Paracetamol causes mitochondrial toxicity in massive overdose

In massive paracetamol overdose, N-acetyl-p-benzo-quinone imine (NAPQUI) inhibits the electron transport chain in a manner similar to cyanide.

This actually precedes the fulminant hepatic failure (by a few hours).

paracetamol toxicity leading to lactic acidosis

Thus, aerobic metabolism of glucose is interrupted, and pyruvate is shunted into the synthesis of lactate.

And of course, once established hepatic failure takes hold, no lactate is being cleared except by renal mechanisms.

Not only that, but paracetamol can also cause pyroglutamic acidosis, even without overdose (though overdose seems to help).


Shah, Anoop D., David M. Wood, and Paul I. Dargan. "Understanding lactic acidosis in paracetamol (acetaminophen) poisoning." British journal of clinical pharmacology 71.1 (2011): 20-28.