What is the standard antidote for acetaminophen toxicity in cats, and why are cats susceptible?

• A. N-acetylcysteine; cats have abundant glucuronidation
• B. Activated charcoal; cats susceptible
• C. Vitamin C therapy
• D. N-acetylcysteine; cats have limited glucuronidation and low hepatic glutathione stores

Answer: (A)

N-acetylcysteine is the standard antidote for acetaminophen toxicity in cats because it replenishes hepatic glutathione and provides a thiol group that helps detoxify the toxic metabolite formed from acetaminophen. Cats are particularly susceptible because they have limited glucuronidation capacity and relatively low hepatic glutathione stores. Glucuronidation is a major pathway to safely detoxify acetaminophen, and when this pathway is weak in cats, more acetaminophen is shunted toward oxidation by liver enzymes to NAPQI, a highly reactive metabolite. Without enough glutathione to neutralize it, NAPQI binds to liver proteins, causing oxidative damage and hepatotoxicity. N-acetylcysteine serves two critical roles: it acts as a precursor to glutathione synthesis, restoring the liver’s ability to detoxify NAPQI, and its thiol groups can directly conjugate with NAPQI, reducing injury. Early administration is important for best outcomes. While activated charcoal can help limit absorption if given soon after ingestion, it is not the specific antidote, and vitamin C is not a standard treatment for this condition.