Aminosalicylic acid gastrointestinal effects

Sulfasalazine has been used for the management of RA and ankylosing spondylitis with apparently similar effectiveness as penicillamine and with less toxicity. While 5-aminosalicylic acid is the active agent in inflammatory bowel disease, it is believed that sulfapyridine is mostly responsible for the antirheumatoid effects. Gastrointestinal complaints, dizziness and photosensitivity are the most frequently observed adverse events. With levamisole and also with sulfasalazine and olsalazine a delay of 2-3 months is to be expected before positive responses will be observed. 

Sulfasalazine is metabolized to sulfapyridine and 5-aminosalicylic acid, and it is thought that the sulfapyridine is probably the active moiety when treating rheumatoid arthritis (unlike inflammatory bowel disease see Chapter 63 Drugs Used in the Treatment of Gastrointestinal Diseases). Some authorities believe that the parent compound, sulfasalazine, also has an effect. In treated arthritis patients, IgA and IgM rheumatoid factor production are decreased. Suppression of T cell responses to concanavalin and inhibition of in vitro B cell proliferation have also been documented. It is not clear how these findings relate to the clinical efficacy of sulfasalazine in rheumatoid arthritis. 

Sulfasalazine, a prodrug, is cleaved by bacteria in the colon into sulfapyridine and 5-aminosalicylic acid. It is believed that the sul-fapyridine moiety is responsible for the agent s antirheumatic properties, although the exact mechanism of action is not known. Once the colonic bacteria have cleaved sulfasalazine, sulfapyridine and 5-aminosalicylic acid are absorbed rapidly from the gastrointestinal tract. Sulfapyridine distributes rapidly throughout the body, but higher concentrations are found in certain tissues such as serous fluid, liver, and intestines. Both sulfasalazine and its metabolites are excreted in the urine. Antirheumatic effects should be seen within 2 months. 

The idiopathic inflammatory bowel disease includes ulcerative colitis and granulomatous disease of the gastrointestinal tract (Crohn s disease). The newer derivatives of 5-aminosalicylic acid, namely balsalazine, sulfasalazine, or olsalazine, may be effective for treating ulcerative colitis but not Crohn s disease. 

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