Olsalazine ulcerative colitis

Bismudi subsalicylate is used in combination witii otiier dru > to treat gastric and duodenal ulcers caused by H. pylori bacteria Mesalamine is used in the treatment of chronic inflammatoiy bowel disease Misoprostol is used to prevent gastric ulcers in those taking aspirin or nonsteroidal anti-inflammatory dragp 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. 

Olanzapine (Zyprexa) Antipsychotic Olopatadine (Patanol) Antihistamine Olsalazine (Dipentum) Ulcerative colitis Omeprazole (Prilosec) Proton pump inhibitor... 

Pharmacology Olsalazine sodium is a sodium salt of a salicylate compound that is effectively bioconverted to 5-aminosalicylic acid (mesalamine 5-ASA), which has anti-inflammatory activity in ulcerative colitis. Approximately 98% to 99% of an oral dose will reach the colon, where each molecule is rapidly converted into 2 molecules of 5-ASA by colonic bacteria. The liberated 5-ASA is absorbed slowly, resulting in very high local concentrations in the colon. 

Olsalazine sodium (Dipentum) links two 5-ASA molecules with an azo linkage. Following cleavage of the azo linkage in the colon, two 5-ASA molecules are released. Olsalazine is approved for maintenance of remission of ulcerative colitis, but a commonly reported side effect is a paradoxical increase in diarrhea. The U. S. Food and Drug Administration (FDA) has approved balsalazide disodium (Colazal) as a treatment of mild to moderately active ulcerative colitis. Balsalazide... 

In a 12-week trial in 168 patients with mild to moderate ulcerative colitis, olsalazine 3 g/day was as effective as mesalazine 3 g/day in inducing a remission (5). There were more adverse effects in patients taking olsalazine (41 of 88) than mesalazine (29 of 80). Most of the adverse effects related to bowel disturbances diarrhea, vomiting, abdominal discomfort, heartburn, flatulence, and nausea. Diarrhea was more common in patients taking olsalazine. One patient taking mesalazine developed a lupus-like syndrome. 

Nephrotoxicity has been described during treatment with olsalazine (SEDA-21, 364). To assess the effects of 9 months of treatment with oral mesalazine 1.2 g/day and olsalazine 1 g/day on renal function, a randomized trial has been performed in 40 patients with ulcerative colitis in complete remission (91). Neither drug had a significant effect on glomerular filtration rate. Adverse effects (all mild to moderate) were more common in the mesalazine group they included abdominal pain and distension, dyspepsia, nausea, and diarrhea. 

Kruis W, Brandes JW, Schreiber S, Theuer D, Krakamp B, Schutz E, Otto P, Lorenz-Mayer H, Ewe K, Judmaier G. Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis. Aliment Pharmacol Ther 1998 12(8) 707-15. 

Stoa-Birketvedt G, Florholmen J. The systemic load and efficient delivery of active 5-aminosalicylic acid in patients with ulcerative colitis on treatment with olsalazine or mesalazine. Aliment Pharmacol Ther 1999 13(3) 357-61. 

Meyers S, Sachar DB, Present DH, Janowitz HD. Olsalazine sodium in the treatment of ulcerative colitis among patients intolerant of sulfasalazine. A prospective, randomized, placebo-controlled, double-blind, doseranging clinical trial. Gastroenterology 1987 93(6) 1255-62. 

Birketvedt GS, Berg BCJ, Fausa O, Florhohnen J. Glomerular and tubular renal functions after long-term medication of sulphasalazine, olsalazine, and mesalazine in patients with ulcerative colitis. Inflamm Bowel Dis 2000 6(4) 275-9. 

Chemical modification is also used to a limited extent to facilitate a dnig reaching its desired target (sec Chapter 3). An example is olsalazine. used in the treatment of ulcerative colitis. This drag is a dimer of (he pharmacologically active mesalamine (3-aminosalicylic acid). The latter is not effective orally because it is metabolized to inactive forms... 

Nilsson, A. et al. (1995) Olsalazine versus sulfasalazine for relapse prevention in ulcerative colitis A multicenter study. Am. / Gastroenterol., 90.381 387. Primatesta, P. et al. (1995) Crohn s disease and ulcerative colitis in Ei land and the Oxford Record Linkage Study area A prt ile of hospital morbidity. Int. 

Azo Prodrugs Amines have been incorporated into an azo linkage to form prodrugs that can be activated through azo reduction. In fact, sulfa dmgs were discovered because of prontosil (93), an inactive azo dye that was converted in vivo to the active sulfanilamide (95) (Scheme 15). Clinically useful balsalazide (23), olsalazine (25), and sulfasalazine (26) are azo prodrugs of mesalazine (27). They are converted in vivo by bacterial azo reductases in the gut to the active 5-aminosalicylic acid (5-ASA or mesalazine, 27), which is responsible for their anti-inflammatory activity in the treatment of ulcerative colitis, as discussed earlier. 

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. 

Olsalazine (Dipentum) Pro-drug is metabolized to 5-aminosalicylic acid (aspirin). It is retained in the colon, making it effective against ulcerative colitis. Also see sulfasalizine (Table 7.6). 

Haematologic A 63-year-old woman was diagnosed with ulcerative colitis and started on oral treatment with olsalazine (1.5 g daily). After 8 weeks, her platelet count decreased, and the olsalazine dose was adjusted down to 0.75 g/daily. One month later, the patient developed malaise, nausea, diarrhoea and petechiae on her legs and chest. Laboratory tests displayed severe thrombocytopenia. Olsalazine was discontinued, and about 2 weeks later her platelet count improved and thrombocytopenia-related symptoms subsided. Subsequently, the patient was re-challenged with olsalazine (0.75 mg/daily). Within 1 month, her platelet count decreased dramatically. Upon olsalazine discontinuation, her platelet count improved again [91 ]. 

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