General Pharmacology for Physiotherapists

Pharmacodynamics and Pharmacokinetics

1. GeneralPharmacologyforPhysiotherapists
CourseCode:CLSC204
Dr.SanjibKumarDas
MPT (Musculoskeletal),
FellowPhD(ErgonomicsandHumanFactors)

2. DEFINITIONS
•ThewordpharmacologyisderivedfromtheGreekword—
Pharmaconmeaninganactiveprincipleordrugandlogos
meaningastudy(discourse).
•Drug:“Adrugisanysubstanceorproductthatisusedorintended
tobeusedtomodifyorexplorephysiologicalsystemsor
pathologicalstatesforthebenefitoftherecipient.”(WHO)
•Pharmacodynamicsisthestudyoftheeffectsofthedrugsonthe
bodyandtheirmechanismsofaction,i.e.whatthedrugdoestothe
body.
•Pharmacokineticsisthestudyoftheabsorption,distribution,
metabolismandexcretionofdrugs,i.e.whatthebodydoestothe
drug

3. •Pharmacoepidemiologyisthestudyofboththeusefuland
adverseeffectsofdrugsonlargenumbersofpeople.
•Pharmacovigilanceisabranchofpharmacoepidemiology
whichdealswiththeepidemiologicstudyofadversedrug
effects.
•Toxicologydealswiththeadverseeffectsofdrugsandalsothe
studyofpoisons.
•Pharmacyisthescienceofidentification,compoundingand
dispensingofdrugs.
DEFINITIONS

4. DEFINITIONS
•Pharmacopoeia(inGreekPharmacon=drug;poeia=to
make)istheofficialpublicationcontainingalistofdrugs
andmedicinalpreparationsapprovedforuse,their
formulaeandotherinformationneededtoprepareadrug;
theirphysicalproperties,testsfortheiridentity,purityand
potency.
•Eachcountrymayfollowitsownpharmacopoeiatoguide
itsphysiciansandpharmacistslikeIndianPharmacopoeia
(IP),theBritishPharmacopoeia(BP)andtheUnited
StatesPharmacopoeia(USP).
•Thelistisrevisedatregularperiodstodeleteobsolete
drugsandtoincludenewlyintroducedones.

5. SOURCESOFDRUGS
•Thesourcesofdrugscouldbenaturalorsynthetic.
•Naturalsources:Drugscanbeobtainedfrom:
1.Plants,e.g.atropine,morphine,quinineanddigoxin.
2.Animals,e.g.insulin,heparin,gonadotrophinsandantitoxicsera.
3.Minerals,e.g.magnesiumsulphate,aluminiumhydroxide,iron,sulphur
andradioactiveisotopes.
4.Microorganisms—antibacterialagentsareobtainedfromsomebacteria
andfungi.Wethushavepenicillin,cephalosporins,tetracyclinesandother
antibiotics.
5.Human—somedrugsareobtainedfromhumanbeings,e.g.
immunoglobulinsfromblood,growthhormonefromanteriorpituitaryand
gonadotrophinsfromtheurineofpregnantwomen.
•Synthetic:Mostdrugsusednowaresynthetic,e.g.quinolones,
omeprazole,neostigmine,sulfonamides.

6. ROUTESOFDRUGADMINISTRATION
Theroutescanbebroadlydividedinto:
•Enteral(OralIngestion):Itisthemostcommonlyused,oldest
andsafestrouteofdrugadministration.
•Parenteral:Routesofadministrationotherthantheenteral
(intestinal)routeareknownasparenteralroutes.Herethedrugs
aredirectlydeliveredintotissuefluidsorblood.Parenteralroutes
include:
1.Injections-Intradermal,Subcutaneous,Intramuscular,
Intravenous
2.Inhalation-Volatileliquidsorgases
3.Transdermalroute-Highlylipidsolubledrugscanbeapplied
overtheskinforslowandprolongedabsorption.
4.Transmucosalrouteincludessublingual,nasalandrectalroutes.

7. Topical
•Drugsmaybeappliedontheskinforlocalactionas
ointment,cream,gel,powder,paste,etc.
•Drugsmayalsobeappliedonthemucousmembrane
asintheeyes,earsandnoseasointment,dropsand
sprays.
ROUTESOFDRUGADMINISTRATION

8. PHARMACOKINETICS
•Pharmacokineticsisthestudyoftheabsorption,distribution,
metabolismandexcretionofdrugs,i.e.themovementofthe
drugsinto,withinandoutofthebody.
•Foradrugtoproduceitsspecificresponse,itshouldbepresent
inadequateconcentrationsatthesiteofaction.
•Oncethedrugisadministered,itisabsorbed,i.e.entersthe
blood,isdistributedtodifferentpartsofthebody,reachesthe
siteofaction,ismetabolisedandexcreted.
•Alltheseprocessesinvolvepassageofthedrugmoleculesacross
variousbarriers—liketheintestinalepithelium,cellmembrane,
renalfilteringmembrane,capillarybarrierandsoon.

9. SCHEMATICREPRESENTATIONOFMOVEMENT
OFDRUGINTHEBODY

10. MECHANISMSOFTRANSPORTOFDRUGSACROSSBIOLOGICAL
MEMBRANES
PassiveTransfer
•Thedrugmovesacrossamembranewithoutany
needforenergy.
•Simplediffusionisthetransferofadrugacrossthe
membraneinthedirectionofitsconcentration
gradient.
•Filtrationisthepassageofdrugsthroughaqueous
poresinthemembrane.

11. Carrier-mediatedTransport
•Activetransportisthetransferofdrugsagainstaconcentrationgradient
andneedsenergy.Onlydrugsrelatedtonaturalmetabolitesare
transportedbythisprocess,e.g.levodopa,iron,aminoacids.
•Facilitateddiffusionisauniqueformofcarriertransportwhichdiffers
fromactivetransportinthatitisnotenergydependentandthe
movementoccursinthedirectionoftheconcentrationgradient.
•Thecarrierfacilitatesdiffusionandishighlyspecificforthesubstance,
e.g.uptakeofglucosebycells,vitaminB12fromintestines.
Endocytosis
•Endocytosisistheprocesswheresmalldropletsareengulfedbythe
cell.
MECHANISMSOFTRANSPORTOFDRUGSACROSSBIOLOGICAL
MEMBRANES

12. ABSORPTION
•Absorptionisdefinedasthepassageofthedrugfrom
thesiteofadministrationintothecirculation.Fora
drugtoreachitssiteofaction,itmustpassthrough
variousmembranesdependingontherouteof
administration.
•Absorptionoccursbyoneoftheprocessesi.e.passive
diffusionorcarrier-mediatedtransport.
•Thusexceptforintravenousroute,absorptionis
importantforallotherroutesofadministration.

13. •Bioavailabilityisthefractionofthedrugthatreachesthe
systemiccirculationfollowingadministrationbyanyroute.
Thusforadruggivenintravenously,thebioavailabilityis
100%.
•OnIM/SCinjection,drugsarealmostcompletelyabsorbed
whilebyoralroute,bioavailabilitymaybelowdueto
incompleteabsorption
BIOAVAILABILITY

14. BIOEQUIVALENCE
•Comparisonofbioavailabilityofdifferentformulations
ofthesamedrugisthestudyofbioequivalence.
•Oftenoralformulationscontainingthesameamountof
adrugfromdifferentmanufacturersmayresultin
differentplasmaconcentrations,i.e.thereisno
bioequivalenceamongthem.
•Variationsinbioavailability(nonequivalence)canresult
intoxicityortherapeuticfailureindrugsthathavelow
safetymargin.

15. DISTRIBUTION
•Afteradrugreachesthesystemiccirculation,itgetsdistributed
toothertissues.
•Itshouldcrossseveralbarriersbeforereachingthesiteofaction.
•Likeabsorption,distributionalsoinvolvesthesameprocesses,
i.e.filtration,diffusionandspecializedtransport.
•Variousfactorsdeterminetherateandextentofdistribution,viz
lipidsolubility,ionization,bloodflowandbindingtoplasma
proteinsandcellularproteins.

16. PLASMAPROTEINBINDING
•Onreachingthecirculationmostdrugsbindtoplasmaproteins;
acidicdrugsbindmainlyalbuminandbasicdrugstoalpha-
glycoprotein.
•Thefreeorunboundfractionofthedrugistheonlyform
availableforaction,metabolismandexcretionwhiletheprotein
boundformservesasareservoir.
•Theextentofproteinbindingvarieswitheachdrug,e.g.warfarin
is99%andmorphineis35%proteinboundwhilebindingof
ethosuximide(seizures)andlithium(antidepressant)is0%,i.e.
theyaretotallyfree.

17. BIOTRANSFORMATION(METABOLISM)
•Biotransformationistheprocessofbiochemicalalterationofthe
druginthebody.
•Bodytreatsmostdrugsasforeignsubstancesandtriesto
inactivateandeliminatethembyvariousbiochemicalreactions.
•Theseprocessesconvertthedrugsintomorepolar,water-
solublecompoundssothattheyareeasilyexcretedthroughthe
kidneys.
•Somedrugsmaybeexcretedlargelyunchangedintheurine,e.g.
frusemide,atenolol.
•Themostimportantorganofbiotransformationistheliver.But
drugsarealsometabolizedbythekidney,gut,mucosa,lungs,
bloodandskin.

18. PHASESINMETABOLISMOFDRUG
I

19. EXCRETION
•Drugsareexcretedfromthebodyafterbeing
convertedtowater-solublemetaboliteswhilesome
aredirectlyeliminatedwithoutmetabolism.
•Themajororgansofexcretionarethekidneys,the
intestine,thebiliarysystemandthelungs.
•Drugsarealsoexcretedinsmallamountsinthe
saliva,sweatandmilk.

20. PLASMAHALF-LIFE
•Plasmahalf-life(t½)isthetimetakenfortheplasma
concentrationofadrugtobereducedtohalfit’svalue.
•Fourtofivehalflivesarerequiredforthecompleteeliminationof
adrug.
•Eachdrughasitsownt½andisanimportantpharmacokinetic
parameterthatguidesthedosingregimen.

21. STEADYSTATECONCENTRATION
•Biologicalhalf-lifeisthetimerequiredfortotalamountofthedrug
inthebodytobereducedtohalf.
•Ifadrugisadministeredrepeatedlyatshortintervalsbefore
completeelimination,thedrugaccumulatesinthebodyand
reachesa‘state’atwhichtherateofeliminationequalstherateof
administration.Thisisknownasthe‘Steady-state’orplateaulevel.
•Afterattainingthislevel,theplasmaconcentrationfluctuates
aroundanaveragesteadylevel.

22. PHARMACODYNAMICS
•Pharmacodynamicsisthestudyofactionsofthedrugsonthe
bodyandtheirmechanismsofaction,i.e.toknowwhatdrugs
doandhowtheydoit.
•Drugsproducetheireffectsbyinteractingwiththe
physiologicalsystemsoftheorganisms.
•Thusdrugsactby:
1.Stimulation
2.Depression
3.Irritation
4.Replacement
5.Anti-infectiveorcytotoxicaction
6.Modificationoftheimmunestatus.

23. •Stimulationistheincreaseinactivityofthespecialized
cells,e.g.adrenalinestimulatestheheart.
•Depressionisthedecreaseinactivityofthespecialized
cells,e.g.quinidinedepressestheheart;barbiturates
depressthecentralnervoussystem.
•Somedrugsmaystimulateonesystemanddepress
another,e.g.morphinedepressestheCNSbutstimulates
thevagus.
•Irritation:Thiscanoccuronalltypesoftissuesinthe
bodyandmayresultininflammation,corrosionand
necrosisofcells.

24. •Replacement:Drugsmaybeusedforreplacementwhen
thereisdeficiencyofnaturalsubstanceslikehormones
ornutrients,e.g.insulinindiabetesmellitus,ironin
anaemia,vitaminCinscurvy.
•Anti-infectiveandcytotoxicaction:Drugsmayactby
specificallydestroyinginfectiveorganisms,e.g.
penicillins,orbycytotoxiceffectoncancercells,e.g.
anticancerdrugs.
•Modificationofimmunestatus:Vaccinesactby
improvingourimmunitywhileimmunosuppressantsact
bydepressingimmunity,e.g.glucocorticoids.

25. MECHANISMSOFDRUGACTION
•Mostdrugsproducetheireffectsbybindingtospecific
targetproteinslikereceptors,enzymesandionchannels.
•Thefundamentalmechanismsofdrugactionmaybe:
-throughreceptors
-throughenzymesandpumps
-throughionchannels
-byphysicalaction
-bychemicalinteraction
-byalteringmetabolicprocesses.

26. ThroughReceptors
•Drugsmayactbyinteractingwithspecificreceptorsinthebody.
ThroughEnzymesandPumps
•Drugsmayactbyinhibitionofvariousenzymes,thusaltering
theenzyme-mediatedreactions,e.g.allopurinol(decreaseuric
acidlevels)inhibitstheenzymexanthineoxidase;acetazolamide
(forepilepsy)inhibitscarbonicanhydrase,enalapril(highblood
pressure)inhibitsangiotensinconvertingenzyme,aspirin(for
pain&inflammation)inhibitscyclo-oxygenase,neostigmine
(formyastheniagravis)inhibitsacetylcholinesterase.
•MembranepumpslikeH+K+ATPaseandNa+K+ATPasemay
beinhibitedbydrugslikeomeprazole(forpepticulcer)and
digoxin(forheartfailure)respectively.

27. ThroughIonChannels
•Drugsmayinterferewiththemovementofionsacrossspecific
channels,e.g.calciumchannelblockers,sodiumchannel
blockers,potassiumchannelopeners.
PhysicalAction
•Theactionofadrugcouldresultfromitsphysicalproperties
like:
Absorption–Activatedcharcoalinpoisoning
Massofthedrug–Bulklaxativeslikepsyllium,bran
Osmoticproperty–Osmoticdiuretics–Mannitol
–Osmoticpurgatives-Magnesiumsulphate

28. ChemicalInteraction
•Drugsmayactbychemicalreaction.
Antacids–neutralizegastricacids
Oxidizingagents–likepotassiumpermanganateisgermicidal
Chelatingagents–bindheavymetalsmakingthemnontoxic.
AlteringMetabolicProcesses
•Drugslikeantimicrobialsalterthemetabolicpathwayinthe
microorganismsresultingindestructionofthemicroorganism

29. RECEPTOR
•Areceptorisamacromolecularsiteonthecellwithwhichanagonist
bindstobringaboutachange.
•Affinityistheabilityofadrugtobindtoareceptor.
•Intrinsicactivityorefficacyistheabilityofadrugtoelicitaresponse
afterbindingtothereceptor.
•Agonistisasubstancethatbindstothereceptorandproducesaresponse.
Ithasaffinityandintrinsicactivity.E.g.adrenalineisanagonistat
adrenergicreceptors.
•Antagonistisasubstancethatbindstothereceptorandpreventsthe
actionoftheagonistonthereceptor.Ithasaffinitybutnointrinsic
activity.E.g.Tubocurarine(musclesrelaxant)isanantagonistatnicotinic
receptors.

30. RECEPTOR
•Partialagonistbindstothereceptorbuthaslowintrinsic
activity.Pentazocine(forpain)isapartialagonistatopioid
receptors.
•InverseagonistSomedrugs,afterbindingtothereceptors
produceactionsoppositetothoseproducedbyapureagonist.
Theyareknownasinverseagonists,e.g.Diazepamactingon
benzodiazepinereceptorsproducessedation,anxiolysis,muscle
relaxationandcontrolsconvulsions,whileinverseagonistsβ-
carbolinesbindtothesamereceptorstocausearousal,anxiety,
increasedmuscletoneandconvulsions.
•Ligandisamoleculewhichbindsselectivelytoaspecific
receptor.

31. RECEPTOR
•Site:Thereceptorsmaybepresentinthecellmembrane,in
thecytoplasmoronthenucleus.
•Natureofreceptors:Receptorsareproteins.
•Synthesisandlifespan:Receptorproteinsaresynthesizedby
thecells.Theyhaveadefinitelifespanafterwhichthe
receptorsaredegradedbythecellandnewreceptorsare
synthesized.

32. FUNCTIONSOF RECEPTORS
Thetwofunctionsofreceptorsare-
•Recognitionandbindingoftheligand.
•Propagationofthemessage.
RECEPTORFAMILIES
Fourtypes/familiesofreceptorsareidentified.Thereceptortypes
are:
1.Ionchannels(inotropicreceptor)
2.G-proteincoupledreceptors(metabo-tropicreceptor)
3.Enzymaticreceptors(kinaselinkedreceptor)
4.Transcriptionfactors(receptorsthatregulategenetranscription
ornuclearreceptors).

33. (1) Binding of the agonist directly regulates the opening of the ion channel.
(2) Agonist binding activates the receptor that is linked to an effector system by a G protein.
(3) Agonist binding to extracellular domain activates enzymatic activity of its catalytic domain.
(4) Agonist binds to the intracellular receptor, the complex moves to the nucleus and directs
protein synthesis

34. RECEPTORREGULATION
•Thenumberofreceptorsandtheirsensitivitycanbealteredinmany
situations.
•Denervationorprolongeddeprivationoftheagonistorconstant
actionoftheantagonistallresultinanincreaseinthenumberand
sensitivityofthereceptors.Thisphenomenoniscalled‘up
regulation’.
•Prolongeduseofaβadrenergicantagonistlikepropranolol(for
cardiacarrhythmia)resultsinupregulationofβadrenergicreceptors.
Afterprolongedadministration,areceptorantagonistshouldalways
betapered.
•Forexample,ifpropranolol,aβadrenoceptorblockerissuddenly
withdrawnafterlongtermuse,itprecipitatesangina.

35. CLINICALCONSEQUENCESANDIMPLICATIONSOF
RECEPTORREGULATION
•Ontheotherhand,continuedstimulationofthereceptors
causesdesensitizationandadecreaseinthenumberof
receptors—knownas‘downregulation’ofthereceptors.
•Constantuseofβadrenergicagonistsinbronchialasthma
resultsinreducedtherapeuticresponseduetodownregulation
ofβ2receptors.

36. DRUGPOTENCYANDMAXIMALEFFICACY
•Theamountofdrugrequiredto
producearesponseindicatesthe
potency.
•Forexample,1mgofbumetanide
producesthesamediuresisas50mg
offrusemide.Thusbumetanideis
morepotentthanfrusemide.
•InFigure,drugsAandBaremore
potentthandrugsCandD,drugA
beingthemostpotentanddrugD—
theleastpotent.
•HencehigherdosesofdrugsCand
Daretobeadministeredas
comparedtodrugsAandB.

37. DRUGADDITIVEEFFECTANDSYNERGISM
•Whentwoormoredrugsaregivenconcurrently,theeffectmaybe
additive,synergisticorantagonistic.
•Additiveeffect:Theeffectoftwoormoredrugsgetsaddedupand
thetotaleffectisequaltothesumoftheirindividualactions.
•Examplesareephedrine(bronchodilator)withtheophylline(relax
muscles)inbronchialasthma;nitrousoxideandetherasgeneral
anaesthetics.
•Synergism:Whentheactionofonedrugisenhancedorfacilitated
byanotherdrug,thecombinationissynergistic.
•InGreek,ergon=work;syn=with.Here,thetotaleffectofthe
combinationisgreaterthanthesumoftheirindependenteffects.It
isoftencalled‘potentiation’or‘supra-additive’effect.

38. DRUGANTAGONISM
•Antagonism:Onedrugopposingorinhibitingtheactionof
anotherisantagonism.
•Basedonthemechanism,antagonismcanbe
Chemicalantagonism
Physiologicalantagonism
Antagonismatthereceptorlevel
–Reversible(Competitive)
–Irreversible
Non-competitiveantagonism.

39. DRUGANTAGONISM
•Chemicalantagonism:Twosubstancesinteractchemicallyto
resultininactivationoftheeffect
•E.g.chelatingagentsinactivateheavymetalslikeleadandmercury
toforminactivecomplexes;antacidslikealuminiumhydroxide
neutralizegastricacid.
•Physiologicalantagonism:Twodrugsactatdifferentsitesto
produceopposingeffects.
•Forexample,histamineactsonH1receptorstoproduce
bronchospasmandhypotensionwhileadrenalinereversesthese
effectsbyactingonadrenergicreceptors.
•Insulinandglucagonhaveoppositeeffectsonthebloodsugar
level.
•Antagonismatthereceptorlevel:Theantagonistinhibitsthe
bindingoftheagonisttothereceptor.Suchantagonismmaybe
reversibleorirreversible.

40. REVERSIBLEORCOMPETITIVEANTAGONISM
•Theagonistandantagonist
competeforthesamereceptor.
Byincreasingtheconcentration
oftheagonist,theantagonism
canbeovercome.Itisthus
reversibleantagonism.
•Acetylcholineandatropine
(slowsheartrate)competeat
muscarinicreceptors.The
antagonism(atropine)canbe
overcomebyincreasingthe
concentrationofacetylcholine
atthereceptor.
Dose response curves of an agonist:A
inthe absenceofcompetitive
antagonist; B, C and D inthe presence
of increasing doses of a competitive
antagonist

41. IRREVERSIBLE ANTAGONISM
•Irreversibleantagonism:The
antagonistbindssofirmlyby
covalentbondstothereceptor
thatitdissociatesveryslowlyor
notatall.Thusitblocksthe
actionoftheagonistandthe
blockagecannotbeovercomeby
increasingthedoseoftheagonist
andhenceitisirreversible
antagonism.
•E.g. adrenaline and
phenoxybenzamine (lowers
bloodpressure)atalpha
adrenergicreceptors.
Dose response curves of an agonist:A
inthe absenceof antagonist. B, C, and
D in the presenceof increasingdoses of
an irreversible antagonist.

42. FACTORSTHATMODIFYTHE EFFECTSOFDRUGS
•Variousfactorsmodifytheresponsetoadrug.Theyare:
1.Bodyweight:Therecommendeddoseiscalculatedformedium
builtpersons.Fortheobeseandunderweightpersons,thedosehas
tobecalculatedindividually.
2.Age:Thepharmacokineticsofmanydrugschangewithage
resultinginalteredresponseinextremesofage.Inthenewborn,
theliverandkidneysarenotfullymaturetohandlethedrugs.The
gastricacidityislow,intestinalmotilityisslow,skinisdelicate.
Alsopharmacodynamicdifferencescouldexist,e.g.barbiturates
whichproducesedationinadultsmayproduceexcitationin
children.

43. FACTORSTHATMODIFYTHE EFFECTSOFDRUGS
3.Sex:Specialcareisnecessarywhileprescribingforpregnantand
lactatingwomenandduringmenstruation.
4.SpeciesandRace:Responsetodrugsmayvarywithspeciesand
race.Forexample,rabbitsareresistanttoatropine.Blacksneedhigher
dosesofatropinetoproducemydriasis(fordilationofthepupil).
5.Dietandenvironment:Foodinterfereswiththeabsorptionofmany
drugs.Forexample,tetracyclines(antibioticsforinfections)form
complexeswithcalciumpresentinthefoodandarepoorlyabsorbed.
6.Routeofadministration:Occasionallyrouteofadministrationmay
modifythepharmacodynamicresponse,e.g.magnesiumsulfategiven
orallyisapurgative.ButgivenIVitcausesCNSdepressionandhas
anticonvulsanteffects.Ifappliedtopically,itreduceslocaledema.

44. FACTORSTHATMODIFYTHE EFFECTSOFDRUGS
7.Geneticfactors:Variationsinanindividual’sresponsetodrugs
couldbegeneticallymediatedandthedifferencesismostcommonly
duetovariationsintheamountofdrugmetabolisingenzymessince
theproductionoftheseenzymesisgeneticallycontrolled.
8.Dose:Itisfascinatingthattheresponsetoadrugmaybemodified
bythedoseadministered.Generallyasthedoseisincreased,the
magnitudeoftheresponsealsoincreasesproportionatelytillthe
‘maximum’isreached.Furtherincreasesindosesmaywithsome
drugsmayproduceoppositeeffects.
e.g.(i)Neostigmineinmyastheniagravisenhancesmusclepowerin
therapeuticdoses,butinhighdosesitcausesmuscleparalysis,
(ii)physiologicaldosesofvitaminDpromotescalcificationwhile
hypervitaminosismayleadstodecalcification.

45. FACTORSTHATMODIFYTHE EFFECTSOFDRUGS
9.Diseases:Presenceofcertaindiseasescaninfluencedrugresponses,
e.g.
•Liverdiseases:Rateofdrugmetabolismisreducedduetodysfunction
ofhepatocytes.
•Cardiacdiseases:InCCF,thereisedemaofthegutmucosaand
decreasedperfusionofliverandkidneys.Thesemayresultin
cumulationandtoxicityofdrugs.
•Renaldysfunction:Drugsmainlyexcretedthroughkidneysarelikely
toaccumulateandcausetoxicity.
10.Repeateddosingcanresultin
•Cumulation:Drugslikedigoxin(treatheartconditions)whichare
slowlyeliminatedmaycumulateresultingintoxicity.
•Tolerance:Itistherequirementofhigherdosesofadrugtoproducea
givenresponse.

46. FACTORSTHATMODIFYTHEEFFECTSOFDRUGS
•Tachyphylaxis:Itistherapiddevelopmentoftolerance.When
somedrugsareadministeredrepeatedlyatshortintervals,
tolerancedevelopsrapidly.Thusephedrinegivenrepeatedlyin
bronchialasthmamaynotgivethedesiredresponse.
11.Psychologicalfactor:Thepatientsconfidenceinthedoctor
mayitselfbesufficienttorelieveasuffering,particularlythe
psychosomaticdisorders.Thiscanbesubstantiatedbythefact
thatlargenumberofpatientsrespondtoplacebo.

47. ADVERSEDRUGREACTIONS
•WHOhasdefinedanadversedrugreactionas“anyresponsetoadrug
thatisnoxiousandunintendedandthatoccursatdosesusedinmanfor
prophylaxis,diagnosisortherapy.”
1.SideEffectsareunwantedeffectsofadrugandareseenwiththe
therapeuticdoseofthedrug.Theyarepredictable,commonandcan
occurinallpeople,e.g.hypoglycaemiaduetoinsulin;hypokalaemia
(electrolyteabnormality)followingfrusemide.
2.ToxicEffectsareseenwithhigherdosesofthedrugandcanbeserious,
e.g.morphinecausesrespiratorydepressioninoverdosage.
3.Intolerancetheinabilityofapersontotolerateadrug.Patientsshow
exaggeratedresponsetoevensmalldosesofthedrug.Intolerancecould
alsobequalitative,e.g.idiosyncrasyandallergicreactions.

48. ADVERSEDRUGREACTIONS
•Idiosyncrasyisageneticallydeterminedabnormalreactiontoadrug.
Insomecasesthepersonmaybehighlysensitiveeventolowdosesof
adrugorhighlyinsensitiveeventohighdosesofthedrug.
4.IatrogenicDiseases:Thesearedruginduceddiseases.Evenafterthe
drugiswithdrawn,toxiceffectscanpersist,e.g.isoniazid(forTB
infections)inducedhepatitis;chloroquine(treatmalaria)induced
retinopathy.
5.DrugDependence:Drugsthatinfluencethebehaviourandmoodare
oftenmisusedtoobtainpleasurableeffects.Repeateduseofsuchdrugs
resultindependence.Drugdependenceisastateofcompulsiveuseof
drugsinspiteoftheknowledgeoftherisksassociatedwithitsuse.Itis
alsoreferredtoasdrugaddiction.Dependencecouldbepsychological
(e.g.cigarettesmokingtoobtainitspleasurableeffects)orphysical
dependence(withdrawalsyndrome).Withdrawalsyndromearedisturbing
andthepersonthencravesforthedrug,e.g.alcohol,opioidsand
barbiturates.

49. ADVERSEDRUGREACTIONS
6.Teratogenicityistheabilityofadrugtocausefoetal
abnormalitieswhenadministeredtoapregnantwoman.
Thesedativethalidomidetakenduringearlypregnancyforrelief
frommorningsicknessresultedinthousandsofbabiesbeing
bornwithphocomelia(seallimbs).
7.CarcinogenicityandMutagenicity:Somedrugscancause
cancersandgeneticabnormalities.Forexampleanticancerdrugs
canthemselvesbecarcinogenic.

50. ThankYou
Dr.SanjibKumarDas
MPT(Musculoskeletal),
FellowPhD(ErgonomicsandHumanFactors)
[email protected]