Principles of PharmacologyDefinitions PharmacologyIs defined as the study of the effects of chemical substances (Drugs) on the function of living systems. DrugIs any biologically active substance that alters biological system (cell structure or function) chemically. Drugs:

Pharmacodynamics What the drug does to the body Mechanism of action Pharmacological effects Side effects Pharmacokinetics What the body does to the drug Absorption Distribution Elimination ( Biotransformation , excretion) Drug Actioninteraction of drug molecule with biological tissue. Mechanism of actionspecific drug action e.g. morphine binding to opioid receptors. Drug effectbehavioral effectsNo Magic Bullets! Drug delivered into biological system Effects all cells that have receptors Desired effect = Therapeutic effect All other effects = Side effects All drugs have multiple effects Drug NamesAt least three names Chemical nameDescribes molecular structure Generic name (non proprietary )Official legal name Trade name (proprietary)Brand name Street name

Example: Amphetamine

dl-2 amino-1 phenylpropane dl-amphetamineBenzedrinespeed, bennies, whites, etc.chemical

Generic

trade street

Drug Equivalence Chemical equivalenceIdentical chemical compounds Biological equivalenceAffect the same systems in the same way Clinical equivalenceSame behavioral effectDifferent molecules affecting different systemsPharmacodynamics:The action of a drug on the body, includes:1- Receptor interactions.2- Dose-response phenomena.3- Mechanisms of therapeutic and toxic action.

Drug Receptor A macromolecular component of a cell with which a drug interacts to produce a response. Usually it is a protein.Types of Protein Receptors1- Regulatory change the activity of cellular enzymes2- Enzymes may be inhibited or activated.3- Transport e.g. Na+ /K+ ATPase .4- Structural Skeleton of the cells

Drug-receptor interaction

Agonist Drugs Drugs that interact with and activate receptors; they possess both affinity and efficacy Two types Full an agonist with maximal efficacy Partial an agonist with less then maximal efficacy

Antagonist DrugAntagonists interact with the receptor but do NOT change the receptor they have affinity but NO efficacy two types Competitive NoncompetitiveCompetitive Antagonist Competes with agonist for receptor Surmountable with increasing agonist concentration Displaces agonist dose response curve to the right (dextral shift) Reduces the apparent affinity of the agonist .Non competitive Antagonist Drug binds to receptor and stays bounded irreversibly does not leave receptor Produces slight dextral shift in the agonist DR curve in the low concentration range this looks like competitive antagonist But, as more and more receptors are bound (and essentially destroyed), the agonist drug becomes incapable of eliciting a maximal effectDrug Receptor Curve

Effectiveness, toxicity, lethality ED50 - Effective Dose 50; the dose at which 50 % of the population or sample manifests a given effect; used with quantal drug receptor curves. LD50 lethal Dose 50 - dose which kills 50 % of the subjectsQuantification of drug safety

The therapeutic index The higher the TI the better the drug.TI vary from :1.0 (some cancer drugs)to:>1000 (penicillin)Drugs acting on the same receptor or enzyme system often have the same TI: (eg 50 mg of hydrochlorothiazide about the same as 2.5 mg of indapamide)

Second Messengers Small, non protein, water-soluble molecules or ions Readily spread throughout the cell by diffusion Two most widely used second messengers are:1.Cycle AMP2.Calcium ions Ca2+

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