gg
lOMoAR cPSD| 36278399
(COMPLETE)NRNPg6566gWEEKg1,2,3,4,5,6,7,8,9,10,11&gFINALgEXAMSgTESTg
BANKgQUESTIONgANDgCORRECTgVERIFIEDgANSWERSgLATESTg2024-
2025gA+GRDADED
TablegofgContents
NRNPg6566gWEEKg1-5gKNOWLEDGEgCHECKgEXAMgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gCOMPLETEgCONCEPTg ...................................2
NRNPg6566gWEEKg3gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg2024 ............................................................................... 17
NRNPg6566gWEEKg4gKNOWLEDGEgCHECKgQUESTIONgANDgVERIFIEDgANSWERSgLATESTg(2024-2025)gA+gSCOREg........................................................ 24
NRNPg6566gWEEKg5gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTg......................................................................................................... 31
VERIFIEDg ANSWERg LATESTg(2024-2025)........................................................................................................................................................................................................ 31
NRNPg6566gWEEKg6gKNOWLEDGEgCHECKgQUESTIONgANDgANSWERgLATESTg(2024-2025)gCOMPLETEA+gSCOREg .................................................... 35
NRNPg6566gWEEKg7gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gA+gSCOREg ........................................................ 42
NRNPg6566gWEEKg7gEXAMg1gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gA+gSCOREg.............................................. 50
NRNPg6566gWEEKg8gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gA+gSCORE ......................................................... 55
NRNP6566gWEEKg9gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gA+gSCORE........................................................... 60
NRNPg6566gWEEKg10gKNOWLEDGEgQUESTIONgANDgCORRECTgANSWERSgLATESTg2024 ..................................................................................... 66
NRNPg6566gWEEKg11gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgVERIFIEDgANSWERSgLATESTg(2024-2025)gA+gSCORE ........................................... 74
NRNPg 6566g FINALg EXAMg 75g QUESTIONSg ANDg CORRECTg VERIFIEDg ANSWERSg LATESTg (2024-2025)g COMPLETEg A+g SCORE........................................ 82
NRNPg6566gKNOWLEDGEgCHEC
K
,NRNPg6566gWEEKg1-5gKNOWLEDGEgCHECKgEXAMgQUESTIONgANDgCORRECT
ANSWERgLATESTg(2024-2025)gCOMPLETEgCONCEPT
Weekg1
1. DescribegthegcytochromegP450gsystem.gDescribeghowginducersgandginhibitorsgaffectgth
egcytochromegsystemgandghowgthatgaffectsgtheghalf-lifegofgmedications.
CytochromesgP450g(CYPs)garegagsuperfamilygofgenzymesgcontainingghemegasgagcofactorgthatggf
unctiongasgmonooxygenases.gIngmammals,gthesegproteinsgoxidizegsteroids,gfattygacids,gandggxen
obiotics,gandgaregimportantgforgthegclearancegofgvariousgcompounds,gasgwellgasgforghormoneggsy
nthesisgandgbreakdown.gCytochromegP450genzymesgcangbeginhibitedgorginducedgbygdrugs,ggresu
ltinggingclinicallygsignificantgdrug-
drugginteractionsgthatgcangcausegunanticipatedgadverseggreactionsgorgtherapeuticgfailures.gFluoxe
tine,gsertraline,gandgfluvoxaminegaregbelievedgtoginhibitggcytochromegP450g2Cgbecausegofgobser
vedginteractionsgwithgphenytoin,gdiazepam,gandgotherggdrugsgmetabolizedgbygthesegenzymes.gRi
fampicingandgisoniazidgaregkeygdrugsgusedgingtheggtreatmentgofgtuberculosis,gwhilegrifampicingisg
highlygeffectiveginginducingghepatic,gdruggmetabolicgP450genzyme.
ThegmnemonicgSICKFACES.COMgcangbegusedgtogeasilygremembergcommongcytochromegP
450ginhibitors.
1. Sodiumgvalproate.
2. Isoniazid.
3. Cimetidine.
4. Ketoconazole.
5. Fluconazole.
6. Alcoholg&gGrapefruitgjuice.
7. Chloramphenicol.
8. Erythromycin.
2. Describegthegaffectgonglowgandghighgalbuminglevelsgongactivegdrugglevelsgespeciallygf
orgdrugsgthatgareghighlygproteingbound.
Albumingisgthegplasmagproteingwithgtheggreatestgcapacitygforgbindinggdrugs.gBindinggtogplasmag
gproteinsgaffectsgdruggdistributiongintogtissues,gbecausegonlygdruggthatgisgnotgboundgisgavailablegt
oggpenetrategtissues,gbindgtogreceptors,gandgexertgactivity.gAsgfreegdruggleavesgthegbloodstream,gm
oregboundgdruggisgreleasedgfromgbindinggsites.gSomegdrugsghavegaghighgaffinitygforgbindinggtogse
rumggproteinsgandgmaygbeg95%gtog98%gproteingbound.gWithghighlygproteingboundgdrugs,glowgal
bumingglevelsg(asgingprotein-
caloriegmalnutrition,gorgchronicgillness)gmaygleadgtogtoxicitygbecausegthereggaregfewergthangthegn
ormalgsitesgforgthegdruggtogbind.gThegamountgofgfreegdruggisgsignificantlyggincreasedgingthatgcase
.gCompetitiongforgbindinggsitesgisgonegimportantgwaygthatgdrugsgmightgginteract.gIfgagpatientgisgu
singgtwoghighlygproteingboundgdrugsgatgthegsamegtime,gtheregwillgbeggcompetitiongforgbindinggsit
esgongthegalbumin.gThegdruggwithgtheggreatestgaffinitygforgthegalbumin
NRNPg6566gKNOWLEDGEgCHEC
K
, gg
lOMoAR cPSD| 36278399
willgbind,gandgisgthoughtgtogdisruptgthegnormalgratiogofgfreegtogboundgdruggforgthegsecondggmedi
cation.gAsgagresult,gthegsecondgmedicationgwillgbegmoregavailablegtogdistributegtogthegsitegofgactio
ngandgpotentiallygcausegsidegeffects.
3. Describegwaysgtoglessengtheghepaticgfirstgpassgeffect
Somegdrugs,gsuchgasgpropranololgorgenalapril,gundergogsignificantgmetabolismgduringgagsinglegg
passagegthroughgthegliver.gThisgisgcalledgthegfirst-
passgeffect.gWhengdrugsgareghighlygsusceptibleggtogthegfirst-
passgeffect,gthegoralgdosegneededgtogcausegagresponsegwillgbegsignificantlyghighergthanggthegintra
venousgdosegusedgtogcausegthegsamegresponse.gAlternativegroutesgofgadministration,gsuchggasgsup
pository,gintravenous,gintramuscular,ginhalationalgaerosol,gtransdermal,gorgsublingual,gavoidgthegf
irst-passgeffectgbecausegtheygallowgdrugsgtogbegabsorbedgdirectlygintogthegsystemicggcirculation.
4. BegablegtogcalculategcreatininegclearancegusinggthegCockgraftgGaultgequation
ThegCockcroft-
Gaultgformulagforgestimatinggcreatininegclearanceg(CrCl)gshouldgbegusedgroutinelygasgagsimplegm
eansgtogprovidegagreliablegapproximationgofgresidualgrenalgfunctiongingallgpatientsggwithgCKD.gT
hegformulasgaregasgfollows:
- CrClg(male)g=g([140-age]g×gweightgingkg)/(serumgcreatinineg×g72)
- CrClg(female)g=gCrClg(male)g×g0.85
5. Describegwhatgdeterminesgthegfrequencygofgdruggadministration
Plasmagconcentrationgdatagcollectedgfromgthisgtypegofgstudygisgplottedgagainstgtimegandganalyze
dgingordergtogunderstandgthegbehaviorgofgagspecificgdruggingthegbody.gThisgtypegofgpharmacokin
eticgdata,gcollectedgfromgaveragegadults,gisgthegbasisgforgdetermininggdose,gdosinggintervals,gan
dgglimitationsgongthegsafegusegofgagdrug.gAbsorption,gdistribution,gmetabolism,gandgelimination
gorggADME.
6. BegfamiliargwithgthegBeersgcriteriagandghowgtogusegit
Theg2019gupdategusesgthegfivegcriteriagoutlinedging2015;gthesegincludegmedicationsgthatgshouldgg
typicallygbegavoidedgingmostgoldergpatients,gmedicationsgthatgshouldgbegavoidedgingoldergpatients
gwithgcertaingconditions,gmedicationsgthatgshouldgbegusedgwithgcautiongbecausegofgbenefitsgthatg
gmaygoffsetgrisks,gmedicationginteractions,gandgchangesgingdosinggbasedgongkidneygfunction.gIng
gadditiongtogthesegcriteria,gdecisionsgaboutgmedicationsgshouldgtakegintogaccountgagvarietygofggfa
ctors,gincludinggstoppinggmedicationsgwhengtheygaregnoglongergbeneficial.
7. Describegfactorsgthatgaffectgabsorption,gdistribution,gmetabolismgandgexcretion
Thegrategandgextentgofgabsorptiongdependsgongthegroutegofgadministration,gthegformulationgandgg
chemicalgpropertiesgofgthegdrug,gandgphysiologicgfactorsgthatgcangimpactgthegsitegofgabsorption.g
gThegacidgenvironmentgorgpresencegofgfoodgingthegstomach,gthegsolubilitygandgothergchemicalggp
ropertiesgofgthegdrug,gandgthegeffectgofgtheginitialgexposuregtogmetabolicgprocessesgingtheglivergg
maygallgreducegthegamountgofgdruggthatgreachesgthegsystemicgcirculationgaftergoralgadministration
,gtherebygreducinggthegbioavailabilitygofgthegdrug.gPatientgvariablesgthatgcangaffectgdistribution
NRNPg6566gKNOWLEDGEgCHEC
K
, gg
lOMoAR cPSD| 36278399
includegbodygcomposition,gcardiacgdecompensationg(heartgfailure),gagegofgthegpatient,gandggalbu
minglevels.gFactorsgaffectinggmetabolismgincludeggenetics,gage,gandgdrug/druggreactions.
8. Definegnarrowgtherapeuticgindexg Howgwouldgyougmonitorgagpatientgwithgagnarro
wgtherapeuticgindex?
Narrowgtherapeuticgindexg(NTI)gdrugsgaregdefinedgasgthosegdrugsgwheregsmallgdifferencesgingdos
egorgbloodgconcentrationgmaygleadgtogdosegandgbloodgconcentrationgdependent,
seriousgtherapeuticgfailuresgorgadversegdruggreactions.gWegdefinedgthegfollowinggdrugsgtogbegNTI
-
gdrugs:gaminoglycosides,gciclosporin,gcarbamazepine,gdigoxin,gdigitoxin,gflecainide,glithium,ggp
henytoin,gphenobarbital,grifampicin,gtheophyllinegandgwarfarin.gFrequentglabgmonitoringgwouldg
begneededgtogmaintaingthegnarrowgindex.
9. Describeghowgaginggaffectgabsorption,gdistribution,gmetabolism,gandgexcretion
Withgage,gbodygfatggenerallygincreasesgandgtotalgbodygwatergdecreases.gIncreasedgfatgincreasesgth
egvolumegofgdistributiongforghighlyglipophilicgdrugsgandgmaygincreasegtheirgeliminationghalf-
lives.ggAginggresultsgingagnumbergofgsignificantgchangesgingtheghumanglivergincludinggreductionsg
ingliverggbloodgflow,gsize,gdrug-
metabolizinggenzymegcontent,gandgpseudocapillarization.gDrugggmetabolismgisgalsoginfluencedgb
ygcomorbidgdisease,gfrailty,gconcomitantgmedicines,gandggenetics.gOrgangfunctionggraduallygdecl
inesgwithgagegandgthegelderlygmaygpoorlygtolerategdrugsgthatgrequiregmetabolism.gUsually,gagegd
oesgnotggreatlygaffectgclearancegofgdrugsgthatgaregmetabolizedgbyggconjugationgandgglucuronidat
iong(phasegIIgreactions).gFirst-
passgmetabolismg(metabolism,ggtypicallyghepatic,gthatgoccursgbeforegagdruggreachesgsystemicgcir
culation)gis
alsogaffectedgbygaging,gdecreasinggbygaboutg1%/yrgaftergageg40.
NRNPg6566gKNOWLEDGEgCHEC
K
lOMoAR cPSD| 36278399
(COMPLETE)NRNPg6566gWEEKg1,2,3,4,5,6,7,8,9,10,11&gFINALgEXAMSgTESTg
BANKgQUESTIONgANDgCORRECTgVERIFIEDgANSWERSgLATESTg2024-
2025gA+GRDADED
TablegofgContents
NRNPg6566gWEEKg1-5gKNOWLEDGEgCHECKgEXAMgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gCOMPLETEgCONCEPTg ...................................2
NRNPg6566gWEEKg3gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg2024 ............................................................................... 17
NRNPg6566gWEEKg4gKNOWLEDGEgCHECKgQUESTIONgANDgVERIFIEDgANSWERSgLATESTg(2024-2025)gA+gSCOREg........................................................ 24
NRNPg6566gWEEKg5gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTg......................................................................................................... 31
VERIFIEDg ANSWERg LATESTg(2024-2025)........................................................................................................................................................................................................ 31
NRNPg6566gWEEKg6gKNOWLEDGEgCHECKgQUESTIONgANDgANSWERgLATESTg(2024-2025)gCOMPLETEA+gSCOREg .................................................... 35
NRNPg6566gWEEKg7gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gA+gSCOREg ........................................................ 42
NRNPg6566gWEEKg7gEXAMg1gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gA+gSCOREg.............................................. 50
NRNPg6566gWEEKg8gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gA+gSCORE ......................................................... 55
NRNP6566gWEEKg9gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgANSWERgLATESTg(2024-2025)gA+gSCORE........................................................... 60
NRNPg6566gWEEKg10gKNOWLEDGEgQUESTIONgANDgCORRECTgANSWERSgLATESTg2024 ..................................................................................... 66
NRNPg6566gWEEKg11gKNOWLEDGEgCHECKgQUESTIONgANDgCORRECTgVERIFIEDgANSWERSgLATESTg(2024-2025)gA+gSCORE ........................................... 74
NRNPg 6566g FINALg EXAMg 75g QUESTIONSg ANDg CORRECTg VERIFIEDg ANSWERSg LATESTg (2024-2025)g COMPLETEg A+g SCORE........................................ 82
NRNPg6566gKNOWLEDGEgCHEC
K
,NRNPg6566gWEEKg1-5gKNOWLEDGEgCHECKgEXAMgQUESTIONgANDgCORRECT
ANSWERgLATESTg(2024-2025)gCOMPLETEgCONCEPT
Weekg1
1. DescribegthegcytochromegP450gsystem.gDescribeghowginducersgandginhibitorsgaffectgth
egcytochromegsystemgandghowgthatgaffectsgtheghalf-lifegofgmedications.
CytochromesgP450g(CYPs)garegagsuperfamilygofgenzymesgcontainingghemegasgagcofactorgthatggf
unctiongasgmonooxygenases.gIngmammals,gthesegproteinsgoxidizegsteroids,gfattygacids,gandggxen
obiotics,gandgaregimportantgforgthegclearancegofgvariousgcompounds,gasgwellgasgforghormoneggsy
nthesisgandgbreakdown.gCytochromegP450genzymesgcangbeginhibitedgorginducedgbygdrugs,ggresu
ltinggingclinicallygsignificantgdrug-
drugginteractionsgthatgcangcausegunanticipatedgadverseggreactionsgorgtherapeuticgfailures.gFluoxe
tine,gsertraline,gandgfluvoxaminegaregbelievedgtoginhibitggcytochromegP450g2Cgbecausegofgobser
vedginteractionsgwithgphenytoin,gdiazepam,gandgotherggdrugsgmetabolizedgbygthesegenzymes.gRi
fampicingandgisoniazidgaregkeygdrugsgusedgingtheggtreatmentgofgtuberculosis,gwhilegrifampicingisg
highlygeffectiveginginducingghepatic,gdruggmetabolicgP450genzyme.
ThegmnemonicgSICKFACES.COMgcangbegusedgtogeasilygremembergcommongcytochromegP
450ginhibitors.
1. Sodiumgvalproate.
2. Isoniazid.
3. Cimetidine.
4. Ketoconazole.
5. Fluconazole.
6. Alcoholg&gGrapefruitgjuice.
7. Chloramphenicol.
8. Erythromycin.
2. Describegthegaffectgonglowgandghighgalbuminglevelsgongactivegdrugglevelsgespeciallygf
orgdrugsgthatgareghighlygproteingbound.
Albumingisgthegplasmagproteingwithgtheggreatestgcapacitygforgbindinggdrugs.gBindinggtogplasmag
gproteinsgaffectsgdruggdistributiongintogtissues,gbecausegonlygdruggthatgisgnotgboundgisgavailablegt
oggpenetrategtissues,gbindgtogreceptors,gandgexertgactivity.gAsgfreegdruggleavesgthegbloodstream,gm
oregboundgdruggisgreleasedgfromgbindinggsites.gSomegdrugsghavegaghighgaffinitygforgbindinggtogse
rumggproteinsgandgmaygbeg95%gtog98%gproteingbound.gWithghighlygproteingboundgdrugs,glowgal
bumingglevelsg(asgingprotein-
caloriegmalnutrition,gorgchronicgillness)gmaygleadgtogtoxicitygbecausegthereggaregfewergthangthegn
ormalgsitesgforgthegdruggtogbind.gThegamountgofgfreegdruggisgsignificantlyggincreasedgingthatgcase
.gCompetitiongforgbindinggsitesgisgonegimportantgwaygthatgdrugsgmightgginteract.gIfgagpatientgisgu
singgtwoghighlygproteingboundgdrugsgatgthegsamegtime,gtheregwillgbeggcompetitiongforgbindinggsit
esgongthegalbumin.gThegdruggwithgtheggreatestgaffinitygforgthegalbumin
NRNPg6566gKNOWLEDGEgCHEC
K
, gg
lOMoAR cPSD| 36278399
willgbind,gandgisgthoughtgtogdisruptgthegnormalgratiogofgfreegtogboundgdruggforgthegsecondggmedi
cation.gAsgagresult,gthegsecondgmedicationgwillgbegmoregavailablegtogdistributegtogthegsitegofgactio
ngandgpotentiallygcausegsidegeffects.
3. Describegwaysgtoglessengtheghepaticgfirstgpassgeffect
Somegdrugs,gsuchgasgpropranololgorgenalapril,gundergogsignificantgmetabolismgduringgagsinglegg
passagegthroughgthegliver.gThisgisgcalledgthegfirst-
passgeffect.gWhengdrugsgareghighlygsusceptibleggtogthegfirst-
passgeffect,gthegoralgdosegneededgtogcausegagresponsegwillgbegsignificantlyghighergthanggthegintra
venousgdosegusedgtogcausegthegsamegresponse.gAlternativegroutesgofgadministration,gsuchggasgsup
pository,gintravenous,gintramuscular,ginhalationalgaerosol,gtransdermal,gorgsublingual,gavoidgthegf
irst-passgeffectgbecausegtheygallowgdrugsgtogbegabsorbedgdirectlygintogthegsystemicggcirculation.
4. BegablegtogcalculategcreatininegclearancegusinggthegCockgraftgGaultgequation
ThegCockcroft-
Gaultgformulagforgestimatinggcreatininegclearanceg(CrCl)gshouldgbegusedgroutinelygasgagsimplegm
eansgtogprovidegagreliablegapproximationgofgresidualgrenalgfunctiongingallgpatientsggwithgCKD.gT
hegformulasgaregasgfollows:
- CrClg(male)g=g([140-age]g×gweightgingkg)/(serumgcreatinineg×g72)
- CrClg(female)g=gCrClg(male)g×g0.85
5. Describegwhatgdeterminesgthegfrequencygofgdruggadministration
Plasmagconcentrationgdatagcollectedgfromgthisgtypegofgstudygisgplottedgagainstgtimegandganalyze
dgingordergtogunderstandgthegbehaviorgofgagspecificgdruggingthegbody.gThisgtypegofgpharmacokin
eticgdata,gcollectedgfromgaveragegadults,gisgthegbasisgforgdetermininggdose,gdosinggintervals,gan
dgglimitationsgongthegsafegusegofgagdrug.gAbsorption,gdistribution,gmetabolism,gandgelimination
gorggADME.
6. BegfamiliargwithgthegBeersgcriteriagandghowgtogusegit
Theg2019gupdategusesgthegfivegcriteriagoutlinedging2015;gthesegincludegmedicationsgthatgshouldgg
typicallygbegavoidedgingmostgoldergpatients,gmedicationsgthatgshouldgbegavoidedgingoldergpatients
gwithgcertaingconditions,gmedicationsgthatgshouldgbegusedgwithgcautiongbecausegofgbenefitsgthatg
gmaygoffsetgrisks,gmedicationginteractions,gandgchangesgingdosinggbasedgongkidneygfunction.gIng
gadditiongtogthesegcriteria,gdecisionsgaboutgmedicationsgshouldgtakegintogaccountgagvarietygofggfa
ctors,gincludinggstoppinggmedicationsgwhengtheygaregnoglongergbeneficial.
7. Describegfactorsgthatgaffectgabsorption,gdistribution,gmetabolismgandgexcretion
Thegrategandgextentgofgabsorptiongdependsgongthegroutegofgadministration,gthegformulationgandgg
chemicalgpropertiesgofgthegdrug,gandgphysiologicgfactorsgthatgcangimpactgthegsitegofgabsorption.g
gThegacidgenvironmentgorgpresencegofgfoodgingthegstomach,gthegsolubilitygandgothergchemicalggp
ropertiesgofgthegdrug,gandgthegeffectgofgtheginitialgexposuregtogmetabolicgprocessesgingtheglivergg
maygallgreducegthegamountgofgdruggthatgreachesgthegsystemicgcirculationgaftergoralgadministration
,gtherebygreducinggthegbioavailabilitygofgthegdrug.gPatientgvariablesgthatgcangaffectgdistribution
NRNPg6566gKNOWLEDGEgCHEC
K
, gg
lOMoAR cPSD| 36278399
includegbodygcomposition,gcardiacgdecompensationg(heartgfailure),gagegofgthegpatient,gandggalbu
minglevels.gFactorsgaffectinggmetabolismgincludeggenetics,gage,gandgdrug/druggreactions.
8. Definegnarrowgtherapeuticgindexg Howgwouldgyougmonitorgagpatientgwithgagnarro
wgtherapeuticgindex?
Narrowgtherapeuticgindexg(NTI)gdrugsgaregdefinedgasgthosegdrugsgwheregsmallgdifferencesgingdos
egorgbloodgconcentrationgmaygleadgtogdosegandgbloodgconcentrationgdependent,
seriousgtherapeuticgfailuresgorgadversegdruggreactions.gWegdefinedgthegfollowinggdrugsgtogbegNTI
-
gdrugs:gaminoglycosides,gciclosporin,gcarbamazepine,gdigoxin,gdigitoxin,gflecainide,glithium,ggp
henytoin,gphenobarbital,grifampicin,gtheophyllinegandgwarfarin.gFrequentglabgmonitoringgwouldg
begneededgtogmaintaingthegnarrowgindex.
9. Describeghowgaginggaffectgabsorption,gdistribution,gmetabolism,gandgexcretion
Withgage,gbodygfatggenerallygincreasesgandgtotalgbodygwatergdecreases.gIncreasedgfatgincreasesgth
egvolumegofgdistributiongforghighlyglipophilicgdrugsgandgmaygincreasegtheirgeliminationghalf-
lives.ggAginggresultsgingagnumbergofgsignificantgchangesgingtheghumanglivergincludinggreductionsg
ingliverggbloodgflow,gsize,gdrug-
metabolizinggenzymegcontent,gandgpseudocapillarization.gDrugggmetabolismgisgalsoginfluencedgb
ygcomorbidgdisease,gfrailty,gconcomitantgmedicines,gandggenetics.gOrgangfunctionggraduallygdecl
inesgwithgagegandgthegelderlygmaygpoorlygtolerategdrugsgthatgrequiregmetabolism.gUsually,gagegd
oesgnotggreatlygaffectgclearancegofgdrugsgthatgaregmetabolizedgbyggconjugationgandgglucuronidat
iong(phasegIIgreactions).gFirst-
passgmetabolismg(metabolism,ggtypicallyghepatic,gthatgoccursgbeforegagdruggreachesgsystemicgcir
culation)gis
alsogaffectedgbygaging,gdecreasinggbygaboutg1%/yrgaftergageg40.
NRNPg6566gKNOWLEDGEgCHEC
K
