Severe Hepatotoxicity, Acute Renal Failure, and Pancytopenia in a Young Child After Repeated Acetaminophen Overdosing

Douidar, Samir M.; Al-Khalil, Ihsan; Habersang, Rolf

doi:10.1177/000992289403300107

Cited by 13 publications

(3 citation statements)

References 11 publications

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“…However, following excessive repeated paracetamol dosing, there is no evidence that children are relatively protected. In fact, infants and children with acute febrile illnesses comprise one of the few groups in which toxicity after repeated excessive dosing has been described (43,49,52,65,74,99,151,201,208). In any child with acute febrile illness and reported dosing that exceeds 75 mg/kg in any 24-h period, or if symptoms or signs of hepatotoxicity are evident, regardless of reported dosing, blood levels of paracetamol and aspartate aminotransferase (AST) must be measured (26).…”

Section: Toxicologymentioning

confidence: 99%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It occupies a unique position among analgesic drugs. Unlike NSAIDs it is almost unanimously considered to have no antiinflammatory activity and does not produce gastrointestinal damage or untoward cardiorenal effects. Unlike opiates it is almost ineffective in intense pain and has no depressant effect on respiration. Although paracetamol has been used clinically for more than a century, its mode of action has been a mystery until about one year ago, when two independent groups (Zygmunt and colleagues and Bertolini and colleagues) produced experimental data unequivocally demonstrating that the analgesic effect of paracetamol is due to the indirect activation of cannabinoid CB 1 receptors. In brain and spinal cord, paracetamol, following deacetylation to its primary amine (p-aminophenol), is conjugated with arachidonic acid to form N-arachidonoylphenolamine, a compound already known (AM404) as an endogenous cannabinoid. The involved enzyme is fatty acid amide hydrolase. N-arachidonoylphenolamine is an agonist at TRPV1 receptors and an inhibitor of cellular anandamide uptake, which leads to increased levels of endogenous cannabinoids; moreover, it inhibits cyclooxygenases in the brain, albeit at concentrations that are probably not attainable with analgesic doses of paracetamol. CB 1 receptor antagonist, at a dose level that completely prevents the analgesic activity of a selective CB 1 receptor agonist, completely prevents the analgesic ac- 250CNS Drug Reviews Vol. 12, No. 3-4, pp. 250-275 © 2006 tivity of paracetamol. Thus, paracetamol acts as a pro-drug, the active one being a cannabinoid. These findings finally explain the mechanism of action of paracetamol and the peculiarity of its effects, including the behavioral ones. Curiously, just when the first CB 1 agonists are being introduced for pain treatment, it comes out that an indirect cannabinomimetic had been extensively used (and sometimes overused) for more than a century.

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Section: Toxicologymentioning

confidence: 99%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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“…This appears to be the only case of severe acetaminophen toxicity with an altered mental state, metabolic acidosis, and preserved renal and hepatic function in a young child. Douidar et al 4 presented a case of severe hepatotoxicity, renal failure, and pancytopenia in a 3 1 ⁄ 2-year-old child after repeated acetaminophen overdosing who survived with supportive care and late N-acetylcysteine therapy. In children, toxicity may be expected with the ingestion of 150 mg/kg of acetaminophen.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Acidosis and Coma in a Child with Acetaminophen Toxicity

Steelman

Goodman

Biswas

et al. 2004

Clin Pediatr (Phila)

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“…Patients in whom the INR and/or plasma creatinine are abnormal or whose plasma paracetamol concentrations exceed10 mg/ litre at 24 h after ingestion require further monitoring. All patient should have their INR and plasma creatinine concentration determined before being considered fit for discharge from medical care, whether or not they have received NAC.…”

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confidence: 99%