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B.Pharm Lab. Instruction Manuals

Pharmacology I

APHE Anatomy, Physiology, and Health Education

Pharmaceutical Analysis

Pharmacy study material

General Pharmacology

Bones and Skeleton System

Bone disease (Gout) (Rheumatoid arthritis) (Osteoarthritis) (Osteoporosis)

Cancer and music therapy

Memory of water

Disease

It is the changes of organ(s) from normal physiological state to pathological state (morphological and functional changes, including the homeostatic changes of internal environment of the organism) [McCann WS, 1952, Kumar V et. al., 2008].

Steps of drug development

Before a new drug comes in the market for therapeutic use, it has to be passed from different tests in an organized way [Rang MP et. al., 2007]. The whole process is divided in three main parts:

1. Drug discovery

This is the process of selecting a molecule (called lead), might have potential to be used as drug in future.

It is done by further four steps

i. Target selection

Understanding the pathogenesis of a disease, we can find the affected organ or system. For example, hyperactivity of angiotensin converting enzyme (ACE) causes the excess production of angiotensin II (acts through AT1 receptor), followed by vasoconstriction and increased re-absorption of sodium and water (activating the aldosterone) and thus increase the blood pressure. Therefore, we can target ACE or AT1 receptor to develop an anti-hypertensive agent. However, there are other targets to develop an anti-hypertensive agent (calcium channel, sodium channel, $\alpha$-adrenergic receptor, potassium channel etc) [Rang MP et. al., 2007]

ii. Target validation

Target validation is the process to determine that the target is expressed in the disease-relevant cells/tissues, can be directly modulated by a drug with adequate potency in biochemical assay, and that target modulation in cell and/or animal models ameliorates the relevant disease phenotype [Lindsay MA, 2003, Vidalin O et. al., 2009].

iii. Assay development

After the target is validated, the bioassay for evaluating a new drug is developed.
Example: If we want to evaluate the anti-inflammatory activity of a new molecule, a model must be developed inducing the inflammation in the animal model to compare the anti-inflammatory effects of the new molecule with the existing conventional anti-inflammatory agents.

Reference

[Kumar V et. al., 2008] Kumar V, Abbas AK, Fautso N, Robbins and Cotran Pathologic Basis of Disease, 7th Edition, Saunders (Elsevier), 3-46, 2008.
[McCann WS, 1952] McCann WS, The Meaning of Disease, Calif Medicine, vol. 77, issue 3, 169-171, 1952.
[Lindsay MA, 2003] Lindsay MA, Target discovery, Nature Reviews Drug Discovery, vol. 2, issue 10, 831-838, 2003.
[Rang MP et. al., 2007] Rang HP, Dale MM, Ritter J M, Moore P K, Pharmacology, 5th Edition, Elsevier, 2-752, 2007.
Vidalin O et. al., 2009] Vidalin O, Muslmani M, Estienne C, Echchakir H, Abina AM, In vivo target validation using gene invalidation, RNA interference and protein functional knockout models: it is the time to combine, Current Opinion in Pharmacology, vol. 9, issue 5, 669-76, 2009.

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