How does an overdose of acetaminophen cause liver injury?
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) – (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, as you might expect, 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 availa
