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Should a Lower Treatment Line Be Used When Treating Paracetamol Poisoning in Patients with Chronic Alcoholism?

A Case For

Drug Safety volume 25, pages 619–624 (2002)Cite this article

Abstract

A lower threshold for treatment of paracetamol (acetaminophen) poisoning has been advocated in chronic heavy users of alcohol, based originally on animal studies indicating that chronic alcohol ingestion increased hepatotoxicity. This was attributed to increased production of the toxic metabolite, N-acetyl-p-benzoquinoneimine, by cytochrome P450 (CYP)2E1 induction. The clinical evidence for increased risk is limited to four retrospective studies with potential for referral and reporting bias and conflicting results. No study has specifically addressed the issue of the treatment threshold for acute paracetamol overdose in chronic alcohol users. However, animal studies in multiple species have consistently shown a lower dose of paracetamol is required to produce hepatotoxicity after chronic alcohol use. The knowledge of potential mechanisms has expanded to include effects of other alcohols, such as isopentanol, induction of CYP enzymes other than CYP2E1 and glutathione depletion. There are no convincing reasons or data to suggest these findings do not apply to humans. However, further human toxicokinetic and clinical research is required to quantify the extent of the interaction. Arguments about treating overdoses should not be confused with those about whether there is an alcohol-paracetamol interaction at therapeutic doses. Halving the threshold dose/concentration for treatment is a conservative educated guess that has been widely adopted. In overdose, the potential benefits of treatment at this lower threshold clearly outweigh the minimal risks of acetylcysteine.

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Acknowledgements

The authors have received no funding for the preparation of this article, nor have any conflicts of interest that are directly relevant to its contents.

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Affiliations

  1. Department of Clinical Pharmacology & Toxicology, The Canberra Hospital, P.O. Box 11, Woden, Australian Capital Territory, 2606, Australia

    Nicholas A. Buckley

  2. Department of Clinical Pharmacology & Toxicology, Royal Adelaide Hospital, Adelaide, South Australia, Australia

    Jayasri Srinivasan

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Buckley, N.A., Srinivasan, J. Should a Lower Treatment Line Be Used When Treating Paracetamol Poisoning in Patients with Chronic Alcoholism?. Drug-Safety 25, 619–624 (2002). https://doi.org/10.2165/00002018-200225090-00001

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  • DOI: https://doi.org/10.2165/00002018-200225090-00001

Keywords

  • Paracetamol
  • Toxic Metabolite
  • Chronic Alcohol
  • Acetylcysteine
  • Chronic Alcoholism