Pharmacokinetics
Acetaminophen is completely and rapidly absorbed from the gastrointestinal tract.
80%-90% is conjugated with glucuronic or sulfuric acid in the liver and then excreted in the urine.
At high doses, one of these metabolites undergoes spontaneous dehydration to form N-acetyl-P-benzoquinone, the metabolite thought to be responsible for hepatotoxicity.
Adverse effects:
A. At therapeutic doses, acetaminophen is well tolerated; however, untoward effects include:
- Skin rash and drug fever (an allergic reaction to the drug).
- Rare instances of blood dyscrasias (haemolyticanaemia in with G6PD deficiency, less than with phenacetin).
- Renal tubular necrosis and renal failure (more with phenacetin).
B.An overdose of acetaminophen(about 15 gm in an adult; about 4 gm in a child)
- can result in severe hepatotoxicity, resulting in centrilobular hepatic necrosis. Doses greater than 20 gm are potentially fatal.
- The toxic metabolite of acetaminophen appears to be inactivated in the liver via glutathione.
- It is thought that when glutathione stores are consumed, the N-acetyl-p-benzoquinone metabolite binds covalently to cellular constituents, producing hepatocellular damage.
- Although clinical symptoms, such as nausea and vomiting, occur during the first 24 hours after toxic ingestion, signs of hepatic damage (e.g. enzyme abnormalities) may not occur for 2 - 6 days).
Treatment consists of:
- Emptying the stomach & administering activated charcoal
- Hemodialysis, if begun within the first 12 hours after ingestion.
- Administration of sulfhydryl compounds (e.g. acetylcysteine) which probably replenish hepatic stores of glutathione.