures (Pages et al, 2011).
An antioxidant, !-lipoic acid, has also shown neuroprotective
effects in an animal model by reducing inflammatory markers,
preserving BBB permeability, and reducing brain edema (Toklu
et al, 2009). Another agent called Resveratrol, which is a
polyphenol, also has antioxidant properties and has been
shown to improve behavioral outcome in a rat TBI model
(Maroon & Bost, 2011). Zinc protoporphyrin has also been
shown to attenuate brain edema and BBB permeability in an
animal model (Vannemreddy et al, 2006).
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1060

REFERENCES
1061
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1061

1062
3827_Ch35_1035-1062 01/07/15 6:33 PM Page 1062

1063
CHAPTER 36
Laura Rosenthal
PATHOPHYSIOLOGY, 1063
Types of Heart Failure
Classifications of Heart Failure
Symptoms of Heart Failure
PHARMACODYNAMICS, 1065
GOALS OF TREATMENT, 1067
RATIONAL DRUG SELECTION, 1067
Guidelines
Diagnosis of Heart Failure
Treatment Recommendations Based on Stage
of Heart Failure
Cost
Additional Patient Variables
Drug Combinations
MONITORING, 1076
OUTCOME EVALUATION, 1077
PATIENT EDUCATION, 1078
H
PATHOPHYSIOLOGY
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1063

Types of Heart Failure
1064
Decreased cardiac output
Decreased systemic
blood pressure
Increased sympathetic
discharge
Decreased renal blood flow
Decreased oxygen
supply to kidney
Increased renin release
Increased angiotensin IIIncreased norepinephrine
Increased remodelingIncreased afterloadIncreased preload
Increased heart rate
Increased contractility
Figure 36–1. Compensatory responses in heart failure.
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1064

Classifications of Heart Failure
Symptoms of Heart Failure
PHARMACODYNAMICS
1065
Table 36–1 Comparison of Classification Systems for Heart Failure (HF)
American College of Cardiology/
New York Heart Association American Heart Association
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1065

1066
Table 36–2 Drugs Commonly Used: Heart Failure
Drug Indication Dosage Form Initial Dose Target Dose
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1066

GOALS OF TREATMENT
RATIONAL DRUG SELECTION
Guidelines
Diagnosis of Heart Failure
1067
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1067

1068
St
ag
e
A
At
h
ig
h
ris
k
fo
r h
ea
rt
fa
ilu
re
b
ut
w
ith
ou
t s
tru
ct
ur
al
h
ea
rt
di
se
as
e
fo
r
sy
m
pt
om
s
of
h
ea
rt
fa
ilu
re
St
ag
e
B
St
ru
ct
ur
al
h
ea
rt
di
se
as
e
bu
t w
ith
ou
t s
ym
pt
om
s
of
h
ea
rt
fa
ilu
re
St
ag
e
C
St
ru
ct
ur
al
h
ea
rt
di
se
as
e
w
ith
p
rio
r o
r c
ur
re
nt
sy
m
pt
om
s
of
h
ea
rt
fa
ilu
re
St
ag
e
D
R
ef
ra
ct
or
y
he
ar
t f
ai
lu
re
re
qu
iri
ng
s
pe
ci
al
ize
d
in
te
rv
en
tio
ns
Pa
tie
nt
s
w
ith
•
hy
pe
rte
ns
io
n
•
co
ro
na
ry
a
rte
ry
di
se
as
e
•
di
ab
et
es
m
el
lit
us

or
Pa
tie
nt
s
•
us
in
g
ca
rd
io
to
xi
ns
•
w
ith
fa
m
ily
h
is
to
ry
o
f
ca
rd
io
m
yo
pa
th
y
Th
er
ap
y
•
Tr
ea
t h
yp
er
te
ns
io
n
•
En
co
ur
ag
e
sm
ok
in
g
ce
ss
at
io
n
•
Tr
ea
t l
ip
id
d
is
or
de
rs
•
En
co
ur
ag
e
re
gu
la
r
ex
er
ci
se
•
D
is
co
ur
ag
e
al
co
ho
l
in
ta
ke
, i
llic
it
dr
ug
u
se
•
AC
E
in
ih
ib
iti
on
in

ap
pr
op
ria
te
p
at
ie
nt
s
(s
ee
te
xt
)
Pa
tie
nt
s
w
ith
•
pr
ev
io
us
M
I
•
LV
s
ys
to
lic
d
ys
fu
nc
tio
n
•
as
ym
pt
om
at
ic
v
al
vu
la
r
di
se
as
e
St
ru
ct
ur
al
he
ar
t d
is
ea
se
D
ev
el
op
m
en
t
of
s
ym
pt
om
s
of
h
ea
rt
fa
ilu
re
R
ef
ra
ct
or
y
sy
m
pt
om
s
of

he
ar
t f
ai
lu
re
at
re
st
Th
er
ap
y
•
Al
l m
ea
su
re
s
un
de
r
st
ag
e
A
•
AC
E
in
hi
bi
to
rs
in

ap
pr
op
ria
te
p
at
ie
nt
s
(s
ee
te
xt
)
•
Be
ta
b
lo
ck
er
s
in

ap
pr
op
ria
te
p
at
ie
nt
s
(s
ee
te
xt
)
Pa
tie
nt
s
w
ith
•
kn
ow
n
st
ru
ct
ur
al
h
ea
rt
di
se
as
e
•
sh
or
tn
es
s
of
b
re
at
h
an
d
fa
tig
ue
, r
ed
uc
ed
e
xe
rc
is
e
to
le
ra
nc
e
Th
er
ap
y
•
Al
l m
ea
su
re
s
un
de
r
st
ag
e
A
•
D
ru
gs
fo
r r
ou
tin
e
us
e:
D
iu
re
tic
s
AC
E
in
hi
bi
to
rs
Be
ta
b
lo
ck
er
s
D
ig
ita
lis
•
D
ie
ta
ry
s
al
t r
es
tri
ct
io
n
Pa
tie
nt
s
w
ho
h
av
e
m
ar
ke
d
sy
m
pt
om
s
at
re
st
d
es
pi
te

m
ax
im
al
m
ed
ic
al
th
er
ap
y
(e
.g
.,
th
os
e
w
ho
a
re

re
cu
rre
nt
ly
h
os
pi
ta
liz
ed
o
r
ca
nn
ot
b
e
sa
fe
ly
d
is
ch
ar
ge
d
fro
m
th
e
ho
sp
ita
l w
ith
ou
t
sp
ec
ia
liz
ed
in
te
rv
en
tio
ns
)
Th
er
ap
y
•
Al
l m
ea
su
re
s
un
de
r
st
ag
es
A
, B
, a
nd
C
•
M
ec
ha
ni
ca
l a
ss
is
t
de
vi
ce
s
•
H
ea
rt
tra
ns
pl
an
ta
tio
n
•
C
on
tin
uo
us
(n
ot

in
te
rm
itt
en
t)
IV

in
ot
ro
pi
c
in
fu
si
on
s
fo
r
pa
llia
tio
n
•
H
os
pi
ce
c
ar
e
Fi
gu
re
3
6–
2.
S
ta
ge
s
in
th
e
ev
ol
ut
io
n
of
H
F
an
d
re
co
m
m
en
de
d
th
er
ap
y
by
s
ta
ge
.
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1068

Treatment Recommendations Based
on Stage of Heart Failure
Stage A
Angiotensin-Converting Enzyme Inhibitors
1069
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1069

Beta Blockers
Stage B
1070
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1070

Stage C
Diuretics
1071
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1071

Cardiac Glycosides
1072
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1072

Angiotensin II Receptor Blockers
Calcium Channel Blockers
Nitrates
Stage D
1073
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1073

Patients With Heart Failure With Preserved Ejection
Fraction (HF-pEF)
Cost
Additional Patient Variables
Concomitant Diseases
Chronic Atrial Fibrillation and the Use
of Anticoagulants
Diabetes and the Use of ACE Inhibitors
1074
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1074

Hypertension and the Early Use of Diuretics
Hyperlipidemia and the Use of Statins
Other Comorbidities
1075
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1075

Age and Gender
Pregnancy
Drug Combinations
MONITORING
1076
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1076

OUTCOME EVALUATION
PATIENT EDUCATION
1077
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1077

REFERENCES
1078
HEART FAILURE PA
TIENT
EDUCATION
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of heart failure, its prognosis, and its long-term effects on other organs of the body besides the heart
■■ Role of lifestyle modifications, including dietary and activity modifications, in improving prognosis and keeping the
number and cost of required drugs down
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of symptoms of worsening failure, including daily weights
■■ What to do when symptoms worsen
■■ Need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Reason for the drug being given and its anticipated action in the disease process
■■ Doses and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur
■■ Coping mechanisms for complex and costly drug regimens
■■ Interactions between other treatment modalities and these drugs
Reasons for Taking the Drug(s)
Patient education about specific drugs is provided in Chapter 16. Specifically for HF, additional information includes the
following: These drugs are given to reduce mortality, reduce symptoms, and improve functional status. Some drugs do all
of these (ACE inhibitors); most do only one. The expectations should be clear about what the drugs can and cannot do.
HF is a chronic condition that rarely occurs in a short period of time, and it is not likely to be corrected in a short period
of time, if at all. Patients with HF must understand the seriousness of this diagnosis, including the 5-year mortality rate of
50% and the potential need for surgeries such as heart transplantation. All of this must be done while maintaining hope
and emphasizing that a good quality of life is possible.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes sodium restriction and avoidance of excessive fluid intake. Diuretics reduce fluid
volume and may interact with dietary restrictions, resulting in orthostatic hypotension. Care should be taken not to reduce
fluid volume too quickly, which exacerbates the problem of decreased cardiac output and may lead to hypotension or renal
insufficiency. Patients should report symptoms of fluid volume deficit. They should be told to rise slowly from a supine to
a standing position to permit the body to redistribute body fluids. Sodium restriction may lead some patients to seek salt
substitutes that have a potassium salt as part of their contents. For patients taking ACE inhibitors, this can result in exces-
sively high potassium levels. Such salt substitutes should be avoided. Nonsalt herbal seasoning is more appropriate.
Regular aerobic exercise such as walking or cycling may improve functional status and decrease symptoms. Regular,
gradually increased exercise may lead to enough improvement, in some cases, to reduce the drugs needed. Timing of exer-
cise with the peak action of drugs is important. Patients are often able to predict the timing of voiding after taking a diuretic
or times when other drugs are more likely to produce dizziness. Exercise timing should take these into consideration.
Adherence Issues
Nonadherence with the treatment regimen in HF may reduce life expectancy and certainly affects functional status. Health-care
providers should be aware of the potential problem of nonadherence, discuss the importance of adherence at each follow-
up visit, and assist patients in removing barriers to adherence (e.g., cost, adverse effects, or complexity of the regimen).
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1078

1079
3827_Ch36_1063-1080 01/07/15 3:05 PM Page 1079

1080
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1081
CHAPTER 37
James Raper • Gina Dobbs
PATHOPHYSIOLOGY, 1082
HIV-1
HIV-2
Transmission
Stages—Natural History of HIV
HIV Life Cycle
GOALS OF TREATMENT, 1085
Rationale for ART Medication Selection
Principles of Therapy
INITIATING ART MEDICATIONS, 1086
Medications Used to Treat HIV
Reverse Transcriptase Inhibitors
Protease Inhibitors
Integrase Strand Transfer Inhibitors
CCR5 Antagonists
Fusion Inhibitors
COST CONSIDERATIONS, 1094
AIDS Drug Assistance Program
Patient Assistance Programs
MEDICATION RESISTANCE, 1096
Pretreatment
Virological Failure
Causes of ART Failure
DISCONTINUATION OR INTERRUPTION
OF ANTIRETROVIRAL MEDICATIONS, 1099
Monitoring
OUTCOME EVALUATION, 1099
CONCLUSION, 1100
N
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PATHOPHYSIOLOGY
HIV-1
1082
3827_Ch37_1081-1102 02/07/15 2:45 PM Page 1082

HIV-2
Transmission
Stages—Natural History of HIV
Viral Structure and Genetic Material
HIV Life Cycle
1083
3827_Ch37_1081-1102 02/07/15 2:45 PM Page 1083

Fusion and Entry
Reverse Transcription and Integration
Transcription and Translation
Assembly, Budding, and Maturation
1084
1. Fusion of HIV
to the host
cell surface. 2. HIV RNA, reverse transcriptase, integrase, and other viral
proteins enter the host cell.
3. Viral DNA is formed by reverse transcription.
4. Viral DNA is transported
across the nucleus
and intergrates into
the host DNA.
5. New viral RNA is
used as genomic
RNA and to make
viral proteins.
6. New viral RNA and proteins
move to the cell surface and
a new, immature HIV forms.
7. The virus matures by
protease-releasing
indivdual HIV proteins.
Viral DNA
Host DNA
New viral RNA
Viral
RNA
gp120
CD4
Co-receptor
(CCR5 or CXCR4)
Host cell
Mature Virion
Reverse
transcriptase
Intergrase
Preintegration
complex
Figure 37–1. HIV replication cycle. Courtesy: National Institute of Allergy and Infectious Diseases (NIAID, 2013).
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1084

GOALS OF TREATMENT
Rationale for ART Medication Selection
Principles of Therapy
1085
BOX 37–1 HIV TREATMENT GOALS
• Improve quality of life
• Obtain maximal and durable suppression of HIV
• Prevent vertical HIV transmission
• Prolong survival
• Reduce HIV-related morbidity
• Reduce transmissibility of HIV
• Restore and preserve immunological function
BOX 37–2 PREDICTORS OF ART
VIROLOGICAL SUCCESS
• High-level patient adherence to ART regimen
• High potency of antiretroviral medication regimen
• Higher baseline CD4 T-cell count
• Low baseline HIV plasma viral RNA level
• Rapid (i.e., equal to or greater than 1 log10 in 1 to
4 mo) reduction of viral RNA level in response
to ART
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1085

INITIATING ART MEDICATIONS
1086
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1087
BOX 37–3 POTENTIAL BENEFITS AND RISKS OF ART
Potential Benefits of Early Therapy
• Maintenance of a higher CD4 T-cell count and prevention of potentially irreversible damage to the immune system
• Decreased risk for HIV-associated complications that can sometimes occur at CD4 counts more than 350 cells/!L,
including tuberculosis, non-Hodgkin lymphoma, Kaposi’s sarcoma, peripheral neuropathy, HPV-associated malignan-
cies, and HIV-associated cognitive impairment
• Decreased risk of nonopportunistic medical conditions, including cardiovascular disease, renal disease, liver disease,
and non–AIDS associated malignancies and infections
• Decreased risk of HIV transmission to others, which will have positive public health implications
Potential Risks of Early Therapy
• Treatment-related side effects and toxicities
• Viral resistance to medications because of incomplete viral suppression, resulting in loss of future treatment options
• Less time for the patient to learn about HIV and its treatment and less time to prepare for the need for adherence
to ART
• Increased total time exposed to medication, with greater chance of treatment fatigue
• Premature use of ART before the development of more effective, less toxic, and/or better studied combinations of
antiretroviral medications
• Transmission of medication-resistant virus in patients who do not maintain full viral suppression
Table 37–1 ART Medications and Treatment Strategies, Naïve Patients
NNRTI-Based Regimen
PI-Based Regimens (in alphabetical order)
INSTI-Based Regimen
Preferred Regimen† for Pregnant Women
NNRTI-Based Regimens (in alphabetical order)
PI-Based Regimens (in alphabetical order)
INSTI-Based Regimen
NNRTI-Based Regimen
Comments
Comments
Comments
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1088
Table 37–1 ART Medications and Treatment Strategies, Naïve Patients—cont’d
PI-Based Regimen
INSTI-Based Regimen
CCR5 Antagonist-Based Regimens
Medications Used to Treat HIV
Reverse Transcriptase Inhibitors
Nucleoside Reverse Transcriptase Inhibitors
3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1088

1089
Ta
bl
e
37
–2

A
nt
ir
et
ro
vi
ra
l A
ge
nt
C
ha
ra
ct
er
is
ti
cs
Re
na
l F
ai
lu
re
D
os
in
g
Li
ve
r
Fo
od

Cr
Cl

Cr
Cl

Cr
Cl

Fa
ilu
re

D
ru
g
N
am
e
Fo
rm
U
su
al
A
du
lt
D
os
e
Ef
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s
30
–5
9
m
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in
10
–2
9m
L/
m
in
<1 0 or D ia ly si s D os in g To xi ci ty N uc le os id e Re ve rs e Tr an sc rip ta se In hi bi to rs (N RT Is ) 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1089 1090 Ta bl e 37 –2 A nt ir et ro vi ra l A ge nt C ha ra ct er is ti cs — co nt ’d Re na l F ai lu re D os in g Li ve r Fo od Cr Cl Cr Cl Cr Cl Fa ilu re D ru g N am e Fo rm U su al A du lt D os e Ef fe ct s 30 –5 9 m L/ m in 10 –2 9m L/ m in <1 0 or D ia ly si s D os in g To xi ci ty Pr ot ea se In hi bi to rs (P Is ) 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1090 1091 N on nu cl eo si de R ev er se T ra ns cr ip ta se In hi bi to rs (N N RT Is ) 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1091 1092 Ta bl e 37 –2 A nt ir et ro vi ra l A ge nt C ha ra ct er is ti cs — co nt ’d Re na l F ai lu re D os in g Li ve r Fo od Cr Cl Cr Cl Cr Cl Fa ilu re D ru g N am e Fo rm U su al A du lt D os e Ef fe ct s 30 –5 9 m L/ m in 10 –2 9m L/ m in <1 0 or D ia ly si s D os in g To xi ci ty Fu si on In hi bi to rs CC R5 A nt ag on is ts In te gr as e St ra nd T ra ns fe r I nh ib ito rs 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1092 Nonnucleoside Reverse Transcriptase Inhibitors Protease Inhibitors Integrase Strand Transfer Inhibitors 1093 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1093 CCR5 Antagonists Fusion Inhibitors COST CONSIDERATIONS AIDS Drug Assistance Program Patient Assistance Programs 1094 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1094 1095 Table 37–3 Brand-Name Antiretroviral Medications, Usual Adult Dosing, and Monthly Average Wholesale (AWP) Price by Mechanistic Class RTV AWP Generic Name Brand Name Usual Adult Dose AWP Price* Total Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (N/NTRTIs) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Protease Inhibitors (PIs) 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1095 1096 Table 37–3 Brand-Name Antiretroviral Medications, Usual Adult Dosing, and Monthly Average Wholesale (AWP) Price by Mechanistic Class—cont’d RTV AWP Generic Name Brand Name Usual Adult Dose AWP Price* Total Fusion Inhibitors (FIs) CCR5 Antagonists Integrase Strand Transfer Inhibitors (INSTIs) Fixed-Dose Tablets From More Than One Class MEDICATION RESISTANCE 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1096 1097 Table 37–4 Resistance Mutations to Antiretroviral Medicine Antiretroviral Medicine Codon Mutation Multi-NRTI Resistance: 69 Insertion Complex (affects all NRTIs) Multi-NRTI Resistance: 151 Insertion Complex (affects all NRTIs) Multi-NRTI Resistance: Thymidine Analogue-Associated Mutations (TAMS; affects all NRTIs) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Mutation in the Protease Gene Associated With Resistance to Protease Inhibitors (PIs) PIs Critical Secondary Mutations in the Envelope Gene Associated With Resistance to Fusion Inhibitors (FIs) and CCR5 Antagonists Mutations in the Integrase Gene Associated With Resistance to Integrase Inhibitors (IIs) 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1097 Pretreatment Virological Failure Causes of ART Failure 1098 BOX 37–4 HIV DRUG RESISTANCE TESTING: EIGHT IMPORTANT CONSIDERATIONS AND LIMITATIONS 1. Biological cutoffs are based on normal distribution of susceptibility to drug for wild-type strain from treatment-naïve patients. 2. Clinical cutoffs are based on data from clinical trials or cohort studies to determine change in susceptibility that results in reduced virological response. 3. Clinical phenotypic cutoff values include diminished versus no response; partial activity may be useful when treatment options are limited. Analysis compli- cated by prior drug exposure and activity of other drugs in salvage regimen. 4. Consider phenotyping over genotyping when treat- ment history is complex and/or significant resistance is expected. 5. May detect resistance only in species that make up more than 10% to 20% of viral population. 6. Measures susceptibility to individual medicines, not medication combinations. 7. Phenotypic resistance reported as fold change in IC50 for the test strain versus reference wild-type strain. 8. Testing should be performed on therapy whenever possible or within 4 weeks of stopping antiretroviral medicines and is not recommended when VL is less than 1,000 copies/mL. BOX 37–5 FACTORS ASSOCIATED WITH ART FAILURE Patient factors at baseline: • AIDS diagnosis • Comorbid conditions (e.g., affective mental health disorders and active substance use) • Earlier calendar year of starting ART when less- potent regimens or more poorly tolerated antiretroviral medicines were used • Higher pretreatment HIV RNA level (regimen- specific) • Lower pretreatment or nadir CD4 T-cell count • Pretreatment drug-resistant virus • Prior ART failure, with development of drug resis - tance or cross-resistance • ART adverse effects and toxicity • Nonadherence to ART and medical appointments • Suboptimal pharmacokinetics caused by variable absorption, metabolism, and/or penetration into HIV reservoirs, food or fasting requirements, ad- verse drug–drug interactions with concomitant medications and foods • Suboptimal potency of the ART regimen • Unknown causes 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1098 DISCONTINUATION OR INTERRUPTION OF ANTIRETROVIRAL MEDICATIONS Monitoring OUTCOME EVALUATION 1099 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1099 CONCLUSION 1100 On The Horizon FIVE DRUGS FOR THE FUTURE New HIV-drug development continues. • GS-7340 (tenofovir alafenamide, TAF), a new oral pro- drug, was well tolerated and had better antiviral activity at lower doses than tenofovir disoproxil fumarate (Viread, TDF) in early studies. Reportedly, in 38 people over 10 days, 25 mg of GS-7340 outperformed 300 mg of the currently approved tenofovir formulation. Along with fewer side effects, GS-7340 showed higher potency, which could mean longer and better viral suppression over time. • Dolutegravir (GSK-572) is an investigational integrase inhibitor, but it has distinguished itself from the two ap- proved integrase inhibitors, raltegravir (Isentress) and elvitegravir. Dolutegravir has a long half-life of 15 hours, indicating it can be taken once a day. It does not require pharmacokinetic boosting. Although resistance can occur, dolutegravir shows activity against raltegravir- and elvitegraivr-resistant viral strains. The drug may be coformulated in a once-daily pill with abacavir and lamivudine. • S/GSK-1265744 (744), an integrase inhibitor similar to dolutegravir, shows high potency and an exceedingly long half-life. Orally at once-daily doses of 30 mg, pa- tients showed a median 2.6 log reduction in viral load. Interestingly, when using nanotechnology to formulate 744 to be injected subcutaneously or intramuscularly, a single dose showed a half-life between 21 and 50 days. After a single dose, patients had detectable levels of 744 up to 48 weeks after injection. Like dolutegravir, 744 seems to have a high barrier to drug resistance. 744 showed activity against raltegravir- and elvitegraivr- resistant viral strains. In terms of safety, there were some injection-site reactions and nodules associated with sub- cutaneous dosing. But conceivably, 744 could be taken as infrequently as every 3 months for treatment, or even as PrEP (pre-exposure prophylaxis). • Cenicriviroc (CVC), an investigational CCR5 antagonist, not only antagonize CCR5 binding, it also antagonizes CCR2 binding. CCR2 is a receptor that sits on the surface of macrophages and may be involved in inflammation. CVC showed potent antiretroviral activity. Cenicriviroc has been found to be well absorbed and within the ex- pected therapeutic range of potency. Further studies will assess the safety, efficacy, and effect of CCR2 inhibition on inflammatory biomarkers. • Albuvirtide is a fusion inhibitor like enfuvirtide that of- fers a lot of activity against HIV but requires twice-daily injections. Albuvirtide, on the other hand, is an investi- gational fusion inhibitor that when given intravenously has a long average half-life of 11 days, warranting weekly dosing. Albuvirtide has a similar design to enfu- virtide. It is a peptide that is an analogue of gp41, one of the envelope proteins on HIV’s surface, and thereby blocks HIV through CD4 membrane fusion. In very early studies, Albuvirtide was generally well tolerated, with no injection-site reactions and no serious adverse events. 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1100 REFERENCES 1101 HIV DISEASE PA TIENT EDUCATION Related to the Overall Treatment Plan/Disease Process ■■ After diagnosis, patients need to be educated regard- ing what it means to be HIV positive (they are in- fected with the HIV virus) versus what AIDS is (their immune system has been affected and they are at risk for life-threatening infections). ■■ Patients need education regarding the chronicity of HIV treatment. The clinician may make an analogy of HIV disease to diabetes; diabetics need insulin for the rest of their life and patients with HIV disease must take their medications daily for the rest of their lives. ■■ HIV-infected patients need to be vaccinated with the recommended adult vaccines, including an annual influenza vaccine. ■■ Symptoms of opportunistic infections should be dis- cussed so that patients receive early treatment. Specific to the Drug Therapy ■■ Highly active antiretroviral therapy (HAART) is a combination of medications and all should be taken together as prescribed to decrease viral load. ■■ Adherence to HAART is critical to prevent the development of drug resistance. Reasons for Taking the Drug(s) ■■ Prevention of serious complications from AIDS. ■■ Prevention of transmission of infection to the uninfected (public health issue). Drugs as Part of the Total Treatment Regimen ■■ Importance of seeking treatment when symptoms appear. ■■ Patients need routine preventive care, including lipid monitoring, cardiovascular health screening, cervical cancer screening, STI screening, and immunizations. Adherence Issues ■■ Importance of following the HAART treatment regi- men instructions to prevent resistance and to keep viral loads low. ■■ Importance of contacting the health-care provider if side effects or rash appears. ■■ The potential for drug interactions. 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1101 1102 3827_Ch37_1081-1102 02/07/15 2:46 PM Page 1102 1103 CHAPTER 38 Marylou V. Robinson HORMONE REPLACEMENT THERAPY, 1103 Pathophysiology Pharmacodynamics Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education OSTEOPOROSIS, 1114 Pathophysiology Ethnic Differences Pharmacodynamics Goals of Treatment Rational Drug Selection Combination Therapy Monitoring Outcome Evaluation HORMONE REPLACEMENT THERAPY 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1103 Pathophysiology ! Physiological Effects of Estrogen Physiological Effects of Progestin 1104 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1104 Physiological Effects of Androgens Menopausal Changes in Hormones 1105 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1105 Pharmacodynamics Estrogens Progestogens 1106 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1106 Goals of Treatment Rational Drug Selection Cardiac Disease Prevention Osteoporosis Prevention 1107 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1107 Cognitive Performance, Sleep Disturbance, and Skin Changes Relief of Perimenopausal and Postmenopausal Symptoms 1108 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1108 1109 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1109 1110 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1110 Progestin Therapy Combination Therapy with Estrogen and Progestins 1111 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1111 Testosterone Therapy Monitoring Outcome Evaluation Patient Education OSTEOPOROSIS 1112 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1112 1113 Ho rm on e re pl ac em en t t he ra py (H RT )/ Es tro ge n re pl ac em en t t he ra py (E RT ) Ne ga tiv e fa m ily hi st or y fo r C HD ? Pa tie nt p re fe re nc e Po sit ive fa m ily h ist or y fo r br ea st c an ce r w ith se co nd -d eg re e clo se re la tiv e No s ym pt om s; pa tie nt p re fe re nc e Po sit ive fo r f am ily ca rd io va sc ul ar d ise as e (C VD ) Po sit ive fo r sy m pt om s Us e ER T if no C HD is p re se nt . Co ns id er tr an sd er m al . If ut er us is p re se nt co ns id er m icr on ize d pr og es tin . Us e HR T/ ER T. Ad d pr og es te ro ne if ut er us is p re se nt . No fo r H RT /E RT O ffe r r al ox ife ne , al en dr on at e, c al cit on in . No o r y es fo r HR T/ ER T Re ev al ua te b en ef it ve rs us ri sk a nn ua lly . Ye s fo r H RT /E RT No fo r H RT /E RT Re ev al ua te ri sk v er su s be ne fit s an nu al ly. Us e ca lci um , v ita m in D wi th a ll t he ra pi es . Fi gu re 3 8– 1. T re at m en t a lg or ith m : H or m on e re pl ac em en t t he ra py /e st ro ge n re pl ac em en t t he ra py . 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1113 Pathophysiology Normal Bone Physiology 1114 HORMONE REPLACEMENT THERAPY PA TIENT EDUCATION Related to the Overall Treatment Plan/Disease Process ■■ Pathophysiology of the changes that take place in the female physiology at menopause that make a woman vulnerable to atrophy of the genital organs, vasomotor instability, and emotional lability, and when lower estrogen levels cause undesirable lipid patterns ■■ Role of lifestyle modifications and the various treatment protocols and medications available ■■ Importance of adherence to the treatment regimen ■■ Need for regular follow-up visits with the primary care provider, including annual screening tests such as mammography Specific to the Drug Therapy ■■ Reasons for the drug’s being given ■■ Doses and schedules for taking the drug ■■ Possible adverse effects and what to do if they occur, especially if uterine bleeding occurs ■■ Interactions between other treatment modalities and these drugs Reasons for Taking the Drug(s) Additional information includes the following: Quality-of-life issues such as relief of hot flashes; target organ atrophy preven- tion; treatment of osteoporosis; prevention of early heart disease, which may be more successful, especially in families who have a hereditary tendency for cardiac disease; and the preliminary data on retention of cognition, which seems promising. Drugs as Part of the Total Treatment Regimen The total treatment regimen includes the following: therapy with alternative herbs and healthier lifestyle, which may relieve symptoms but have not proved to bestow reduced morbidity, as has drug therapy; hormonal therapy is indicated for vaginal atrophy and bladder outlet syndrome; and referral to an appropriate specialist to provide the appropriate care when adverse effects occur as a result of estrogen therapy. Adherence Issues Nonadherence to the treatment regimen may be a result of various causes. Concerns about the WHI results should be dis- cussed with correction of any inaccurate interpretations of media messages. Nonadherence due to the possible risk of can- cer should be discussed, and the absolute risk of cancer rather than relative risk of cancer should be calculated annually. The possibility of minor discomforts, such as breast tenderness, bloating, fluid retention, and the need for follow-up visits, should be discussed prior to therapy. If irregular or unexpected bleeding occurs, patients should be advised to contact their health-care provider for modifications to the treatment regimen rather than stop therapy on their own. 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1114 1115 Table 38–1 Medical Conditions and Drugs That Increase the Risk for Development of Osteoporosis Medical Conditions Drugs 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1115 Bone Loss (Osteoporosis) Ethnic Differences African American Women 1116 Normal Osteoporotic Figure 38–2. Micrographs of normal and osteoporotic bone. Table 38–2 Risk Factors for Osteoporosis and Resultant Fractures Risk Factors for Osteoporosis Risk Factors for Fracture Secondary to Osteoporosis 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1116 Asian Women Hispanic Women Pharmacodynamics 1117 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1117 Goals of Treatment Rational Drug Selection Estrogen Therapy 1118 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1118 Calcium Therapy 1119 Table 38–3 Recommendations for Adequate Dietary Calcium Intake in the United States Calcium Intake Upper Intake Age (mg/d) Levels (mg) Table 38–4 Calcium Preparations Drug Active Calcium How Supplied 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1119 Bisphosphonate Therapy 1120 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1120 Selective Estrogen Receptor Modulators Human Parathyroid Hormone 1121 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1121 Combination Therapy Comparisons Monitoring 1122 Table 38–5 Fracture Risk Reduction Comparisons Vertebral Fracture Non-Vertebral Reduction Reduction 3827_Ch38_1103-1128 01/07/15 5:49 PM Page 1122 1123 Prevention of osteoporosis (no current osteoporosis) Diet Exercise Other DXA: BMD between –1 and –2.5 SD of young normal (osteopenia) Alendronate 5 mg/day or 35 mg/wk OR Risendronate 5 mg/day or 35 mg/wk OR Raloxifen 60 mg/day DXA: > –2.5 SD of
young normal
(osteoporosis)
If fracture risk
See Figure 38–4
Calcium intake:
Adults 19–50 yr: 1,000 mg/day
Adults >50 yr: 1,200 mg/day
Postmenopausal: 1,200 mg/day
Vitamin D:
Adults 19–50 yr: 600 IU/day
Adults 51–70 yr: 800 IU/day
Adults >70 yr: 800 IU/day
Poor sun exposure: 800 IU/day
Low-impact weight-bearing or
aerobic exercise for at least
20 min 3 times/wk
Smoking cessation:
(see Chapter 43)
Alcohol:
Limit alcohol to no more than
2 drinks per day. One drink = 12
oz of beer, 5 oz of wine or 1.5 oz
of 80-proof distilled spirits
Lifestyle modifications
Figure 38–3. Prevention of osteoporosis in patients without the disease.
Estrogen
Calcium
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1124
Low-impact fracture Male with idiopathic or
hypogonadal osteoporosis
Long-term
glucocorticoid
therapy
1. No contraindication
to estrogen therapy
2. Cost considerations
1. Contraindication
to estrogen therapy
2. Risk for breast cancer
3. Hyperlipidemia
Raloxifen 60 mg/day
Teriparatide
Estrogen (see HRT) Alendronate 10 mg/day
or 70 mg/wk
Ibandronate 2.5 mg/day
(equivalent monthly dose)
Risedronate 5 mg/day or
35 mg/wk
1. Contraindication
to estrogen therapy
or male
2. Frail elderly (>80 yr
with or without fracture)
(See Fig. 38–3 with
fracture risk and
osteopenia)
If history of fracture
or failed other therapy
Lifestyle modifications (see Fig. 38–3)
If postmenopausal with multiple fractures,
intensify bisphosphonate therapy or
increase bisphosphonate intensity or
terparatide or consider IV bisphosphonate
or teriparatide
Figure 38–6. Treatment algorithm:
Osteoporosis. (Adapted from Osteo-
porosis and African American Women;
Osteoporosis and Asian American
Women; Osteoporosis and Hispanic
Women [all from NIAMS documents,
2005]; and National Osteoporosis
Foundation, 2004, Physician’s Guide.)
Table 38–6 Common Methods for Bone Density Measurements
Test Sites Measured Comments
Bisphosphonates SERMs
Outcome Evaluation
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1125
OSTEOPOROSIS PA
TIENT
EDUCATION
Patient education should include a discussion of information related to the overall treatment plan as well as that specific to
the drug therapy, reasons for taking the drug, drugs as part of the total treatment regimen, and adherence issues. Patients
who have taken teriparatide should take advantage of the voluntary patient registry to help track the rare occurrence of
osteosarcoma.
Related to the Overall Treatment Plan/Disease Process
■■ Pathophysiology of the dynamic relationship between the osteoclasts and osteoblasts in the process of bone metabo-
lism to help the patient understand how the lack of estrogen begins a cascade of events ending with the increased
risk of osteoporosis in the early years after cessation of menses. For men, discussion of the role of other factors is
important.
■■ The role of excessive intake of alcohol, nicotine, and caffeine and low intake of calcium and vitamin D as modifiable risks
for osteoporosis and how nondrug treatments such as diets high in calcium and vitamin D, exercise, and avoidance of the
high-risk lifestyles can help to prevent osteoporosis.
■■ An understanding of how knowledge of family history, ethnicity, and genetic characteristics helps to identify patients
with nonmodifiable risk factors for osteoporosis.
■■ Importance of adherence to the treatment regimen
■■ Importance of supplementing the diet with additional calcium (up to 1,500 mg) and vitamin D (800 mg) to the osteoporosis
therapy
■■ Self-monitoring of symptoms
■■ What to do when symptoms worsen
■■ Need for regular follow-up visits with the primary care provider and for screening tests such as BMDs every 2 years.
Specific to the Drug Therapy
■■ Reason for the drug(s) to be taken and anticipated action in the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse effects and what to do if they occur
■■ Interactions between other treatment modalities and these drugs
Reasons for Taking the Drug(s)
Patient education specifically for osteoporosis should include the following: that prevention of osteoporosis is more
successful than having to treat it later, especially in those who have a hereditary tendency for bone loss disease;
treatment of fractures is far more expensive than drug therapy; and postmenopausal fractures are associated with
early loss of independent living and reduced life expectancy.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes lifestyle modification: healthy diet, dietary supplements, and exercise. However,
these lifestyle modifications may not be enough, especially in older patients. Some form of drug therapy is usually neces-
sary. A variety of therapies are available, and selection of estrogen versus nonestrogen therapy is possible with the same
results for prevention and treatment of spine, hip, and wrist fractures associated with osteoporosis.
Adherence Issues
Adherence issues include the following:
■■ Media reports about disease and drug therapies have an increasing impact on patients and primary care practices.
■■ Membership in health maintenance organizations may affect the choice of drugs patients will receive.
■■ Patients’ fears or issues about drug therapy may not be based on facts.
■■ Drug therapy educational handouts should be available to patients and their families.
■■ Monitoring appointments are problematic if patients are homebound or transportation is difficult.
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REFERENCES
1126
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1127
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1129
CHAPTER 39
Marylou V. Robinson
C
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY, 1129
Exogenous Pathway
Endogenous Pathway
Atherogenesis
VDRL Levels
GOALS OF TREATMENT, 1132
RATIONAL DRUG SELECTION, 1133
Risk Stratification
Treatment Algorithms
Additional Patient Variables
Cost
MONITORING, 1149
OUTCOME EVALUATION, 1150
PATIENT EDUCATION, 1150
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1129

Exogenous Pathway
Endogenous Pathway
Atherogenesis
1130
On The
Horizon
Drugs in the pipeline are seeking to interfere with the synthe-
sis of PCSK9 (proprotein convertase subtilisin/kexin type 9)
in the liver. This liver protein is part of the natural synthesis of
cholesterol in the body. If blocked with a targeted RNA particle,
cholesterol levels drop (Fitzgerald et al, 2013).
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1130

1131
VLDL, LDL, HDL synthesized by liver
VLDL in plasma VLDL in arterial wallHDL in plasma
Excess LDL embedded
in arterial wall undergoes
oxidation and takes up free
fatty acids from VLDL to
produce cholesterol within
the arterial lumen.
Macrophages within the
vessel wall take up the
cholesterol to become foam
cells (the basic unit of
atherosclerotic plaque).
HDL takes up excess
cholesterol from arterial wall
and carries it to the liver.
Metabolized by the liver
LDL in plasma
Excreted in bile
LDL in arterial wall
Hydrolyzed to IDL
and enriched with
cholesterol by hepatic
triglyceride lipase
Figure 39–1. Relationship of lipid metabolism to atherosclerotic plaque formation. Excess LDL embedded in
the arterial wall undergoes oxidation and takes up free fatty acids from VLDL to produce cholesterol within the
arterial lumen. If the excess cholesterol is not taken up by HDL and carried to the liver, macrophages within
the vessel wall create atherosclerotic plaque from this excess cholesterol.
Table 39–1 Factors That Contribute to Low HDL
Cholesterol Levels
VDDL Levels
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1131

GOALS OF TREATMENT
1132
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1132

RATIONAL DRUG SELECTION
Risk Stratification
1133
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1133

1134
Table 39–2 Major Risk Factors for Coronary Heart Disease (CHD) (Exclusive of LDL Cholesterol)
Risk Factor Positive Risk Negative Risk
Table 39–3 Factors to Be Considered in Future
Guidelines
Table 39–4 Individualized Considerations When Risk
Assessment Places Patient in Uncertain
Category for Pursuing Statin Therapy
Support Raising No Support for
Factor Risk Score Revising Risk Score
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1134

High Risk: CVD or CV Risk Equivalent
Lower Risk: Zero or One Risk Factor
1135
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1135

Treatment Algorithms
Lifestyle Modifications
1136
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1136

Drug Therapy
1137
• Emphasize healthy, balanced diet.
• Encourage moderate physical activity.
• Consider referral to a dietitian.
• Reinforce healthy diet.
• Consider adding plant stanols/sterols.
• Increase fiber intake.
• Consider referral to a dietitian.
• Initiate Tx for
metabolic syndrome.
• Intensify weight
management and
physical activity.
• Increase fiber intake.
• Consider referral
to a dietitian.
Visit 1: Begin lifestyle therapies
6 wk
Visit 2: Evaluate LDL response
If LDL reduction not achieved,
intensify LDL-lowering Tx.
6 wk
Visit 3: Evaluate LDL response.
If LDL reduction not achieved,
consider adding drug Tx.
Visit N: Monitor
adherence to TLC.
Q 4–6 mo
Figure 39–2. Model of steps in Therapeutic Lifestyle
Changes (TLC).
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1137

1138
Table 39–6 Definitions of High-to Low-Intensity
Statin Treatment
High-Intensity Moderate-Intensity Low-Intensity
Rx Daily Rx Daily Rx Daily
* Therapeutic options include intensifying LDL-lowering dietary or drug therapies, emphasizing
weight reduction and increased physical activity, adding drugs to lower triglycerides, and
intensifying control of other risk factors (ATP III).
CHD and CHD
risk equivalents
LDL <100 LDL <100 LDL 100–129 LDL 100–129 LDL >130
TLC + control
other risk factors
TLC + therapeutic
options
TLC + LDL-lowering
drug(s)
Continue TLC
and current drug(s).
Consider other
therapeutic options.*
The LDL cholesterol goal is <100 mg/dL (Intense Therapy). Figure 39–3. Traditional therapeutic approaches for patients with CHD or CHD risk equivalents. Table 39–5 The Four Statin Benefit Groups 3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1138 Drug Therapy 1139 Table 39–7 ATP III Classification of LDL Cholesterol (reference only) LDL Cholesterol Level (mg/dL) Category Table 39–8 ATP III Low-Density Lipoprotein Goals (reference only) LDL Cholesterol Patient Category Goal (mg/dL) Figure 39–4. Traditional approaches for patients with multiple risk factors and 10 year CHD risk 10% to 20%. Multiple (2+) risk factors 7-yr risk 10%–20% LDL >130
LDL >130 LDL <130 LDL <130 TLC 3 mo Control other risk factors Public health message on healthy life habits Reevaluation in 1 yr Continue TLC.Continue TLC and consider adding LDL-lowering drugs. The LDL cholesterol goal is <130 mg/dL. Drugs can be considered if necessary to attain the LD cholesterol goal if the LDL cholesterol level is >130 mg/dL after
a trial of TLC (not targets, but general preferred range based on risk).
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1139

1140
LDL <130 Multiple (2+) risk factors 7-yr risk <10% LDL >130
LDL >160 LDL <160 TLC Control other risk factors Public health message on healthy life habits Reevaluation in 1 yr Continue TLC.Continue TLC and consider adding LDL-lowering drugs. The LDL cholesterol goal is <130 mg/dL. Drug therapy can be considered if LDL cholesterol is >160 mg/dL after a trial of TLC (not targets, but desired
range based on risk).
3 mo
0–1 risk factor
(7-yr risk usually <10%) LDL >160
LDL >190 LDL <160 LDL <130 TLC Public health message on healthy life habits Reevaluation in 5 yr Public health message on healthy life habits Consider drugs if benefits outweigh risk. Continue TLC.Continue TLC and consider adding LDL-lowering drugs. LDL 160–189 Continue TLC and LDL-lowering drugs optional.* The LDL cholesterol goal is <160 mg/dL. Drug therapy can be considered if LDL cholesterol is >190 mg/dL after a trial of TLC. If LDL cholesterol is 160–189 mg/dL,
drug therapy is optional depending on clinical judgment and individual risks.
*Factors favoring drug use are a severe single risk factor, a family history of premature CHD,
and underlying or emerging risk factors in addition to a single major risk factor.
3 mo
LDL 130–159
Figure 39–5. Traditional approaches for patients
with multiple risk factors and 10 year CHD risk
less than 10%.
Figure 39–6. Traditional approaches for
patients with 0 or 1 risk factor.
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1140

1141
Table 39–9 Classification of Triglyceride Levels
Triglyceride Level (mg/dL) Category
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1141

Additional Patient Variables
Children and Adolescents
1142
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1142

1143
Assessment
Repeat lipoprotein analysis; average with first measurement.
Obtain total
blood cholesterol
Obtain lipoprotein analysis.
Blood cholesterol <170 mg/dL (acceptable) Blood cholesterol 170–199 mg/dL (borderline) Blood cholesterol >200 mg/dL
or higher (high)
LDL cholesterol
<110 mg/dL (acceptable) LDL cholesterol >130 mg/dL (high)
LDL cholesterol
110–129 mg/dL (borderline)
LDL cholesterol
<100 mg/dL (acceptable) LDL cholesterol >130 mg/dL (high)
LDL cholesterol
100–129 mg/dL (borderline)
Repeat lipoprotein
analysis within 5 yr.
Provide patient education.
Initiate clinical evaluation.
Initiate Step 1, then
Step 2 diet.
Set goal for LDL cholesterol.
Assess other family members.
Repeat lipoprotein
analysis within 1 yr.
Provide patient education.
Encourage Step 1 diet and
other risk-management
strategies.
Blood cholesterol
<170 mg/dL Blood cholesterol >170 mg/dL
Family history (parent)
of blood cholesterol
level >240 mg/dL
Repeat cholesterol;
average with
first measurement
Family history (parent or
grandparent) of premature
(before age 55)
cardiovascular disease
Repeat total blood
cholesterol within 5 years.
Provide patient education.
Figure 39–7. Management of blood cholesterol in children.
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1143

Middle-Aged Men
Women
1144
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1144

Older Adults
1145
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1145

Young Adults
African Americans
1146
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1146

Hispanic Americans
Native Americans (American Indians)
Asian and Pacific Islanders
Concomitant Disease States
1147
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1147

1148
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1148

Cost
MONITORING
1149
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1149

OUTCOME EVALUATION
PATIENT EDUCATION
1150
HYPERLIPIDEMIA PA
TIENT
EDUCATION
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of lipid disorders and their long-term effects on cardiovascular morbidity and mortality
■■ Role of lifestyle modification, especially dietary therapy, in improving outcomes and keeping the number and cost of
required drugs down
■■ Importance of adherence to the treatment regimen
■■ Need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Reason for the drug(s) being given and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse reactions, how to prevent them, and what to do if they occur
■■ Interaction between lifestyle modifications and the drug(s)
Reasons for Taking the Drug(s)
Patient education about specific drugs is provided in Chapter 16. Specific information related to hyperlipidemia includes
the reasons for drug(s) being taken: Antilipidemics are given to reduce morbidity and mortality from the leading cause
of death in the United States—cardiovascular disease. Discuss the risk of cardiovascular disease with the patient while
maintaining the potential for good quality of life with adequate treatment.
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1150

REFERENCES
1151
HYPERLIPIDEMIAcont’d PA
TIENT
EDUCATION
Drugs as Part of the Total Treatment Regimen
The expectations should be clear about what the drugs can and cannot do. Drugs are supplements to dietary and other
lifestyle modifications, not substitutes for them. Lipid disorders are chronic conditions. Lifestyle modifications and drug
regimens need to be incorporated into patients’ everyday lives. Discontinuation of treatment will result in return of lipids
to pretreatment levels.
Adherence Issues
Nonadherence to the treatment regimen may increase patients’ risk for cardiovascular morbidity and reduce their life
expectancy. Health-care providers should be aware of potential problems with adherence, discuss the importance of
adherence at each follow-up visit, and assist patients in removing barriers to adherence, such as lack of social support
and fear of side effects. Utilization of other health team members, especially the dietitian, should be maximized. Patient
education booklets available from the American Heart Association and the National Cholesterol Education Program may
supplement dietary instruction.
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1151

1152
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1152

1153
3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1153

3827_Ch39_1129-1154 01/07/15 3:01 PM Page 1154

1155
CHAPTER 40
Marylou V. Robinson
H PATHOPHYSIOLOGY
PATHOPHYSIOLOGY, 1155
Factors That Regulate Blood Pressure
Laboratory Tests and Other Diagnostic Procedures
Classification of Blood Pressure for Adults
PHARMACODYNAMICS, 1158
GOALS OF TREATMENT, 1158
Barriers to Goal Attainment
RATIONAL DRUG SELECTION, 1159
Algorithm for Management of Hypertension
Stepped Therapy
Patient Variables
Surgery Patients
Cost
MONITORING, 1173
OUTCOME EVALUATION, 1173
Adherence Issues
PATIENT EDUCATION, 1174
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1155

Factors That Regulate Blood Pressure
Baroreceptors
Endothelial Factors
Kidneys
1156
Systemic arterial pressure
Cardiac output
Stroke volume
SNS/norepinephrine activity
Heart rate
Total peripheral resistance
Arteriolar radius Blood viscosity
PNS activity SNS vasoconstrictor
Plasma norepinephrine
Local controls
—O2
—K+
—CO2
—H+
Hematocrit
SNS vasodilator
End-diastolic ventricular volume
Atrial pressure
Venous return
Venous pressure Skeletal muscle pump
Blood volume
R-A-A system (kidney)
SNS activity on veins
Figure 40–1. Regulation of blood pressure. Systemic arterial pressure is determined by cardiac output and total peripheral resistance. Increases
in cardiac output or total peripheral resistance increase systemic arterial pressure, and decreases in these factors decrease systemic arterial
pressure. Antihypertensive drugs act at one or more of these anatomical sites of blood pressure control.
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1156

Genetic Influences
Laboratory Tests and Other
Diagnostic Procedures
Classification of Blood Pressure for Adults
1157
Table 40–1 Blood Pressure Classifications and Management
Systolic BP Diastolic BP Lifestyle No Compelling Indication Compelling Indication
Classification (mm Hg) (mm Hg) Modification (Drug Therapy) (Drug Therapy)
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1157

PHARMACODYNAMICS
GOALS OF TREATMENT
1158
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1158

Barriers to Goal Achievement
RATIONAL DRUG SELECTION
Algorithm for Management
of Hypertension
Lifestyle Modifications
1159
60
50
40
30
20
10
0
SBP 120 SBP 180
10
-Y
ea
r R
isk
o
f C
HD
(%
)
Cholesterol 180 240 240 240 240 240
HDL 50 50 35 35 35 35
Smoking No No No Yes Yes Yes
Diabetes No No No No Yes Yes
LVH No No No No No Yes
Figure 40–2. Ten-year risk for CHD
by SBP and presence of other risk
factors. (Source: Adapted from
Anderson, K., Wilson, P., Odell. P.,
& Kannel, W. [1991]. An updated
coronary risk profile: A statement
for health professionals. Circulation,
83, 356–362.)
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1159

Stepped Therapy
Initial Drug Therapy
1160
Table 40–2 Lifestyle Modifications
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1160

1161
Lifestyle modifications
Initial drug choices
Without compelling
indications
With compelling
indications
Not at goal blood pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
Not at goal blood pressure (<150/90 mm Hg) (<140/90 mm Hg for those with diabetes or 140/80 chronic kidney disease) SPB 159 or DBP 90–99 mm Hg 150 Thiazide-type diuretics for most; may consider ACEI, ARB, CCB, or combination SPB >160 or
DBP >100 mm Hg
2-drug combination for most
(usually thiazide-type) diuretics
and ACEI, ARB, BB, or CCB
Drug(s) for
compelling indication
Other antihypertensive drugs
(other diuretics, ACEI,
ARB, alpha blockers,
CCB as needed)
Figure 40–3. James et al. (2014).
2014 evidence-based guideline for
the management of high blood
pressure in adults: Report from
the panel members appointed to
the eighth joint national committee
(JNC-8). Journal of the American
Medical Association. 311(5), 507-
520. doi: 10.1001/jama. 2013.284427
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1161

Stepping Up to Multiple Drugs
1162
Table 40–3 Clinical Trial and Guideline Basis for Compelling Indications for Individual Drug Classes
Recommended Drugs
Compelling
Indication* Diuretic BB ACEI ARB CCB Aldo ANT Clinical Trial Basis†
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1162

1163
Table 40–4 Common Combinations of Antihypertensive Drugs
Combination* Fixed-Dose Combination (mg)† Brand Name
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1163

1164
Table 40–5 Drug Choice Based on Concomitant Disease States
Disease State Drug Choice
Compelling Indications Unless Contraindicated
May Have Favorable Effects on Comorbid Conditions
Stepping Down
Patient Variables
Children and Adolescents
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1164

1165
Table 40–5 Drug Choice Based on Concomitant Disease States—cont’d
Disease State Drug Choice
May Have Unfavorable Effects on Comorbid Conditions (May Be Used With Special Monitoring Unless Contraindicated)
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1165

Older Adults
1166
Table 40–6 Max Blood Pressure Readings in Children and Adolescents (mm Hg) by Height at
95th Percentile to Diagnose HTN
Age Girls Girls Boys Boys
50th Percentile 75th Percentile 50th Percentile 75th Percentile
for Height for Height for Height for Height
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1166

Women
1167
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1167

1168
Table 40–7 Antihypertensives in Pregnancy
Acceptable Drug Comments
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1168

Racial and Ethnic Minorities
1169
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1169

Concomitant Diseases and Therapies
1170
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1170

1171
On The
Horizon
Renal GFR values that incorporate cystatin C levels become
more reliable and uncover renal impairment earlier than the
standard measurements. This can dramatically increase the
number of patients requiring renal dosing of medications
(Inkler et al, 2012).
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1171

Surgery Patients
1172
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1172

Cost
MONITORING
OUTCOME EVALUATION
1173
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1173

Adherence Issues
PATIENT EDUCATION
1174
Table 40–8 Factors to Improve Adherence to Therapy
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1174

REFERENCES
1175
HYPERTENSION PA
TIENT
EDUCATION
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of hypertension and its long-term effects on target organs
■■ Role of lifestyle modifications in improving prognosis and keeping the number and cost of required drugs down
■■ Importance of adherence to the treatment regimen
■■ Self-monitoring of blood pressure
■■ Indications of target organ damage
■■ Need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Reason for taking the drug(s) and the anticipated action of the drug(s) on the disease process
■■ Doses and schedules for taking the drug(s)
■■ Possible adverse reactions and what to do when they occur
■■ Coping mechanisms for complex and costly drug regimens
■■ Interaction between lifestyle modifications and these drugs
Reasons for Taking the Drug(s)
Patient education about specific drugs is provided in Chapters 14 and 16. Specific information related to hypertension
includes the reasons for taking the drugs. Antihypertensive drugs are given to reduce mortality and decrease target
organ damage. Some drugs do both; most do one or the other. The expectations should be clear about what the drugs
can and cannot do. Hypertension is a chronic condition that rarely develops in a short space of time and is not likely to
be corrected in a short space of time, if at all. Patients with hypertension must understand the lifelong nature of the dis-
order and the need to incorporate the treatment regimen into their everyday lives. The risk of target organ damage must
be discussed, but hope must be maintained, and the potential for a good quality of life with adequate treatment must
be emphasized.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes salt reduction and avoidance of excessive fluid intake. Diuretics reduce fluid volume and
may interact with dietary sodium reduction, resulting in orthostatic hypotension (OH). Care should be taken not to reduce salt
and fluid too quickly. Patients should be taught to report signs and symptoms of fluid volume deficit. Sodium reduction may
lead some patients to seek salt substitutes that have potassium as part of their contents. For patients taking ACE inhibitors or
ARBs, this choice can result in excessively high potassium levels. Such salt substitutes should be avoided. Nonsalt herbal
seasoning is more appropriate.
Vasodilators can produce OH. Tell patients to rise slowly from a supine position to permit the body to redistribute
body fluids.
Regular aerobic exercise such as walking or cycling can improve blood pressure control. Gradually increased, regular
exercise may lead to improvement in blood pressure level and reduce the drug(s) needed.
Adherence Issues
Nonadherence with the treatment regimen may reduce life expectancy and affect the functioning of target organs.
Health-care providers should be aware of the potential problem of nonadherence, discuss the importance of adherence
at each follow-up visit, and assist patients in removing barriers to adherence, such as the complexity and cost of the
treatment regimen and the presence of adverse reactions.
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1175

1176
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1176

1177
3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1177

3827_Ch40_1155-1178 01/07/15 3:00 PM Page 1178

1179
CHAPTER 41
Marylou V. Robinson
T
THYROID HORMONE SYNTHESIS
THYROID HORMONE SYNTHESIS, 1179
THYROID FUNCTION TESTS, 1180
SCREENING, 1181
HYPERTHYROIDISM, 1182
Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Lifestyle Management
Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
SUBCLINICAL HYPERTHYROIDISM, 1188
HYPOTHYROIDISM, 1188
Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
SUBCLINICAL HYPOTHYROIDISM, 1193
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1179

THYROID FUNCTION TESTS
1180
Table 41–1 Drug Effects on Thyroid Function
Drug Effect on Thyroid Function
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1180

!
SCREENING
1181
Table 41–2 Adult Thyroid Function Tests
Values in Values in
Test Normal Value Hyperthyroidism Hypothyroidism
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1181

HYPERTHYROIDISM
Pathophysiology
Ophthalmopathy
1182
Table 41–3 Systemic Effects of Hyperthyroidism
Body System Clinical Manifestation Underlying Mechanism
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1182

Myxedema
Pharmacodynamics
1183
Table 41–3 Systemic Effects of Hyperthyroidism—cont’d
Body System Clinical Manifestation Underlying Mechanism
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1183

Goals of Treatment
Rational Drug Selection
Lifestyle Management
Drug Therapy
Preoperative Preparation
Patient Variables
1184
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1184

1185
Subclinical hyperthyroidism
TSH and free T4 every 3–4 wk
Presence of atrial fibriliation, ischemic heart disease,
CHF, or pronounced osteoporosis?
Consider treatment
with antithyroid drugs.
Remeasure TSH every
3–6 mo for 1 yr and
then 6–12 mo.
Initial drug choice
Yes No
Euthyroid and stable
Continue therapy and recheck at 6–12 mo.
Disease not under control or relapse
Consult with endocrinologist.
Hyperthyroidism
Presence of pregnancy, ophthalmopathy,
difficulty swallowing, or overt cardiac symptoms?
Consult with/refer
to endocrinologist.
Increase dietary iodine intake
and begin drug therapy based
on TSH, free T4, and WBC lab data.
Patients with short-term
disorder (e.g., thyroiditis)—
beta-adrenergic blockers,
aspirin, or NSAIDs
Children—
Check with specialists
for current RX
Patients with mild disease—
propylthiouracil or methimazole
with beta-adrenergic blocker
to control symptoms
Young or middle-aged—
propylthiouracil or methimazole
with beta-adrenergic blocker
to control symptoms
Graves’ disease without significant ophthalmopathy—
propylthiouracil or methimazole
with beta-adrenergic blocker
to control symptoms
Pregnant patients—
Older adults and cardiac patients—
radioactive iodine; may be pretreated
with propylthiouracil or methimazole
Yes No
Figure 41–1. Drug therapy algorithm: Hyperthyroidism.
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1185

Drug-Related Variables
Monitoring
1186
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1186

Outcome Evaluation
Patient Education
1187
HYPERTHYROIDISM PA
TIENT
EDUCATION
Related to the Overall Treatment Plan
and Disease Process
Understanding the pathophysiology of hyperthy-
roidism and its prognosis
Role of iodine intake in thyroid hormone
production
Importance of adherence to the treatment regimen
Need to take the drug for at least 1 year
Indications of relapse or complications that need to
be reported
Importance of discussing pregnancy or the potential
for pregnancy with the primary care provider
Need for regular follow-up visits with the primary
care provider
Specific to the Drug Therapy
Discussion of the reasons for taking the drug(s) and
the anticipated action of the drug(s) on the dis-
ease process. It is especially important to inform
the patient that antithyroid drugs take 4 to
8 weeks to have a noticeable effect.
Doses and schedules for taking the drug(s)
Possible adverse reactions and what to do when
they occur
Patient education specific to antithyroid drugs is
provided in Chapter 21.
Patient education specific to beta-adrenergic blockers
is provided in Chapter 14.
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1187

SUBCLINICAL HYPERTHYROIDISM
HYPOTHYROIDISM
Pathophysiology
Primary Disease
Secondary Disease
1188
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1188

Pharmacodynamics
Goals of Treatment
1189
Table 41–4 Systemic Effects of Hypothyroidism
Body System Clinical Manifestation Underlying Mechanism
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1189

Rational Drug Selection
Drug Therapy
Patient Variables
1190
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1190

1191
Cl
in
ica
lly
e
ut
hy
ro
id
bu
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SH
s
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le
va
te
d
Pr
im
ar
y
hy
po
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yr
oi
di
sm
If
po
ss
ib
le
, s
to
p
al
l d
ru
gs
wi
th
p
ot
en
tia
l a
nt
ith
yr
oi
d
ef
fe
ct
s.
Yo
un
g
an
d
ot
he
rw
ise
h
ea
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y
In
itia
te
le
vo
th
yr
ox
in
e
50
–1
00
m
cg
d
ai
ly.
Cl
in
ica
lly
a
nd
la
b
eu
th
yr
oi
d
Co
nt
in
ue
c
ur
re
nt
d
os
e
an
d
re
ch
ec
k T
SH
in
6
w
ee
ks
.
If
st
ill
eu
th
yr
oi
d,
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on
tin
ue
cu
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nt
d
os
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an
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TS
H
ev
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y
6–
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m
o.
If
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on
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nt
d
os
e
an
d
re
pe
at
T
SH
e
ve
ry
6–
12
m
o.
If
st
ill
hy
po
th
yr
oi
d,
in
cr
ea
se
in
in
cr
em
en
ts
a
bo
ve
;
re
pe
at
T
SH
in
4
–8
w
k.
If
st
ill
hy
po
th
yr
oi
d,
re
fe
r
to
e
nd
oc
rin
ol
og
ist
.
If
eu
th
yr
oi
d,
co
nt
in
ue
c
ur
re
nt
do
se
a
nd
re
pe
at
TS
H
ev
er
y
6–
12
m
o.
If
TS
H
st
ill
el
ev
at
ed
, r
ef
er
to
en
do
cr
in
ol
og
ist
.
Co
nt
in
ue
c
ur
re
nt
d
os
e
an
d
re
pe
at
T
SH
in
4
–8
w
k.
In
cr
ea
se
d
os
e
by
2
5
m
cg
/d
ay
fo
r >
50
y
r a
nd
/o
r k
no
wn
ca
rd
ia
c
di
se
as
e;
in
cr
ea
se
d
os
e
by
5
0
m
cg
/d
ay
fo
r y
ou
ng
an
d
ot
he
rw
ise
h
ea
lth
y;
ch
ec
k T
SH
in
4
–8
w
k.
Cl
in
ica
lly
h
yp
ot
hy
ro
id
an
d
TS
H
st
ill
el
ev
at
ed
>5
0
yr
a
nd
/o
r k
no
wn
c
ar
di
ac
d
ise
as
e
In
itia
te
le
vo
th
yr
ox
in
e
12
.5
–5
0
m
cg
d
ai
ly.
TS
H
an
d
fre
e
T 4
le
ve
ls
TS
H
an
d
fre
e
T 4
in
4
w
k
Fi
gu
re
4
1–
2.
D
ru
g
th
er
ap
y
al
go
rit
hm
: H
yp
ot
hy
ro
id
is
m
.
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1191

Drug-Related Variables
Monitoring
1192
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1192

Outcome Evaluation
Patient Education
SUBCLINICAL HYPOTHYROIDISM
1193
HYPOTHYROIDISM PA
TIENT
EDUCATION
Related to the Overall Treatment Plan
and Disease Process
Understanding the pathophysiology of hypothy-
roidism and its prognosis.
Role of iodine intake in thyroid hormone production.
Importance of adherence to the treatment regimen.
Length of time the drug will need to be taken. For
those with thyroiditis, this may be less than
12 months. For many with primary hypothy-
roidism, the treatment will be lifelong. The patient
should be informed not to stop taking the drug
without first consulting the health-care provider.
Indications of relapse or complications that need to
be reported.
Importance of discussing pregnancy or the poten-
tial for pregnancy with the primary care provider.
Need to wear a medical identification bracelet stating
that patient is taking thyroid hormone replace-
ment and to inform any provider who sees him or
her that this is the case. This is especially impor-
tant if this provider prescribes any new drugs for
the patient.
Need for regular follow-up visits with the primary care
provider, which will include laboratory monitoring
of thyroid function to determine the status of the
hypothyroidism and any needed dosage adjust-
ments of the drug therapy.
Specific to the Drug Therapy
Discussion of the reasons for taking the drug(s) and
the anticipated action of the drug(s) on the disease
process. It is especially important to inform the
patient that thyroid hormone replacement may
take 4 to 8 weeks to have a noticeable effect.
Doses and schedules for taking the drug(s).
Possible adverse reactions (e.g., rapid heart rate,
cardiac arrhythmias, chest pain, insomnia,
diarrhea, or heat intolerance) and what to do
when they occur.
Additional patient education specific to thyroid
hormones is provided in Chapter 21.
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1193

REFERENCES
1194
3827_Ch41_1179-1194 01/07/15 3:14 PM Page 1194

1195
CHAPTER 42
Anne Hedger
P
ADULT PATIENTS WITH PNEUMONIA
Pathophysiology
ADULT PATIENTS WITH PNEUMONIA, 1195
Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
PEDIATRIC PATIENTS WITH PNEUMONIA, 1199
Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1195

Goals of Treatment
Rational Drug Selection
Clinical Guidelines
1196
Table 42–1 Community-Acquired Pneumonia: Common Pathogens by Age
Age Common Pathogens
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1196

1197
Patient presents with clinical findings of pneumonia
Previously healthy and no
risk factors for drug-resistant
S.pneumoniae (DRSP) infection
Presence of comorbidities, such as chronic
heart, lung, liver, or renal disease; diabetes
mellitus; alcoholism; malignancies; asplenia;
immunosuppressing conditions or drugs;
use of antimicrobials within the previous
3 mo; or other risks for DRSP infection
Clinical improvement in 48–72 hr
Macrolide (azithromycin,
clarithromycin, or
erythromycin)
OR
Doxycycline
A respiratory fluoroquinolone (moxifloxacin,
gemifloxacin, or levofloxacin)
OR
A !-lactam plus a macrolide
(High-dose amoxicillin or amoxicillin-
clavulanate preferred)
Consider resistance.
Broader spectrum antibiotic
Continue to monitor.
Yes No
Figure 42–1. Treatment algorithm: Outpatient treatment of adults with community-acquired pneumonia.
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1197

Dosing Regimen
Patient Variables
1198
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1198

Lifestyle Modifications
Monitoring
Outcome Evaluation
Patient Education
PEDIATRIC PATIENTS
WITH PNEUMONIA
1199
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1199

Pathophysiology
Goals of Treatment
Rational Drug Selection
Patient Variables
1200
CLINICAL PEARLS
Immunizations
Pneumococcal vaccine is recommended for specific
groups of patients. Pneumococcal conjugate (PCV13) is
recommended universally for all infants as part of the
routine infant series, for children aged 6 to 18 years with
immunocompromising conditions (CDC, 2013) and for
adults aged 19 years or older with immunocompromising
conditions, functional or anatomic asplenia, CSF leaks,
or cochlear implants (CDC, 2012a). All patients with
chronic medical conditions who are at high risk for infec-
tions should get a pneumococcal polysaccharide vaccine.
Chronic medical conditions that warrant pneumococcal
vaccination include chronic lung disease (including
asthma); chronic cardiovascular diseases; diabetes mel-
litus; chronic liver diseases, cirrhosis; chronic alcoholism;
functional or anatomic asplenia; immunocompromising
conditions (including chronic renal failure or nephrotic
syndrome); and cochlear implants and cerebrospinal
fluid leaks (ACIP Adult Immunization Work Group, 2013;
ACIP Childhood/Adolescent Immunization Work Group,
2013).
The influenza vaccine is recommended that all per-
sons older than age 6 months be vaccinated annually,
including pregnant women.
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1200

1201
Table 42–2 ! Drugs Commonly Used: Community-Acquired Pneumonia
Drug Dose Length of Treatment Strengths Available Comments
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1201

1202
Table 42–2 ! Drugs Commonly Used: Community-Acquired Pneumonia—cont’d
Drug Dose Length of Treatment Strengths Available Comments
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1202

Monitoring
Outcome Evaluation
Patient Education
1203
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1203

REFERENCES
1204
3827_Ch42_1195-1204 01/07/15 3:10 PM Page 1204

1205
CHAPTER 43
Benjamin J. Miller
T
PATHOPHYSIOLOGY, 1206
Nicotine Delivery
Nicotinic Receptors
Nicotine Withdrawal Syndrome
GOALS OF TREATMENT, 1206
RATIONAL DRUG SELECTION, 1207
Nicotine Replacement Therapy
Antidepressants
Nicotinic Receptor Partial Agonists
Combination Therapy
Nonpharmacological Treatment of Nicotine Addiction
Patient Variables
MONITORING, 1212
OUTCOME EVALUATION, 1213
PATIENT EDUCATION, 1213
Educational Resources
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1205

PATHOPHYSIOLOGY
Nicotine Delivery
Nicotinic Receptors
Nicotine Withdrawal Syndrome
GOALS OF TREATMENT
1206
On The
Horizon TOBACCO-CESSATION THERAPIES
The future looks promising for tobacco-cessation therapies.
Currently, a sublingual form of nicotine replacement, in a 2 mg
or 4 mg dose, is available in Europe and Canada. Scientists are
also investigating the potential of a vaccine that stimulates
antibodies that block nicotine receptors in the brain and will
be used to prevent relapse in smokers who quit. A recent
study examining nicotine vaccinations found the vaccines
were safe and well tolerated; however, insufficient antibodies
developed that would lead to a significant long-term effect on
relapse prevention (Tonstad et al, 2013).
BOX 43–1 ELECTRONIC CIGARETTES
Electronic cigarettes or e-cigarettes are growing in popu-
larity as an alternative to traditional tobacco use,
with U.S. sales expected to exceed $1 billion in 2013.
E-cigarettes are battery-operated devices that deliver
nicotine via inhaled vapor, eliminating the harmful tars
and carbon monoxide. At present, there is considerable
controversy over the health implications of e-cigarettes,
which has attracted the attention of the FDA and the
CDC (Sutfin, McCoy, Morrell, Hoeppner, & Wolfson, 2013).
Because of the ability to regulate the nicotine content,
there may be a role for e-cigarettes in nicotine replace-
ment therapy and tobacco cessation. In a small study of
86 tobacco users, the use of 18 mg of nicotine resulted in
a significant decrease in withdrawal symptoms com-
pared to a control group (Dawkins, Turner, Hasna, & Soar,
2012). These data suggest there may be a future role for
e-cigarettes; however, no evidence-based recommenda-
tions can be made at this time. Further study of the
potential toxic effects of e-cigarette chemicals is
warranted before large scale studies occur.
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1206

RATIONAL DRUG SELECTION
Nicotine Replacement Therapy
Nicotine Gum
Nicotine Lozenge
1207
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1207

Nicotine Nasal Spray
1208
CLINICAL PEARL
Nicotine Gum
Patients complain about the taste of the nicotine gum.
Suggest that the patient try the flavored variety, which
patients seem to tolerate better.
Nicotine Transdermal System
CLINICAL PEARL
Nicotine Patch
Advise patients to dispose of used nicotine patches out
of the reach of children or animals. Enough nicotine is
left in a used patch to lead to toxic levels in a child or
small animal.
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1208

1209
Table 43–1 ! Drugs Commonly Used: Smoking Cessation
Drug Strength Available Dosage Comments
Nicotine Gum
Nicotine Transdermal Patch
Nicotine Nasal Spray
Nicotine Inhaler
Nicotinic Receptor Partial Agonists
Antidepressant
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1209

Nicotine Inhaler
Antidepressants
Bupropion
Nicotinic Receptor Partial Agonists
1210
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1210

Alpha2 Adrenergic Agonists
Combination Therapy
Nonpharmacological Treatment
of Nicotine Addiction
1211
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1211

Patient Variables
Pregnant Women
Children
Adolescents
1212
CLINICAL PEARL
Constipation and Tobacco Cessation
Many patients experience constipation during tobacco
cessation as the stimulating effects of nicotine on the
GI system are decreased. Increased dietary fiber, in-
creased fluids, and use of a bulk-producing laxative
(Metamucil or Citrucel) or osmotic laxative (Miralax) will
help with this problem.
MONITORING
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1212

OUTCOME EVALUATION
PATIENT EDUCATION
Educational Resources
1213
BOX 43–2 NICOTINE POISONING
Nicotine poisoning is a concern if children or pets
ingest nicotine replacement products. There has been
a rise in nicotine poisonings since e-cigarettes have
appeared on the market (Chatham-Stephens et al,
2014). Ingesting even a small amount of nicotine may
be toxic to young children. Symptoms of nicotine poi-
soning include nausea, vomiting, increased salivation,
headache, and sweating. Seizures and respiratory fail-
ure may occur (Toxnet, 2014). Treatment for nicotine
poisoning for mild toxicity is supportive (IV fluids, ob-
servation). Treatment for severe toxicity includes IV flu-
ids, airway support, and mechanical ventilation, with
atropine given for bradycardia or muscarinic signs
(Toxnet, 2014).
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1213

1214
SMOKING CESSATION PA
TIENT
EDUCATION
Related to the Overall Treatment Plan/Disease Process
■■ Education regarding the physical and psychological aspects of tobacco addiction
■■ Role of lifestyle modifications
■■ Importance of adherence to the treatment regimen
■■ Need for regular follow-up visits with the primary care provider
Specific to the Drug Therapy
■■ Doses and schedules for taking the drug
■■ Possible adverse effects and what to do if they occur
■■ Interactions between other treatment modalities and these drugs
Reasons for Taking the Drug(s)
These drugs are given to help a person stop smoking. The medications that are used for smoking cessation need to be used
as prescribed; overuse or underuse will increase treatment failure or lead to adverse effects. The patient needs to under-
stand the danger of nicotine toxicity, know the symptoms, and have clear instructions to cease the medication and notify
the health-care provider. The patient must not smoke while using a nicotine replacement. Nicotine replacement products,
even after they are used, can be toxic to children and to pets; therefore, all of the products need to be handled carefully and
disposed of properly after use.
Drugs as Part of the Total Treatment Regimen
The total treatment regimen includes nonpharmacological strategies. Nonpharmacological strategies such as relaxation,
acupuncture, massage, exercise, and group therapy should be discussed and patients encouraged to incorporate multiple
strategies to help them be successful.
A weight gain of 5 to 8 lb is common during tobacco cessation. Patients need to avoid strict diets during tobacco cessa-
tion and increase exercise during cessation treatment. After they have been tobacco-free for a few months, they can then
work on weight reduction. Encouraging exercise during treatment will decrease the amount of weight gained.
Adherence Issues
Patients should know that having quit before and resumed their habit does not predict that they cannot be successful and
that patients often quit for a while and then lapse 2 or 3 times before they succeed.
Many patients need external motivation to be successful at tobacco cessation. Identifying each patient’s motivation and
reminding her or him of it at each visit will assist patients in refocusing their goals when they feel like giving up. Common
motivators include the health of their children or spouse and their own health. Pointing out the cost savings of quitting
smoking, which can add up to over $250 a month for a pack-a-day smoker in New York City, where cigarettes are $9.00 a
pack, can also help patients focus on their goal. Have them place a photo of what they will buy with their savings in a
prominent place (the refrigerator or bathroom mirror) as a reminder.
REFERENCES
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1214

1215
3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1215

3827_Ch43_1205-1216 01/07/15 5:51 PM Page 1216

1217
CHAPTER 44
Theresa Granger
SEXUALLY TRANSMITTED INFECTIONS, 1217
Populations at Risk
STI as Precursor to Cancer
Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
VAGINITIS, 1231
Pathophysiology
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
T
SEXUALLY TRANSMITTED
INFECTIONS
Populations at Risk
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1217

STI as Precursor to Cancer
Pathophysiology
1218
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1218

Goals of Treatment
Rational Drug Selection
Guidelines
1219
Table 44–1 Differential Diagnosis of Vaginal Discharge
Discharge Disease/
Appearance Symptoms pH Diagnostic Tests Microscope Findings Syndrome
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1219

1220
Table 44–2 ! Drugs Commonly Used: Sexually Transmitted Infections
Pathogen First Choice Alternative Choice
Bacterial Pathogens
Viral Pathogens First Episode Recurring Episodes
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1220

1221
Table 44–2 ! Drugs Commonly Used: Sexually Transmitted Infections—cont’d
Pathogen First Choice Alternative Choice
Human Papillomavirus
Fungal Pathogen Intravaginal Oral
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1221

1222
Table 44–2 ! Drugs Commonly Used: Sexually Transmitted Infections—cont’d
Pathogen First Choice Alternative Choice
Pathogen
PROTOZOAN PATHOGEN
ECTOPARASITIC PATHOGENS
First Choice Alternative Choice
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1222

1223
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1223

1224
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1224

1225
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1225

1226
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1226

1227
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1227

Special Treatment Situations
1228
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1228

1229
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1229

Monitoring
1230
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1230

Outcome Evaluation
Patient Education
VAGINITIS
Pathophysiology
Cytolytic Vaginosis
Atrophic Vaginitis
1231
BOX 44–1 VACCINE-PREVENTABLE
SEXUALLY TRANSMITTED
INFECTIONS
Many of the sexually transmitted infections are vaccine
preventable (HAV, HBV, and HPV). Due to growing pub-
lic health concerns, escalating costs of treatment, and
lack of insurance, preventing infections is, in most cases,
easier and less expensive than treatment. Whenever
possible, patients should be educated early and often
regarding the type of vaccines that they would be
successful candidates to receive. Currently, there is no
approved vaccine available for hepatitis C virus (HCV).
Prophylaxis treatment after exposure to the virus has
not been shown to be effective (CDC, 2010).
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1231

1232
SEXUALLY TRANSMITTED INFECTIONS
Related to the Overall Treatment Plan/Disease Process
■■ Importance of routine Pap smears in women and testicular self-examinations (TSE) in men
■■ Prevention of high-risk sexual behaviors
■■ Avoidance of sexual intercourse until the organism is either eradicated (bacterial) or under control (viral)
■■ Include immunization against selected STDs as part of treatment regimen
Specific to the Drug Therapy
■■ Many OTC products are available to treat symptoms.
■■ Douching is no longer recommended because of the potential for pelvic infection and destroying the normal flora
of Lactobacillus.
■■ BV must be diagnosed and treated on the same day in patients suspected of being pregnant (BV may cause preterm
labor).
■■ Importance of assessment of pregnancy status in all women of childbearing years before prescribing
■■ Choosing a generic agent that has daily or twice-daily dosing increases patient compliance with treatment.
Reasons for Taking the Drug(s)
■■ Prevention of serious complications such as PID and infertility
■■ Prevention of transmission of infection to the uninfected (public health issue)
■■ Prevention of dyspareunia, which affects normal sexual relations
Drugs as Part of the Total Treatment Regimen
■■ Importance of seeking treatment when symptoms appear
■■ Importance of culturing asymptomatic young persons (aged 15 to 24) every 6 months
Adherence Issues
■■ Importance of following the labeled instructions to totally eradicate the infection
■■ Importance of finishing the full course of antibiotics
■■ Importance of contacting the health-care provider if side effects or rash appears
■■ The potential for drug interactions (the macrolides with antifungal, systemic antifungals, and birth control pills)
PATIENT
EDUCATION
Toxic Shock Syndrome
Noninfectious Vaginal Conditions
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1232

Other Conditions
Goals of Treatment
1233
Table 44–3 Treatment for Noninfectious Vulvovaginal Conditions
Condition Drug Used Nondrug Treatment
Hormonal Changes (normal responses)
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1233

Rational Drug Selection
Guidelines
Cost
Patient Variables
Drug Variables
Monitoring
Outcome Evaluation
Patient Education
1234
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1234

REFERENCES
1235
VAGINITIS PA
TIENT
EDUCATION
Related to the Overall Treatment Plan/Disease Process
■■ Knowledge of many causes of vaginal irritation, ranging from allergy to inflammatory conditions associated with local
and systemic disease
■■ Knowledge of the physiological changes in vaginal epithelium from age 12 to 50
■■ Hygiene issues such as types of clothing for underwear, wiping correctly, and emptying bladder before and after
intercourse
Specific to the Drug Therapy
■■ Many OTC products that were previously under prescriptive authority are available to treat symptoms and are still
efficacious.
■■ Douching is no longer recommended because of the potential for pelvic infection and its destruction of the normal flora
of Lactobacillus.
Reasons for Taking the Drug(s)
■■ Prevention of dyspareunia, which affects normal sexual relations
■■ Control of miserable chronic conditions like lichen sclerosus
Drugs as Part of the Total Treatment Regimen
■■ Importance of seeking treatment when symptoms first appear to obtain the correct diagnosis
■■ Drug treatment early may prevent long-term morbidity (atrophy, sclerosis, and cancers).
Adherence Issues
■■ Importance of following the labeled instructions to totally eradicate the infection
■■ Importance of contacting the health-care provider if side effects or rash appears
■■ Potential for drug interactions (the macrolides with antifungal, systemic antifungals, and birth control pills)
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1235

1236
3827_Ch44_1217-1236 01/07/15 3:07 PM Page 1236

1237
CHAPTER 45
Teri Moser Woo
OUTCOME EVALUATION, 1248
PATIENT EDUCATION, 1248
PREVENTION OF TUBERCULOSIS, 1248
Pathophysiology
Drug Therapy
Monitoring
Outcome Evaluation
Patient Education
T
PATHOPHYSIOLOGY, 1238
GOALS OF TREATMENT, 1238
RATIONAL DRUG SELECTION, 1239
Risk Stratification
Screening
Drug Therapy for Infectious Tuberculosis
Drug Therapy for Drug-Resistant Tuberculosis
Algorithm
Extrapulmonary Tuberculosis
Patient Variables
MONITORING, 1247
Adverse Reactions to the Medications
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1237

PATHOPHYSIOLOGY
GOALS OF TREATMENT
1238
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1238

RATIONAL DRUG SELECTION
Risk Stratification
Screening
Drug Therapy for Infectious
Tuberculosis
1239
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1239

1240
Table 45–1 Drug Regimens for Culture-Positive Pulmonary Tuberculosis Caused by
Drug-Susceptible Organisms
Initial Phase Continuation Phase Rating (Evidence)
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1240

Six-Month Regimen
Nine-Month Regimen
1241
Table 45–2 ! Drugs Commonly Used: Tuberculosis
Doses*
First-Line Drugs
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1241

1242
Table 45–2 ! Drugs Commonly Used: Tuberculosis—cont’d
Doses*
Second-Line Drugs
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1242

Drug Therapy for Drug-Resistant
Tuberculosis
1243
Table 45–2 ! Drugs Commonly Used: Tuberculosis—cont’d
Doses*
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1243

Algorithm
Extrapulmonary Tuberculosis
Patient Variables
Pregnancy and Lactation
1244
BOX 45–1 DIRECTLY OBSERVED THERAPY
Directly observed therapy (DOT) reduces the risk of de-
veloping drug resistance. In DOT, the patient is required
to take all of the medication in front of a health-care or
other service provider. The Centers for Disease Control
and Prevention (CDC), the American Thoracic Society
(ATS), and the World Health Organization (WHO)
recommend the widespread or universal use of DOT in
the treatment of TB. DOT has been demonstrated to
ensure the highest degree of compliance with the
medication regimen. Compliance with DOT can be in-
creased in many ways, including convenient clinic times
and locations and incentives such as food, clothing, bus
or carfare money, and gifts.
3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1244

Pediatric Patients
1245
2 mo
culture negative
Cavitation
on CXR
or
Positive AFB
smear at 2 mo No cavitation
CavitationHigh clinicalsuspicion
for active
tuberculosis
No cavitation
on CXR
and
Negative AFB smear
at 2 mo
INH/RIF
INH/RIF
INH/RIF
INH/RIF
INH/RIF
INH/RIF/EMB*/PZA†
INH/RPT‡§
2 mo
culture positive
0 1 2 3 4 6 9
Time (months)
Patients in whom tuberculosis is proved or strongly suspected should have treatment initiated with isoniazid,
rifampin, pyrazinamide, and ethambutol for the initial 2 months. A repeat smear and culture should be performed
when 2 months of treatment have been completed. If cavities were seen on the initial chest radiograph or the
acid-fast smear is positive at completion of 2 months of treatment, the continuation phase of treatment should
consist of isoniazid and rifampin daily or twice weekly for 4 months to complete a total of 6 months of treatment. If
cavitation was present on the initial chest radiograph and the culture at the time of completion of 2 months of therapy
is positive, the continuation phase should be lengthened to 7 months (total of 9 months of treatment). If the patient
has HIV infection and the CD4+ cell count is <100/µL, the continuation phase should consist of daily or 3 times weekly isoniazid and rifampin. In HIV-uninfected patients having no cavitation on chest radiograph and negative acid-fast smears at completion of 2 months of treatment, the continuation phase may consist of either once weekly isoniazid and rifapentine, or daily or twice weekly isoniazid and rifampin, to complete a total of 6 months (bottom). Patients receiving isoniazid and rifapentine, and whose 2-month cultures are positive, should have treatment extended by an additional 3 months (total of 9 months). *EMB may be discontinued when results of drug susceptibility testing indicate no drug resistance. †PZA may be discontinued after it has been taken for 2 months (56 doses). ‡RPT should not be used in HIV-infected patients with tuberculosis or in patients with extrapulmonary tuberculosis. §Therapy should be extended to 9 months if 2-month culture is positive. CXR = chest radiograph; EMB = ethambutol; INH = isoniazid; PZA = pyrazinamide; RIF = rifampin; RPT = rifapen- tine. Source: American Thoracic Society, CDC, and Infectious Diseases Society of America (2003). Treatment of Tuberculosis. MMWR, 52 (RR11), 1–77. Figure 45–1. Treatment algorithm for TB. 3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1245 1246 Table 45–3 Treatment of Tuberculosis in Infants, Children, and Adolescents Disease Category Drug Therapy Comments 3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1246 Newborn Infants The HIV-Positive Patient MONITORING 1247 3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1247 Adverse Reactions to the Medications OUTCOME EVALUATION PATIENT EDUCATION PREVENTION OF TUBERCULOSIS 1248 3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1248 Pathophysiology Drug Therapy 1249 Table 45–4 Latent TB Treatment Regimens Dosing Total Number Drug Duration Schedule of Doses 3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1249 Monitoring Outcome Evaluation 1250 On The Horizon DRUGS IN THE PIPELINE Significant TB drug research has been spawned by the Global Alliance for TB Drug Development, which was established in 2000 to address the need for new and better TB drug treat- ment (www.tballiance.org). Child-appropriate formulations of the standard four-drug therapy (isoniazid + rifampin + pyrazi- namide + ethambutol) are currently in development and un- dergoing phase I clinical trials, as current formulations require either crushing of tablets or cannot easily be measured in the mg/kg dose required for infants less than 5 kg. The following are currently in early phase II trials: • A combination of bedaquiline, clofazamine, and PA-824 in a less than 4-month, all-oral regimen for MDR TB. PA-824 is a nitroimidazole, a novel antibacterial class. • A combination of bedaquiline, pyrazinamide, and PA-824 in a less than 4-month, all-oral regimen for MDR TB. • A combination of bedaquiline, clofazimine, pyrazinamide, and PA-824 in a less than 4-month, all-oral regimen for MDR TB. • A combination of bedaquiline, clofazimine, and pyrazi- namide in a less than 4-month, all-oral regimen for MDR TB. Late phase II trials include a combination of PA-824, moxi- floxacin, and pyrazinamide that is showing promise for curing TB and some forms of MDR TB in 4 months using an oral regi- men that can be administered in a fixed dose. Phase III trials include investigation of a combination of isoniazid, rifampin, pyrazinamide, and moxifloxacin that is demonstrating prom- ise in shortening the length of TB treatment from 6 months to 4 months. Another phase III trial is investigating a combina- tion of ethambutol, rifampin, pyrazinamide, and moxifloxacin in a 4-month regimen to treat TB. The Global Alliance continues to focus funds and scientific energy toward developing drugs that simplify and shorten treatment regimens, are effective against MDR TB, are com- patible with antiretroviral therapies for HIV, and expand the pediatric formulations available. Patient Education 3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1250 REFERENCES 1251 TUBERCULOSIS PA TIENT EDUCATION Related to the Overall Treatment Plan and Disease Process ■■ A clear description of the pathophysiology and mode of transmission of TB: patients need to understand that they can be infectious to their close contacts if they do not receive adequate treatment. ■■ A thorough outline of the complete treatment regimen, including an estimated length of time for treatment: patients need to know up front that they will be receiving months and possibly more than a year of treatment. ■■ Importance of adherence to the treatment regimen. ■■ Importance of regularly scheduled follow-up appointments. Specific to the Drug Therapy ■■ A written plan of the medication schedule is essential, especially with multidrug regimens. ■■ Possible adverse effects of the medications and the importance of reporting immediately to the health-care provider any vague, flu-like symptoms. Reasons for Taking the Drug(s) ■■ The drugs are given to prevent or eliminate infection by M. tuberculosis. Drugs as Part of the Total Treatment Regimen Tuberculosis medications are a part of the total treatment regimen, which also includes strict pulmonary care. Adherence Issues Extensive patient education is essential to successful treatment. The patient must understand the purpose for the long, multidrug treatment regimen and be a partner in the treatment. Adherence is a major issue; therefore, all teaching should have the underlying theme of taking all medication as scheduled. The long period of treatment requires education that is repeated and reviewed at the monthly visits. To teach patients who may be illiterate or who understand English only mini- mally, education should be conducted in a variety of media, such as videos in the patient’s primary language. Peer health counselors may also help to educate patients with TB. DOT may enhance compliance with and adherence to therapy. 3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1251 1252 3827_Ch45_1237-1252 01/07/15 3:06 PM Page 1252 1253 CHAPTER 46 Teri Moser Woo VIRAL UPPER RESPIRATORY INFECTION, 1253 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education SINUSITIS, 1256 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education OTITIS MEDIA, 1259 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education OTITIS EXTERNA, 1264 Pathophysiology Goals of Treatment Rational Drug Selection Monitoring Outcome Evaluation Patient Education U VIRAL UPPER RESPIRATORY INFECTION 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1253 Pathophysiology Goals of Treatment Rational Drug Selection Drug Therapy 1254 Table 46–1 ! Drugs Commonly Used: Viral Upper Respiratory Infections Drug Adult Dose Pediatric Dose Strengths Available Comments Oral Decongestants Topical Decongestants 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1254 Nonpharmacological Therapy Monitoring Outcome Evaluation Patient Education 1255 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1255 SINUSITIS Pathophysiology 1256 CLINICAL PEARL Nutritional or herbal therapy Nutritional or herbal therapy is often thought to de- crease symptoms of the common cold. In the 1970s, Linus Pauling first brought forward the idea that vitamin C prevents and alleviates episodes of the common cold. Although this has still not been scientifically proven, many patients continue to take vitamin C at the first sign of a cold. Zinc lozenges have also been proposed as a treat- ment for the common cold. It is thought that zinc ions inhibit rhinovirus replication in vitro. In a systematic re- view of seven randomized controlled trials (RCTs) (754 patients total), two of the studies suggested reduced duration and severity of upper respiratory infection (URI) symptoms (Marshall, 2000). Another review of 14 placebo-controlled trials published from 1966 to 2000 found that one well-designed study showed im- provement with the use of zinc nasal gel (Caruso, Prober, & Gwaltney, 2007). In a more recent RCT, a group of patients took a 13.3 mg zinc lozenge every 2 to 3 hours while awake and had a significantly shorter duration of cold symptoms (4.0 days versus 7.1 days; P less than 0.0001), shorter duration of cough (2.1 days versus 5.0 days), and nasal discharge (3.0 versus 4.5 days) than did the placebo control group (Prasad, Beck, Bao, Snell, & Fitzgerald, 2008). In light of these studies, zinc lozenges may decrease URI symptoms in some patients. Zinc nasal gels (Zicam) should be avoided after reports of permanent anosmia and an FDA warning to avoid their use. Another common herbal therapy that patients may be using for their cold symptoms is echinacea. Echi- nacea is widely used in Europe for the prevention and treatment of colds and flu. Its use is increasing in the United States. A number of European studies have demonstrated the immune-enhancing properties of echinacea, specifically increasing T-cell activity and in- terferon. Among European providers, echinacea is the leading herbal recommendation for the prevention of colds and flu. It is available in tablet, liquid, and tea bag form. The correct dosage is 900 mg daily divided into two or three doses, or 40 drops of the juice 3 times a day. Length of therapy should not exceed 8 weeks. There are no reported side effects at the recommended dosages. It appears to be safe during pregnancy and lactation. The only true contraindication is having a pro- gressive systemic disease such as tuberculosis or mul- tiple sclerosis or an autoimmune illness. Echinacea is a relative of the daisy; therefore, patients who are allergic to daisies should also avoid any form of echinacea. 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1256 Goals of Treatment Rational Drug Selection 1257 Table 46–2 ! Drugs Commonly Used: Sinusitis and Otitis Media Length of Drug Dose Treatment Strengths Available Comments 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1257 1258 Table 46–2 ! Drugs Commonly Used: Sinusitis and Otitis Media—cont’d Length of Drug Dose Treatment Strengths Available Comments Monitoring Outcome Evaluation Patient Education 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1258 OTITIS MEDIA 1259 Common cold or allergic rhinitis, which develops purulent nasal discharge No Improvement Treat for 5–7 days (10 days in children) Refer to otolaryngologist Worsening or no improvement after 3 days Treat for 7–10 days (10 days in children) Improvement Yes • Symptoms persistent and not improving for ≥10 days • Severe symptoms for 3–4 days • “Double sickening” or worsening of symptoms after 3–4 days Initiate antibiotic treatment with first line treatment: amoxicillin OR amoxicillin-clavulanate OR beta lactamase cephalosporin Initiate treatment with second-line antibiotic: amoxicillin-clavulanate OR beta lactamase stable cephalosporin OR respiratory fluoroquinolone (adults) Worsening or no improvement after 3 days • Age < 2 years • Daycare attendance • Antibiotics in past month • Comorbidities • Immunocompromised • Hospitalized in past 5 days At risk for resistance? Figure 46–1. Algorithm for treatment of sinusitis. 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1259 Pathophysiology Goals of Treatment Rational Drug Selection Guidelines 1260 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1260 Antimicrobial Resistance Dosing Regimen Length of Treatment Watchful Waiting (No Antibiotics) 1261 3827_Ch46_1253-1266 01/07/15 6:26 PM Page 1261 Pain Relief 1262 Child presents with confirmed diagnoses of AOM. Age >2 yr with
nonsevere illness, or
uncertain diagnosis
Observe for 48–72 h
with assurance of
appropriate follow-up.
Age <2 yr and certain diagnosis or older child with severe illness Follow up patient 3–4 wk. Begin appropriate antimicrobial therapy. Does child have fever >39°C
or severe otalgia?
Improvement after
observation period
Yes No
Patient follow-up
on completion of
antibiotics (3–4 wk)
Reassess and confirm
diagnosis AOM, change
antimicrobial therapy
(see Table 47–2)
Yes No
Amoxicillin/clavulanate
90 mg/kg/day of amoxicillin
or appropriate alternative
for penicillin-allergic patient
(see Table 47–2)
Amoxicillin 80–90 mg/kg/day
is first-choice antibacterial.
Patient responds to
initial treatment.
Yes No
Length of treatment
< 2 years: 10 days 2–5 years (mild/moderate AOM): 7 days >6 years (mild/moderate AOM): 5–7 days
Figure 46–2. Algorithm for treatment of AOM.
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1263
Table 46–3 Treatment Options for Otitis Media
Temperature >39°C Antibiotic Treatment
(102.2°F) and Severe Alternative Treatment After 48–72 h of Failure of Initial
Otalgia; or 2 weeks,
consult/refer for work-up.
?Chlamydia
(see Table 47–3)
Culture urine
Symptomatic after 3 days of therapy
STD
(see Chapter 44 )
+ UA/UTI – UA
Begin antimicrobial therapy
(see Table 47–3).
Teach lifestyle management.
Work-up for
other diagnosis
Suspect lower UTI
Urinalysis
Figure 47–1. Treatment protocol: Urinary tract infections in women.
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1274

Male Gender
Pregnancy
1275
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1275

Underlying Cause
MONITORING
1276
Urinary tract infection confirmed by urinalysis and culture
Complicated
Inpatient with IV antibiotics
Repeat culture in 48 h.
Refer to urologist.
Ultrasound before discharge
VUR+
VUR
Urine sterile, asymptomatic
Complete antimicrobial therapy.
Urine not sterile, symptomatic
If urine not sterile, refer to urologist.
Check antibiotic used against sensitivities.
Ultrasound in <10 days if: male, female <36 months or febrile UTI in females age 3–7 yr with a fever >38.5°
Repeat culture after 48 h of antibiotic therapy.
Repeat culture after 48 h of antibiotic therapy.
If urine not sterile, continue therapy to 14 days and
reculture 24–48 h after completion of therapy.
Organism sensitive Organism not sensitive
Antibiotic therapy for 7–14 days (see Table 47–3)
Teach lifestyle management, including toileting habits.
Continue antibiotic for 14 days.
Work-up for complications
Change antibiotic and give
new drug for 14 days.
Recurrent UTI (>2/yr)
Start prophylactic drug for 6 mo.
UTI No UTI
Change drug
for prophylaxis.
Discontinue drug and monitor.
Uncomplicated
Outpatient with oral or IM antibiotics
Figure 47–2. Treatment protocol: Urinary tract infections in children.
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1276

OUTCOME EVALUATION
1277
Dysuria, frequency, urgency
+ UA and culture/UTI + UA and + for prostatitis + only for prostatitis
(Not covered here)
– UA and culture
Refer for work-up.
Reculture in 72 h.
Reculture in 72 h.
Suspect STD.
Culture any urethral discharge.
Urine for gonorrhea/clamydia NAAT
(see Chapter 44)
Begin antimicrobial therapy
(may begin empiric with
trimethoprim-sulfamethoxazole,
but will need to adjust based on culture).
Suspect prostatitis.
Three-void urine specimen for
urinalysis and culture
Choose antimicrobial that
covers both common UTI
organisms and prostatitis.
Suspect UTI.
Urinalysis and urine culture
Urine sterile/asymptomatic
Complete antimicrobial
therapy.
Change antimicrobial
if needed based on culture.
May require 6–12 wk of
antimicrobial therapy.
Consider referral for work-up.
Urine not sterile/symptomatic
Urine not sterile
Figure 47–3. Treatment protocol: Urinary tract infections in men.
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1277

PATIENT EDUCATION
Lifestyle Management
1278
URINARY TRACT INFECTIONS PA
TIENT
EDUCATION
Related to the Overall Treatment Plan or Disease Process
■■ Understanding the causes of UTIs and their prognoses.
■■ Role of lifestyle modifications in preventing UTIs, especially ingestion of cranberry juice or cranberry extract; avoidance of
diaphragms and spermicides, especially those containing nonoxynol-9; voiding 10 to 15 minutes after sexual intercourse
to wash out the bacteria from the urethra that may have entered the bladder during intercourse; maintaining fluid intake
of at least 2,000 mL/d of noncaffeinated fluids; and not resisting the urge to void.
■■ Importance of adherence to the treatment regimen.
■■ Indications of relapse or complications that need to be reported.
■■ Need for a follow-up visit only if patient remains symptomatic.
Specific to the Drug Therapy
■■ Discussion of the reasons for taking the drug(s) and the anticipated action of the drug(s) on the disease process. The patient
should be asymptomatic within 48 hours for simple, uncomplicated lower UTIs and within 7 days for upper UTIs. Urinary
analgesics should relieve symptoms within 24 hours.
■■ Doses and schedules for taking the drug and the length of time the drug will need to be taken. Possible adverse reactions
and what to do when they occur. For patients given phenazopyridine, warn them that the drug turns the urine bright orange
and that this is not an indication of hematuria.
■■ Additional patient education specific to antimicrobials is provided in Chapter 24.
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1278

REFERENCES
1279
3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1279

3827_Ch47_1267-1280 01/07/15 3:25 PM Page 1280

UNIT IV
3827_Ch48_1281-1302 01/07/15 3:23 PM Page 1281

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1283
CHAPTER 48
Priscilla M. Nodine
PHARMACOKINETICS AND PHARMACODYNAMICS
IN WOMEN, 1285
Pharmacokinetics
Pharmacodynamics
FACTORS THAT INFLUENCE MEDICATION
ADMINISTRATION, 1287
Puberty
Pregnancy
Menopause
Older Age
FACTORS THAT INFLUENCE
POSITIVE OUTCOMES, 1292
Number of Drugs Taken
Duration of Medication Therapy
Fear That Medications Cause Disease
Nutritional Status
Safety of Medications While Breastfeeding
Ethnic, Cultural, and Religious Differences
COMMON PROBLEMS THAT REQUIRE
MEDICATIONS, 1293
Menopause
Dysmenorrhea, Premenstrual Syndrome,
and Premenstrual Dysphoric Disorder
Endometriosis
HIV/AIDS in Pregnancy
Infertility
Polycystic Ovarian Syndrome
HEALTH PROMOTION, DISEASE PREVENTION,
AND SCREENING, 1298
GAY AND LESBIAN HEALTH, 1298
D
3827_Ch48_1281-1302 01/07/15 3:23 PM Page 1283

1284
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1284

PHARMACOKINETICS AND
PHARMACODYNAMICS IN WOMEN
Pharmacokinetics
1285
Table 48–1 Gender Differences in Pharmacokinetic Parameters
Pharmacokinetic Parameter Sex-Based Difference
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1285

Pharmacodynamics
1286
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1286

FACTORS THAT INFLUENCE
MEDICATION ADMINISTRATION
Puberty
1287
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1287

Pregnancy
1288
CLINICAL PEARL
Prescribing for adolescents
State laws vary regarding consent for treatment of sex-
ually transmitted infections, contraception, and medical
record confidentiality in minor patients. Nurse practi-
tioners should become familiar with what health-care
services can be provided to minors without parental
consent.
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1288

1289
Table 48–2 Use of Selected Herbs During Pregnancy
Common Name Comments
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1289

Menopause
1290
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1290

1291
Table 48–3 Alternative Therapies for Menopause Symptoms
Symptom Alternative Therapy and Its Effects
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1291

Older Age
FACTORS THAT INFLUENCE
POSITIVE OUTCOMES
Number of Drugs Taken
Duration of Medication Therapy
Fear That Medications Cause Disease
Nutritional Status
1292
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1292

Safety of Medications While Breastfeeding
Ethnic, Cultural, and Religious Differences
COMMON PROBLEMS THAT
REQUIRE MEDICATIONS
Menopause
1293
CLINICAL PEARL
Prescribing in pregnancy and lactation
The pregnancy risk categories (A, B, C, D, X) should be
used as a guide only. Category X (known teratogenic
effects on the fetus) must be avoided in pregnancy. Cat-
egory D drugs should be used only in a life-threatening
situation (i.e., chemotherapy drugs), as known fetal
risks exist. Categories A, B, and C may have some risks.
Every prescription drug now provides “Pregnancy
Implications” and “Lactation” labeling and these should
be read and understood before prescribing.
In 2014 the Food and Drug Administration passed
The Pregnancy and Lactation Labeling Rule that will af-
fect all prescription drugs and biological products. The
pregnancy risk categories (A, B, C, D, X) will be elimi-
nated and replaced with a summary of risks of using
the drug during pregnancy and while breastfeeding.
There will be a new section on drug labels titled
“Female and Male of Reproductive Potential” that will
include information about the need for pregnancy test-
ing, contraceptive recommendations, and drug effects
on fertility. All new drugs approved after June 30, 2015,
will have the new labeling format (with no A, B, C, D,
or X). The new format will be phased in gradually for
previously approved drugs.
CLINICAL PEARL
Prescribing in a diverse culture
Be aware of the common ethnic groups in your patient
population. Get to know the cultures. Frequently, com-
munity programs that teach cultural awareness and
some simple ethnic phrases are available for health-care
personnel. Bookstores carry pocket-sized books to facil-
itate a simple medical interview in different languages.
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1293

Dysmenorrhea, Premenstrual Syndrome,
and Premenstrual Dysphoric Disorder
Dysmenorrhea
1294
CLINICAL PEARL
Progesterone-only therapies
Women who have contraindications to estrogen use
need to be counseled that there are several easy-to-use
progesterone methods, without estrogen, that offer
effective contraception and treatment for dysmenorrhea.
Premenstrual Syndrome (PMS)
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1294

Premenstrual Dysphoric Disorder
Pathophysiology
Treatments
Nutritional Supplements
1295
Table 48–4 Treatment Options for PMDD
Therapy Dosing Symptom Improvement
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1295

Herbals
Drug Therapies
Psychotherapeutics
Endometriosis
1296
Table 48–4 Treatment Options for PMDD—cont’d
Therapy Dosing Symptom Improvement
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1296

Pathophysiology
Drug Therapies
HIV/AIDS in Pregnancy
1297
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1297

Infertility
Polycystic Ovarian Syndrome
HEALTH PROMOTION, DISEASE
PREVENTION, AND SCREENING
GAY AND LESBIAN HEALTH
1298
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1298

REFERENCES
1299
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1299

1300
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1300

1301
3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1301

3827_Ch48_1281-1302 01/07/15 3:24 PM Page 1302

1303
CHAPTER 49
James Raper
HYPOGONADISM, 1304
Pathophysiology
Classifications
Signs and Symptoms of Hypogonadism Across
the Life Span
Older Men
Diagnosis
TESTOSTERONE REPLACEMENT THERAPY, 1307
Pharmacodynamics
Testosterone Clinical Use and Dosing
COMMON PROBLEMS THAT REQUIRE
MEDICATIONS, 1312
Erectile Dysfunction
Benign Prostatic Hyperplasia
Prostatitis and Male Pelvic Pain Syndrome
Hair Loss
HEALTH PROMOTION, DISEASE PREVENTION,
AND SCREENING IN MEN, 1315
ETHNIC AND RACIAL ISSUES, 1315
HEALTH ISSUES FOR MEN WHO HAVE SEX
WITH MEN, 1316
HIV Infection and Sexually Transmitted Infections
Anal Cancer
Tobacco Abuse
CONCLUSION, 1317
G
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1303

HYPOGONADISM
Pathophysiology
Classifications
1304
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1304

Signs and Symptoms of Hypogonadism
Across the Life Span
1305
Dihydrotestosterone (DHT) Estradiol (E2)
• Muscle mass
• Sexual function
• Skeletal growth
• Spermatogenesis
• Bone formation
• Breast tissue
• Acne
• Alopecia
• Facial and body hair
• Prostate growth
Testosterone
Figure 49–1. Effects of testosterone
and its metabolites in men.
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1306
BOX 49–1 COMMON CAUSES OF PRIMARY AND SECONDARY HYPOGONADISM
Primary Hypogonadism
Cancer treatment. Chemotherapy or radiation therapy for the treatment of cancer can interfere with testosterone and
sperm production. The effects of both treatments are often temporary, but permanent infertility may occur. Although
many men regain their fertility within a few months after treatment ends, preserving sperm before starting cancer
therapy is a consideration.
Hemochromatosis. Excess iron in the blood can cause testicular failure or pituitary gland dysfunction, affecting testos-
terone production.
Klinefelter syndrome. In this congenital abnormality of the sex chromosomes, X and Y, a male has two or more X chro-
mosomes in addition to one Y chromosome. The Y chromosome contains the genetic material that determines the
sex of a child and related development. In addition to other defects, the extra X chromosome causes abnormal
development of the testicles, which in turn results in underproduction of testosterone.
Mumps orchitis. If a mumps infection involving the testicles (mumps orchitis) occurs during adolescence or adult-
hood, long-term testicular damage may occur. This may affect normal testicular function and testosterone
production.
Normal aging. As men age, testosterone production slowly and continuously decreases. The rate of decline varies greatly
among men. As many as 30% of men older than 75 years have a low testosterone level, according to the American
Association of Clinical Endocrinologists. The value of treatment is controversial.
Trauma to the testicles. The testicles are prone to injury. Damage to normally developed testicles can cause hypogo-
nadism. Damage to one testicle may not impair testosterone production.
Undescended testicles. Before birth, the testicles develop inside the abdomen and normally move down into their
permanent place in the scrotum. Sometimes, one or both of the testicles do not descend at birth. This condition often
corrects itself within the first few years of life without treatment. If not corrected in early childhood, it may lead to
malfunction of the testicles and reduced production of testosterone.
Secondary Hypogonadism
HIV/AIDS. This virus can cause low levels of testosterone by affecting the hypothalamus, the pituitary, and the
testes.
Inflammatory disease. Certain inflammatory diseases, such as sarcoidosis, histiocytosis, and tuberculosis, involve the
hypothalamus and pituitary gland and can decrease testosterone production.
Kallmann syndrome. Abnormal development of the hypothalamus can cause hypogonadism. This abnormality is also
associated with impaired development of the ability to smell (anosmia).
Medications. Certain drugs and some hormones can affect testosterone production.
Obesity. Being significantly overweight at any age may be linked to hypogonadism.
Opioid users. Commonly prescribed opioids in sustained-action dosage forms usually produce subnormal sex hormone
levels, which may contribute to a diminished quality of life for many patients with painful chronic illness.
Pituitary disorders. An abnormality in the pituitary gland can impair the release of hormones from the pituitary gland to
the testicles, affecting normal testosterone production. A pituitary tumor or other type of brain tumor located near the
pituitary gland may cause testosterone or other hormone deficiencies. Surgery or radiation therapy for the treatment
of brain tumor may impair pituitary function and cause hypogonadism.
Older Men
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1306

Diagnosis
TESTOSTERONE REPLACEMENT
THERAPY
Pharmacodynamics
Anemia
Bone Mineral Density
1307
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1308
Table 49–1 Postpubertal Hypogonadal-Related Problems and Effectiveness of Testosterone
Replacement
Postpubertal Problems Associated With
Hypogonadism Evidence of Improvement With Administration of Testosterone
Cognitive Function
Lower Urinary Tract Symptoms
Metabolic Syndrome and Type 2 Diabetes
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1308

Cardiovascular Disease
Mood and Energy and Quality of Life
Muscle Mass and Strength
1309
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1309

Sexual Desire, Function, and Performance
Testosterone Clinical Use and Dosing
1310
Table 49–2 ! Testosterone Preparations Available in the United States for Replacement in the
Hypogonadal Male
Drug Dose
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1310

Risks and Contraindications
Drug-Drug Interactions
Monitoring
1311
Table 49–3 Comparison of Testosterone Replacement Therapies
Topical Gels
Buccal Intramuscular Subcutaneous & Liquids Topical Patch
Convenience
Cost
Physiological
Side effects
Stigma
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1311

Patient Education
COMMON PROBLEMS THAT
REQUIRE MEDICATIONS
Erectile Dysfunction
Pathophysiology
Phosphodiesterase Type 5 (PDE-5) Inhibitors
1312
Table 49–4 Contraindications and Associated
Potential Risk for Testosterone
Replacement Therapy
Contraindication
Parameter vs. Potential Risk
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1312

1313
Table 49–5 ” Dosing Schedule of PDE-5 Inhibitors
Drug Name How Supplied Dose
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1313

Benign Prostatic Hyperplasia
Prostatitis and Male Pelvic Pain Syndrome
Hair Loss
1314
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1314

HEALTH PROMOTION, DISEASE
PREVENTION, AND SCREENING
IN MEN
ETHNIC AND RACIAL ISSUES
1315
Table 49–6 Screening Tests and Immunization Guidelines for Men by Age
Screening Tests Ages 18–39 Ages 40–49 Ages 50–64 Ages 65 and Older
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1315

HEALTH ISSUES FOR MEN
WHO HAVE SEX WITH MEN
HIV Infection and Sexually Transmitted
Infections
1316
Table 49–6 Screening Tests and Immunization Guidelines for Men by Age—cont’d
Screening Tests Ages 18–39 Ages 40–49 Ages 50–64 Ages 65 and Older
Immunizations
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1316

Anal Cancer
Tobacco Abuse
CONCLUSION
REFERENCES
1317
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1317

1318
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1318

1319
3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1319

3827_Ch49_1303-1320 03/07/15 10:29 AM Page 1320

1321
CHAPTER 50
Teri Moser Woo
HISTORICAL PERSPECTIVE ON PEDIATRIC
PRESCRIBING, 1321
Federal Drug Regulation
Best Pharmaceuticals for Children Act
PHARMACOKINETIC AND PHARMACODYNAMIC
DIFFERENCES IN CHILDREN, 1322
Pharmacokinetics
Pharmacodynamics
DEVELOPMENTAL ASPECTS OF PEDIATRIC
MEDICATION ADMINISTRATION, 1325
Breastfed Infants
Infants
Toddlers and Preschoolers
School-Age Children
Adolescents
FACTORS THAT INFLUENCE
POSITIVE OUTCOMES, 1331
Specific Factors That Influence Compliance
Improving Compliance in the Pediatric Patient
Childhood Obesity Influences Outcomes
P
HISTORICAL PERSPECTIVE
ON PEDIATRIC PRESCRIBING
Federal Drug Regulation
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1321

Best Pharmaceuticals for Children Act
1322
PHARMACOKINETIC AND
PHARMACODYNAMIC DIFFERENCES
IN CHILDREN
Pharmacokinetics
The Pediatric Trials Network is funded by the Best
Pharmaceuticals for Children Act via the Eunice Shriver
National Institute of Child Health and Human Develop-
ment (NICHD). The purpose of the Pediatric Trials Net-
work (PTN) is to create an infrastructure to study critical
drugs and diagnostic devices in children to improve
labeling for pediatric use. The PTN will conduct 16 tri-
als over the next 5 years, adding to critical information
on pediatric drug safety and efficacy. For more informa-
tion see PTN’s website, www.pediatrictrials.org.
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1322

Drug Absorption
Distribution
Metabolism
1323
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1323

1324
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1324

Excretion
Pharmacodynamics
DEVELOPMENTAL ASPECTS
OF PEDIATRIC MEDICATION
ADMINISTRATION
Breastfed Infants
1325
BOX 50–1 PRESCRIBING TO LACTATING WOMEN
Prescribing medications for lactating women should be undertaken with the same caution as prescribing for pregnant women.
Assume that any drug prescribed will, in some amount, be found in the breast milk. Therefore, knowledge regarding safety of
medications for lactating women is essential for all primary care practitioners. When prescribing, take the following steps:
1. Review the safety of the drug during lactation.
2. If the drug is relatively safe, discuss the risks with the mother and explain the symptoms of drug toxicity.
3. Explain that the drug should be taken just after nursing or before infant’s sleep.
4. Measure drug concentrations in milk or infant’s serum when toxicity is likely.
5. Monitor the infant for signs of pharmacological action or drug toxicity.
6. Report any symptoms or signs of drug toxicity to the American Academy of Pediatrics, Committee on Drugs.
A few medications are absolutely contraindicated in lactating women (see Table 50-1). Contraindications include anti-
neoplastic drugs because of immediate or delayed toxicity in the infant. Weekly use of methotrexate for rheumatic disease is
acceptable during lactation, but the infant needs to be monitored closely, with routine laboratory analysis of complete blood
count with differential, liver enzymes, and renal function essential to infant safety. Another contraindication to breastfeeding
Continued
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1325

Drug Excretion in Breast Milk
Factors Influencing an Infant’s Exposure
to Drugs in Breast Milk
1326
BOX 50–1 PRESCRIBING TO LACTATING WOMEN—cont’d
is iodine-containing radioactive medications used in nuclear medicine studies. In this case, temporary cessation of breast-
feeding (“pump and dump”) is indicated. The length of time before resumption of breastfeeding is determined by the
half-life of the radiopharmaceutical agent.
Drugs that should be avoided include lithium and oral contraceptives, yet both have been used in lactating women. Lithium
is excreted in breast milk at about 40% of the concentration of maternal serum, and milk and infant serum levels are
approximately equal. If, for maternal health reasons, lithium needs to be prescribed, the infant’s serum lithium level needs
to be monitored closely. The main contraindication to oral contraceptives containing estrogen is that they may decrease milk
supply. An oral contraceptive with low estrogen levels can be prescribed once the milk supply is well established (more than
6 weeks’ postpartum), but the first choice should be a progestin-only oral contraceptive. Decreased milk supply should be
discussed with the mother as an adverse effect of estrogen-containing oral contraceptives prior to prescribing.
All illicit drugs are contraindicated in lactating women, specifically cocaine, heroin, and methamphetamine. Infants
exposed to cocaine via breast milk may show signs of toxicity (irritability, tremors, increased startle response). Cocaine
metabolites can be found in breast milk for up to 36 hours after the mother’s last dose. Heroin enters breast milk and can cause
neonatal depression. Amphetamines are excreted in breast milk and cause excitation in the infant. Methamphetamine poses
an additional concern because some of the chemicals used to manufacture the illicit drug are toxic to both mother and
infant, specifically lead, which is quite harmful to the infant. Any drug use during lactation should be explored and the
mother encouraged to discontinue breastfeeding if illicit drug use is a concern.
Alcohol and tobacco are two commonly used legal drugs that can affect the breastfed infant. Alcohol passes freely into
breast milk and reaches levels close to maternal serum levels. High levels of alcohol in the breast milk put the infant at risk for
sedation and cause a reduction in the maternal milk-ejecting response. There is controversy regarding maternal alcohol use
during lactation. It is probably safe for the mother to ingest small amounts of alcohol timed just after a feeding, when levels
in the milk are the lowest possible. Tobacco is a concern because of both secondhand smoke exposure and the nicotine that
passes into breast milk. Nicotine passes freely into breast milk, and therefore the breastfed infant is exposed to this toxin. If a
nicotine replacement patch is used for maternal smoking cessation, then the nicotine blood levels and therefore breast milk
levels are lower than with smoked tobacco.
Because drugs are almost never tested for use in lactating women prior to their release onto the market, questions regard-
ing their safety during breastfeeding always exist. Understanding some basic principles regarding the transfer of drugs into
breast milk and their pharmacokinetic actions helps the practitioner make decisions about safe prescribing. The practitioner
should have ready reference to the most current information available about drugs during lactation, including Drug Facts and
Comparisons; Drugs in Pregnancy and Lactation by Biggs, Freeman, and Yaffe; and Teratogen Information Services, available
from your local Poison Control Center.
The National Library of Medicine TOXNET (Toxicology Data Network) maintains a peer-reviewed, searchable online
database of drugs in lactation: LactMed (http://toxnet.nlm.nih.gov/index.html).
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1326

1327
Table 50–1 Effects of Commonly Prescribed Medications on Infants During Lactation
Drug Effect on Infant Comments
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1327

1328
Table 50–1 Effects of Commonly Prescribed Medications on Infants During Lactation—cont’d
Drug Effect on Infant Comments
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1328

Infants
1329
Table 50–1 Effects of Commonly Prescribed Medications on Infants During Lactation—cont’d
Drug Effect on Infant Comments
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1329

School-Age Children
Adolescents
1330
CLINICAL PEARL
Infants
• Parents are often unsure how to administer medica-
tion to an infant. While the parents are in the clinic
with the child, the practitioner should address this
issue and demonstrate how to do it. For ease of ad-
ministration, use a medication syringe and insert the
syringe into the mouth along the inner cheek. To de-
crease choking, advise parents to squirt small
amounts (1 mL) of medication at a time into the inner
buccal space. Wait until the infant swallows, and then
administer another small amount until all the medica-
tion is administered. Direct parents not to administer
the medication directly over the tongue, which in-
creases choking and allows the infant more easily to
spit out the medication.
• Advise parents to check with the pharmacist before
mixing any medication with formula or breast milk;
some medications are bound with the calcium or
other ingredients in the formula, causing them to be
less effective.
• Breastfed infants often choke and sputter when med-
ications are first administered because these infants
are used to only the feel of the breast in their mouths.
Warning parents of this response and teaching them
proper technique will help them gain confidence in
medication administration.
• Giving acetaminophen in suppository form is an
option if administering oral medications to the infant
is difficult. The practitioner can demonstrate this
procedure, which works well in breastfed infants
especially.
Toddlers and Preschoolers
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1330

FACTORS THAT INFLUENCE
POSITIVE OUTCOMES
Specific Factors That Influence
Compliance
Long-Term Medication Regimens
Number of Medications Prescribed
Medication Interval
1331
CLINICAL PEARL
Electrolyte solutions
• Pediatric electrolyte solutions are often not well ac-
cepted by children. One trick is to use electrolyte
popsicles (Pedialyte) or freeze the bottled solution
into homemade popsicles. The cold taste seems to
be better accepted.
• Sugar-free Kool-Aid or another drink mix sweetened
with Nutrasweet can be added to unflavored elec-
trolyte solutions to make the taste of the electrolyte
solution more acceptable to children.
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1331

Palatability
Cost
Family Issues
Improving Compliance in
the Pediatric Patient
Medication Concentration
Written Versus Oral Instructions
Self-Monitoring Calendars
1332
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1332

Telephone/E-mail Reminders
Mobile Phone Medication Adherence Apps
Contracts and Reinforcement Programs
1333
Pain in children can range from teething pain to pain associated with otitis media. Parents often ask the practitioner
about using acetaminophen or ibuprofen for the treatment of pain in children. For the safety of their children and the ef-
ficacy of the medication, parents should be taught how to administer over-the-counter (OTC) pain medications properly.
The two most commonly used analgesics in pediatric patients are acetaminophen and ibuprofen. Aspirin should never be
given to children for acute pain management due to the risk of Reye syndrome, and the practitioner should teach parents this rule.
Acetaminophen can be administered orally or rectally (suppository), and it peaks in 30–60 minutes. Dosage for children is
10–15 mg/kg/dose q4–6h.
Ibuprofen is effective for pain control and has an additive anti-inflammatory effect, which appears to provide better pain
control in acute otitis media than acetaminophen. The correct dosage is 5–10 mg/kg/dose q6–8h. Ibuprofen should not be
administered by parents to children under age 6 months because immature kidneys are unable to excrete it, leading to
increased risk of toxicity and renal damage. All children receiving ibuprofen should be well hydrated to prevent renal damage.
Avoid ibuprofen if fluid intake is decreased.
Although acetaminophen and ibuprofen provide good pain relief for mild to moderate pain and both have antipyretic
effects, ibuprofen may be the drug of choice for night pain associated with otitis media because of its longer duration. Both
drugs are equally easy to administer, although ibuprofen is not available in suppository form. Combining acetaminophen
and ibuprofen in an alternating schedule for fever or pain is not recommended in the outpatient setting. One or the other,
properly dosed, should be used. The goal of antipyretic therapy is not to reduce temperature to normal, but to decrease
discomfort associated with fever.
Give parents a dosing chart with their child’s dose based on weight. The different strengths of acetaminophen must be
dosed correctly.
BOX 50–2 PRESCRIBING OVER-THE-COUNTER PAIN MEDICATIONS
FOR PEDIATRIC PATIENTS
CLINICAL PEARL
Improving compliance with ophthalmic
preparations
• Administration of ophthalmic preparations to tod-
dlers and preschoolers is often difficult, and the in-
cidence of noncompliance increases with each dose
that is a battle to administer. Parents can safely
restrain the child to administer eye medications as
follows:
1. Sit on the floor with the child sitting on the floor
between the parent’s legs.
2. Place the child’s feet near the parent’s feet and the
child’s head between the parent’s thighs.
3. Slip the child’s arms under the parent’s thighs and,
with the legs, hold the child’s head and arms still.
The parent then has both hands free to administer
the eye medication. Although this procedure may
sound drastic, it is a quick way for a parent to administer
the medication when no other adult is around to assist
with a squirming, resistant child.
• Older preschoolers and school-age children often co-
operate with administration of eyedrops if they are
told to lie back and close their eyes. Eyedrops can
then be applied to the inner corner of the eyes (while
the eyes are closed). Next, children are told to open
their eyes, without any head movement. The medica-
tion rolls into the eye when the eye is opened. This
is much easier than the bull’s-eye approach of trying
to get children to keep their eyes open for squeezing
in drops.
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1333

Childhood Obesity Influences Outcomes
REFERENCES
1334
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1334

1335
3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1335

3827_Ch50_1321-1336 01/07/15 6:26 PM Page 1336

1337
CHAPTER 51
Joan M. Nelson
DEMOGRAPHICS, 1337
Diseases Associated With Aging
Pharmacological Issues in Aging
PHYSICAL CHANGES ASSOCIATED WITH AGING, 1338
Mental Changes
Sensory Changes
Musculoskeletal Changes
PHARMACOKINETIC CHANGES, 1339
Absorption and Distribution
Metabolism and Excretion
PHARMACODYNAMIC CHANGES, 1341
PHARMACOTHERAPEUTICS, 1341
Polypharmacy
Adverse Drug Reactions
Drug-Drug and Drug-Food Interactions
Alternative Medicines
Assessment
Adherence
Advice to Prescribers
Self-Medication Practices
Inappropriate Prescribing: Drugs to Be Avoided
in Older Adults
TRANSITIONS OF CARE AND CARE SETTINGS, 1346
GENERAL PRINCIPLES FOR PRESCRIBING
FOR OLDER ADULTS, 1348
P DEMOGRAPHICS
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1337

Diseases Associated With Aging
Pharmacological Issues in Aging
PHYSICAL CHANGES ASSOCIATED
WITH AGING
Mental Changes
Sensory Changes
Sight
Hearing
1338
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1338

Smell and Taste
Peripheral Sensation
Musculoskeletal Changes
PHARMACOKINETIC CHANGES
Absorption and Distribution
Metabolism and Excretion
1339
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1339

1340
Table 51–1 Common Pharmacokinetic and Pharmacodynamic Changes in Older Adults
Pharmacokinetic Process Changes in Older Adults Implications
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1340

PHARMACODYNAMIC CHANGES
PHARMACOTHERAPEUTICS
Polypharmacy
1341
CLINICAL PEARL
Start low, go slow
The Golden Rule of geriatrics: Start low, go slow, but
go! Treat the problem, starting at lower dosages, and
titrate up slowly over a longer period of time than for
a younger person. Evaluate for ADRs before they
become serious and costly.
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1341

Drug-Drug and Drug-Food Interactions
1342
CLINICAL PEARL
Avoiding ADRs
The first step in avoiding ADRs is to establish risk pre-
dictions. Polypharmacy is only part of the picture. Take
into account age, gender, multiple comorbidities, body
weight, renal and hepatic failure, and previous drug
reactions. Avoid medications that create unnecessary
risk for patients who are determined to be at high risk
for ADR.
Adverse Drug Reactions
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1342

Alternative Medicines
Assessment
1343
Table 51–2 Selected Common Drug-Drug Interactions in Older Adults
Drug Drug Interaction
CLINICAL PEARL
Medication review
Have the older adult bring all the drugs he or she is taking,
including herbs, vitamins, and OTC drugs, in a brown
bag to the annual visit. This will enable you to see all
the drugs and to determine if there are overlapping
drugs that could be eliminated, combinations that could
reduce the total number of drugs, or drugs prescribed
by other providers that the patient failed to mention. It
also helps to evaluate the patient’s knowledge of the
drugs, including why the drug is being taken and if he
or she understands the ADRs.
Using a thorough and quick checklist at each clinic
visit with older adult patients provides an accurate eval-
uation of their understanding of the drugs and their ability
to manage the regimen. Box 51-1 is a questionnaire that
may be used for this assessment.
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1343

1344
CLINICAL PEARL
Resources
• A helpful resource to evaluate the quality and content
of herbs and supplements: National Center for Com-
plementary and Integrative Health https://nccih.nih.gov/
• Helpful assessment tools: Try This and How to Try
This Series—Resources for the care of older adults,
including assessment tools and instructions for the
proper use of those tools: http://consultgerirn.org/
• Did you bring all of your medications with you?
• List your medications, and tell me how you
take them.
• Do you have any new eye drops, either over the
counter or from your eye doctor?
• What over-the-counter medications are you taking,
such as food supplements, vitamins, laxatives,
pain relievers, and herbal or natural products?
• What medicine or herbs do you use for headaches,
muscle aches or pains, nausea, or constipation?
• Do you have any problems opening the bottles?
• Do you sometimes skip some of the medicine?
Why?
• What do you do when you run out of your pills?
• At what time of the day do you take your pills,
and do you do this the same every day?
• How do you remember to take your pills? Do you
use a pill box?
• How do you tell the difference between your
medications (size, color)?
• What questions do you have about your
medications?
• Do you have any difficulty paying for your
medications?
• Who sets up and orders your medications?
BOX 51–1 QUESTIONNAIRE FOR
ASSESSING MEDICATION
MANAGEMENT
Adherence
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1344

Advice to Prescribers
Self-Medication Practices
Inappropriate Prescribing: Drugs
to Be Avoided in Older Adults
1345
• Using another’s medications or remedies.
• Changing the prescribed medication regimen
without informing the provider.
• Utilizing self-care practices based on no or poor
information.
• Neglecting to inform the health-care provider
about all therapies being utilized.
• Hoarding medications.
BOX 51–2 POOR DRUG PRACTICES
COMMONLY SEEN IN OLDER
ADULTS
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1345

TRANSITIONS OF CARE
AND CARE SETTINGS
1346
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1346

1347
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1347

GENERAL PRINCIPLES FOR
PRESCRIBING FOR OLDER ADULTS
REFERENCES
1348
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1348

1349
3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1349

3827_Ch51_1337-1350 01/07/15 3:30 PM Page 1350

1351
CHAPTER 52
Ruth L. Schaffler
OVERVIEW OF PAIN CONCEPTS, 1351
The Experience of Pain
Pain Threshold and Pain Tolerance
Neurological Basis of Pain
Special Populations
ACUTE PAIN, 1356
Pathophysiology
Signs and Symptoms
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
CHRONIC PAIN, 1364
Pathophysiology
Pharmacodynamics
Goals of Treatment
Rational Drug Selection
Monitoring
Outcome Evaluation
Patient Education
OVERVIEW OF PAIN CONCEPTS
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1351

The Experience of Pain
Pain Threshold and Pain Tolerance
1352
Table 52–1 Comparisons of Acute and Chronic Pain
Acute Chronic
Etiology
Onset
Localization
Duration
Character
Temporal pattern
Associated symptoms
Prognosis
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1352

Neurological Basis of Pain
Anatomy and Physiology
1353
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1353

Pain Modulation
! ” #
! ”
!
”
#
! #
$
Special Populations
1354
Cerebrum
Midbrain
Pons
NE and 5-HT
(efferent)
Medulla
NE and 5-HT
(efferent)
Spinal cord
Receptor
Substance P
Neurokinin A
Calcitonin gene–related peptide
(afferent)
Somatic sensory area
of cerebal cortex
Tertiary
sensory neuron
Secondary
sensory neuron
Collateral fibers to
reticular formation
Lateral
spinothalamic
tractDorsal root
ganglion
Primary
sensory neuron
Thalamus
Figure 52–1. Anatomy of pain
transmission.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1354

Pediatric Patients
Older Adults
Cognitive Impairment
Comorbid Chronic Illnesses
Pregnancy
Substance Abuse
1355
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1355

ACUTE PAIN
Pathophysiology
Signs and Symptoms
1356
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1356

1357
Lung and
diaphragm
Small
intestine
Heart
Liver Liver
Pancreas
Stomach
Ovary
Kidney
Colon
Bladder
Ureter
Appendix
A B
Kidney
Figure 52–2. Referred pain sites.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1357

1358
C2
C3
C4
C5
T1
T2
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
T1
T2
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12L1
L2
L3
L1
L2
L3
L4
L5
S1
L4
L5
S1
S2
S2
S3
S4
S5
C6
C5
C6
C6
C7
C7
C8
C8
C8
C7
C6
C5
C4
C3
C2
C8
T1
L4
L5
L5
L4
L3
S3
S2
L2
L1
S1
Levels of principal dermatomes
C5
C5, 6, 7
C8, T1
C6
C6, 7, 8
C8
T4
Clavicles
Lateral parts of upper limbs
Medial sides of upper limbs
Thumb
Hand
Ring and little fingers
Level of nipples
T10
T12
L1, 2, 3, 4
L4, 5, S1
L4
S1, S2, L5
S1
S2, 3, 4
Level of umbilicus
Inguinal or groin regions
Anterior and inner surfaces of lower limbs
Foot
Medial side of great toe
Posterior and outer surfaces of lower limbs
Lateral margin of foot and little toe
Perineum
Figure 52–3. Spinal dermatomes.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1358

1359
Table 52–2 Behavioral Responses to Pain
Age Group Vocalizations Facial Expressions Body Movements Coping Strategies
Pharmacodynamics
Anti-Inflammatory Drugs
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1359

1360
Table 52–3 Common Analgesics Used for Pain Relief
Classification Drug Indication Contraindications Side Effects Route
Nonopioids
Selected
Analgesic
Adjuncts
Opioids
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1360

1361
Opioids
! ”
!
!
!
”
! ”
Goals of Treatment
Addiction and Dependency
Table 52–3 Common Analgesics Used for Pain Relief—cont’d
Classification Drug Indication Contraindications Side Effects Route
Local
Anesthetics/
Analgesics
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1361

Rational Drug Selection
1362
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1362

1363
Patient assessment
Assess response to therapy.
If pain relief still ineffective or becomes chronic,
move to Chronic Pain algorithm (Fig. 52–5).
Interventions to resolve cause of pain
(e.g., rest, ice, compression, and elevation)
Analgesia
Adequate pain relief with
tolerable side effects. Goal:
Return to normal ADLs
Adequate pain relief
but intolerable side effects
Inadequate pain relief
or increased pain not
explained by initial cause
Adequate pain relief with
tolerable side effects
Ineffective pain relief
Taper off drugs.
Continue to treat with
drug and adjunct therapy
as needed.
Treat side effects.
• Constipation is common.
• Nausea may not be
related to drugs.
New pain cause
Return to interventions to
resolve cause of pain.
Change medication
May require opiates
Mild to moderate pain
Salicylates
NSAIDs
Acetaminophen
Severe pain
Increased doses of drugs
for mild to moderate pain
Use opiates.
Figure 52–4. Acute pain manage-
ment algorithm.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1363

Monitoring
Outcome Evaluation
Patient Education
CHRONIC PAIN
1364
ACUTE PAIN MANAGEMENT PA
TIENT
EDUCATION
Related to the Overall Treatment
Plan and Disease Process
■■ Pathophysiology of pain and its cause (where
appropriate), at a level the patient can understand,
to explain how the drugs work.
■■ Importance of adherence to the treatment regimen.
■■ Indications for contacting the health-care provider
when pain relief is ineffective.
■■ Need for follow-up visit(s) with the primary care
provider.
Specific to the Drug Therapy
■■ Reasons for taking the drug(s) and the anticipated
action of these drug(s) in pain relief.
■■ Doses and schedules for taking the drug(s), including
early round-the-clock dosing of drugs.
■■ Possible adverse reactions and what to do if they
occur.
Reasons for Taking the Drug(s)
■■ Patient education about specific drugs is provided in
Chapters 15 and 25. The explanations should be clear
about what pain drugs can and cannot do.
Drugs as Part of the Total Treatment Regimen
■■ Role of both pharmacological and nonpharmacological
treatments for pain and their interconnection.
Adherence Issues
■■ The fact that most acute pain can be resolved should
be stressed. The importance of that resolution to avoid
the development of chronic pain should be addressed.
■■ Adherence to the drug regimen is important to
resolving acute pain.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1364

Pathophysiology
Nociceptive Pain
Neurogenic Pain
Psychogenic Pain
Pharmacodynamics
1365
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1365

Goals of Treatment
Rational Drug Selection
Lifestyle Modifications
Cognitive-Behavioral Interventions
Drug Therapy
Anti-Inflammatories
1366
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1366

1367
In
fre
qu
en
t f
la
re
s
<4 d ay s/ wk Ef fe ct ive ? Co nt in ue th er ap y. An al ge sic s (n on op io id ) To pi ca l li do ca in e Ca ps ai cin c re am Ps yc ho lo gy Ad d sh or t-a ct in g op ia te s. (U p to 6 0 ta bl et s/ m o. If >6
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la
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s
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Tr
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r p
oi
nt
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er
ap
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Re
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xa
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n
St
re
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m
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en
t
Pa
in
fr
eq
ue
nc
y
Ph
ys
ica
l t
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ra
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Ps
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ho
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gy
Ph
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ica
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he
ra
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Fr
eq
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nt
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o
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an
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o
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Re
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o
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ic
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An
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(T
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, S
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tic
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s
Lo
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-a
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in
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op
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te
s
St
ru
ct
ur
al
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at
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,
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Ne
ur
op
at
hi
c
Ne
rv
e
in
ju
ry
In
ef
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ive
?
CR
PS
Re
co
nd
itio
ni
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St
re
tc
h
ex
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es
Bo
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m
ec
ha
ni
cs
Co
gn
itiv
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be
ha
vio
ra
l s
tra
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gi
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Re
la
xa
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St
re
ss
m
an
ag
em
en
t
An
tid
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re
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an
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Sl
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p
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gi
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m
ea
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Re
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o
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Fi
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5
2–
5.
C
hr
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ai
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m
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lg
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ith
m
.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1367

Adjuvant Analgesics
!
Opioids
1368
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1368

Outcome Evaluation
Patient Education
1369
Monitoring
RECLASSIFICATION OF HYDROCODONE
AS SCHEDULE II
In 2013 the U.S. Food and Drug Administration (FDA)
recommended that the U.S. Drug Enforcement Adminis-
tration (DEA) reclassify hydrocodone from a Schedule III
to a Schedule II drug due to the misuse and abuse
of the drug. In October 2014 the DEA reclassified hy-
drocodone, the most prescribed opioid in the United
States, as a Schedule II drug.
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1369

REFERENCES
1370
CHRONIC PAIN MANAGEMENT
Related to the Overall Treatment Plan and Disease Process
■■ Pathophysiology of pain and its cause (where appropriate), at a level the patient can understand, to explain how the
drugs work.
■■ Role of lifestyle modification in improving prognosis and keeping the number and cost of required drugs and other
treatments down.
■■ Indications for contacting the health-care provider when pain relief is ineffective.
■■ Need for follow-up visit(s) with the primary care provider.
Specific to the Drug Therapy
■■ Reasons for taking the drug(s) and the anticipated action of these drug(s) in pain relief.
■■ Doses and schedules for taking the drug(s), including round-the-clock dosing of drugs.
■■ Possible adverse reactions and what to do if they occur.
■■ Coping mechanisms to deal with the complex and costly treatment regimens.
Reasons for Taking the Drug(s)
■■ Patient education about specific drugs is provided in Chapters 15 and 25. The explanations should be clear about what
pain drugs can and cannot do.
■■ Patient should be made aware that the drug(s) may need to be taken over a long period of time, so interventions to
reduce adverse reactions and reporting them when they occur are important.
Drugs as Part of the Total Treatment Regimen
■■ Role of both pharmacological and nonpharmacological treatments for pain and their interconnection.
Adherence Issues
■■ The fact that most chronic pain cannot be resolved should be addressed.
■■ Adherence to the drug regimen is important to improving chronic pain.
■■ Adherence to lifestyle issues is equally important.
■■ Discussion of ways to remove barriers to adherence should occur.
PATIENT
EDUCATION
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1370

1371
3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1371

3827_Ch52_1351-1372 01/07/15 6:51 PM Page 1372

A
1373
Index
3827_Index_1373-1398 10/07/15 10:10 AM Page 1373

1374
3827_Index_1373-1398 10/07/15 10:10 AM Page 1374

1375
3827_Index_1373-1398 10/07/15 10:10 AM Page 1375

B
1376
3827_Index_1373-1398 10/07/15 10:10 AM Page 1376

1377
C
3827_Index_1373-1398 10/07/15 10:10 AM Page 1377

1378
3827_Index_1373-1398 10/07/15 10:10 AM Page 1378

1379
D
3827_Index_1373-1398 10/07/15 10:10 AM Page 1379

1380
3827_Index_1373-1398 10/07/15 10:10 AM Page 1380

1381
E
3827_Index_1373-1398 10/07/15 10:10 AM Page 1381

F
1382
3827_Index_1373-1398 10/07/15 10:10 AM Page 1382

1383
G
3827_Index_1373-1398 10/07/15 10:10 AM Page 1383

H
1384
3827_Index_1373-1398 10/07/15 10:10 AM Page 1384

1385
3827_Index_1373-1398 10/07/15 10:10 AM Page 1385

I
1386
3827_Index_1373-1398 10/07/15 10:10 AM Page 1386

1387
J
K
L
3827_Index_1373-1398 10/07/15 10:10 AM Page 1387

M
1388
3827_Index_1373-1398 10/07/15 10:10 AM Page 1388

1389
N
3827_Index_1373-1398 10/07/15 10:10 AM Page 1389

O
1390
3827_Index_1373-1398 10/07/15 10:10 AM Page 1390

1391
P
3827_Index_1373-1398 10/07/15 10:10 AM Page 1391

1392
3827_Index_1373-1398 10/07/15 10:10 AM Page 1392

1393
Q
R
3827_Index_1373-1398 10/07/15 10:10 AM Page 1393

S
1394
3827_Index_1373-1398 10/07/15 10:10 AM Page 1394

1395
T
3827_Index_1373-1398 10/07/15 10:10 AM Page 1395

1396
3827_Index_1373-1398 10/07/15 10:10 AM Page 1396

1397
U
V
3827_Index_1373-1398 10/07/15 10:10 AM Page 1397

W
X
Y
Z
1398
3827_Index_1373-1398 10/07/15 10:10 AM Page 1398

Cover
Title Page
Copyright
Dedication
PREFACE
ABOUT THE AUTHORS
CONTRIBUTORS
REVIEWERS
CONTENTS
UNIT I
Chapter 1
THE ROLE OF THE ADVANCED PRACTICE NURSE AS PRESCRIBER
Chapter 2
REVIEW OF BASIC PRINCIPLES OF PHARMACOLOGY
Chapter 3 RATIONAL DRUG SELECTION
Chapter 4
LEGAL AND PROFESSIONAL ISSUES IN PRESCRIBING
Chapter 5
ADVERSE DRUG REACTIONS
Chapter 6 FACTORS THAT FOSTER POSITIVE OUTCOMES
Chapter 7
CULTURAL AND ETHNIC INFLUENCES IN PHARMACOTHERAPEUTICS
Chapter 8
AN INTRODUCTION TO PHARMACOGENOMICS
Chapter 9
NUTRITION AND NUTRACEUTICALS
Chapter 10 HERBAL THERAPY AND NUTRITIONAL SUPPLEMENTS
Chapter 11
INFORMATION TECHNOLOGY AND PHARMACOTHERAPEUTICS
Chapter 12
PHARMACOECONOMICS
Chapter 13
OVER-THE-COUNTER MEDICATIONS
UNIT II PHARMACOTHERAPEUTICS WITH SINGLE DRUGS
Chapter 14 DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM
Chapter 15 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM
Chapter 16 DRUGS AFFECTING THE CARDIOVASCULAR AND RENAL SYSTEMS
Chapter 17 DRUGS AFFECTING THE RESPIRATORY SYSTEM
Chapter 18 DRUGS AFFECTING THE HEMATOPOIETIC SYSTEM
Chapter 19 DRUGS AFFECTING THE IMMUNE SYSTEM
Chapter 20 DRUGS AFFECTING THE GASTROINTESTINAL SYSTEM
Chapter 21 DRUGS AFFECTING THE ENDOCRINE SYSTEM
Chapter 22 DRUGS AFFECTING THE REPRODUCTIVE SYSTEM
Chapter 23 DRUGS AFFECTING THE INTEGUMENTARY SYSTEM
Chapter 24 DRUGS USED IN TREATING INFECTIOUS DISEASES
Chapter 25 DRUGS USED IN TREATING INFLAMMATORY PROCESSES
Chapter 26 DRUGS USED IN TREATING EYE AND EAR DISORDERS
UNIT III PHARMACOTHERAPEUTICS WITH MULTIPLE DRUGS
Chapter 27 ANEMIA
Chapter 28 CHRONIC STABLE ANGINA AND LOW-RISK UNSTABLE ANGINA
Chapter 29 ANXIETY AND DEPRESSION
Chapter 30 ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Chapter 31 CONTRACEPTION
Chapter 32 DERMATOLOGICAL CONDITIONS
Chapter 33 DIABETES MELLITUS
Chapter 34 GASTROESOPHAGEAL REFLUX AND PEPTIC ULCER DISEASE
Chapter 35 HEADACHES
Chapter 36 HEART FAILURE
Chapter 37 HUMAN IMMUNODEFICIENCY VIRUS DISEASE AND ACQUIRED IMMUNODEFICIENCY SYNDROME
Chapter 38 HORMONE REPLACEMENT THERAPY AND OSTEOPOROSIS
Chapter 39 HYPERLIPIDEMIA
Chapter 40 HYPERTENSION
Chapter 41 HYPERTHYROIDISM AND HYPOTHYROIDISM
Chapter 42 PNEUMONIA
Chapter 43 SMOKING CESSATION
Chapter 44 SEXUALLY TRANSMITTED INFECTIONS AND VAGINITIS
Chapter 45 TUBERCULOSIS
Chapter 46 UPPER RESPIRATORY INFECTIONS, OTITIS MEDIA, AND OTITIS EXTERNA
Chapter 47 URINARY TRACT INFECTIONS
UNIT IV SPECIAL DRUG TREATMENT CONSIDERATIONS
Chapter 48 WOMEN AS PATIENTS
Chapter 49 MEN AS PATIENTS
Chapter 50 PEDIATRIC PATIENTS
Chapter 51 GERIATRIC PATIENTS
Chapter 52 PAIN MANAGEMENT: ACUTE AND CHRONIC PAIN
Index