IMPROVING THE GASTROINTESTINAL SAFETY OF NSAIDS - THE DEVELOPMENT OF MISOPROSTOL - FROM HYPOTHESIS TO CLINICAL-PRACTICE

Arthritis is a major source of disability for the American population. It results in significant morbidity for the millions of patients affe cted and costs billions of dollars yearly for diagnosis and management . Nonsteroidal antiinflammatory drugs (NSATDs) are the principal thera py for the majority of arthritis patients. It has been estimated that more than 15 million people with arthritis take these drugs daily. Thi s use is predicted to increase greatly not only as a result of an agin g population, with the consequent increase in the prevalence of arthri tis, but also because NSAIDs may prove to have a role in decreasing co lonic neoplasia and in reducing the likelihood of conditions such as A lzheimer's disease. It is therefore increasingly important to understa nd the nature of the side effects associated with these agents as well as ways of decreasing or preventing their occurrence. NSAIDs inhibit the enzymes cyclooxygenase-l and cyclooxygenase-2. This reduces the sy nthesis of prostaglandins and therefore decreases joint inflammation, but it may also lead to the development Of gastric and duodenal ulcers . For this reason, exogenous prostaglandins have been studied for thei r potential role in preventing NSATD-associated ulcers and ulcer compl ications. This paper reviews the development of the prostaglandin E-1 analog misoprostol, the theory behind its use as a mucosal protective agent, and the results of studies in animals as well as in normal volu nteers and patients with arthritis. Ultimately, a study was performed to evaluate whether misoprostol reduces the incidence of serious ulcer complications in patients taking NSAIDs. It is an interesting story, which promises to be of increasing importance as NSAID use expands to new indications while concern remains about their associated complicat ions, especially those related to the gastrointestinal tract.