Paracetamol Poisoning：对乙酰氨基酚中毒.pptVIP

Paracetamol Poisoning Kent R. Olson, M.D. Clinical Professor of Medicine University of California, San Francisco Medical Director, San Francisco Division California Poison Control System Case Study: A 17 year old young man took “pills” and some alcohol after failing his exams. He is drunk and depressed. BP 120/80 HR 105 Resp 14/min Temp 37 C His airway is patent, he is breathing normally Case, continued: He is treated with intravenous fluids, watched until sober, given a psychiatric referral, and sent home with his family. 3 days later he returns with jaundice. WHAT IS YOUR DIAGNOSIS? Paracetamol poisoning Diagnosis easily missed often overlooked in history no characteristic early symptoms or signs Paracetamol Poisoning Common analgesic often found in combination products eg, with antihistamines, codeine Paracetamol Toxicity: Overdose: sulfation and glucuronidation saturated increased production of p-450 metabolite glutathione eventually depleted reactive intermediate NAPQI injures cells PCM toxicity, cont. High-risk groups: enhanced p-450 activity chronic alcoholics chronic use of isoniazid (INH) Pharmacokinetics Tablets dissolve rapidly Peak level 3-4 hours after ingestion May be delayed in the presence of other drugs (eg, antihistamines, anticholinergics, opiates) Pharmacokinetics, cont. Volume of Distribution approx. 1L/kg Ingestion of 200 mg/kg ~ 200 mg/L est. blood level Elimination half-life normally 1-3 hours Increased to 4-6 hours or more after overdose Clinical Manifestations of Toxicity: Early: non-specific anorexia, vomiting Clinical toxicicity, cont. 24-48 hrs: onset of liver injury AST, ALT may exceed 10,000 IU renal injury may also occur Paracetamol Toxicity, continued: 2-5 days: liver kidney injury resolve in most patients some patients may develop fulminant liver failure progressive rise in PT/INR, bilirubin metabolic acidosis, hypoglycemia encephalopathy DEATH Rarely - massive ingestions only: 600 mg/kg: early onset metabolic acid