American Board of Medicolegal Death Investigators (ABMDI) Practice Exam

Which substance is known to cause liver necrosis?

1. Ibuprofen

2. Acetaminophen

3. Carbamazepine

4. Alprazolam

The correct answer is: Acetaminophen

Acetaminophen is well-documented as a substance that can cause liver necrosis, particularly in cases of overdose. The liver metabolizes acetaminophen through multiple pathways, and a significant amount is processed via the cytochrome P450 enzyme system into a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI). In normal doses, NAPQI is detoxified by conjugation with glutathione. However, when acetaminophen is taken in excessive amounts, the levels of NAPQI can exceed the liver's capacity to neutralize it, leading to hepatotoxicity and ultimately liver cell necrosis. This phenomenon is particularly significant because acetaminophen is often perceived as a safe over-the-counter medication, leading individuals to underestimate the risk associated with high doses. Liver necrosis can result in severe liver damage, necessitating medical intervention, and in severe cases, a liver transplant may be needed. In contrast, while ibuprofen, carbamazepine, and alprazolam can have adverse effects in specific circumstances, they are not typically associated with causing liver necrosis in the same manner as acetaminophen. Ibuprofen, for instance, primarily poses risks related to gastrointestinal bleeding and renal impairment rather