NUR 641E FINAL
Pharmacokineticsooinvolvesoo-ans--
absorption,oodistribution,oometabolismooandooelimination).
Absorption:oo-ans--
absorptionoofromootheooadministrationoositeooeitheroodirectlyooorooindirectlyoointoootheooblo
od/plasma.
Distribution:oo-ans--
reversiblyooorooirreversiblyoomoveoofromootheoobloodstreamoointoootheoointerstitialooandooi
ntracellular
Metabolism:oo-ans--biotransformedooviaoohepaticoometabolismoooroobyoootherootissues.
Elimination:oo-ans--
tissues.oolastly,ootheoodrugooandooitsoometabolitesooareooeliminatedoofromootheoobody.
routeooofooadministrationoowithootheoohighestoobioavailabilityoo-ans--
intravenous;ooputtingooentireoodoseoointoooaoopatient'sooveinooandoobypassingooabsorptio
n.
avoidsoofirst-passoometabolismoo-ans--Intravenousooroute
administrationoohasoovariableooandooerraticooabsorption.oonoo-ans--Rectalooadministration
4.ooSteadyoostateoo(SS)oo-ans--absorption.oonooisoousuallyooreachedoowithinoo4-5oohalf-
livesooofoodrug.
Half-lifeooofooaoodrugooisoo-ans--
howoolongooitootakesooforoohalfootheoodrugootooobeooexcretedoofromootheoobody.ooDetermin
esoohowoofrequentlyootheoodrugoomustoobeooadministered.ooPredictsoohowoolongootoxicooe
ffectsoocanoolast.isooconstantoowithoofirst-orderoopharmacokineticsooofooaoodrug.
Zero-orderoo(nonlinear)oopharmacokineticsoo-ans--
meansooaoodrugooisoometabolizedooatooaooconstantoorateooperoounitootime.
CYP3A4oosubstrateoodrugsoo-ans--
mayoohaveooenhancedooactivityooifooanyooCYP3A4ooinduceroodrugsooareoousedooalongoow
ithooit.
,DrugoodevelopmentooprocessooinvolvesootheseoostepsooaccordingootoootheooFDA:oo-ans--
Discovery:oolaboratoryooresearchootooodevelopootheoonewoodrug.ooPreclinicalooresearchoo
withooanimalootestingooforoosafetyoo(PhaseooI).ooClinicalooresearchooonoohumanoosubjects
ooforoomedicationoosafetyoo(PhaseooII).ooClinicalooresearchooinoohumansoocomparingoothe
oonewoodrugootoooacceptedoomedicationsooplacebooodependingooonootheoostudyoo(Phaseo
oIII).ooFDAooreviewooofootheooresultsootooodetermineooapproval.ooPostoomarketingoostudyoo
toooidentifyooadverseooeffectsoonotoofoundooinooearlierooclinicaloostudiesoo(PhaseooIV)
2.ooMedicationoosafetyooorganizationsoo-ans--
TheooInstituteooforooSafeooMedicationooPracticesoo(ISMP)ooTheooInstituteooofooMedicineoo
(IOM)ooTheooJointooCommissionooTheooNationalooCoordinatingooCouncilooforooMedication
ooErrorooReportingooandooPreventionoo(NCCooMERP)ooFoodooandooDrugooAdministrationo
o(FDA)ooSafeooUseooInitiative
TwooobasicootypeooofooADRS:oo-ans--pharmacologicalooandooidiosyncratic.
85%ootooo90%ooofooADRSoo-ans--areoopharmacological.
Adverseoodrugooreactionsooareoousuallyoopreventable,oo-ans--
frequentlyoooccurooinooaoohospitaloooroonursingoohomeoosetting,ooandooincludeoomedicatio
nooerrors,ooadverseoodrugooeffects,ooandooallergicooidiosyncraticootypeooreactions.
ADRSooareoonotoocommonlyooreported;oo-ans--
theooFDAoodoesoonotoomandateoothatooADRSoobeooreported.
Polypharmacyoo-ans--
involvesoousingoomultipleoohealthoocareooprovidersooforoocare,oousingoomultipleoomedicati
ons,ooandoousingooseveraloopharmaciesooprescriptionoofilling.
Angiotensinooconvertingooenzymeooinhibitorsoo(ACEIS):oo-ans--
lisinopril,oocaptopril,ooenalapril,ooramipril,oobenazepril,oofosinopril.
ACEISooreduceoobloodoopressureooenzyme.oo-ans--
byoosuppressingootheooreleaseooofooangiotensin-convertingooenzyme.
ImportantoosideooeffectsooofooACEooinhibitorsoo-ans--
Importantooincludeoocoughooandooangioedema;oodiscontinueootheooACEIooifooangioedem
aoooccurs.
AngiotensinooIIooreceptorooblockingooagentsoo(ARBS):oo-ans--
Icandesartanoo(Atacand),ooeprosartanoo(Teveten),ooirbesartanoo(Avapro),oolosartanoo(Co
zaar),ootelmisartanoo(Micardis)ooandoovalsartanoo(Diovan).
ARBSooreduceoobloodoopressureoo-ans--byooblockingooangiotensinooIIooreceptors.
, Essentialoo(primary)oohypertensionoo-ans--
Essentialoo(primary)ooaccountsooforoo90%ooofoocases;oosecondaryoohypertensionoomayoo
causedoobyoochronicoorenaloofailure.
Nitroglycerinoo-ans--
NitroglycerinooisooaoonitrateoodrugoothatoocanoobeooadministeredooIV,ooSL,ooaootopicaloooin
tmentooandooasooaootransdermaloopatch.
Nitratesooareoocontraindicatedoo-ans--withooPDE-
5ooinhibitorsoo(e.g.,oosildenafilooandoovardenafil)
Amiodaroneooisootheooantiarrhythmicoo-ans--
Ofoochoiceoowhenoothereooisoocoexistingooheartoofailure;oocanoocauseoothyroidooandoopul
monaryootoxicity.
Alpha-1ooadrenergicoostimulationoo-ans--
resultsooinoovasoconstrictionooandooincreasedoobloodoopressure.
Alpha-1ooadrenergicooblockadeoo-ans--
resultsooinoovasodilationooandooreducedoobloodoopressure.
Beta-1ooadrenergicoostimulationoo-ans--
byoobetaooagonistsoo(e.g.,ooisoproterenol)ooresultsooinooincreasedooheartoorate,ooincrease
doobloodoopressure,ooandooincreasedoocardiacoooutput.
Beta-1ooadrenergicooblockadeooresultsoo-ans--
inooreducedooheartoorate,ooreducedoobloodoopressure,ooandooreducedoocardiacoooutput.
Leftooheartoofailureoo-ans--
causesooreducedoodeliveryooofoooxygenatedoobloodootoootheoobodyootissues.
Rightooheartoofailureoo-ans--
isooassociatedoowithoopulmonaryoodiseaseooandooincreasedoopulmonaryoovascularooresist
ance.
drugoothatoorelievesooheartoofailureoosymptomsoobutoodoesoonotooreduceoomortalityoo-
ans--furosemide.
Loopoodiureticsoolikeoofurosemideoo-ans--
areoopotentoodiuretics,oocanoocauseoodiureticooresistanceooandoohypokalemia,ooandoowor
kooonooreceptorsooinootheoothickooascendingoorenalooloopooofooHenle.
Loopoodiureticsooinhibitoo-ans--
reabsorptionooofoosodiumooandoochlorideooatoothisoositeooinootheookidney.
Potassium-sparingoodiuretics:oo-ans--spironolactone,ootriamterene.
Pharmacokineticsooinvolvesoo-ans--
absorption,oodistribution,oometabolismooandooelimination).
Absorption:oo-ans--
absorptionoofromootheooadministrationoositeooeitheroodirectlyooorooindirectlyoointoootheooblo
od/plasma.
Distribution:oo-ans--
reversiblyooorooirreversiblyoomoveoofromootheoobloodstreamoointoootheoointerstitialooandooi
ntracellular
Metabolism:oo-ans--biotransformedooviaoohepaticoometabolismoooroobyoootherootissues.
Elimination:oo-ans--
tissues.oolastly,ootheoodrugooandooitsoometabolitesooareooeliminatedoofromootheoobody.
routeooofooadministrationoowithootheoohighestoobioavailabilityoo-ans--
intravenous;ooputtingooentireoodoseoointoooaoopatient'sooveinooandoobypassingooabsorptio
n.
avoidsoofirst-passoometabolismoo-ans--Intravenousooroute
administrationoohasoovariableooandooerraticooabsorption.oonoo-ans--Rectalooadministration
4.ooSteadyoostateoo(SS)oo-ans--absorption.oonooisoousuallyooreachedoowithinoo4-5oohalf-
livesooofoodrug.
Half-lifeooofooaoodrugooisoo-ans--
howoolongooitootakesooforoohalfootheoodrugootooobeooexcretedoofromootheoobody.ooDetermin
esoohowoofrequentlyootheoodrugoomustoobeooadministered.ooPredictsoohowoolongootoxicooe
ffectsoocanoolast.isooconstantoowithoofirst-orderoopharmacokineticsooofooaoodrug.
Zero-orderoo(nonlinear)oopharmacokineticsoo-ans--
meansooaoodrugooisoometabolizedooatooaooconstantoorateooperoounitootime.
CYP3A4oosubstrateoodrugsoo-ans--
mayoohaveooenhancedooactivityooifooanyooCYP3A4ooinduceroodrugsooareoousedooalongoow
ithooit.
,DrugoodevelopmentooprocessooinvolvesootheseoostepsooaccordingootoootheooFDA:oo-ans--
Discovery:oolaboratoryooresearchootooodevelopootheoonewoodrug.ooPreclinicalooresearchoo
withooanimalootestingooforoosafetyoo(PhaseooI).ooClinicalooresearchooonoohumanoosubjects
ooforoomedicationoosafetyoo(PhaseooII).ooClinicalooresearchooinoohumansoocomparingoothe
oonewoodrugootoooacceptedoomedicationsooplacebooodependingooonootheoostudyoo(Phaseo
oIII).ooFDAooreviewooofootheooresultsootooodetermineooapproval.ooPostoomarketingoostudyoo
toooidentifyooadverseooeffectsoonotoofoundooinooearlierooclinicaloostudiesoo(PhaseooIV)
2.ooMedicationoosafetyooorganizationsoo-ans--
TheooInstituteooforooSafeooMedicationooPracticesoo(ISMP)ooTheooInstituteooofooMedicineoo
(IOM)ooTheooJointooCommissionooTheooNationalooCoordinatingooCouncilooforooMedication
ooErrorooReportingooandooPreventionoo(NCCooMERP)ooFoodooandooDrugooAdministrationo
o(FDA)ooSafeooUseooInitiative
TwooobasicootypeooofooADRS:oo-ans--pharmacologicalooandooidiosyncratic.
85%ootooo90%ooofooADRSoo-ans--areoopharmacological.
Adverseoodrugooreactionsooareoousuallyoopreventable,oo-ans--
frequentlyoooccurooinooaoohospitaloooroonursingoohomeoosetting,ooandooincludeoomedicatio
nooerrors,ooadverseoodrugooeffects,ooandooallergicooidiosyncraticootypeooreactions.
ADRSooareoonotoocommonlyooreported;oo-ans--
theooFDAoodoesoonotoomandateoothatooADRSoobeooreported.
Polypharmacyoo-ans--
involvesoousingoomultipleoohealthoocareooprovidersooforoocare,oousingoomultipleoomedicati
ons,ooandoousingooseveraloopharmaciesooprescriptionoofilling.
Angiotensinooconvertingooenzymeooinhibitorsoo(ACEIS):oo-ans--
lisinopril,oocaptopril,ooenalapril,ooramipril,oobenazepril,oofosinopril.
ACEISooreduceoobloodoopressureooenzyme.oo-ans--
byoosuppressingootheooreleaseooofooangiotensin-convertingooenzyme.
ImportantoosideooeffectsooofooACEooinhibitorsoo-ans--
Importantooincludeoocoughooandooangioedema;oodiscontinueootheooACEIooifooangioedem
aoooccurs.
AngiotensinooIIooreceptorooblockingooagentsoo(ARBS):oo-ans--
Icandesartanoo(Atacand),ooeprosartanoo(Teveten),ooirbesartanoo(Avapro),oolosartanoo(Co
zaar),ootelmisartanoo(Micardis)ooandoovalsartanoo(Diovan).
ARBSooreduceoobloodoopressureoo-ans--byooblockingooangiotensinooIIooreceptors.
, Essentialoo(primary)oohypertensionoo-ans--
Essentialoo(primary)ooaccountsooforoo90%ooofoocases;oosecondaryoohypertensionoomayoo
causedoobyoochronicoorenaloofailure.
Nitroglycerinoo-ans--
NitroglycerinooisooaoonitrateoodrugoothatoocanoobeooadministeredooIV,ooSL,ooaootopicaloooin
tmentooandooasooaootransdermaloopatch.
Nitratesooareoocontraindicatedoo-ans--withooPDE-
5ooinhibitorsoo(e.g.,oosildenafilooandoovardenafil)
Amiodaroneooisootheooantiarrhythmicoo-ans--
Ofoochoiceoowhenoothereooisoocoexistingooheartoofailure;oocanoocauseoothyroidooandoopul
monaryootoxicity.
Alpha-1ooadrenergicoostimulationoo-ans--
resultsooinoovasoconstrictionooandooincreasedoobloodoopressure.
Alpha-1ooadrenergicooblockadeoo-ans--
resultsooinoovasodilationooandooreducedoobloodoopressure.
Beta-1ooadrenergicoostimulationoo-ans--
byoobetaooagonistsoo(e.g.,ooisoproterenol)ooresultsooinooincreasedooheartoorate,ooincrease
doobloodoopressure,ooandooincreasedoocardiacoooutput.
Beta-1ooadrenergicooblockadeooresultsoo-ans--
inooreducedooheartoorate,ooreducedoobloodoopressure,ooandooreducedoocardiacoooutput.
Leftooheartoofailureoo-ans--
causesooreducedoodeliveryooofoooxygenatedoobloodootoootheoobodyootissues.
Rightooheartoofailureoo-ans--
isooassociatedoowithoopulmonaryoodiseaseooandooincreasedoopulmonaryoovascularooresist
ance.
drugoothatoorelievesooheartoofailureoosymptomsoobutoodoesoonotooreduceoomortalityoo-
ans--furosemide.
Loopoodiureticsoolikeoofurosemideoo-ans--
areoopotentoodiuretics,oocanoocauseoodiureticooresistanceooandoohypokalemia,ooandoowor
kooonooreceptorsooinootheoothickooascendingoorenalooloopooofooHenle.
Loopoodiureticsooinhibitoo-ans--
reabsorptionooofoosodiumooandoochlorideooatoothisoositeooinootheookidney.
Potassium-sparingoodiuretics:oo-ans--spironolactone,ootriamterene.