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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