Toxic Syndromes: Acetaminophen

ACETAMINOPHEN

Acetaminophen is one of the drugs commonly involved in suicide attempts and accidental poisonings, both as the sole agent and in combination with other drugs. Acute ingestion of more than 150–200 mg/kg (children) or 7 g total (adults) is considered potentially toxic. A highly toxic metabolite is produced in the liver (see Figure 4–5).

Initially, the patient is asymptomatic or has mild gastrointestinal upset (nausea, vomiting). After 24–36 hours, evidence of liver injury appears, with elevated aminotransferase levels and hypoprothrom-binemia. In severe cases, fulminant liver failure occurs, leading to hepatic encephalopathy and death. Renal failure may also occur.

The severity of poisoning is estimated from a serum acetamin-ophen concentration measurement. If the level is greater than 150–200 mg/L approximately 4 hours after ingestion, the patient is at risk for liver injury. (Chronic alcoholics or patients taking drugs that enhance P450 production of toxic metabolites are at risk with lower levels.) The antidote acetylcysteine acts as a gluta-thione substitute, binding the toxic metabolite as it is produced. It is most effective when given early and should be started within 8–10 hours if possible. Liver transplantation may be required for patients with fulminant hepatic failure.