Clinical Implication of COX-2 Inhibitors in the Treatment of Arthitis

Abstract

It is now recognized that the prostaglandin synthesis in humans is caused by the 2

cyclooxygenase (COX) enzymes, COX-1 and COX-2. The COX-1 enzyme is expressed constitutively, and is responsible for homeostasis of the body eg, vascular dilatation, mucous production in the stomach, platelet aggregation and the control of renal blood flow. The COX-2 enzyme, which is present in leukocytes, vascular smooth muscles and synoviocytes, is induced by a variety of stimulators including cytokines, endotoxins and mitogens. The prostaglandins produced by the COX-2 enzyme are responsible for inflammatory reaction. Inhibition of the COX-1 enzyme is responsible for adverse reactions, particularly in the gastrointestinal system (dyspepsia, ulcers and bleeding), while inhibition of the COX-2 enzyme will decrease inflammation. Traditional nonsteroidal antiinflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2 enzymes. The recent development of new drugs (both preferential COX-2 and specific COX-2 inhibitors), which have more selectivity to the COX-2 enzyme, possesses the same potency in decreasing pain and inflammation as non-specific COX inhibitors, but with a significant reduction in adverse GI reactions. These new classes of drugs might change the role of treatment for arthritis in the future.