Tuesday, December 25, 2012


     Shortly after I posted my blog on aspirin, several readers asked for similar information on Tylenol. Tylenol is the trade name for acetaminophen. Paracetamol is the chemical name throughout Europe. Phenacitin used to be marketed for the same purposes, since it is metabolized to acetaminophen in the body, but several studies suggested that phenacitin was carcinogenic, while paracetamol was not. The abbreviation for paracetamol is APAP.

     APAP is used for pain relief and to reduce fever, and its potency for both purposes is equivalent to aspirin. At high doses (1,000 mg) there is some evidence of an anti-inflammatory effect, but it is never marketed as such. Unlike aspirin, APAP as a fever reducer is safe for children of all ages, provided the dosage limits are observed. Traditionally the dose of APAP  for adults has been 2x325=650 mg or 2x500=1,000mg per dose. The suggested maximum dose used to be 4,000 mg/day. However, one very good article in NEJM showed that cirrhotics could suffer increased liver damage at total doses above 3,600 mg/day, and since APAP toxicity is the leading cause of acute liver failure in the world, the suggested maximum has been lowered to 3,000 mg/day by the FDA. The FDA can only suggest this maximum dose, and is not permitted to mandate it.

     APAP starts to work to relieve pain within 10 minutes of ingestion. It is metabolized by the liver, and its half-life varies between one and four hours. The liver's act of metabolizing it depletes the liver's store of glutathione, and this in turn makes APAP potentially toxic to the liver, an effect which is worsened by the simultaneous ingestion of alcohol. APAP is metabolized  by three different chemical processes in the liver; the one mediated by cytochrome P450 (a name familiar to doctors and pharmacists) produces the toxic metabolite.

     APAP will relieve the pain of osteoarthritis, but unlike aspirin and other NSAIDs does not affect the inflammation of the joint. Although APAP does not attach to platelets and is not a blood thinner or anti-coagulant, sustained daily use may increase the chance of gastric bleeding. The underlying process is poorly understood because we still do not know the full mechanism of action of APAP, although several suggestions have been advanced. One is that its pain-relieving action involves cannabinoid receptors in the brain(!). As a side note, APAP can relieve pain in dogs, but is toxic to cats through the formation of methemoglobin which inhibits the oxygen-carrying ability of the blood.

     And it is a tribute to the power of advertising that so many customers still will pay extra for the brand name Tylenol rather than the generic acetaminophen.



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