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1、ParacetamolPoisoningKentR.Olson,M.D.ClinicalProfessorofMedicineUniversityofCalifornia,SanFranciscoMedicalDirector,SanFranciscoDivisionCaliforniaPoisonControlSystemCaseStudy:A17yearoldyoungmantook“pills”andsomealcoholafterfailinghisexams.Heisdrunkanddepressed.BP120/80HR105Resp14/minTemp37CHisairwa
2、yispatent,heisbreathingnormallyCase,continued:Heistreatedwithintravenousfluids,watcheduntilsober,givenapsychiatricreferral,andsenthomewithhisfamily.3dayslaterhereturnswithjaundice.WHATISYOURDIAGNOSIS?ParacetamolpoisoningDiagnosiseasilymissedoftenoverlookedinhistorynocharacteristicearlysymptomsors
3、ignsParacetamolPoisoningCommonanalgesicoftenfoundincombinationproductseg,withantihistamines,codeineAcetaminophen MetabolismGlucuronidation(nontoxic)Sulfation(nontoxic)NAPQIP450~5%Glutathione+NAPQI=nontoxicproductLivercelldamageN-acetylcysteine(NAC)~45%~50%ParacetamolToxicity:Overdose:sulfationand
4、glucuronidationsaturatedincreasedproductionofp-450metaboliteglutathioneeventuallydepletedreactiveintermediateNAPQIinjurescellsPCMtoxicity,cont.High-riskgroups:enhancedp-450activitychronicalcoholicschronicuseofisoniazid(INH)PharmacokineticsTabletsdissolverapidlyPeaklevel3-4hoursafteringestionMaybe
5、delayedinthepresenceofotherdrugs (eg,antihistamines,anticholinergics,opiates)Pharmacokinetics,cont.VolumeofDistributionapprox.1L/kgIngestionof200mg/kg~200mg/Lest.bloodlevelEliminationhalf-lifenormally1-3hoursIncreasedto4-6hoursormoreafteroverdoseClinicalManifestationsofToxicity:Early:non-specific
6、anorexia,vomitingClinicaltoxicicity,cont.24-48hrs:onsetofliverinjuryAST,ALTmayexceed10,000IUrenalinjurymayalsooccurParacetamolToxicity,continued:2-5days:liver&kidneyinjuryresolveinmostpatientssomepatientsmaydevelopfulminantliverfailureprogressiveriseinPT/INR,bilirubinmetabolicacidosis,hypoglycemi
7、aencephalopathyDEATHRarely-massiveingestionsonly:>600mg/kg:earlyonsetmetabolicacidosisNotduetoliverfailureProbablymitochondrialpoisoningOnecaseofmassiveingestion>1500mg/kgComaHypotensionAcidosisPredictionofParacetamolT
