肾衰竭时药物应用肾衰竭时药物应用

DrugapplicationinrenalDrugapplicationinrenalfailurefailureJohnsJohnsHopkinHopkinUniUniReportReport（（20012001））„„141141mol/L(mol/L(),124),124mol/L(mol/L())3%3%„„70%70%,,75%75%,84%,84%仅仅11,,11%11%130/85mmHg130/85mmHg,,27%27%140/90mmHg140/90mmHg„„147/77mmHg,147/77mmHg,CRFinUSACRFinUSA（（JanJan，，0909，，20032003））in15,625adultpersonsin15,625adultpersons0.20.2〈〈1515550.20.21515～～292944443030～～595933336060～～8989223.33.3,,11Incidencerate(%)Incidencerate(%)GFRGFR（（ml/min)ml/min)StageStage„„::,,,,„„„„::,,,,„„遗传肾脏遗传肾脏::肾肾,,„„统关肾统关肾::,,肾肾糖尿病40%高血壓25%腎炎15%免疫10%藥物10%引起尿毒症原因構成比Thenaturalhistoryofdiabeticnephropathy(())(0.6g/kg/d)ACEImicroalbuminuriamicroalbuminuria„„GHbAGHbA1C1C7%7%7.5%7.5%((microalbuminuriamicroalbuminuria,,proteinuriaproteinuria))„„血壓控制血壓控制::健康人健康人130130～～140/80140/80～～8585mmHgmmHg蛋白尿或腎衰病人蛋白尿或腎衰病人:125:125～～130/75130/75～～8080mmHgmmHg„„首选首选ACEI,ARB,CCBACEI,ARB,CCB降压降压相關策略相關策略„„dipyridamoledipyridamole,,pentoxifyllinepentoxifylline碱碱„„statinsstatins„„„„,,„„,,reninAnginotensinⅡACEIARB+Prostacyclin-NSAIDsRenoprotectiveRenoprotectivedoseofACEIdoseofACEI„„RamiprilRamipril(()3.0)3.0mgdailymgdaily„„EnalaprilEnalapril(()5)5mgdailymgdaily„„BenazeprilBenazepril(()10)10mgdailymgdaily„„CaptoprilCaptopril(()25)25mgthreetimesdailymgthreetimesdaily„„ImprovedBPcontrolanddecreasedImprovedBPcontrolanddecreasedproteinuriaproteinuria(1g/24hr)(1g/24hr)1150%50%10ml/min10ml/min222233225%5%1010～～50ml/min50ml/minACEIACEI应避免使用应避免使用3.43.4300300在专家指导下小心使用在专家指导下小心使用2.22.2~3.4~3.4200200~300~300仍可使用仍可使用2.22.2200200ACEIACEImg/dlmg/dl血肌酐血肌酐μμmol/Lmol/L11angiotensinangiotensinreceptor1blockersreceptor1blockersARBARB„„::((losartanlosartan))irbesartanirbesartantelmisartantelmisartanvalsartanvalsartan„„RENAALRENAAL試驗試驗::11,,300mg/g300mg/g,,5050100mg100mg缓肾缓肾,,使使16%16%抗高血壓葯及腎保護抗高血壓葯及腎保護腎保護中性，腎保護中性，HydralazineHydralazine腎保護中性，不長期應用腎保護中性，不長期應用ClonidineClonidine可能有腎保護，建議作輔助葯用可能有腎保護，建議作輔助葯用DiurecticsDiurectics腎保護中性，改善血脂和前列腺肥大腎保護中性，改善血脂和前列腺肥大αα--blockersblockers非二氫吡啶類有心腎保護作用非二氫吡啶類有心腎保護作用CCBCCB有心腎保護作用，腎衰時注意血鉀有心腎保護作用，腎衰時注意血鉀ββ--blockerblocker有腎保護作用，注意血肌酐和血鉀有腎保護作用，注意血肌酐和血鉀ACEIACEI或或ARBARB説明説明藥物藥物IbopamineIbopamine„„„„„„--„„100mg100mg„„20ml/min20ml/min200mg200mgSulfonamides,Sulfonamides,OxypurinolOxypurinol,Uricacid,UricacidAminoglycosidesAminoglycosidesCyclosporine,Analgesics(toxic)Cyclosporine,Analgesics(toxic)PGsPGs，，Sulfonamides(immunologic)Sulfonamides(immunologic)NSAIDsNSAIDs,Gold,,Gold,PenicillaminePenicillamine(toxic)(toxic)SulfonamideSulfonamidevasculitisvasculitis,Druglupus,,Druglupus,Organsolvent(immunologic)Organsolvent(immunologic)ACEI,ACEI,NSAIDsNSAIDs,Cyclosporine,CyclosporineGlucocorticoidsGlucocorticoids,,TetracyclinesTetracyclines，，CimetidineCimetidine„„:(~0.6gofprotein/kgof:(~0.6gofprotein/kgofIBW/dIBW/d„„60%60%„„(~35(~35kcal/kg/d)kcal/kg/d)„„BB族維生素和維生素族維生素和維生素CC足夠足夠„„(())„„„„„„„„„„((,,„„ACEI,NSAID,ACEI,NSAID,„„(erythropoietindeficiency)(erythropoietindeficiency)CreatinineCreatininebloodconcentrationandbloodconcentrationandClClcrcr„„((AgeAge))BWBW„„„„CLcrCLcrcrcrcrcrCBWAgeCACL72140(⋅−==Acr:肌酐日產量,以mg為單位Ccr:血肌酐穩態濃度，以mg/dl（mg/100ml）為單位Age:年齡以歲為單位BW:體重以Kg為單位血肌酐以mg/dl為單位，μmol/L除以88.4z血葯濃度的肌酐清除率0.85z腎功能急劇下降時，血肌酐到達穩態的時間延長zCLcr明顯墮後於腎功能改變。腎功能下降50%、25%和10%時，血肌酐濃度到達穩態的時間將分別延長到0.92，1.85和4.6日UrinaryexcretionofunchangeddrugUrinaryexcretionofunchangeddrug„„„„0011100ml/min100ml/min„„11000.80.9cephradine0.540.79罗meropenem0.96呋cefuroxime0.60.75亚imipenem0.49ceftriaxone0.60.7aztreonam0.84肟ceftazidime0.80吡肟cefepime0.67cefotetan0.84ceftazidime0.55噻肟cefotaxime0.20.3哌cefoperazone0.41肟cefixime0.850.9cefoxitin0.80啉cephazolin0.60.8cefotiam0.92噻cephalothin0.52cefaclor0.91苄cephalexinefefe„„苷苷--„„„„„„用肌酐清除率估计病人的肾功能用肌酐清除率估计病人的肾功能„„„„„„„„„„„„SelectedDrugswithDecreasedProteinSelectedDrugswithDecreasedProteinBindinginUremiaBindinginUremiaAcidsAcids„„BarbituratesBarbiturates„„CephalosporinsCephalosporins„„ClofibrateClofibrate„„DicloxacillinDicloxacillin„„DiazoxideDiazoxide„„FurosemideFurosemide„„PenicillinGPenicillinG„„PhenytoinPhenytoin„„SalicylateSalicylate„„SulfonamidesSulfonamides„„ValproateValproate„„WarfarinBasesBases„„DiazepamDiazepam„„MorphineMorphine„„TriamtereneTriamtereneWarfarin„„（（clearanceofclearanceofcreatininecreatinine„„urinaryexcretionratiourinaryexcretionratio„„[[CLCL(f)](f)][[CLCL(n)],(n)],renalfractionofelimination,renalfractionofelimination,rfrf)(n)CL(f)CL(ferfcrcr−⋅−=11„„(loadingdose)(loadingdose)„„(maintenancedose)(maintenancedose)rfrfrfrf药药rfrf給葯間隔對血葯濃度波動的影響„„250L250L，不必調整劑量，不必調整劑量„„55100ml/min100ml/min500500700ml/min700ml/min„„（（22hh以内以内))迅速迅速在在„„250L250L500500ml/minml/min22在在