LED全彩P16电子显示屏

GeneralClinicalPharmacokineticsReview2UniversityofFloridaWorkingProfessionalDoctorofPharmacyProgramChristineCrain,Pharm.D.,BCPSClinicalQuestion?A60yearoldwomanistakingquinidinefortreatmentofatrialfibrillation.ShehasalsobeenprescribedfluconazolefortreatmentofaCandidaUTIandcisapridetocontrolsxofGERD.Wouldyouexpectanyofthesedrugstointeractbasedonthehepaticenzymesbywhichtheyaremetabolized?AnswertoClinicalQuestionHepaticEnzyme(s)AffectedQuinidineInhibits2D6Metabolizedby3A4FluconazolePotentialinhibitorof3A4CisaprideMetabolizedby3A4DrugEliminationLiver-PrimarilyMetabolismKidney-PrimarilyExcretionHepaticClearanceTheefficiencyoftheliverinremovingdrugfromthebloodstreamisreferredtoastheextractionratio(E).Withhighextractiondrugs,Eiscloserto1Withlowextractiondrugs,Eiscloserto0HepaticClearanceCLH=QHFpCLiQH+FpCLiQH=HepaticbloodflowFp=FractionoffreedruginplasmaCLi=IntrinsicclearanceHepaticClearanceCLH=QHFpCLiQH+FpCLiDrugswithahighintrinsicclearance=QHFpCLiFpCLiCLH=QHHepaticClearanceCLH=QHFpCLiQH+FpCLi=QHFpCLiQHCLH=FpCLiDrugswithalowintrinsicclearanceIntrinsicClearanceHighCLiLowCLipropranololwarfarinlidocainephenytoinmorphinetheophyllinenitroglycerindiazepamClinicalQuestion?Smokingisknowntoincreasetheenzymesresponsiblefortheophyllinemetabolism.Wouldapatientwithahistoryofsmokinglikelyrequireahigher,lower,orequivalenttheophyllinetotaldailydosecomparedtoanonsmoker?ClinicalQuestion?Apatientinthecoronarycareunitisstartedonlidocainefortreatmentofventriculararrhythmias.Ifthispatienthasseverecongestiveheartfailure(EF20%),howwouldtherequireddailydosageoflidocainelikelybeaffected?AnswertoClinicalQuestionCLH=QHFpCLiQH+FpCLiCLH=QHCHFDecreasesQHHalf-LifeThetimefortheconcentrationofdrugintheplasmatodecreasebyone-half1051**Time(hours)123SteadyStateTimeCavg,ssCmax,ssCmin,ssSteadyStateDurationofDrugAdministration(Half-Lives)SteadyStateConcentrationReached150275387.5493.75596.875698.4735799.25ClinicalQuestion?Apatientisadmittedtothehospitalwithcarbamazepinetoxicity.Aninitialserumconcentrationis24mcg/ml.Assumingahalf-lifeofapproximately18hours,howlongwillittakeforthispatienttoreachaserumlevelof6mcg/ml?AnswertoClinicalQuestion24mcg/ml12mcg/ml6mcg/ml18hours18hours36hrsClinicalQuestion?Apatientisstartedondiltiazemforthetreatmentofhypertension.(InitialaverageBP=160/98)Adosageregimenofdiltiazem60mgpotidisinitiated.Approx.howlongwillittakeforthispatienttoreachsteadystate?AnswertoClinicalQuestionHalf-lifeofdiltiazem=6hoursSteadystateshouldbeachievedinapproximately5half-lives.Therefore,thispatientshouldreachsteadystateinapproximately30hours.ClinicalQuestion?A65yearoldmanisstartedondigoxin0.125mgpoqdforthetreatmentofcongestiveheartfailure.Ifaloadingdoseisnotgiven,approxi-matelyhowlongwillittakeforthispatienttoreachasteadystatedigoxinlevel?AnswertoClinicalQuestionThehalf-lifeofdigoxinisapprox.40hoursSteadystateshouldbeachievedbyapproximately5half-lives.Therefore,thispatientshouldachievesteadystatedigoxinlevelsinapproxi-mately8-9days.EliminationRateConstant(ke)Thefractionofdrugremovedperunitoftime(e.g.hour-1)Time(hours)123456512.3DrugConc.(logscale)**(Co,to)(C1,t1)lnC1=-ket+lnCoFirst-OrderEliminationTime(hours)123456512.3DrugConc.(logscale)**(Co,to)(C1,t1)slope=-ke=lnC1-lnCot1-toEliminationRateConstantTime(hours)123456512.3DrugConc.(logscale)**(Co,to)(C1,t1)slope=-ke=ln5-ln12.34hr-0hrEliminationRateConstantTime(hours)123456512.3DrugConc.(logscale)**(Co,to)(C1,t1)slope=-ke=-0.225hrClinicalQuestion?A45yearoldmanisreceivinggentamicin160mgIVq12hr.Apeakandtroughlevelweredrawnatsteadystate.Peak=8.4mcg/ml0900Trough=1.0mcg/ml2000Whatisthispatient’seliminationrateconstant(ke)andhalf-life?FirstOrderEliminationconctimekeslope=-ke=lnC1-lnC0T1-T0**AnswertoClinicalQuestion-ke=lnC1-lnC2t1-t2-ke=ln8.4-ln1.011hr=-0.1935/hrRelationshipBetweenDrugEliminationandHalf-lifeke=0.693t1/2AnswertoClinicalQuestionHalf-life=0.693keHalf-life=0.6930.1935=3.58hrClinicalQuestion?A65yearoldpatientisadmittedtothehospitalwithdigoxintoxicity.Thedigoxinserumconc.is5ng/ml.Howlongshouldittakefortheserumdigoxinconc.todecreaseto1ng/ml?First-OrderEquationCt=Coxe-ketAnswertoClinicalQuestionThehalf-lifeofdigoxinisapproximately40hours.ke=0.693t1/2=0.0173/hrCt=Coxe-ket1=5xe-.0173tt=93hoursMaintenanceDoseEquationko=CssxCLsMD=CssxCLsCL=kexVdMD=CssxkexVdRelationshipBetweenClearance,VdandHalf-lifeCL=0.693t1/2VdLDvsMDEquationsLD=CpxVdMD=CssxkexVdClinicalQuestion?A50yearoldmanistobestartedonamaintenancedoseofprocainamideforthetreatmentofseveralepisodesofatrialfibrillation.CalculateaMDthatwillproduceanaveragesteadystateprocainamideconcentrationsofapproximately6mcg/ml.Assumenlrenalfunction.Wt:68kgAnswertoClinicalQuestionMD=CssxkexVd=MD=Cssx0.693xVdt1/2=6mg/Lx0.6934hrx2L/kgx68kg=141mg/hrx24hours=3400mgAnswertoClinicalQuestionAssumingapprox.85%absorption,totaldailydose=4000mgGiveasProcanSR1000mgq6hORProcanbid2000mgpoq12hRenalEliminationGlomerularFiltrationTubularsecretionTubularreabsorptionCreatinineClearanceCockcroft&GaultEquationCLcr(ml/min,males)=(140-age)(weight)Crsx72CLcr(ml/min,fem)=(0.85)(CLcrinmales)