Paracetamol causes:
Correct Answer: Hepatotoxicity
Description: Ref: Goodman & Gillman 13th ed. P 696* Paracetamol/Acetaminophen is a non-selective COX inhibitor* Use: Analgesic and antipyretic agent. Preferred in patients where aspirin is contraindicated* Usual dose: 325-650mg every 4-6 hours. Maximum FDA recommended dose is 4gm/day* Peak plasma concentration: 30-60 minutes* Half-life: 2 hours* Metabolism of acetaminophen in liver by:# Hepatic conjugation with glucuronic acid (~60%),# Sulfuric acid (~35%),# Cysteine (~3%);# CYP mediated N-hydroxylation to form NAPQI (N-acetyl-p-benzoquinone imine)* Note: NAPQI is one of the highly reactive intermediate metabolite of acetaminophen metabolism. This usually reacts with sulfhydryl groups is GSH - rendered harmless.* In hepatotoxicity condition GSH level depleted.SIDE EFFECTS* The most serious acute adverse effect of over dosage of acetaminophen is a potentially fatal hepatic necrosis.* Due to hepatotoxicity there is saturation of glucuronide and sulfate conjugation and increasing amounts undergo CYP-mediated N-hydroxylation to form excess of NAPQI (it accumulates due to depletion of GSH).* The highly reactive NAPQI causes enzymatic dysfunction, produces oxidative stress and apoptosis.* In adults hepatotoxicity may occur after ingestion of single dose of 10-15g. Doses of 20-25g is potentially fatal.TREATMENT OF ACETAMINOPHEN TOXICITY:* Activated charcoal within 4 hours of ingestion decreases absorption by 50-90%* N-acetylcysteine: antidote of choice for acetaminophen toxicity. It acts by detoxifying NAPQI by:# Repleting GSH stores# Conjugate directly with NAPQI by serving as a GSH substituteIn Paracetamol Toxicity:* Liver enzyme abnormalities typically peak 72-96 hours after ingestion* Biopsy: Centrilobular necrosis with sparing of the periportal area* Other side effects: Renal tubular necrosis and Hypoglycemic coma
Category:
Pharmacology
Get More
Subject Mock Tests
Practice with over 200,000 questions from various medical subjects and improve your knowledge.
Attempt a mock test nowMock Exam
Take an exam with 100 random questions selected from all subjects to test your knowledge.
Coming SoonGet More
Subject Mock Tests
Try practicing mock tests with over 200,000 questions from various medical subjects.
Attempt a mock test now