Education And Debate

Controversies in management: Should methionine be added to every paracetamol tablet?

BMJ 1997; 315 doi: (Published 02 August 1997) Cite this as: BMJ 1997;315:303

Yes: but perhaps only in developing countries

  1. Edward P Krenzelok (, directora
  1. a Pittsburgh Poison Center, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA
  1. Correspondence to


    The paracetamol era began in 1886 when it was recognised that acetanilide had analgesic and antipyretic properties.1 What went unrecognised for years was that acetanilide's therapeutic properties were secondary to paracetamol. The toxicity of acetanilide's other metabolite, aniline, was unacceptable, and various derivatives were synthesised to find a suitable alternative with analgesic and antipyretic properties. Phenacetin was soon recognised as a viable alternative, and paracetamol was first used for medicinal purposes in 1893.1 However, it did not become popular until 1949.1 In 1995 paracetamol sales in the United States were roughly $965m (personal communication, IMS America, Plymouth Meeting, PA 19462-1048).

    Poison or remedy?

    To paraphrase the Swiss philosopher and physician Paracelsus: only the dose differentiates a poison from a remedy. Paracetamol is not an exception to this rule. At therapeutic doses paracetamol is relatively benign, but when it is ingested in excessive amounts endogenous hepatic glutathione is depleted and the toxic metabolite of paracetamol (N-acetyl- p-benzoquinoneimine) binds covalently with hepatocytes causing cellular death and hepatic necrosis.2 In 1991-5 paracetamol exposure was the most common incident reported to American …

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