The evolution of arthritis antiinflammatory care: where are we today?

Abstract

Nonsteroidal antiinflammatory drugs (NSAID) are among the most commonly used drugs. Due to age-related changes in the gastrointestinal (GI) mucosa, the elderly are at increased risk of NSAID-induced gastropathy. Known risk factors include age > 60 years, concomitant glucocorticoid therapy, history of peptic ulcer disease or GI bleeding, and presence of significant comorbid conditions. Combinations of these risk factors substantially increase the likelihood of the development of a serious GI event in patients taking NSAID. The pathogenesis of NSAID-induced GI mucosal injury involves depletion of prostaglandins. Prostaglandin analog misoprostol is effective in preventing NSAID-induced gastric and duodenal ulcers and serious ulcer complications. The single tablet formulation of diclofenac and misoprostol is for patients at high risk of developing GI toxicity. This agent has been shown to provide antiinflammatory and analgesic activity equivalent to that of diclofenac, but with a significantly reduced incidence of GI ulceration compared with traditional NSAID. The finding that there are two isoforms of the enzyme prostaglandin synthase or cyclooxygenase (COX) has led to the search for compounds that inhibit only the isoform associated with the development of inflammation (COX-2), while sparing the isoform involved in normal physiologic processes. All NSAID inhibit both isoforms. Compounds specific for COX-2 promise to provide potent antiinflammatory and analgesic effects without the toxicity of NSAID, as well as having potential applications in other medical conditions.