3. PHARMACODYNAMICS

7/21/2019 3. PHARMACODYNAMICS

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PHARMACODYNAMICS

Dr Jatin Dhanani



Site of

ActionDosage Effects

Plasma

Concen.

Pharmacokinetics Pharmacodynamics

The study of biochemical & physiological

effects of drugs on the body & their

mechanisms of action



Principles of Dr! Action

Stimlation Depression Replacement

Irritation Cytoto"ic action



Mechanism of Dr! Action

Physical action Chemical action Action thro!h

#iomolecle

$n%ymes Ion channels &ransporters Receptors

AdsorptionPhysical mass

Osmolality

Demlcent

Astrin!ent

Radioacti'ity

Radio(opacity

Netrali%ation) alkali%ation) acidification

Chelation

Ion e"chan!e

O"idation

Antio"idant action



R$C$P&ORS

Definition

macromolecle or *indin! site) located on the

srface or inside the effector cell) that ser'es to

reco!ni%e the si!nal molecle+dr! and initiatethe response to it) *t itself has no other

fnction,

Strctre - protein in natre ./aternary0

Ligand

any molecle 1hich attaches selecti'ely to

particlar receptor or sites



Dr! - Receptor *indin!

2an der 1all forceHydro!en *ond

Ionic *ond

Co'alent *ond

Dr! - Receptor interaction A!onist

Partial a!onist

anta!onist

In'erse a!onist



3ock 4 5ey &heorem

A li!and acts as a 6key7 *ind to specific receptors

6lock8 and unlocks the cell9s response

Many dr!s 1ork *y mimickin! a natrally occrrin!

hormone or Nerotransmitter .agonist!

Some dr!s *ind to the receptor) *t do not prodce

any response, &hey :st occpy the receptor site

.antagonists0



Receptor Occpation &heory

D ; R < DR = $

Occpation of receptors only not sfficient to prodce

effect, Acti'ation of the receptors is necessary

Se'eral li!and :st occpy the receptors ( antagonist

Concept of affinity and intrinsic activity (efficacy)

D ; R < DR > S = $ Clark?s e/ation



Agonist - hi!h affinity and ma"imm

intrinsic acti'ity .IA@0

Competiti"e antagonist - hi!h affinity *t

no intrinsic acti'ity .IA@B0

Partial agonist - hi!h affinity *t

s*ma"imal intrinsic acti'ity .IA@B to 0

#n"erse agonist - hi!h affinity *t acti'ity

in opposite direction .IA@ ( to B 0



&1o state receptor model



$ECEPT%$ TPES

&

T$A'SD(CE$ )EC*A'#S)



Receptors

PCR

Ion channels

$n%yme linked

Nclear receptors



$n%ymes

Active Enzyme

Substrate Product

Cellular Function

Inactive Enzyme

Substrate

Bound Enzyme

Inhibitor (Drug)

Bound Enzyme

stimulator (Drug)

Increased Cellular

Function



Drugs stimulate the en+

Pyrido"ine Decar*o"ylase acti'ity

Adrenaline .thro!h *eta receptor0 lyco!en phosphorylate

Drugs inhibits the en+

Physosti!mine Acetylcholinesterase

Captopril An!iotensin Con'ertin! $n%

Sim'astatin+ 3o'astatin HM(CoA redctase

ido'dine Re'erse transcriptase

Aspirin &hrom*o"ane AE

Alloprinol Fanthine o"idase

Di!o"in Na - 5 A&Pase



Ion Channels

E,amplesGinidine *locks

myocardial 'a- channels Nifedipine blocks Ltype

"oltage gated Ca-

channels

Amioderone *locksmyocardial /-channels

Phenytoin modlate

'olta!e sensiti'e 'a-

channels



&ransporters

Drugs Transporters

Desipramine) Cocaine Norepinephrine transporter.N$&0

lo"etine Serotonin transporter .S$R&0

rosemide Na 5 ECl co(transporter



(Protein Copled Receptor

.PCR0





Nm*ers of proteins are identifieds adenylyl cyclase) Ca ;E channel

i K adenylyl cyclase) K Ca ;E channel/ phospholipase

o K Ca ;E channel

L Na ; +H ; e"chan!en) k) t







(protein copled receptors



Receptors 1ith

$n%ymatic Acti'ity Intrinsic en%yme receptors

JA5(S&A&(kinase *indin! receptors

#nsulin0 E120 '12 receptors



Receptors re!latin!

!ene e"pression



Receptor Re!lation

Prolon!ed depri'ation of a!onist reslts in

supersensiti"ity of the receptor

Mechanism - p re!lation of thereceptors or amplification of transdcer

mechanism

$!, - sdden discontination ofpropranolol in an!ina pectoris



Desensiti%ation - contined+intense

receptor stimlation cases less response

on ne"t stimlation

Mechanism - maskin!+internali%ation of

the receptors or decreased

synthesis+increase destrction .do1n

re!lation0 of receptors



D%SE 3 $ESP%'SE

$ELAT#%'S*#P

B, E LE B

E

L

Q

raded DRC Gantal DRC



raded Dose(Response Cr'e



Potency amont of dr! to prodce certain

response

$fficacy a*ility of a dr! to illicit re/ired

response



Gantal Dose(Response Cr'e



&herapetic Inde"

Therapeutic inde, ( the ratio of the dose that

prodces to"icity to the dose that prodces

a clinically desired or effecti'e response

in a poplation of indi'idal



&herapetic indo1 Phenomenon

Optimal therapetic effect seen only o'er a narro1 ran!e of the plasmaconc, #oth a*o'e and *ello1 the therapetic effect is s*optimal or

to"ic effect starts appearin!



COM#IN$D $$C& O

DRS

SYN$RISM AN&AONISM



Syner!ism

Additi"e

4A-56A5!

$"amples, I*profen ;

Paracetamol

.com*iflam0

E, Amlodipine ;atenolol

Supraadditi"e

4A-57A5! $"amples

, 3e'odopa ; Car*idopa

E, Ach ; Physisti!mine

L, Slfmetho"a%ole ;trimethoprime



Anta!onism

Receptor

anta!onists

Nonreceptor

anta!onists

Chemical

Physiolo!ical

Acti'e site

*indin!allosteric site

*indin!

Re'ersi*le Irre'ersi*le

Re'ersi*le Irre'ersi*le

Competiti'e

anta!onist

Noncompetiti'e

anta!onist

Physical



Difference *+1 competiti'e and

noncompetiti'e anta!onism



2actors )odifying The Drug

Actions



#ody si%e

Accordin! to #ody ei!ht or Accordin! to srface area indi'idal dose is

@

A!eYon!?s formla child dose @ T

Dillin!?s formla child dose @ T

Se" smaller *ody si%e) hormonal

difference) pre!nancy and lactation



Species and race

$", - *lack 4 1hite difference for ppilaryreaction to atropine and adrenaline

enetics$", - Acetylation of dr!s) PD def,)

Mali!nant Hyperthermia) atypical

psedochlinesterase

Diet and en'ironment

$", - tetracycline 1ith calcim) polycyclichydrocar*on of ci!arette smoke

Rote of administration

M!SO *y oral or i' rote



Disease statesI& diseases) 3i'er diseases) 5idney disease)

CH

Psycholo!ical factorsPlace*o

Presence of other dr! Repeated dosin!Cmlation

&olerance&achyphyla"is



&hank Yo

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3. PHARMACODYNAMICS