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oxicological screening , Paracetamol

المؤلف:  Sue Jickells , Adam Negrusz (Editors)

المصدر:  Clarkes Analytical Forensic Toxicology

الجزء والصفحة:  P232-233

2026-10-17

54

oxicological screening

Paracetamol

Paracetamol is widely available as an over the-counter medicine and is frequently taken in overdose. Paracetamol is metabolised by the liver to N-acetyl-p-benzoquinoneimine (NAPQI), which is normally inactivated by liver glutathione. After paracetamol overdose, the glutathione stores become depleted to leave toxic amounts of NAPQI to bind to proteins and cause centilobular necrosis. Drugs that induce hepatic P450 enzymes (e.g. phenobarbital) and chronic high ethanol abuse may enhance para cetamol toxicity. Intravenous infusion of N acetylcysteine to replenish the glutathione stores is an effective treatment, especially when given during the early stages of poisoning. During the first 12 h after ingestion of a severe overdose no clinical features other than vomiting may occur. After 12 h, hepatic necrosis causes continued vomiting, which may also induce abdominal pain after 24 h. Signs of jaundice become apparent after 36–72 h and the patient may develop hepatic encephalopathy and hepatic failure. Serum or plasma paracetamol measurements play a crucial role in the early diagnosis; management protocols, and nomograms that relate these to time after ingestion and the likelihood of developing liver damage have been published (Smilstein et al. 1991). The sample analysed should ideally not be taken until 4 h after ingestion, since before then the processes of absorption and distribution are incomplete. However, in practice this is not always feasible since the exact time of ingestion may not be known. Measuring a second paracetamol level about 4 h after the first can be useful, especially in cases of staggered overdose, and can give a better indication of prognosis. A half-life of about 4 h indicates a healthy liver and one of about 12 h predicts severe necrosis. Reliable commercial kits are available for paracetamol measurements in serum or plasma, designed for use on routine clinical analysers and based either on immunoassays (Edinbora et al. 1991) or enzymatic reactions (Morris et al. 1990). Numerous GC and HPLC methods have also been published.