hepatotoxicity of anti-tb agents课件

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1、Hepatotoxicityofanti-TBagentsRi陳怡中Nov11,2002DiagnosisofTBSymptoms/signsSputumsmearSputumcultureCXRTSTPCRTreatmentofActivetuberculosisS/S:dyspnea,fever,coughwithsputum,andnightsweatingCXR:S1,S2,S6radiologicalchangeS/CorS/S:acid-fastbacilliHERZ2months+HER4

2、monthsHER9monthsTreatmentofPPDreactors5-mm:immunocompromised,closecontactofTBp’t,typicalCXRchange10-mm:high-prevalencegroup15-mm:low-prevalencegroupINHfor6~12monthsRIF+PZAfor2months(X)Underlyingliverdisease(X)PriorINH-associatedliverdiseaseRiskofReactiva

3、tionTBRecentTSTresultchangeCXRdefinitefindingsExposuretoactiveTBImmunocompromisedFirst-lineAnti-TBDrugsIsoniazid(INH)“Duracrin”100mg/tabEthambutol(EMB)“Myambutol”400mg/tabRifampin(RIF)“Mycobutin”150mg/capPyrazinamide(PZA)“Pyramide”250mg/tabStreptomycin1g

4、/vial“Rifinah”300mg/tab(INH150+RIF300)Isoniazid(INH)InhibitthesynthesisofmycolicacidsMetabolizedintheliverInhibitcytochromeP-450systemSideeffectsHepatotoxicityPeripheralneuritis–pyridoxinesupportRashesandskineruptionsRiskofIsoniazidHepatitisRiskfactors:o

5、ldage,alcoholism<20y/o:rare20–34y/o:<0.3%35–49y/o:<1.2%>50y/o:<2.3%INHHepatotoxicityIncidence:10~20%(asymptomatic)Liverenzymes↑2to3times:generallyoccur

6、ngofLFTs:notrecommenedRoutinemonitoringofserumtransaminaselevelsissuggestedinpatientswithriskfactorsFulminanthepaticfailure:rareRifampin(RIF)InhibitRNApolymeraseMetabolizedintheliverInducecytochromeP-450systemSideeffectsUrine,sweat,andtearsmaybecomered-o

7、rangeincolorHepatitisGIupset,leucopeniaorthrombocytopeniaRIFHepatotoxicityPrevalence:10%to15%Transienthepaticenzymes↑:usuallywithinthefirst8weeksOverthepatotoxicity:<1%Pyrazinamide(PZA)Mechanism:unknownSideeffectsHepatotoxicityGoutArthralgiaandmyalgiaPZA

8、HepatotoxicityTheriskofdrug-inducedhepatitisisdependentupondosage.Symptomatichepatitis:1%(combinedwithINH)Ethambutol(EMB)InhibitarabinogalactanSideeffectsOpticneuritisorothervisualdisturbancesGoutGIupsetEMBHepatotoxicityNo