Paracetamol methionine

Paracetamol-induced hepatotoxicity can be prevented in animals with SOD, catalase and allopurinol (Kyle et al., 1987 Jaeschke, 1990 Tirmenstein and Nelson, 1990), and by N-acetyl-L-cysteine or methionine in humans (Meredith et al., 1986 Nelson, 1990). The protective efiect of allopurinol in mice only occurred at high concentrations, suggesting that its effect was related to scavenging of ROMs rather than inhibition of their production by XO (Jaeschke, 1990). 

Although the investigation of the mechanism underlying paracetamol hepatotoxicity has been of intrinsic toxicological interest, there has also been a particularly significant benefit that has arisen from this work. This is the development of an antidote that is now successfully used for the treatment of paracetamol overdose. The antidote now most commonly used is N-acetylcysteine, although methionine is also used in some cases, as it can be given orally. There are various mechanisms by which N-a cetyl cysteine may act ... 

Side-effects are rare and may include hematological reactions, leucopenia, agranulocytosis and other hypersensitivity reactions. Paracetamol has a narrow therapeutic dose range and overdosage induces severe liver and renal damage (Lewis and Paloucek, 1991) via accumulation of a toxic metabolite, N- acetyl-benzoquinoneimine (NABQI). Acetylcysteine or methionine, which increase glutathione conjugation of the metabolite, are used as the antidote. 

Supportive treatment is essential, and stomach wash and multiple doses of charcoal may be used. Acetylcysteine or methionine can be given to prevent absorption of charcoal. Antidote treatment must be started after suspected paracetamol ingestion and continued depending on blood levels of paracetamol. Appropriate care must be taken in patients receiving enzyme-inducing drugs.79,80... 

Jones AL, Hayes PC, Proudfoot AT, Vale JA, Prescott LF. Should methionine be added to every paracetamol tablet (No the risks are not well enough known). BMJ 1997 315(7103) 301-3. 

Methionine is included in some proprietary paracetamol products (Pameton Smith Kline Beecham), since it counteracts some serious side-effects that are encountered with paracetamol overdosing through helping to restore glutathione levels that are the body s natural defence against products of oxidised paracetamol. However, the recommended antidote (bearing in mind the toxicity of methionine) is intravenous /V-acetyl-L-cysteine, which, in any case, reaches the liver of the overdosed patient faster. 

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