Inflammatory bowel disease olsalazine

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. 

Drugs that contain 5-aminosalicylic acid (5-ASA) have been used successfully for decades in the treatment of inflammatory bowel diseases (Figure 62-8). 5-ASA differs from salicylic acid only by the addition of an amino group at the 5 (meta) position. Aminosalicylates are believed to work topically (not systemically) in areas of diseased gastrointestinal mucosa. Up to 80% of unformulated, aqueous 5-ASA is absorbed from the small intestine and does not reach the distal small bowel or colon in appreciable quantities. To overcome the rapid absorption of 5-ASA from the proximal small intestine, a number of formulations have been designed to deliver 5-ASA to various distal segments of the small bowel or the colon. These include sulfasalazine, olsalazine, balsalazide, and various forms of mesalamine. 

Apart from classic analgesic nephropathy, this chapter will also handle the possible nephrotoxic role of 5-aminosalicylic acid (5-ASA) used in patients with chronic inflammatory bowel disease (IBD). During the last decade, 5-ASA replaced sulfasalazine as first-line therapy for mildly to moderately active IBD. For decades, sulphasalazine, an azo-compound derived from sulphapyridine and 5-aminosalicylic acid (5-ASA), has been the only valuable non-corticosteroid drug in the treatment of inflammatory bowel disease. Azad Kahn et al. [25] showed that the pharmacologically active moiety in sulphasalazine for the treatment of these diseases was 5-ASA. Consequently, this resulted in a number of new 5-ASA formulations (mesalazine, olsalazine, balsalazine) for topical and oral use. Since the metabolite sulphapyridine was largely responsible for the side effects of sulfasalazine, the primary advantage of the newer 5-ASA agents is their improved adverse effect profile. 

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. 

Bisrnudi subsalicylate is used in combination widi odier dru to treat gastric and duodenal ulcers caused by H. pylori bacteria Mesalamine is used in the treatment of chronic inflammatory bowel disease Misoprostol is used to prevent gastric ulcers in those taking aspirin or nonsteroidal anti-inflammatory dru in high doses for a prolonged time Olsalazine is used in the treatment of ulcerative colitis in those allergic to sulfasalazine. Sulfasalazine is used in the treatment of Crohn s disease and ulcerative colitis. Sucralfate is used in the treatment of duodenal ulcer. 

Figure 7.38 An entire subclass of NSAID prodrugs has been designed for treating chronic inflammatory bowel disease. These possess a central azo group and are not substantially metabolized until they reach the intestines. There bacteria, which are rich in nitroreductase enzymes, metabolize the azo bond, breaking it to form 5-aminosalicylicacid which is the active drug that combats the inflammation. An example is the symmetrical compound olsalazine which releases two molecules of the active amine on metabolic reduction.

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