Need this done with professor plagiarism report. WIll pay well, must be done in 3 days. I will provide a sample paper too once I accept a bid

 DESCRIPTION You are the lead scientist on a pharmaceutical research & development (R&D) team that has developed a new drug to treat disease. As the principal investigator you will write a short paper on the design and efficacy (effectiveness) of the new pharmacological product. Although the drug is imaginary, it must be targeted against a known disease. You can select a pathological condition that affects the physiology of at least one of the following systems:

 • Nervous/Neuromuscular/Muscle 

• Endocrine 

• Cardiovascular 

• Respiratory 

• Gastrointestinal 

• Urinary 

 The paper must contain the following components: 

1. Name of the drug. You can be creative with the invented name but it should relate to the function of the product, e.g., Inhibitol (if the drug has an inhibitory effect on its target) 

2. Paper Title. Again, originality is encouraged but the title must contain the product name and the disease condition it treats. 

3. Pathophysiology. This is the research component of the paper. The cause(s) (etiology), symptoms and effects of the disease should be adequately described. The pathophysiology of your selected illness must include a description of the disease mechanism on a molecular level (participant biomolecules such as enzymes, receptors, hormones, neurotransmitters, etc.). This part of the paper should be well referenced primarily using scientific/medical literature. Avoid citing websites such as WebMD, although government agency websites such as the NIH, CDC, WHO, etc. are permitted. 

4. Drug Design & Efficacy. How does your invented drug work to effectively treat the disease condition? Your description should be consistent with molecular mechanisms of the disease and should involve ligand-based binding to principal targets implicated in the process. 

5. Side Effects. Based on the biomolecule(s) targeted by the designed drug, you should be able predict possible side effects, e.g., Inhibitol inhibits the activity of the enzyme acetylcholinesterase at neuromuscular junctions. This increases the amount and duration of ACh in the NMJ, which helps to improve muscle signaling in myasthenia gravis but may cause spastic paralysis due to neurotransmitter overabundance. Side effects should relate to the specific activity of your drug. 

 Your paper should be 3 – 4 pages in length (min: 3, max: 4) typed, 1.5-spaced 12-pt font. A bibliography is REQUIRED and is not included in your page count. Do not add cover pages, photos, charts or diagrams to your paper. This is an assessment of your original writing 

Name:

Course: PCB4097
Semester: Spring 2016
Instructor: Prof. S. Williams

Drug name: Areinhiterol

Title: Design and Efficacy of Areinhiterol in the Management of Asthma.

Pathophysiology

Asthma is a reversible chronic inflammatory and obstructive disease of the respiratory

system. It is associated with episodes of airway inflammation and narrowing leading to

symptoms of bronchospasm and airway obstruction. Narrowing results from the mucosal

inflammation and the associated increased contraction of the smooth muscles and the

increased mucus production. There is also increased the presence of eosinophils as the lamina

reticularis also thickens. With chronicity, the smooth muscle might eventually hypertrophy

with hyperplasia of the mucous glands. The immune cells and modulators as chemokines,

leukotrienes, histamine, and cytokines are also involved (Ortega, 2014). Affected individuals

report varying episodes characterized mainly by wheezing, breathlessness, chest tightness and

coughing that define a typical asthmatic attack. Sometimes the individual may report thick

sputum production which sometimes may seem pus-like. Symptoms worsen early in the

morning, late in the evening or in association with cold or strenuous exercise. The disease is

diagnosed by its classical clinical symptoms, through spirometry and response to

bronchodilators. Most people associate the disease with both environmental and genetic

causes. The environmental factors are mainly linked to allergens like dust mites and other

pollutants and environmental chemicals. Besides certain drugs like beta blockers,

acetaminophen and aspirin have been incriminated.

Some individuals have also been shown to be genetically predisposed to the disease in

what is referred to as atopy. History of atopic diseases as atopic conjunctivitis, rhinitis and

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eczema increase an individual’s risk for asthma development. Different inheritable genes have

been associated with the development of asthma. The genes are mostly linked to

inflammation and immune modulating processes. Such individuals will mostly develop type I

hypersensitivity reactions. A combination of gene susceptibility and the environmental

factors increase the risk especially in these genetically [predisposed individuals. Currently,

the disease has no cure and the management targets to prevent episodes of asthmatic attack or

to alleviate symptoms and restore airway patency. Management also encourages individuals

to avoid coming into contact with the various allergens and other triggers (Ortega, 2014).

Drug Mechanisms

Areinhiterol is a selective beta-2 adrenergic receptor (AR) agonist owing to its tertiary

butyl group. The drug can be used both as a symptom-reliever and as a disease-controller.

Bronchodilation of the airway smooth muscle is a function of the sympathetic nervous

system. The human airway smooth muscle has not been shown to have any direct nervous

supply. The sympathetic action is mainly due to the effects of circulating catecholamines as

adrenaline from the adrenal glands that act mainly on the beta-2 AR. Beta-AR is widely

spread in the airway smooth muscles (ASM) from the trachea up to the terminal

bronchioles (Barisione, Baroffio, Crimi, & Brusasco, 2010 ). Activation of the beta-2 AR is

associated with the relaxation of the ASM, an increase in the ciliary action, reduced

acetylcholine release, immune modulation and vascular permeability changes that assist in

the therapeutic effect of this drug.

Beta 2 ARs belong to the family G-protein-coupled 7-transmembrane receptors that

act via intracellular guanine nucleotide regulatory proteins.

These receptors are molecular

switches that convert from the inactive guanine-diphosphate to its active triphosphate.

Areinhiterol is molecularly similar to endogenous catecholamines and like them works by

binding to these G-protein receptors. The interaction between the receptor and the ligand is

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responsible for the conformational change of this receptor. It leads to the activation of

adenylyl cyclase resulting to an increase in the concentrations of cyclic AMP that acts

through the activation of protein kinase A (PKA). PKA is responsible for the phosphorylation

of other intracellular proteins that are associated with the relaxation (Barisione et al.2010) .

The termination of the process is associated with the action of the intrinsic GTPase that

reverses the molecular switch. PKA has also been shown to inhibit myosin-light-chain-kinase

reducing muscle contraction. Also, through its action on the calcium-sodium exchange, it

reduces the intracellular levels of calcium while stimulating the Na/K-ATPase. Action on the

receptor has also been shown to reduce the levels of acetylcholine (Ach) released. Ach is

crucial in maintaining the tone of the airway muscle (Barisione et al.2010) .

Drug Design and Efficacy

Various body organs have both the alpha and the beta adrenergic receptors that are

associated with various physiologic functions. Stimulation of the alpha receptors is associated

with the contraction of the ASM. Conversely, if the beta receptors are stimulated the ASM

relaxes. Areinhiterol is less potent towards the alpha receptors and has great actions in the

beta receptors. The beta receptors are further sub-classified into the beta 1 and beta 2 ARs.

Beta 2 receptors are the receptors mostly associated with bronchodilation (Barisione et

al.2010). The drug, unlike endogenous catecholamines, has been modified to incorporate a

tertiary butyl group that makes it more selective to the beta two receptors. It makes the ligand

more likely to bind to these receptors that are mainly associated with the disease process in

asthma pathophysiology. Besides, the lack of a hydroxyl group makes the drug less

susceptible to metabolism by catechol-O-methyl transferase thus ensuring a longer mode of

action, unlike the endogenous catecholamines. It has a duration of action exceeding 12 hours

due to its longer half-life of about ten hours. It has a relative short onset of action of about 3

minutes due to its lipophilic nature. Besides it has a greater affinity and potency when

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compared to other common beta-2 AR as albuterol thus improving its intrinsic efficacy. The

drug is thus useful in rescue, especially when combined with other short-acting drugs

complemented by its mucociliary action.

Side effects

Despite the fact that beta-2 alpha receptors are highly concentrated in the airway

smooth muscle, they are present in other tissues as ciliated epithelium, submucosal glands,

vascular endothelium, inflammatory cells and mast cells. Due to this distribution of receptors,

oral administration of this drug may be associated with systemic side effects (Barisione et

al.2010) . The inhalational route is preferred as it has higher beneficial effects when

compared to the side effects. The effect of the drug on the cardiovascular system receptors

makes the drug be associated with both chronotropic and inotropic effects that would

aggravate cardiomyopathies and arrhythmias especially among individuals with

cardiovascular diseases. In parenteral use, the drug can cause tachycardia due to its peripheral

vasodilation effects in addition to cardiac stimulation. The use of the drug may lead to

symptoms of insomnia, tremor, anxiety, excessive sweating and agitation primarily due to its

extra-ASM actions (Ortega, 2014).

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References

Barisione, G., Baroffio, M., Crimi, E., & Brusasco, V. (2010). Beta-Adrenergic

Agonists. Pharmaceuticals, 1016-1044.

Ortega, V. E. (2014).Pharmacogenetics of beta 2 adrenergic receptor agonists in

asthma management. Clinical Genetics, 86(1), 12-20.