Acetaminophen (Tylenol)

on 16.3.09 with 0 comments

Fast Facts:

  • Introduced in 1950, hepatotoxicity recognized in 1966
  • Accounts for more overdoses and overdose-related deaths than any other drug. (~23%)
  • Most common cause of acute liver failure in alcoholics
  • Generally good outcome if N-acetyl cysteine is given

Effects and mechanism:

Has analgesic and antipyretic (fever-reducing) effects. The mechanism is not really known but it acts centrally to inhibit prostaglandin synthesis. Some theories say it might inhibit a third version of cyclo-oxygenase (COX-3) but that has not been proven. Its antipyretic effects are a result of its effect on the temperature regulating region of the hypothalamus.


Normally, 90% of acetaminophen is conjugated to sulfate or glucuronide. This conjugate is then excreted in urine. 5% is excreted unchanged the remaining 5% is metabolized by the p450 to NAPQI. NAPQI is hepatotoxic (oxidative injury and necrosis) and is conjugated to glutathione and excreted.

Excess NAPQI occurs for these reasons:

  • Excess acetaminophen intake overloads livers ability to conjugate to sulfate or glucuronide

  • Decreased ability to glucuonidate or sulfate

  • Induction of p450 enzymes (Occurs in chronic alcoholism)

  • Depletion stores of glutathione (Chronic alcoholism)

Hepatic injury is caused mainly when glutathione stores are depleted by 70%. To eliminate NAPQI, N-acetyl-cysteine is given which is a precursor to glutathione. With this new glutathione the NAPQI can be excreted.

Note: Acute alcohol intoxication may actually have a slight protective effect by the competition of alcohol for p450 enzymes

Category: Medical Subject Notes , Pharmacology Notes



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