Farmakodinamika

FajarWahyuPribadi
FajarWahyuPribadi

WHATISPHARMACODYNAMICS?
WHATISPHARMACODYNAMICS?

 InGreek

Pharmacon=Drug
Dynamics=Action/Power
ItcoversalltheaspectsrelatingtoWhata
Itcoversalltheaspectsrelatingto
drugdoestothebody
drugdoestothebody
Mechanismofaction

Action:Howand
andWherethe
effectisproducediscalledas
isproducediscalledas
Action.
Effect:Thetypeofresponse
:Thetypeofresponse
producingbydrug.
producingbydrug

SiteofDrugAction
Where:

1.Extracellular
2.Cellular
3.Intracellular
3.Intracellular

TypesofDrugAction
EFFECT(Typeofresponses):
(Typeofresponses):

1.Stimulation
2.Inhibition/Depression
3.Replacement
3.Replacement
4.Irritation
5.Cytotoxic

MechanismofActionofDrugs
Drugacteitherbyreceptor
receptororbynonreceptor
or bytargetingspecific
specificgenetic changes.
Majority of drugsactsby
by(HOW)

Receptor mediated

Nonreceptor mediated
Non

RECEPTORMEDIATEDMECHANISM
Receptor: Itisamembraneboundorintracellular
macromolecularprotein whichiscapableofbinding
thespecificfunctionalgroupsofthedrugor
endogenoussubstance.
Bindingofadrugwithitsreceptorresultsinthe
formationofdrugreceptorcomplex(DR)whichis
responsiblefortriggeringthebiologicalresponse.
D+R=(DR)Response
D+R=(DR)Response

Ligandbinding
domain

Transductionofsignal
intoresponse

ReceptorFunctions:Twoessentialfunctions
1.Recognizationofspecificligandmolecule(Ligand
bindingdomain)
2.Transductionofsignalintoresponse(Effector
domain)

LOCK&KEYmodelofRECEPTORS
LOCK&KEYmodelofRECEPTORS

Drug(D) +Receptor

Drugreceptor complex

Response

Drug receptor interaction:

1. Selectivity: Degree of complimentary co relation
between drug and receptor.
receptor
Ex: Adrenaline Selectivity for
for, Receptor
2. Affinity: Ability of drug to
toget bound to the receptor.
3. Intrinsic activity (IA) or Efficacy:
Efficacy Ability of drug to
produce a pharmacological response after making
the drug receptor complex.
complex

Drugclassification
(onthebasisofaffinity&efficacy)
(onthebasisofaffinity&efficacy)

Ex: Pindolol,
Pentazocine

Inverse agonist: These have full affinity towards the

receptor but intrinsic activity is zero to 1 i.e., produces
effect is just opposite to that
thatof agonist.
Ex: Carboline is inverse agonist for Benzodiazepines
receptors.

Summation
Summation:Twodrugselicitingsameresponse,
butwithdifferentmechanismandtheircombined
effectisequaltotheirsummation.(1+1=2)
Aspirin(
( PG)+Codiene(Opiodsreceptor)=
Analgesic+
Analgesic++
Additive:combinedeffectoftwodrugsactingby
combinedeffectoftwodrugsactingby
samemechanism
Synergism(Supraadditive):
(Supraadditive): (1+1=3)
1.Sulfamethaxazole+
Sulfamethaxazole+Trimethoprim
2.Levodopa
Levodopa+Carbidopa.

Antagonist
1. Competitiveantagonists
2. Irreversibleantagonists
3. Allostericantagonists
When picrotoxin isboundinsidethechannel,no
chloride canpassthroughthechannel,even
whenthereceptorisfullyactivatedbyGABA.
whenthereceptorisfullyactivatedby

4. Functionalantagonism
thefunctionalantagonismbyepinephrinetohistamineinduced
thefunctionalantagonismbyepinephrinetohistamine
bronchoconstriction. Epinephrineisanagonist
Epinephrineisanagonistat2
adrenoceptorsonbronchialsmoothmuscle,whichcauses
adrenoceptorsonbronchialsmoothmuscle,whichcauses
themusclestorelax

 Fourtypesofbindingtakes
placebetweenthereceptorand
thedrugmolecule
1. VanderWaalsforces
2. Hydrogenbonding
3. Ionicinteraction
4. Covalentbonding
Covalentbonding

Receptorfamiliesand
Receptorfamilies
Signaltransductionmechanisms
Fourtypesofreceptorsfamilies
1.Ligandgatedionchannels(inotropic
gatedionchannels(inotropic
receptors)
2.Gprotiencoupledreceptor(Metabotropic
protiencoupledreceptor(Metabotropic
receptors)
3.Enzymaticreceptors(tyrosinekinase)
.Enzymaticreceptors(tyrosinekinase)
4.Receptorregulatinggeneexpression
.Receptorregulatinggeneexpression
(transcriptionfactors/Steroid)

A.Ionotropicreceptors
Ionotropicreceptors/Iongated
receptors/Ligandgatedionchannels
Ligandgatedionchannels
Ex:Nicotiniccholinergicreceptor

B.GProteincoupledreceptors
Proteincoupledreceptors

VarietiesofG
VarietiesofGprotein
Gprotein
Gs
Gi1,2,3
Gq
Go

Receptorfor

Signalingpathway/
Effector
AC cAMP

adrenegic,
H,5HT,Glucagon
2 adrenergic,Ach, AC cAMP,
OpenK+
Ach
PhospholipaseC,
IP3cytoplasmicCa+2
Neurotransmitters Notyetclear
inbrain

Gproteineffectorsystems
proteineffectorsystems
1.Adenylasecyclase::cAMPsystem
2.PhospholipaseC:Inositol
Inositolphosphate
system
3.Ionchannels

cAMPsystem

PhospholipaseCsystem

Ionchannelregulation
Gprotein coupled receptors can control the
functioning of ion channel by don't involving
any secondmessenger
messenger
Ex: In cardiacmuscle

C.Enzymelinkedreceptors
Enzymelinkedreceptors/Enzymatic
receptors
Extracellularreceptor
bindingdomain

Intracellular
changes

D. Receptorregulatinggeneexpression
(transcriptionfactors)
IncreaseRNA
polymeraseactivity

Unfoldsthereceptorand
exposenormally
maskedDNAbinding
site

Receptorregulationtheory
Receptorsareindynamicstate.
Theaffinityoftheresponsetodrugsisnotfixed.It
altersaccordingtosituation.
Receptordownregulation
Receptordownregulation/Desentization:
Prolongeduseofagonist
Receptornumberandsensitivity
Drugeffect
Ex:Chronicuseofsalbutamoldownregulates2 adrenergicreceptors.
Ex:Chronicuseofsalbutamoldownregulates

 Receptorupregulation
regulation:
Prolongeduseofantagonist
Receptornumberandsensitivity
Drugeffect
Ex: propranolol is stopped after prolong use,
produce withdrawal symptoms. Rise BP,
induce of angina.

Nonreceptormediatedmechanisms
receptormediatedmechanisms
Bychemicalaction
1.
2.
3.

Neutralization Eg:Antacids
:Antacids
Chelation Eg:EDTA, Dimercaprol,
Dimercaprol Penicillamine,Deferoxamine
Ionexchangers Eg: Cholestyramine
CholestyramineexchangesClfrombilesalts.

Byphysicalaction
1.
2.
3.
4.
5.
6.

OsmosisEg:MgSO4 aspurgative
Adsorption Eg:Simethiconeadsorsb
Eg:Simethicone
gases,usedas antiflatulent
Protectives Eg:Dustingpowders
:Dustingpowders
Demulcents Eg:Menthol
Eg:Mentholincoughsyrups
Astringents Eg:Tannic acidingumpaints
Saturationinabiophase
phase Eg:General anaesthetics

Nonreceptormediated
receptormediated
mechanisms
BycounterfeitorFalseincorporationmechanisms
Eg:Sulfadrugsandantineoplasticdrugs
neoplasticdrugs

ByvirtueofbeingProtoplasmicpoisons
Eg:Germicidesandantiseptics

Throughformationofantibodies
Eg:Vaccines,Antisera

Throughplaceboaction
Targetingspecificgeneticchanges
Targetingspecificgeneticchanges

DOSERESPONSERELATIONSHIPS
RESPONSERELATIONSHIPS
A. Gradeddoseresponserelations
responserelations
1. Potency

2.Efficacy

B. Effectofdrugconcentrationonreceptor

binding
C.Relationshipofdrugbindingto
pharmacologiceffect
pharmacologiceffect

Potency
Potencyisameasureoftheamountofdrugnecessaryto
produceaneffectofagivenmagnitude.
Theconcentrationofdrugproducing50%ofthe
maximumeffect(EC50)isusuallyusedtodetermine
maximumeffect(EC50)isusuallyusedtodetermine
potency.

Efficacy
Efficacyisthemagnitudeofresponseadrugcauseswhenit
interactswithareceptor.Efficacyisdependentonthenumber
ofdrugreceptorcomplexesformedandtheintrinsicactivity
receptorcomplexesformedandtheintrinsicactivity
ofthedrug(itsabilitytoactivatethereceptorandcausea
cellularresponse).
Maximalefficacyofadrug(Emax)assumesthatallreceptors
areoccupiedbythedrug,andnoincreaseinresponseis
observedifahigherconcentrationofdrugisobtained.
observedifahigherconcentrationofdrugisobtained.

Effectofdrugconcentrationon
receptorbinding
receptorbinding

Relationshipofdrugbindingto
pharmacologiceffect

1receptorsonlymediatechangesinbloodpressure,while2receptorsonlymediate
1receptorsonlymediatechangesinbloodpressure,while2receptorsonlymediate
changesinbronchodilation.

Quiz
Isoproterenolproducesmaximalcontractionofcardiac
muscleinamannersimilartoepinephrine.Whichof
thefollowingbestdescribesisoproterenol?
thefollowingbestdescribesisoproterenol?
A.Fullagonist.
B.Partialagonist.
C.Competitiveantagonist.
D.Irreversibleantagonist.
E. Inverseagonist.
Answer:A

Answer:B
If10mgofnaproxenproducesthesameanalgesicresponseas
100mgofibuprofen,whichofthefollowingstatementsis
correct?
A.Naproxenismoreefficaciousthanisibuprofen.
B.Naproxenismorepotentthanibuprofen.
C.Naproxenisafullagonist,andibuprofenisapartialagonist.
D.Naproxenisacompetitiveantagonist.
E.Naproxenisabetterdrugtotakeforpainreliefthanis
E.Naproxenisabetterdrugtotakeforpainreliefthanis
ibuprofen.

Answer:E
If10mgofmorphineproducesagreateranalgesic
responsethancanbeachievedbyibuprofenatany
dose,whichofthefollowingstatementsiscorrect?
A.Morphineislessefficaciousthanisibuprofen.
B.Morphineislesspotentthanisibuprofen.
C.Morphineisafullagonist,andibuprofenisapartial
agonist.
D.Ibuprofenisacompetitiveantagonist.
E.Morphineisabetterdrugtotakeforpainreliefthan
E.Morphineisabetterdrugtotakeforpainreliefthan
isibuprofen.

Answer:A
Inthepresenceof naloxone,ahigherconcentrationof
naloxone
morphineisrequiredtoelicitfullpainrelief.Naloxone
morphineisrequiredtoelicitfullpainrelief.
byitselfhasnoeffect.Whichofthefollowingiscorrect
regardingthesemedications?
A. Naloxone isacompetitiveantagonist.
B.Morphineisafullagonist,andnaloxone isapartial
B.Morphineisafullagonist,and
agonist.
C.Morphineislessefficaciousthanisnaloxone.
C.Morphineislessefficaciousthanis
D.Morphineislesspotentthanisnaloxone.
D.Morphineislesspotentthanis
E. Naloxone isanoncompetitiveantagonist.
isanoncompetitiveantagonist.

Answer:B
Inthepresenceof pentazocine,ahigherconcentrationof
,ahigherconcentrationof
morphineisrequiredtoelicitfullpainrelief.Pentazocine byitself
morphineisrequiredtoelicitfullpainrelief.
hasasmalleranalgesiceffectthandoesmorphine,evenatthe
hasasmalleranalgesiceffectthandoesmorphine,
highestdose.Whichofthefollowingiscorrectregardingthese
medications?
A. Pentazocine isacompetitiveantagonist.
B.Morphineisafullagonist,andpentazocine isapartial
B.Morphineisafullagonist,and
agonist.
C.Morphineislessefficaciousthanispentazocine.
C.Morphineislessefficaciousthanis
D.Morphineislesspotentthanispentazocine.
D.Morphineislesspotentthanis
E. Pentazocine isanoncompetitiveantagonist.
isanoncompetitiveantagonist.