J Korean Med Assoc.  2013 Dec;56(12):1067-1075. 10.5124/jkma.2013.56.12.1067.

Antidote for acetaminophen poisoning: N-acetylcysteine

• Chun BJ
• Moon JM
• Kim SH

• KMID: 1783721
• DOI: http://doi.org/10.5124/jkma.2013.56.12.1067

Abstract

N-acetylcysteine (NAC) is widely recognized as the antidote of choice for acetaminophen overdose. Acetaminophen is a commonly used analgesic and antipyretic agent, and its use is one of the most common causes of poisoning worldwide. Acetaminophen toxicity may occur acutely when supratherapeutic amounts are ingested purposefully or unintentionally. Liver failure may occur in severe toxicity. However, if treated early, patients with acetaminophen poisoning generally recover uneventfully. Acetaminophen is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by conjugation with glutathione. In overdose, hepatic stores of glutathione are depleted and NAPQI binding to hepatocytes induces cell death and hepatic necrosis. NAC replenishes hepatic glutathione and may also act as a glutathione substitute, combining directly with the toxic metabolite. Intravenous NAC is indicated in patients who present with a history of acetaminophen overdose within the previous 8 to 10 hours, patients unable to tolerate oral NAC, and patients who present with evidence of fulminant hepatic failure. However, caution should be used in patients who have experienced previous hypersensitivity or anaphylactoid reactions to intravenous NAC, as well as in patients with asthma. The most common anaphylactoid reactions include rash, flushing, and bronchospasm. Adults should receive 150 mg/kg administered for 45 minutes, followed by 50 mg/kg administered for 4 hours, followed by 100 mg/kg administered for 16 hours. The total dose is 300 mg/kg delivered over 21 hours. Additionally, caution should always be used when intravenous NAC is prescribed and the amount of diluent is calculated. Monitoring of patients with a should include repeated neurologic and hemodynamic assessment.

Keyword

Acetaminophen; Hepatotoxicity; Antidotes; Acetylcysteine; Anaphylactoid reaction

MeSH Terms

Acetaminophen*
Acetylcysteine*
Adult
Antidotes
Asthma
Benzoquinones
Bronchial Spasm
Cell Death
Exanthema
Flushing
Glutathione
Hemodynamics
Hepatocytes
Humans
Hypersensitivity
Imines
Liver Failure
Liver Failure, Acute
Necrosis
Poisoning*
Acetaminophen
Acetylcysteine
Antidotes
Benzoquinones
Glutathione
Imines

Figure

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  Figure 1 Acetaminophen metabolism. NAPQI, N-acetyl-p-benzoquinone imine; CYP450, cytochrome P450.

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  Figure 2 The Rumack-Matthew nomogram (from Wikipedia. Rumack-Matthew nomogram [Internet]. San Francisco: Wikimedia foundation, according to the Creative Commons Attribution License) [21].

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