药学博士

ImmunosuppressioninLiverTransplantation潘思憓藥學博士Shi-HuiPan,Pharm.D.,FCCPTransplantPharmacistCenterforLiverDiseases&TransplantationCedars-SinaiMedicalCenterLosAngeles,CaliforniaObjectivesCurrentimmunosuppressivedrugsPharmacotherapyandlimitationsPrinciplesofimmunosuppressionIndividualizingTapering(who,when,what,andhow)ImmunosuppressivestrategiesSparing,withdrawal,oravoidanceRejection,diseasespecificPatientSurvivalRateOrganTransplant1yrSR19901yrSR19985yrSR90-98CRenal93%95%82%LRenal97%98%91%Liver82%88%74%Heart85%86%70%Lung75%76%44%GraftSurvivalRateOrganTransplant1yrSR19901yrSR19985yrSR90-98CRenal84%90%65%LRenal94%95%78%Liver75%82%66%Heart84%85%69%Lung73%76%42%LiverTransplantTeamSurgeonsandhepatologistsMedicalconsultantsPsychiatristandsocialworkerCoordinators,OR,andunitnursesPharmacistProcurement/perfusionspecialistFinancialspecialistDietitianResearchandadministrativeteamsChallengesinImmunosuppression1990Improveshort-termsurvivalacuterejectioninfection2000Improvelong-termsurvivalchronicrejectionchronicallograftdysfunctiondruginducedco-morbiditiesImmunosuppressiveAgents1999Sirolimus(Rapamune);Thymoglobulin1998Basiliximab(Simulect)1997Daclizumab(Zenapax)1995Mycophenolate(CellCept);Neoral1994Tacrolimus(Prograf,FK506)1986Muromonab-CD3(OKT3)1983Cyclosporine(Sandimmune)1981Anti-thymocyteglobulin(Atgam)1963Corticosteroid1962AzathioprineChallengesinGraftSurvivalOrganTransplantChronicGraftDysfunctionAcuteRejectionChronicRejectionGRAFTLOSSshort-termlong-termImmunosuppressiveClassesInductionPolyclonalantibodyAtgam,ThymoglobulinMonoclonalantibodyOKT3IL-2Rantagonists(Simulect,Zenapax)ImmunosuppressiveClassesMaintenanceCalcineurininhibitorNeoral,PrografAntimetaboliteImuran,CellCeptTORinhibitorRapamuneCorticosteroidImmunosuppressiveAgentsPharmacologyAzathioprine,Mycophenolate(CellCept)Anti-metaboliteInhibitsT-cellandB-cellproliferationbyblockingpurinesynthesisCorticosteroidAnti-inflammatoryeffectInhibitsT-cellandB-cellproliferationInhibitsphagocytosisImmunosuppressiveAgentsPharmacologyCyclosporine(Neoral),Tacrolimus(Prograf)CalcineurininhibitorInhibitsT-cellactivationbyblockingIL-2productionSirolimus(Rapamune)TOR(targetofrapamycin)inhibitorInhibitsTORenzymeBlocksIL-2drivenT-cellproliferationImmunosuppressiveAgentsPharmacologyOKT3(Muromonab-CD3)MurinemAbblocksT3receptorInhibitsT-cellactivationDaclizumab(Zenapax),Basilixmab(Simulect)IL-2Rantagonist:mAbblocksIL-2RZenapax:humanizedAbSimulect:chimerichuman/mouseAbInhibitsproliferationofactivatedT-cellImmunosuppressiveAgentsPharmacologyAnti-ThymocyteGlobulinPolyclonalAbDepletesT-cellsAtgam:immunizinghorseThymoglobulin:immunizingrabbit排斥某些肝病覆發感染乙肝,丙肝覆發藥物引起副作用癌症(覆發,新生)抗排斥藥的使用不足過多DrugInducedCo-MorbiditiesNephrotoxicityHypertensionHyperglycemiaHyperlipidemiaMyelosuppressionGIcomplicationsMalignancyAllergyreactionSeriousinfectionDelaywoundhealingBonediseasesNeurotoxicityPsychiatricdiseasesHepatotoxicityCosmeticchangesImpairedgrowthCurrentImmunosuppressionLimitationsIneffectivetherapyforchronicrejectionMarginalactivityinpreventingBcellfunctionbutremarkableactivityinsuppressingbonemarrowLackofspecificimmunologicmonitoringSignificantdruginducedco-morbiditiesComplexdruginteractionsExpensiveImmunosuppressiveProtocolsPrincipalIndividualizingHighriskpatientsOptimizingcombinationregimensBalancerejectionandco-morbiditiesImprovinglong-termsurvivalTaperingimmunosuppressionovertimeEnhancingqualityoflife&complianceMinimizingmedicationcostsImmunosuppressiveProtocolsIndividualizingAllograft:size,quality,ischemictimeDonor:BMI,viralandhepatitisserologyRecipient:age,nooftransplantCo-morbiditiesUnderlyingmedicaldiseasesUnderlyingliverdiseaseDruginteractionsDonor-recipientcompatibility:ABOOptimizeImmunosuppressionAllograftandDonorFactorsPreservationinjurySteatosis,BMIFullsizevspartialsizeLivedonorvsdeceaseddonorAnti-HBcpositivityAnti-HCVpositivityEBV,CMVserologyOptimizeImmunosuppressionRecipientFactorsCo-morbiditiesInfection,malnutrition,dialysisUnderlyingmedicaldiseasesDM,CAD,osteoporesis,gastritisUnderlyingliverdiseaseAIH,PSC,PBCHBV,HCV,HepatomaIndicationforre-transplantImmunosuppressiveProtocolsCombinationRegimensRationaleCombineagentswithdifferentmechanismsanddifferenttoxicitiesMaintainimmunosuppressionwhilereducingco-morbiditieswithlowdoseofeachagentSpecificforindividualFK+MMF+CSFK+MMFNeoral+MMFNeoral+MMF+CSFK+Rapa+MMF+CSRapa+MMF+CSFK+Rapa+CSNeoral+RapaFK+Rapa+MMFRapa+MMFFK+CSNeoral+CSNeoral+Rapa+CSFK+RapaImmunosuppression=A+B+C+??ImmunosuppressiveProtocolsLong-TermSurvivalPreventchronicrejectionReduceepisodesofacuterejectionPreventchronicallograftdysfunctionReducedrug-inducedco-morbiditiesinfectionprophylaxisotherconcurrenttherapyPreventrecurrentdiseaseReducedelayedgraftfunctionTaperingImmunosuppressionReviewofliteratureClinicaltrialstoclinicalpractice?Whoisacandidate?LowriskforrejectionHighriskforco-morbiditiesWhentosafelytaper?Whatstrategytouse?Howtoimplement