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7/21/2019 3. PHARMACODYNAMICS
http://slidepdf.com/reader/full/3-pharmacodynamics 1/41
PHARMACODYNAMICS
Dr Jatin Dhanani
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Site of
ActionDosage Effects
Plasma
Concen.
Pharmacokinetics Pharmacodynamics
The study of biochemical & physiological
effects of drugs on the body & their
mechanisms of action
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Principles of Dr! Action
Stimlation Depression Replacement
Irritation Cytoto"ic action
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Mechanism of Dr! Action
Physical action Chemical action Action thro!h
#iomolecle
$n%ymes Ion channels &ransporters Receptors
AdsorptionPhysical mass
Osmolality
Demlcent
Astrin!ent
Radioacti'ity
Radio(opacity
Netrali%ation) alkali%ation) acidification
Chelation
Ion e"chan!e
O"idation
Antio"idant action
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R$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
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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
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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
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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
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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
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&1o state receptor model
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$ECEPT%$ TPES
&
T$A'SD(CE$ )EC*A'#S)
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Receptors
PCR
Ion channels
$n%yme linked
Nclear receptors
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$n%ymes
Active Enzyme
Substrate Product
Cellular Function
Inactive Enzyme
Substrate
Bound Enzyme
Inhibitor (Drug)
Bound Enzyme
stimulator (Drug)
Increased Cellular
Function
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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! $n%
Sim'astatin+ 3o'astatin HM(CoA redctase
ido'dine Re'erse transcriptase
Aspirin &hrom*o"ane AE
Alloprinol Fanthine o"idase
Di!o"in Na - 5 A&Pase
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Ion Channels
E,amplesGinidine *locks
myocardial 'a- channels Nifedipine blocks Ltype
"oltage gated Ca-
channels
Amioderone *locksmyocardial /-channels
Phenytoin modlate
'olta!e sensiti'e 'a-
channels
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&ransporters
Drugs Transporters
Desipramine) Cocaine Norepinephrine transporter.N$&0
lo"etine Serotonin transporter .S$R&0
rosemide Na 5 ECl co(transporter
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(Protein Copled Receptor
.PCR0
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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
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(protein copled receptors
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Receptors 1ith
$n%ymatic Acti'ity Intrinsic en%yme receptors
JA5(S&A&(kinase *indin! receptors
#nsulin0 E120 '12 receptors
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Receptors re!latin!
!ene e"pression
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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
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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
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D%SE 3 $ESP%'SE
$ELAT#%'S*#P
B, E LE B
E
L
Q
raded DRC Gantal DRC
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raded Dose(Response Cr'e
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Potency amont of dr! to prodce certain
response
$fficacy a*ility of a dr! to illicit re/ired
response
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Gantal Dose(Response Cr'e
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&herapetic Inde"
Therapeutic inde, ( the ratio of the dose that
prodces to"icity to the dose that prodces
a clinically desired or effecti'e response
in a poplation of indi'idal
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&herapetic indo1 Phenomenon
Optimal therapetic effect seen only o'er a narro1 ran!e of the plasmaconc, #oth a*o'e and *ello1 the therapetic effect is s*optimal or
to"ic effect starts appearin!
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COM#IN$D $$C& O
DRS
SYN$RISM AN&AONISM
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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
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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
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Difference *+1 competiti'e and
noncompetiti'e anta!onism
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2actors )odifying The Drug
Actions
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#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
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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
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Disease statesI& diseases) 3i'er diseases) 5idney disease)
CH
Psycholo!ical factorsPlace*o
Presence of other dr! Repeated dosin!Cmlation
&olerance&achyphyla"is
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&hank Yo