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    Subjects/Pharmacology/Drug Poisoning and Antidotes
    Drug Poisoning and Antidotes
    medium
    pill Pharmacology

    A 28-year-old woman is brought to the emergency department 2 hours after ingesting approximately 15 g of paracetamol (acetaminophen) in a suicide attempt. She is currently asymptomatic with normal liver function tests. Her serum paracetamol level is 180 µg/mL. What is the most appropriate immediate next step in management?

    A. Administer methionine orally and monitor paracetamol levels
    B. Perform gastric lavage followed by activated charcoal
    C. Administer N-acetylcysteine (NAC) intravenously immediately
    D. Observe for 24 hours and repeat liver function tests

    Explanation

    ## Management of Paracetamol Overdose ### Timing and Nomogram Interpretation **Key Point:** The Rumack-Matthew nomogram guides NAC initiation based on serum paracetamol level and time since ingestion. At 2 hours post-ingestion with a level of 180 µg/mL, this patient falls in the **high-risk zone** and requires immediate antidote therapy. ### Why NAC is the Correct Answer **High-Yield:** NAC is most effective when started within 8–10 hours of ingestion but can be beneficial up to 24 hours if hepatotoxicity has not yet developed. At 2 hours with a level above the nomogram threshold, immediate IV NAC initiation is the standard of care. **Clinical Pearl:** NAC works by: 1. Replenishing hepatic glutathione stores 2. Conjugating toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) 3. Preventing hepatocellular necrosis ### Nomogram Reference | Time (hours) | High-Risk Level | Low-Risk Level | |---|---|---| | 4 | 200 µg/mL | 150 µg/mL | | 8 | 100 µg/mL | 75 µg/mL | | 12 | 50 µg/mL | 37.5 µg/mL | | 16 | 25 µg/mL | 18.75 µg/mL | At 2 hours with 180 µg/mL, this patient is **above the high-risk line** and requires NAC. ### Standard NAC Regimen (IV) 1. **Loading dose:** 150 mg/kg over 1 hour 2. **Second dose:** 50 mg/kg over 4 hours 3. **Third dose:** 100 mg/kg over 16 hours **Warning:** Oral methionine is an older antidote (now rarely used) and is less effective than NAC. Do not delay NAC for methionine. [cite:Harrison 21e Ch 468]

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