UMEM Educational Pearls



What is the mechanism of action of N-acetylcysteine that is used to treat acetaminophen induced liver injury/toxicity?










Excess production of NAPQI via CYP 2E1 from acetaminophen overdose depletes gluthathione, which detoxifies NAPQI. Gluthathione consists of 3 amino acids: glutamate, cysteine and glycine. cysteine availability is the rate limiting step in gluthathione synthesis. hepatotoxicity occurs when gluthathione store is depleted below 30% of the baseline. 


Thus NAC works by:

  1. providing cycteine to promote gluthathion synthesis
  2. directly detoxifies NAPQI (minor role)



Goldfrank's Toxicologic Emergencies. Ch35 Acetaminophen A3: antidote in depth - N-acetylcysteine