pharmacodynamipharmacodynamicscsInIn

AnaesthesiaAnaesthesia

PharmacodynamicsPharmacodynamics

The study of how drug affects the The study of how drug affects the body involvingbody involving

Mechanism of actionMechanism of action Interaction between drugsInteraction between drugs Structure activity relationshipStructure activity relationship Dose response curveDose response curve Drug – receptor interactionDrug – receptor interaction

Factors affecting pharmacodynamicsFactors affecting pharmacodynamics AgingAging Genetic factorGenetic factor MalnutritionMalnutrition Disease states like thyrotoxicosisDisease states like thyrotoxicosis mysthenia gravismysthenia gravis Chronic exposure to drugs (up and Chronic exposure to drugs (up and

down regulation of receptors )down regulation of receptors )

Mechanism of actionMechanism of action Chemical reaction eg antacid without Chemical reaction eg antacid without

receptor or cell mediated actionreceptor or cell mediated action drug-receptor interactiondrug-receptor interactionReceptors are macromolecules usually Receptors are macromolecules usually

protiens located on cell membrane or in protiens located on cell membrane or in cytoplasmcytoplasm

-it determine quantitative relation between -it determine quantitative relation between dose and pharmacologic effectdose and pharmacologic effect

-it is responsible for selectivity of drug action-it is responsible for selectivity of drug action-mediate action of agonist and antagonist-mediate action of agonist and antagonist

Mechanism of actionMechanism of action

Ion channel receptorIon channel receptor

e.g nicotinic receptorse.g nicotinic receptors

GABA receptorsGABA receptors

G protien coupled G protien coupled receptorreceptor

e.g muscarinic e.g muscarinic receptorsreceptors

adrenergic adrenergic receptorsreceptors

Protien kinase Protien kinase receptorsreceptors

e.g insuline.g insulin

growth hormonegrowth hormone

DNA TranscriptionDNA Transcription

e.g steroide.g steroid

thyroid thyroid hormonehormone

Dose-response Dose-response relationshiprelationship

EfficacyEfficacy

EfficacyEfficacy

PotencyPotency

PotencyPotency

Efficacy and PotencyEfficacy and Potency

Agonist -AntagonistAgonist -Antagonist Full agonist: has high affinity+ intrinsic activityFull agonist: has high affinity+ intrinsic activity ie high efficiency couplingie high efficiency coupling

Partial agonist: has affinity +modest activityPartial agonist: has affinity +modest activityie less able to promote conformational change of ie less able to promote conformational change of

R eg buperphine an agonist-antagonist narcoticR eg buperphine an agonist-antagonist narcoticWhat are opiate receptors ?What are opiate receptors ?

Antagonist: has affinity but no effect eg naloxonAntagonist: has affinity but no effect eg naloxon

Competitive or reversible Competitive or reversible antagonistantagonist

A R CA R CC forms short lasting bond with R preventing C forms short lasting bond with R preventing

binding of agonist to R, both bind at the binding of agonist to R, both bind at the same site on the R but not activate it.same site on the R but not activate it.

-It can readily dissociate -It can readily dissociate -The extent of inhibition depends on C conc -The extent of inhibition depends on C conc

relative to conc of the competing agonist Arelative to conc of the competing agonist A-According to law of mass action increasing -According to law of mass action increasing

conc of agonist can displace the antagonistconc of agonist can displace the antagonist

Non competitive or Non competitive or irreversibleirreversible

The antagonist forms stable chemical The antagonist forms stable chemical bond with receptor rendering it not bond with receptor rendering it not responsive to agonistresponsive to agonist

Can not be displaced by increasing conc Can not be displaced by increasing conc of the agonistof the agonist

Its duration of action is relatively Its duration of action is relatively independent of rate of elimination rather independent of rate of elimination rather it depends on the rate of turn over of R it depends on the rate of turn over of R molecules eg aspirin as an antiplatelet molecules eg aspirin as an antiplatelet therapytherapy

Other classes of Other classes of antagonistsantagonists

Chemical antagonistChemical antagonist

eg protamine +charged binds to –ve eg protamine +charged binds to –ve charged heparin making it unavailable charged heparin making it unavailable to act on coagulation factorsto act on coagulation factors

Physiological antagonistPhysiological antagonist

Insulin given to antagonise Insulin given to antagonise hyperglycemic effect of steroid both hyperglycemic effect of steroid both have quite different pathwayhave quite different pathway

TachyphylaxisTachyphylaxis ToleranceTolerance IdiosyncracyIdiosyncracy SynergismSynergism PotentiationPotentiation Additive effectAdditive effect

Therapeutic ratioTherapeutic ratio

Median effective dose ED50Median effective dose ED50

Dose required to produce a given Dose required to produce a given effect in 50% of population (MAC )effect in 50% of population (MAC )

Median toxic dose TD50Median toxic dose TD50

Dose required to produce toxicity in Dose required to produce toxicity in 50% of population50% of population

Therapeutic index = TD50/ED50Therapeutic index = TD50/ED50

Therapeutic IndexTherapeutic Index

Therapuetic IndexTherapuetic Index

Applied Applied PharmacodynamicsPharmacodynamics

A.ch receptor is a macromolecule of 5 subunitsA.ch receptor is a macromolecule of 5 subunits Only 1/10 of R needed for normal contractionOnly 1/10 of R needed for normal contraction A binds to 2 alpha subunits leading to A binds to 2 alpha subunits leading to

conformational change open cation channelconformational change open cation channel Irreversible depolarizing sux is bi Ach moleculeIrreversible depolarizing sux is bi Ach molecule Reversible non depolarizing relaxants bind to R Reversible non depolarizing relaxants bind to R

without any conformational change without any conformational change Reverse depends on clearance and neostigmineReverse depends on clearance and neostigmine

Pharmacodynamics are affected by states Pharmacodynamics are affected by states likelike

-Homo zygous atypical pseudo cholinestrase-Homo zygous atypical pseudo cholinestrase

-Mysthenia gravis (downregulation of Ach R -Mysthenia gravis (downregulation of Ach R Muscle relaxants show structural activity Muscle relaxants show structural activity

relationshiprelationship

-steroid compounds as pancronium are -steroid compounds as pancronium are vagolyticvagolytic

-benzylisoquinolines tend to release -benzylisoquinolines tend to release histaminehistamine