Acetaminophen toxicity

Question 1

Facts about acetaminophen

Answer 1

1. most widely used analgesic-antipyretic in US
2. very save if used in therapeutic range
3. # 1 cause of acute liver failure

Question 2

What are the clinical symptoms of acetaminophen toxicity?

Answer 2

1. oftern takes 1-2 days to become apparant (2/2 GSH depletion)
2. RUQ tenderness
3. Elevated liver enzymes (AST/ALT)
4. Jaundice

Question 3

What is the cause for acetaminophen toxicity?

Answer 3

P450 induction and depleted glutathione play a major role

Question 4

95% of acetaminphen is metabolized by?

Answer 4

phase II enzymes into non-toxic conjugates

Question 5

5% of acetaminophen is metabolized by?

Answer 5

1. P450 enzymes into reactive toxic intermediate: N-acetyl-p-benzoquinoeimine (NAPQI).

*P450 induction (ei. chronic alcoholism) incrases rate of NAPQI formation

2. in a nonalcoholic or small overdose, all NAPQI is conjugated to GSH into non toxic met.
3. if intracellular GSH stores are depleted (repeated overdose) or overwhelmed (P450 induction from chronic alcoholism) NAPQI binds to sulhydryl groups on hepatic cells leading to cell death

Question 6

What is the antidote used in acetaminophen toxicity?

Answer 6

N-acetylcysteine: acts as a sulhydryl donor (think os it as a GSH substitute that minds to NAPQI)