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  • Title: Sulphasalazine: a review of 40 years' experience.
    Author: Watkinson G.
    Journal: Drugs; 1986; 32 Suppl 1():1-11. PubMed ID: 2877847.
    Abstract:
    Sulphasalazine, devised by Dr Nana Svartz for the treatment of 'infective polyarthritis', has been used in the treatment of inflammatory bowel disease for more than 40 years. Many controlled trials have shown that sulphasalazine 4g daily will induce remissions in between one-half and three-quarters of patients with acute attacks of ulcerative colitis. When given in a dosage of 2g daily it will prevent relapses in quiescent colitis. Relapses are 5 times more likely in untreated patients. It is less effective in Crohn's disease, where it exerts only a transient benefit in patients with active colonic disease and fails to prevent relapse or recurrence. Sulphasalazine is absorbed from the small intestine, re-excreted in bile and carried to the colon, where its azo bond is split by bacteria to release sulphapyridine, which is absorbed and is responsible for most of the drug's side effects, and 5-aminosalicylic acid, which is the active therapeutic moiety of the drug and exerts a beneficial topical action on the colonic mucosa. Side effects are common but are mainly reversible and not serious. Those related to high concentrations of sulphapyridine and to poor acetylation of the drug include gastrointestinal intolerance, malaise, headache, arthralgia, drug fever, effects on red blood cells and reversible male infertility. More serious, idiosyncratic side effects are skin rashes, leucopenia and agranulocytosis. Rarely, neurotoxicity, hepatotoxicity, polyarteritis, pulmonary fibrosis, a lupus-like syndrome and haemorrhagic colitis are produced. It is possible to desensitise most patients with drug-induced skin rashes. A number of less toxic alternatives to sulphasalazine have been devised and are undergoing trial. They either convey 5-aminosalicylic acid in a coated tablet to the colon or, when conjugated to a non-toxic carrier, release 5-aminosalicylic acid by bacterial cleavage there. Sulphasalazine remains a most useful drug in the treatment of inflammatory bowel disease after 40 years of use.
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