Introduction to Clinical Pharmacology
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Whatpispthepdefinitionpofpclinicalppharmacology?p-p
ppppppppppApdisciplinepspanningpthepspectrumpofpdrugpdelivery,pdrugpdevelopment,pdrugputilization,p
andpdrugpregulation
Whatparepthepwordspforpthepfollowingpblanks?
ClinicalpPharmacologypispaimedpatpadvancingptherapeuticspinphumanspwithpmechanisticpunderst
andingpofpdrugpactionsp_____pandpdrugpdispositionp_____p-p
pppppppppppharmacodynamicspandppharmacokinetics
Whatpispthepdefinitionpofptranslationalpsciences?p-p
ppppppppppKnowledgepacquiredpinpanimalporpinpsilicopmodelspofpdisease,pex-
vivopstudiespinphumanptissues,porpinpvivopstudiespinphealthyporpdiseasedphumanspisptranslatedpint
opeffectiveptreatmentpforppatients
WhatpispthepstartingpdosepofpPhasepIptrial?p-p
pppppppppponeptenthpofpLD50pforpcancerporpphytotoxins
Whatparepthepprofessionalpgoalspofpclinicalppharmacologists?p-p
ppppppppppDiscover,pdeveloppandpevaluatepnewpmedicines,pregulateptheirpusep
Optimizepthepusepofpexistingpmedicines,pfindpnewpindications
Definepthepbasispforpvariabilitypinptherapeuticpandptoxicpresponsesptopmedicines
Whatpispthepmeasurementptopseepwhetherpsomeptoxicitiespcanpbepmanagedpandpmaypbepacceptabl
e?p-p
pppppppppprisk/benefitpratio
WhatpispthepcharacteristicpofpRisk/Benefitpratio?p-p
ppppppppppItpispcontextual,pwhichptellspyoupitpispdependingponpthepdrugpandpdiseasepthatpwepintendptoptr
eat
Forpexample,pitpispnotpthepsameptopconsiderppotentiallypseriousptoxicitypforpapdrugpintendedptoptre
atpHYT,pwhichpispapmedicalpconditionpthatpneedsplifelongptherapy,pcomparedptoptreatmentpofpcan
cer,papdiseasepthatpisppotentiallyplethalpoverpthepshortpterm,pandpthatprequirespverypintenseptreatm
entpwithpcombinationpofpdrugspthatphavepverypsignificantptoxicity
_____pispapconditionporpbringspuppsituations,pifpyoupwill,pwherepanpunderlyingpgeneticpvariantpm
ayppredisposepindividualsptopsevereptoxicityptopdrugsp-p
ppppppppppGenetics
Whatpispthepnamepofpgeneticpvariantpandpthepnamepofpantiviralpdrug?
Individualspthatpcarryp_____pvariantparepatpveryphighpriskpofp_____phypersensitivity.pThispdrugpi
spusedpinptheptreatmentpofpHIVpinfectionspandpAIDS,pandppriorptopinstitutingptreatmentpwithpthep
1p|pP a g e
,drug,peverypptpispfirstptestedpforpthispvariant,p_____,pandpalternativespmustpbepfoundpifptheppatient
phavepthepvariantp-p
ppppppppppHLA-B*5701pandpabacavir
Whatpispthepnamepdrugpthatpcausespthe-drug-
inducedpliverpdiseasep(DILI)pandpthepnamepofpvariantpassociatedpwithpthispDILI?p-p
ppppppppppFlucoxacillinpandpHLA-Bp*5701
Whatpispthepnamepofpgeneticpvariantpandpthepnamepofpdrug?
_____pmayppredisposeptopseverep_____-
induced,papseriouspcutaneouspADRpthatpactuallypcanpbepfatalp-p
ppppppppppHLA-B*1502pandpCarbamazepine
Whatpispthepnamepofpdrug-inducedpdiseasepassociatedpwithpHLA-B*1502?p-p
ppppppppppStevens-Johnsonpsyndrome
Whatpispthepnamepofpdiseasepexemplifiedpaspunacceptablepdrugptoxicitypthatpinducespanpabnorma
l,plife-
threateningpepisode/ADRpofptheppolymorphicpventricularptachycardiapthatpyoupmightpbepableptop
seepinpECGprecordp-p
ppppppppppTorsadespdepPointes
Whatpispthepnamepofpdrugpthatpwasphistoricallypthepfirstpnon-
sedatingpantihistaminepunderpthepbrandpnamepofpSeldane,pbutpsubsequentlypwithdrawnpfrompthep
marketpdueptopthepriskpofpdrug-inducedparrhythmias?p-p
ppppppppppTerfenadine
Whatparepthepwordspinpthepblanks?
_____pispcarboxylicpmetabolitepofp_____pwhichpispapnon-
sedatingpantihistaminepunderpthepbrandnamepofpAllegrapbutpdoespnotphavepthepriskpofpapdrug-
inducedparrhythmia.pRecentlypitpispalsopcalledp_____p-p
ppppppppppTerfenadinepCarboxylate,pTerfenadine,pandpFexofenadine
WhatpwouldpweplearnpfrompthepexamplespofpTerfenadinepandpitspcarboxylicpmetabolite?p-p
ppppppppppItpbringspusptopconsiderpandprememberpthepimportancepofpstudyingpdrugpmetabolismpandpas
sessingpwhetherpmetabolitesparepalsoppharmacologicallypactiveporparepotherwisepinactivepones,p
whetherptransformationphasptakenpplace
WhatpispthepnamepofpdrugpthatpwaspnotpallowedptopenterpthepUSpmarketpafterpapprovedpinpthepUSp
dueptopsomepsevereptoxicityptopunbornpchildrenpexpressedpbypprenatalpdrugpexposure:panpepidem
icpworldwidepofpphocomelia,pchildrenpbornpwithpseverepdefectspinptermspofptheirplimbsp-p
ppppppppppThalidomide
Whatpispthepstartingpsteppinpdevelopmentpandpevaluationpofpnewpdrugs?p-p
ppppppppppDrugpdiscovery
2p|pP a g e
, Whatpispthepsteppthatpanimalptestingpofpcandidatepdrugspandpevaluationptopdemonstratepsafetypinp
humanspandpwhetherporpnotpthepdrugpispeffectivepinpapgivenpclinicalpconditionpwhilepconductedpi
npdevelopmentpandpevaluationpofpnewpdrugs?p-p
ppppppppppPre-clinicalpandpclinicalpevaluation
Whatpispthepsteppinpwhich,poncepthepdrugpenterspthepmarket,pexpertspcontinueptopevaluatepforpthep
possibilitypofprarepADRspthatpwerepnotpdiscoveredpinptheppre-
approvalpstage,pandpalsopperformingpstudiespinpspecialppopulationsplikepgeriatricpandppediatricpp
opulations?p-p
ppppppppppPost-marketingpstudies
WhatparepdonepinpPre-ClinicalpDevelopment?p-p
ppppppppppChemicalpSynthesispandpFormulationpDevelopmentp
AnimalpModelspforpEfficacy
AssaypDevelopmentp
AnimalpPKpandpPD
AnimalpToxicology
WhatpispthepcasepforpwhichpAnimalpToxicologypcontinuespinptheplongpterm?p-p
ppppppppppIfpthepdrugpispintendedpforpchronicpuse
Whatpispthepnextpstepponcepappackagepofpinformationpispdevelopedpthatpindicatespthepcandidatepdr
ugpmay,pinpfact,pbeppromising?p-p
ppppppppppAnpinvestigationalpnewpdrugpapplication,pthepIND,pispfiledpwithpthepFDAporpotherpregulator
ypagenciespandpprocesspofpevaluatingpthepdrugpinphumanspstartspbypClinicalpDevelopment:pPhase
pI,pPhasepII,pandpPhasepIII
WhatpispstudiedpinpPhasepI?p-p
ppppppppppTypically,pitpispconsideredpfirstpdosepinphumanpstudiespandpdosepescalationsparepevaluatedpt
opassessptolerance
WhatpispstudiedpinpPhasepII?p-p
ppppppppppThepproofpofpconceptpstudiespispdonepbyptreatingppatientspwithpthepconditionpthatpmaypbene
fit,ppotentiallypfrompthepdrugs
WhatpispstudiedpinpPhasepIII?p-p
ppppppppppTheplargeprandomizedpclinicalptrialsparepconductedpbypcomparingpthepnewpdrugptopapplaceb
oporptopappreviouslypestablishedptherapy
WhatpwouldpwepseepafterpPhasepIIIpispfinishedpup?p-p
ppppppppppThepfinishpleadsptopthepsubmissionpofpapnewpdrugpapplication,porpNDA,pwherepthepsponsorp
askspthepregulatorypagentsptopreviewpthispbodypofpevidencepandprequestpapprovalpforpmarketingp
ofpthepdrugpandptopbeginpusingpthepdrugpinpclinicalppracticepatphospitals
Inpthepcontextpofp"LearnpandpConfirm"pParadigm,pwhichpphasepispdefinedpaspthepLearningpphase
?p-p
3p|pP a g e
p p p
Whatpispthepdefinitionpofpclinicalppharmacology?p-p
ppppppppppApdisciplinepspanningpthepspectrumpofpdrugpdelivery,pdrugpdevelopment,pdrugputilization,p
andpdrugpregulation
Whatparepthepwordspforpthepfollowingpblanks?
ClinicalpPharmacologypispaimedpatpadvancingptherapeuticspinphumanspwithpmechanisticpunderst
andingpofpdrugpactionsp_____pandpdrugpdispositionp_____p-p
pppppppppppharmacodynamicspandppharmacokinetics
Whatpispthepdefinitionpofptranslationalpsciences?p-p
ppppppppppKnowledgepacquiredpinpanimalporpinpsilicopmodelspofpdisease,pex-
vivopstudiespinphumanptissues,porpinpvivopstudiespinphealthyporpdiseasedphumanspisptranslatedpint
opeffectiveptreatmentpforppatients
WhatpispthepstartingpdosepofpPhasepIptrial?p-p
pppppppppponeptenthpofpLD50pforpcancerporpphytotoxins
Whatparepthepprofessionalpgoalspofpclinicalppharmacologists?p-p
ppppppppppDiscover,pdeveloppandpevaluatepnewpmedicines,pregulateptheirpusep
Optimizepthepusepofpexistingpmedicines,pfindpnewpindications
Definepthepbasispforpvariabilitypinptherapeuticpandptoxicpresponsesptopmedicines
Whatpispthepmeasurementptopseepwhetherpsomeptoxicitiespcanpbepmanagedpandpmaypbepacceptabl
e?p-p
pppppppppprisk/benefitpratio
WhatpispthepcharacteristicpofpRisk/Benefitpratio?p-p
ppppppppppItpispcontextual,pwhichptellspyoupitpispdependingponpthepdrugpandpdiseasepthatpwepintendptoptr
eat
Forpexample,pitpispnotpthepsameptopconsiderppotentiallypseriousptoxicitypforpapdrugpintendedptoptre
atpHYT,pwhichpispapmedicalpconditionpthatpneedsplifelongptherapy,pcomparedptoptreatmentpofpcan
cer,papdiseasepthatpisppotentiallyplethalpoverpthepshortpterm,pandpthatprequirespverypintenseptreatm
entpwithpcombinationpofpdrugspthatphavepverypsignificantptoxicity
_____pispapconditionporpbringspuppsituations,pifpyoupwill,pwherepanpunderlyingpgeneticpvariantpm
ayppredisposepindividualsptopsevereptoxicityptopdrugsp-p
ppppppppppGenetics
Whatpispthepnamepofpgeneticpvariantpandpthepnamepofpantiviralpdrug?
Individualspthatpcarryp_____pvariantparepatpveryphighpriskpofp_____phypersensitivity.pThispdrugpi
spusedpinptheptreatmentpofpHIVpinfectionspandpAIDS,pandppriorptopinstitutingptreatmentpwithpthep
1p|pP a g e
,drug,peverypptpispfirstptestedpforpthispvariant,p_____,pandpalternativespmustpbepfoundpifptheppatient
phavepthepvariantp-p
ppppppppppHLA-B*5701pandpabacavir
Whatpispthepnamepdrugpthatpcausespthe-drug-
inducedpliverpdiseasep(DILI)pandpthepnamepofpvariantpassociatedpwithpthispDILI?p-p
ppppppppppFlucoxacillinpandpHLA-Bp*5701
Whatpispthepnamepofpgeneticpvariantpandpthepnamepofpdrug?
_____pmayppredisposeptopseverep_____-
induced,papseriouspcutaneouspADRpthatpactuallypcanpbepfatalp-p
ppppppppppHLA-B*1502pandpCarbamazepine
Whatpispthepnamepofpdrug-inducedpdiseasepassociatedpwithpHLA-B*1502?p-p
ppppppppppStevens-Johnsonpsyndrome
Whatpispthepnamepofpdiseasepexemplifiedpaspunacceptablepdrugptoxicitypthatpinducespanpabnorma
l,plife-
threateningpepisode/ADRpofptheppolymorphicpventricularptachycardiapthatpyoupmightpbepableptop
seepinpECGprecordp-p
ppppppppppTorsadespdepPointes
Whatpispthepnamepofpdrugpthatpwasphistoricallypthepfirstpnon-
sedatingpantihistaminepunderpthepbrandpnamepofpSeldane,pbutpsubsequentlypwithdrawnpfrompthep
marketpdueptopthepriskpofpdrug-inducedparrhythmias?p-p
ppppppppppTerfenadine
Whatparepthepwordspinpthepblanks?
_____pispcarboxylicpmetabolitepofp_____pwhichpispapnon-
sedatingpantihistaminepunderpthepbrandnamepofpAllegrapbutpdoespnotphavepthepriskpofpapdrug-
inducedparrhythmia.pRecentlypitpispalsopcalledp_____p-p
ppppppppppTerfenadinepCarboxylate,pTerfenadine,pandpFexofenadine
WhatpwouldpweplearnpfrompthepexamplespofpTerfenadinepandpitspcarboxylicpmetabolite?p-p
ppppppppppItpbringspusptopconsiderpandprememberpthepimportancepofpstudyingpdrugpmetabolismpandpas
sessingpwhetherpmetabolitesparepalsoppharmacologicallypactiveporparepotherwisepinactivepones,p
whetherptransformationphasptakenpplace
WhatpispthepnamepofpdrugpthatpwaspnotpallowedptopenterpthepUSpmarketpafterpapprovedpinpthepUSp
dueptopsomepsevereptoxicityptopunbornpchildrenpexpressedpbypprenatalpdrugpexposure:panpepidem
icpworldwidepofpphocomelia,pchildrenpbornpwithpseverepdefectspinptermspofptheirplimbsp-p
ppppppppppThalidomide
Whatpispthepstartingpsteppinpdevelopmentpandpevaluationpofpnewpdrugs?p-p
ppppppppppDrugpdiscovery
2p|pP a g e
, Whatpispthepsteppthatpanimalptestingpofpcandidatepdrugspandpevaluationptopdemonstratepsafetypinp
humanspandpwhetherporpnotpthepdrugpispeffectivepinpapgivenpclinicalpconditionpwhilepconductedpi
npdevelopmentpandpevaluationpofpnewpdrugs?p-p
ppppppppppPre-clinicalpandpclinicalpevaluation
Whatpispthepsteppinpwhich,poncepthepdrugpenterspthepmarket,pexpertspcontinueptopevaluatepforpthep
possibilitypofprarepADRspthatpwerepnotpdiscoveredpinptheppre-
approvalpstage,pandpalsopperformingpstudiespinpspecialppopulationsplikepgeriatricpandppediatricpp
opulations?p-p
ppppppppppPost-marketingpstudies
WhatparepdonepinpPre-ClinicalpDevelopment?p-p
ppppppppppChemicalpSynthesispandpFormulationpDevelopmentp
AnimalpModelspforpEfficacy
AssaypDevelopmentp
AnimalpPKpandpPD
AnimalpToxicology
WhatpispthepcasepforpwhichpAnimalpToxicologypcontinuespinptheplongpterm?p-p
ppppppppppIfpthepdrugpispintendedpforpchronicpuse
Whatpispthepnextpstepponcepappackagepofpinformationpispdevelopedpthatpindicatespthepcandidatepdr
ugpmay,pinpfact,pbeppromising?p-p
ppppppppppAnpinvestigationalpnewpdrugpapplication,pthepIND,pispfiledpwithpthepFDAporpotherpregulator
ypagenciespandpprocesspofpevaluatingpthepdrugpinphumanspstartspbypClinicalpDevelopment:pPhase
pI,pPhasepII,pandpPhasepIII
WhatpispstudiedpinpPhasepI?p-p
ppppppppppTypically,pitpispconsideredpfirstpdosepinphumanpstudiespandpdosepescalationsparepevaluatedpt
opassessptolerance
WhatpispstudiedpinpPhasepII?p-p
ppppppppppThepproofpofpconceptpstudiespispdonepbyptreatingppatientspwithpthepconditionpthatpmaypbene
fit,ppotentiallypfrompthepdrugs
WhatpispstudiedpinpPhasepIII?p-p
ppppppppppTheplargeprandomizedpclinicalptrialsparepconductedpbypcomparingpthepnewpdrugptopapplaceb
oporptopappreviouslypestablishedptherapy
WhatpwouldpwepseepafterpPhasepIIIpispfinishedpup?p-p
ppppppppppThepfinishpleadsptopthepsubmissionpofpapnewpdrugpapplication,porpNDA,pwherepthepsponsorp
askspthepregulatorypagentsptopreviewpthispbodypofpevidencepandprequestpapprovalpforpmarketingp
ofpthepdrugpandptopbeginpusingpthepdrugpinpclinicalppracticepatphospitals
Inpthepcontextpofp"LearnpandpConfirm"pParadigm,pwhichpphasepispdefinedpaspthepLearningpphase
?p-p
3p|pP a g e
