the answer is that liver damage from acetaminophen occurs when the glutathione pathway is overwhelmed by too much of acetaminophen's metabolite napqi. then this toxic compound accumulates in the liver and causes the damage. furthermore alcohol and certain medications such as phenobarbital phenytoin (dilantin) or carbamazepine (tegretol) (anti-seizure medications) or isoniazid (inh nydrazid laniazid) an anti-tuberculosis drug can significantly increase the damage. they do this by making the cytochrome p-450 system in the liver more active. this increased p-450 activity results in an increased formation of napqi from the acetaminophen. additionally chronic alcohol use as well as the fasting state or poor nutrition can each deplete the liver's glutathione. so alcohol both increases the toxic compound and decreases the detoxifying material. accordingly the bottom line in an acetaminophen overdose is that when the amount of napqi is too much for the available glutathione to detoxify liver damage occurs.
how does an overdose of acetaminophen cause liver injury?