Hypokalemia (associated with high 4-hr level).NAC increases availability of glutathione.In overdose, glutathione runs out, NAPQI accumulates → liver injury.APAP toxic metabolite NAPQI usually quickly detoxified by glutathione stores in liver.This process becomes overwhelmed in overdose and metabolism is shifted to the CYP 450 pathway generating toxic NAPQI. Acetaminophen is metabolized by sulfation and glucuronide conjugation.E - Conjugated and unconjugated excreted through kidneys.5-10% - Metabolism through CYP450/CYP2E1 (Forms NAPQI).
Antipyresis through inhibition of hypothalamic heat center.Possibly through inhibition of Cyclooxygenase-3 (COX-3).Initial loading dose of NAC is 150 mg/kg IV (140 mg/kg PO).Give NAC if level is >150 mcg/mL four hours post-ingestion.200 mg/kg in healthy children 1-6 years of age.>6 g or >150 mg/kg per 24hr period x 2days.>10 g or >200 mg/kg as single ingestion or over 24hr period OR.Now the most common cause of acute liver failure in the US.Includes Tylenol and numerous brands and products including acetaminophen.2.4 Stage 4 (after day 5, up to 2 weeks).
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