课件：溃疡性结肠炎的诊断及治疗本院进修讲课描述.pptVIP

THANK YOU SUCCESS * * 可编辑 * 170. AMINOSALICYLATES The development of newer aminosalicylates is based upon efforts to deliver active 5-ASA to the lower GI tract while avoiding the toxicity of sulfapyridine, which is present in sulfasalazine. Suspensions and suppositories of 5-ASA are instilled directly into the rectum (right side of the slide). Oral preparations (left side of the slide) include (1) enteric coated and ethylcellulose encapsulated forms of 5-ASA (mesalamine), or (2) 5-ASA linked by a di-azo bond to a non-toxic polymer (balsalazide), or (3) a dimer of 5-ASA (olsalazine) that is split by intestinal bacterial azo-reductases into two molecules of 5-ASA with no toxic or inert moiety remaining. * 169. SULFASALAZINE METABOLISM Once sulfasalazine is ingested, about 30% of the intact molecule is absorbed from the upper GI tract either to be carried in the entero-hepatic circulation or to be excreted by the kidneys. Almost 90% of the intact sulfasalazine molecule ultimately passes down to the lower GI tract, where intestinal bacterial enzymes cleave the azo bond, thus releasing sulfapyridine and 5-ASA. Most of the sulfapyridine is absorbed, metabolized by the liver, and excreted in the urine. It is the circulating sulfapyridine that is responsible for the principle clinical toxicity, especially in patients who are slow acetylators. Meanwhile, the 5-ASA stays primarily in the bowel lumen, where it is thought to exert its therapeutic effects locally prior to elimination in the feces. ? Schroder H, Campbell DES. Absorption, metabolism, and excretion of the salicylazosulfapyridine in man. Clin Pharmacol Ther 1972;13:539-51. ? Peppercorn MA, Goldman P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther 1972;181:555-62. * 171. AMINOSALICYLATE DISTRIBUTION Mesalamine, the generic name for free 5-aminosalicylate acid (5-ASA), is available in the United States in two oral forms. One form is enteric-coated wi