ImmunosuppressiveAgentsinHeartTransplantationIntern許育偉2008.02.04QuestionsBeforeThisTopic常見的免疫抑制劑,分成哪幾類?Monoclonal和PolyclonalAb有什麼差別?何時要用InductionTherapy?AZA和MMF哪一個比較好?CsA和Tacrolimus哪一個比較好?在腎功能惡化的情況下的用藥原則?什麼是RescueTherapy?OutlinesofToday’sTopicImmuno-suppressionmechanism(1)Inductiontherapy(2)MaintenancetherapyImmunosuppressiveagentsinrenalfunctionimpairmentRescuetherapyCurrentregimensworldwideKobashigawaJAandPatelJK(2006)Immunosuppressionforhearttransplantation:wherearewenow?NatClinPractCardiovascMed3:203–212doi:10.1038/ncpcardio0510Corticosteroids1.Nonspecificanti-inflammatoryagents2.BlockTcellandAPCderivedcytokineandcytokine-receptorexpressionCalcineurinInhibitors1.(1)Cyclosporine(CsA)Neoral(2)Tacrolimus(FK-506)Prograf2.Bindstocalcineurin3.Keyfunctionincurrentimmunosuppressiveagents4.Nephrotoxicity!!!Anti-proliferativeAgents1.(1)AzathioprineImuran(2)MycophenolateMofetil(MMF)Cellcept2.Blockthecellcycle(DeNovosynthesis)ProliferationSignalInhibitors1.(1)SirolimusRapamycin(Rapa)(2)EverolimusCertican2.BlocksignalingdownstreamIL-2RMonoclonalAntibodies1.(1)MuromonabOKT3(2)BasiliximabSimulect(3)DaclizumabZenapax2.BlockTCR,CD3,CD4,orIL-2RPolyclonalAntibodies1.(1)RabbitantithymocytesglobulinRATG(2)HorseantithymocytesglobulinATGAM2.VariousamountsofspecificAbagainstTcellsInductionTherapyUpstreamAbImmunologicablationDivisionofCardiology,DepartmentofMedicine,UniversityOfMaryland,Baltimore,Maryland.JHeartLungTransplant2007;26:205–9.Polyclonalvs.MonoclonalAbDivisionofCardiacSurgery,UniversityofOttawaHeartInstitute,40RuskinStreet,Ottawa,Ontario,K1Y-4W7,CanadaInteractCardioVascThoracSurg2005;4:415-419AveragemeantimetofirstrejectionPolyclonalvs.MonoclonalAbDivisionofCardiacSurgery,UniversityofOttawaHeartInstitute,40RuskinStreet,Ottawa,Ontario,K1Y-4W7,CanadaInteractCardioVascThoracSurg2005;4:415-419GraftRejectionInfectionOne-YearSurvivalPolyclonalvs.MonoclonalAbSide-effectsmoreinmonoclonalAb(OKT3)☆Fever☆Headaches☆Acuterespiratorydistress☆HypotensionDivisionofCardiacSurgery,UniversityofOttawaHeartInstitute,40RuskinStreet,Ottawa,Ontario,K1Y-4W7,CanadaInteractCardioVascThoracSurg2005;4:415-419MonoclonalAb:OKT3vs.IL-2R2006,SIMCORStudyRandomizedMulticenterComparisonofBasiliximabandMuromonab(OKT3)inHeartTransplantation99hearttransplantrecipientsNodifferencein(1)Severityofacuterejectionepisodes(2)Timingofacuterejectionepisodes(3)Incidenceofinfection(4)Actuarialsurvival.OKT3hadahigherincidenceofadverseeventssuchasfever,pulmonaryedema,andhypotensionArandomizedmulticentercomparisonofbasiliximabandmuromonab(OKT3)inhearttransplantation:SIMCORstudy.Transplantation2006;81:1542–8.InductionTherapy:Who?MehraMR,UberPA,UberWE,ScottRLCurrOpinCardiol2003;18:153–8.1.Multiparouswomen2.Reoperativesternotomypatients3.Posttransfusionspatients4.Supportedwithleftventricularassistdevices.HigginsR,KirklinJK,BrownRN,etal;CardiacTransplantResearchDatabase(CTRD).1990~2001,enrolled6553patientsJHeartLungTransplant2005;24:392–400.1.Ventricularassistdevice2.Blackethnicity,3.ExtensivehumanleukocyteantigenmismatchingDivisionofCardiology,DepartmentofMedicine,UniversityOfMaryland,Baltimore,Maryland.JHeartLungTransplant2007;26:205–9.MaintenanceTherapyThree-combinedregimen---Glucocorticosteroids(1...