Paracetamol poisoning in children and hepatotoxicity.

Abstract

1. Paracetamol is one of the most common drugs that children accidentally ingest. Unlike the situation in adults, death and hepatotoxicity in children from paracetamol poisoning are exceedingly uncommon events. A review of the literature has revealed only seven deaths and fourteen cases of hepatotoxicity in children, with most of the cases resulting from chronic poisoning and not acute poisoning. 2. Children may be less prone to paracetamol hepatotoxicity because of developmental differences in the drug's metabolism and its pathways of detoxification. In the therapeutic setting of treatment of fever and pain in children, paracetamol is regarded as a drug with a higher therapeutic index, and as such, there seems to be little concern with strict adherence to dosage regimes. 3. Scrutiny of the above paediatric cases associated with chronic paracetamol poisoning suggests that the margin of safety of frequent therapeutic doses of paracetamol in infants and young children to be a lot lower than previously appreciated. This review highlights the need to re‐evaluate the safety of paracetamol in the context of chronic therapy in infants and young children.

Pharmacokinetics/Pharmacodynamics of Acetaminophen Analgesia in Japanese Patients with Chronic Pain

“…The APAP concentration 4 h after administration in this study was 6.7 mg/ml, while toxic concentrations higher than 120-300 mg/ml appeared 4 h after administration. 18,19) Side effects were not observed in this study. Therefore, a single 1000 mg dose of APAP was considered to be a safe analgesic dose for the Japanese.…”

Lethal Acetaminophen Poisoning Related to Error Prescription: Medico Legal Implications - About a Case Report

“…It may occasionally be due to attempted suicide in older children and is rarely due to intentional poisoning for infants. Children may be less prone to paracetamol hepatotoxicity because of developmental differences in the drug's metabolism and its pathways of detoxification [2]. In fact, acetaminophen is primarily metabolized by conjugation in the liver to non-toxic compounds that are eliminated in the urine.…”

“…It has an excellent safety profile when administered in proper therapeutic doses. However, it still remains the most common substance involved in childhood poisoning [2]. Toxicity with paracetamol may occur in cases of misuse, unintended inappropriate dosage or the failure to recognize children at increased risk in whom standard paracetamol doses have been administered [3].…”

Cebranopadol: novel dual opioid/NOP receptor agonist analgesic

“…38,39 The latter produce the reactive metabolite NAPQI (N-acetyl-p-benzoquinone imine), which, in the absence of an adequate supply of reducing agents, results in covalent binding of NAPQI to hepatocytes, and cell death. 40,41 Opioids. Opioids, natural or synthetic, bind to three major seventransmembrane G-protein-coupled receptor (GPCR) types widely distributed throughout the central and peripheral nervous systems and gastrointestinal tract.…”