Significant upper gastrointestinal events associated with conventional NSAID versus celecoxib

Despite their substantial clinical benefits in the management of rheumatoid arthritis, osteoarthritis, pain, and other musculoskeletal complaints, con ventional nonsteroidal antiinflammatory drugs (NSAID) are associated with s ignificant toxicities that can frequently limit their use. The most common and noteworthy adverse effects of NSAID are gastrointestinal (GI), and rang e from dyspeptic symptoms to ulcers and serious ulcer complications. The up per GI toxicities associated with the use of conventional NSAID led to the search for medications that were as clinically effective as these agents, b ut with a significantly improved GI safety profile. It is now known that th e constitutively expressed isoenzyme cyclooxygenase (COX)-1 catalyzes the s ynthesis of prostanoids that help to regulate normal physiologic processes, including GI mucosa protection, whereas the inducible isoenzyme COX-2 lead s to the generation of prostaglandins that mediate inflammation, pain, and fever. This knowledge has led to the development of new compounds that, at therapeutic concentrations, inhibit COX-2 without affecting COX-1. The firs t COX-2 targeted agent approved by the US Food and Drug Administration (FDA ) was celecoxib. This article reviews the risks of GI complications associa ted with conventional NSAID use and compares these risks with that of the n ew COX-2 specific inhibitor celecoxib.