Acetaminophen Poisoning

Acetaminophen Poisoning

Elimination Process

• Further elimination occurs through hepatic biotransformation.

• Therapeutic doses have an elimination half-life of 1.5-3 hours.

Metabolism

• About 90% is metabolized to inactive sulfate and glucuronide conjugates excreted in urine.

• The remainder is metabolized by cytochrome P450 (chiefly 2E1 and 3A4), producing the highly reactive intermediary compound N-acetyl-p-benzoquinone imine (NAPQI/NAPBQI).

Role of Glutathione

• Normally, NAPQI is bound by intracellular glutathione and eliminated as mercapturic adducts in urine.

• Increased acetaminophen doses can lead to greater NAPQI production, depleting glutathione stores.

• Critical depletion of glutathione (about 30% of normal) can cause NAPQI to bind to other proteins, damaging hepatocytes.

• Depletion of glutathione itself may also be injurious.