Canis ISSN: 2398-2942

Paracetamol poisoning

Synonym(s): Acetaminophen poisoning

Introduction

  • Rapidly absorbed, with peak levels occurring soon after ingestion.
  • Absorption from sustained release preparation can continue for many hours.
  • Signs: hepatotoxicity, can produce multi-organ failure.
  • Diagnosis: history, clinical signs, urinalysis, hematology, biochemistry.
  • Treatment: specific antidoteN-acetylcysteine.
  • Prognosis:guarded.

Pathogenesis

Etiology

  • Access to owner's medication.
  • NB: many cold remedies contain paracetamol.

Pathophysiology

  • Multi-organ failure via the production of a toxic intermediate metabolite,N-acetyl-p-benzoquinonamine.
  • This requires glutathione for further metabolism to non-toxic metabolites (conjugation).
  • Once glutathione depleted, the toxic metabolite binds to cellular proteins causing damage.
  • Any organ that has P450 enzymes can suffer toxicity, ie liver, kidneys, heart and pancreas.
  • Rapidly absorbed from gastrointestinal tract (1 hour).
  • At low doses paracetamol is glucuronidated.
  • High doses result in metabolism by cytochrome P450 to form the reactive metaboliteN-acetyl-p-benzoquinonamine → severe oxidative changes.

Timecourse

  • May recover spontaneously in 48-72 hours.
  • Severe cases usually die 2-5 days after onset of signs.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Avizeh R, Najafzadeh H, Razijalali M, Shirali S (2010) Evaluation of prophylactic and therapeutic effects of silymarin and N-acetylcysteine in acetaminophen-induced hepatotoxicty in cats. J Vet Pharmacol Therap 33 (1), 95-99 PubMed.
  • Yang R, Miki K, He X, Killeen M E, Fink M P (2009) Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity. Crit Care 13 (2), R55 PubMed.
  • Webb C B, Twedt D C, Fetttman M J, Mason G (2003) S-adenosylmethionine (SAMe) in a feline acetaminophen model of oxidative injury. J Fel Med Surg 5 (2), 69-75 PubMed.
  • Thomas A (2002) Paracetamol poisoning. UK Vet (5), 39-42.
  • Wallace K P, Center S A, Hickford F H, Warner K L, Smith S (2002) S-adenosyl-l-methionine (SAMe) for the treatment of acetaminophen toxicity in a dog. JAAHA 38 (3), 246-254 PubMed.
  • Mayer S (1991) Poisons - paracetamol. In Pract 13 (1), 37 VetMedResource.

Other sources of information

  • Thomas A (2002) Paracetamol Poisoning. UK VET 7(5), 39-42.
  • Campbell A & Chapman M (VPIS) (2000) Paracetamol Poisoning. In:Handbook of Poisoning in Cats and Dogs.Blackwell Science. pp 30-38.
  • Janes J & Routeledge P A l (1992) Recent developments in the management of paracetamol (acetaminphen) poisoning. Drug Safety 7(3), 170-177.

Organisation(s)


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