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, conventional nonsteroidal antiinflammatory drugs (NSAID) are associated with significant toxicities that can frequently limit their use. The most common and noteworthy adverse effects of NSAID are gastrointestinal (GI), and range from dyspeptic symptoms to ulcers and serious ulcer complications. The upper GI toxicities associated with the use of conventional NSAID led to the search for medications that were as clinically effective as these agents, but with a significantly improved GI safety profile. It is now known that the constitutively expressed isoenzyme cyclooxygenase (COX)-1 catalyzes the synthesis of prostanoids that help to regulate normal physiologic processes, including GI mucosa protection, whereas the inducible isoenzyme COX-2 leads 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 first COX-2 targeted agent approved by the US Food and Drug Administration (FDA) was celecoxib. This article reviews the risks of GI complications associated with conventional NSAID use and compares these risks with that of the new COX-2 specific inhibitor celecoxib.