[Paracetamol: therapeutic action, pathogenesis and treatment of acute poisonings complicated by severe liver damage]

Przegl Lek. 2003;60(4):218-22.
[Article in Polish]

Abstract

The biosynthesis of prostaglandins proceeds in the presence of fatty acid cycloxygenases (COX-1, COX-2). COX-1 is responsible for the synthesis of prostaglandins indispensable for normal homeostasis, while COX-2 regulates local expression of pro-inflammatory prostaglandins. Paracetamol is a selective inhibitor of COX-2 thus having an analgesic and antipyretic potential. The drug is metabolised primarily in the liver. About 5% of the dose transforms into N-acetylo-p-benzoquinoneimine (NAPQI), a highly active compound. Ingestion of a single paracetamol dose higher than 8 g leads to a depletion of hepatic glutathione reserves and a loss of the detoxifying property of the liver. As a result, hepatic necrosis develops. The specific antidote is N-acetylcysteine (NAC). If applied within 10-15 h since the poisoning it enables complete survival. The efficacy of specific treatment decreases after 24 h but blood paracetamol is an indication for NAC therapy. The surviving patients with advanced paracetamol poisoning require long-lasting conservative treatment with ornithine and phospholipids as well as a light diet.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Acetaminophen / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Benzoquinones / metabolism
  • Cyclooxygenase 1
  • Electron Transport Complex IV / metabolism
  • Humans
  • Imines / metabolism
  • Isoenzymes / metabolism
  • Liver Failure, Acute / chemically induced*
  • Membrane Proteins / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Saccharomyces cerevisiae Proteins

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzoquinones
  • Imines
  • Isoenzymes
  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Acetaminophen
  • Cyclooxygenase 1
  • PTGS1 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • COX3 protein, S cerevisiae
  • Electron Transport Complex IV
  • N-acetyl-4-benzoquinoneimine