质子泵抑制剂与抗血小板药

质子泵抑制剂与抗血小板药第1页，课件共19页，创作于2023年2月Omeprazole奥美拉唑 1988Lansoprazole兰索拉唑 1991Pantoprazole泮托拉唑 1994 Ilaprazole艾普拉唑 1998Rabeprazole雷贝拉唑 1999Esomeprazole埃索美拉唑 2000Dexlansoprazole右旋兰索拉唑 2009ProtonPumpInhibitorsonMarketing解放军总医院消化病中心

GreatsuccesstocontrolAcidrelateddiseasesinthepast2decades-NV-UGIB,PepticUlcer,GERD,etc.第2页，课件共19页，创作于2023年2月Thepotentialbenefitsofantiplatelettherapyforatheroscleroticcardiovascular(CV)diseasehavebeenamplydemonstratedoverthepast20years,especiallythienopyridinedrugsinpreventingstentthrombosis.Antiplateletagentsincreasetheriskofbleedingassociatedwithmucosalbreaksintheupperandlowergastrointestinal(GI)tract.Rationaluseofthienopyridinesisbasedonweighingtheirrisksagainsttheirbenefits.BalancebetweenBenefitsandRisks解放军总医院消化病中心第3页，课件共19页，创作于2023年2月791residentsstudied60wereprescribedclopidogrel248wereonaspirin326wereprescribedaPPI.AmongresidentswhowereprescribedPPIs155wereprescribedomeprazole;72pantoprazole51rabeprazole;44esomeprazole;15lansoprazole.39residentstookacombinationofclopidogrelandaPPI(anyPPI)foramean203days.9residentstookthecombinationofclopidogrel,aspirinandaPPI(anyPPI)forameanof173days.ThePrevalenceofCo-administrationClopidogrelandProtonPumpInhibitorsShresthaK.etal.QualPrimCare.2011;19(1):35-42解放军总医院消化病中心第4页，课件共19页，创作于2023年2月Oralantiplatelettherapymayincreasebleedingcomplications,thelargestproportionduetoGIhemorrhage.GastroprotectionstrategiesconsistofuseofPPIsinpatientsathighriskofGIbleeding.

2008ExpertConsensusACCF/ACG/AHA2008ExpertConsensusDocumentonReducingtheGIRisksofAntiplateletTherapyandNSAIDUse解放军总医院消化病中心第5页，课件共19页，创作于2023年2月2008ExpertConsensusACCF/ACG/AHA2008ExpertConsensusDocumentonReducingtheGIRisksofAntiplateletTherapyandNSAIDUse解放军总医院消化病中心第6页，课件共19页，创作于2023年2月ManyinvestigationsofpotentialadverseinteractionhasbeenconductedrecentlyEvidenceofapossibleadversedruginteractionbetweenPPIsandthienopyridineshasemergedIthasbeendifficultforphysiciansincludingcardiologists,gastroenterologistsandallpractionersHowtotreatourpatientswithbothkindsofdrugs解放军总医院消化病中心Potentialadverseinteraction2010ExpertConsensusDocumentontheConcomitantUseofPPIsandThienopyridines

JACCVol.56,No.24,2010第7页，课件共19页，创作于2023年2月解放军总医院消化病中心MetabolismofclopidogrelandPPI第8页，课件共19页，创作于2023年2月MetabolismofPPIsAllPPIsarehepaticallymetabolizedtoanextentviathecytochromeP450mixedoxidasesystem.TheisoenzymesCYP3A4,particularlyCYP2C19arethemajorisoformsthatcausePPIbiotransformation.TherelativecontributionofCYP2C19pathwaydiffersamongdrugsandhasbeenreportedtobeomeprazole=esomeprazole>pantoprazole>lansoprazole>rabeprazoleingeneralmetabolismIncontrasttothesituationwithclopidogrel,reducedCYP2C19functionresultsinlessinactivationofPPIandanincreaseinpharmacodynamiceffect(greateracidinhibition).解放军总医院消化病中心MetabolismofclopidogrelandPPIFockKMetal.ClinPharmacokinet2008;47:1-6第9页，课件共19页，创作于2023年2月Areductioninactivemetabolitelevelsofabout45%wasfoundinpeoplewhoreceivedclopidogrelwithomeprazolecomparedtothosetakingclopidogrelalone.Theeffectofclopidogrelonplateletswasreducedbyasmuchas47%inpeoplereceivingclopidogrelandomeprazoletogether.解放军总医院消化病中心ThedatafromthemanufacturerofclopidogrelEffectofPPIonthemetabolitelevelsofclopidogrel第10页，课件共19页，创作于2023年2月TheconcomitantuseofomeprazoleandclopidogrelshouldbeavoidedOtherdrugsthatshouldbeavoidedincombinationwithclopidogrelbecausetheymayhaveasimilarinteractioninclude:esomeprazole,cimetidine,fluconazole,etc.解放军总医院消化病中心FDAalertin200911第11页，课件共19页，创作于2023年2月ExceptcimetidineNoevidencethatotherdrugsreducestomachacid,H2blockersranitidine(Zantac)famotidine(Pepcid)nizatidine(Axid)(TagametandTagametHB-aCYP2C19inhibitor)antacidsinterferewiththeanti-clottingactivityofclopidogrel.解放军总医院消化病中心H2

receptorblockers第12页，课件共19页，创作于2023年2月PantoprazoleislesspotentthanomeprazoletoinhibitCYP2C19anddoesnotappeartoattenuatethepharmacodynamicresponsetoclopidogrelPantoprazolehadnoassociationwithrecurrentMIinalargepopulation-based,case-controlstudyofpatientsreceivingclopidogrel解放军总医院消化病中心AlternativePPIPantoprazole第13页，课件共19页，创作于2023年2月噻吩吡啶类抗血小板药包括普拉格雷、替卡格雷.普拉格雷（prasugrel）通过细胞色素P450系统代谢（包括CYP3A、CYP2B6、CYP2C9和CYP2C19）活化CYP2C19不是其主要代谢途径。尚未在我国上市替卡格雷（ticagrelor）替卡格雷通过CYP3A4代谢不受CYP2C19变异的影响尚未在美国及我国上市解放军总医院消化病中心Alternativeantiplatelettherapy第14页，课件共19页，创作于2023年2月Clopidogrelalone,aspirinalone,andtheircombinationareallassociatedwithincreasedriskofGIbleeding.UseofaPPIorhistamineH2receptorantagonist(H2RA)reducestheriskofupperGIbleedingcomparedwithnotherapy.PPIsreduceupperGIbleedingtoagreaterdegreethandoH2RAs.解放军总医院消化病中心2010ExpertConsensus（1）2010ExpertConsensusDocumentontheConcomitantUseofPPIsandThienopyridines

JACCVol.56,No.24,2010第15页，课件共19页，创作于2023年2月Pharmacokineticandpharmacodynamicstudies,usingplateletassaysassurrogateendpoints,suggestthatconcomitantuseofclopidogrelandaPPIreducestheantiplateleteffectsofclopidogrel.Thestrongestevidenceforaninteractionisbetweenomeprazoleandclopidogrel.解放军总医院消化病中心2010ExpertConsensus（2）2010ExpertConsensusDocumentontheConcomitantUseofPPIsandThienopyridines

JACCVol.56,No.24,2010第16页，课件共19页，创作于2023年2月PlateletfunctiontestingReallyreflecttheclinicalevents?PharmacogenomictestingCYP2C19,highcostnopracticalandnofeasibility解放军总医院消化病中心IndividualedTEST第17页，课件共19页，创作于2023年2月Clinicalobservationalstudies:interactionsyesA