Individuals with alcoholic cirrhosis of liver may develop severe hepatotoxicity after doses of acetaminophen that are not toxic to individuals with normal liver function. This increased sensitivity to acetaminophen's toxicity is due to:
When a toxic amount of acetaminophen is ingested, the first two processes are overwhelmed and more acetaminophen is metabolized by the cytochrome P450 system to a hepatotoxic metabolite (N-acetyl-p-benzoquinoneimine, NAPQI). In therapeutic acetaminophen ingestions, the liver generates glutathione, which detoxifies NAPQI. However, in overdose, the glutathione is depleted, leaving the metabolite to produce toxicity. The antidote for acetaminophen toxicity, N-acetylcysteine (NAC), initially works as a glutathione precursor and glutathione substitute and assists with sulfation.
Decrease availability of acetaldehyde dehydrogenase
Decreased hepatocellular stores of glutathione
Decreased activity of Cytochrome P450 enzymes
Increased liver blood flow
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