SELECTIVE CYCLOOXYGENASE-2 INHIBITORS

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed drug class in this country. Their use is indicated for a variety of painful musculoskeletal conditions, including osteoarthritis (OA) and rheumatoid arthritis (RA). As a class, NSAIDs possess antipyretic, anti-inflammatory, and antithrombotic qualities; however, currently available NSAIDs increase the risk of peptic ulcer disease and renal insufficiency. Both the therapeutic benefit and potential toxicity of these drugs are, in large measure, because of their shared ability to inhibit the synthesis of prostaglandins (PG) by the cyclooxygenase (COX) enzyme.

There are at least two distinct isoforms of prostaglandin H synthase, or cyclooxygenase: COX-1 and COX-2. COX-1 is constitutively expressed in many tissues, where it regulates physiological functions. COX-2, an inducible form, is not normally expressed by most tissues, but is upregulated at sites of inflammation by some neoplasms and under certain physiologic circumstances. Much basic and clinical research effort has been directed at formulating selective inhibitors of the COX-2 isoform, which could have anti-inflammatory properties without the adverse gastrointestinal and renal side effects associated with current NSAIDs. This article addresses recent advances in the understanding of the role of the cyclooxygenases and the potential therapeutic value of selective inhibitors of COX-2.