DO YOU KNOW ABOUT DR INTERACTIONS AND ITS WORKING ?

DRUG-RECEPTOR INTERACTION & PHARMACODYNAMICS

DO YOU KNOW ABOUT DR INTERACTIONS AND ITS WORKING ?

Ligand : small molecule that binds to a site on protein receptor---it is drug/natural 

molecule/sec.messenger 

Receptors Classification 

1) Ligand-gated ion receptor=binding of ligand to receptor 

e.g stimulation of nicotine receptor by Ach (Acetylcholine) binding results in Na+ influx, 

generation of action potential,contraction of skeletal muscle

BZD(benzodiazeoine) enhance stimulation of GABA, CI- influx, hyperpolarization 

Very rapid response, few millisecond 

2) G-Protein coupled receptor= linked to G-protein(Gs,Gi etc)----having 3 subunits(α, β, γ)---

ligand bind to receptor---activation of G-protein---GTP replace GDP on α subunit---activate sec-

messenger---produce further action in cell 

e.g activation of Adenylyl Cyclase by α-GTP----production of cAMP---regulates protein 

phosphorylation.

G-protein also activate the Phospholipase C----generation of IP3(inositol 1,4,5 triphosphate) and 

Diacyl glycerol (DAG)----IP3 regulate intracellular free Ca---DAG activate Protein Kinase C—

leading to several physiological effects 

Several seconds to minutes, α & β adrenoreceptor are example 

3) Enzyme-Linked receptors= binding of ligand to receptor---activation of cytosolic enzymes—

involved in met,growth,differentiation 

Minutes to hours, insulin receptors are example

4)Intracellular receptors=ligand –receptor complex---activation of transcription of DNA—

translation of RNA into proteins 

Hours to days, ex. Steroid hormones 

Other targets of ligand are Structural proteins e.g Tubulin target of paclitaxel---Dihydrofolate 

reductase target of Trimethoprim----50S ribosome taget of macrolide antibiotics erythromycin 

Tachyphylaxis= repeated administration of drug diminished the effect---receptor become 

desensitized---

Refractory period= after tachyphylaxis period receptor recovered this recovery period called 

refractory period/rest/unresponsive.

Agonist =an agent that can bind to receptor & elicit the biological response

Full agonist=bind to receptor & produce maximal biologic response that mimics the response of 

endogenous ligand e.g Phenylephrine, 

Partial agonist=have efficacy >0 but less than full agonist e.g Aripiprazole (antipsychotic) 

Inverse agonist= unbound receptors are inactive, reverse agonist stabilize the inactive form 

Exert opposite pharmacological action 

Antagonist = decrease or oppose the action of another drug/endogenous substance 

Produce no effect by themselves 

Competitive Antagonist=if both agonist and antagonist bind to same receptors ,they compete 

for receptor---increase ED50 –reduce potency of agonist 

 e.g Terazocin(antihypertensive) compete with nor-epinephrine 

Irreversible anatagonist=bind covalently with high affinity to receptor—not increase ED50—

reduce efficacy of agonist e.g Phenoxybenzamine of a1 & a2 blocker 

Allosteric anatagonsit= bind on a site other than agonist on receptor, inhibit activation of 

agonist 

Functional anatagonism/Physiological anatgonism=anatagonist at separate receptor but 

function opposite to agonist.

e.g Histamine on H1 receptor causes contraction of bronchial smooth muscles while Epinephrine 

on B1 receptor causes dilation of bronchial smooth muscles 

chemical anatagonism=prevent the action of antagonism by modifying the agonist 

e.g Protamine sulfate(basic) is chemical anatagonist of Heparin(acidic). 

Graded-Dose response= as the conc. Of drug increases, the magnitude of pharmacological 

effect increases…….two properties=1)Potency 2)Efficacy

Potency =measure of amount of drug necessary to produce an effect of given magnitude 

e.g candesartan 4mg more potent than Irbesartan 32mg 

Efficacy/intrinsic property=ability of drug to elicit response when it interact with receptor 

Affinity =strength of interaction b/w ligand and receptor 

EC50=conc of drug that produce response equal to 50% of maximal response—used for potency 

Quantal-dose response=influence of dose on proportion of population that responds.---called 

quantal b/c for every individual it occurs or not

Therapeutic index=ratio of the dose that produce toxicity to the dose produce clinical effect

Therapeutic-index=TD50/ED50

Warfarin , Digoxin have small therapeutic index

Pencillin show large therapeutic index