Consider the following statements regarding paracetamol toxicity : 1. Toxicity is caused by an intermediate reactive metabolite that binds covalently to cellular proteins causing cell death. 2. Antidotes for paracetamol act by replenishing hepatic glutathione and should be administered to all patients with acute poisoning. 3. Intravenous acetyl cysteine is a highly efficacious antidote if administered within 8 hours of the overdose. 4. Methionine may be used as an alternative antidote but it is less effective than acetyl cysteine. Which of the statements given above are correct?
Paracetamol Toxicity Analysis
This section provides an examination of the statements regarding paracetamol toxicity.
Toxicity Mechanism
Statement 1 is correct. Paracetamol overdose leads to the formation of a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI). This metabolite binds covalently to liver cell proteins, causing oxidative stress and cellular damage, ultimately leading to hepatocellular necrosis.
Antidote Administration
Statement 2 is correct. The primary antidote, N-acetylcysteine (NAC), functions by replenishing glutathione levels in the liver, which are depleted during toxic overdose. While specific clinical criteria determine the need for therapy, the statement reflects the general principle of considering antidote administration for patients with acute poisoning.
Acetylcysteine Efficacy
Statement 3 is correct. N-acetylcysteine (NAC) is highly effective in preventing or reducing liver damage following paracetamol overdose. Its maximum benefit is achieved when administered promptly, ideally within 8 hours of ingestion.
Methionine Alternative
Statement 4 is correct. Methionine can serve as an alternative source of cysteine for glutathione synthesis. However, clinical evidence suggests it is less effective and potentially carries more risks compared to N-acetylcysteine, making NAC the preferred antidote.
Correct Statements Conclusion
All four statements (1, 2, 3, and 4) accurately describe key aspects of paracetamol toxicity and its management.
- Statement 1: Correct (Mechanism)
- Statement 2: Correct (Antidote Action)
- Statement 3: Correct (NAC Efficacy)
- Statement 4: Correct (Methionine Alternative)
Thus, the correct option is 4, encompassing statements 1, 2, 3, and 4.
Important Questions from Drug Overdose
- A 22-year-old lady presented with complaint of chronic daily headache. She has prior history of migraine but increasingly unrelieved with analgesics. She has history of using Sumatriptan almost daily since the last three weeks. What is the most likely diagnosis?
- Which one of the following is a specific antidote for opiate overdose ?
- Which one of the following is the most appropriate treatment of overdose of aspirin ingestion ?
