Pharmacology and clinical action of COX-2 selective NSAIDs.

Abstract

The non-steroidal anti-inflammatory analgesics (NSAIDs) are a heterogeneous group of compounds with analgesic, anti-inflammatory and antipyretic properties. Since the experimental observations of Horton in 19631 and the subsequent work of Vane2, Smith and Willis3 and Ferreira4 it has been recognised that the principle mechanism by which the NSAIDs produce their pharmacological effects is inhibition of the enzyme cyclooxygenase. Cyclooxygenase (COX), also known as prostaglandin H2 synthase, catalyses the first two steps in the synthesis of prostaglandins, thromboxane and prostacyclin (collectively known as prostanoids), from arachidonic acid (Figure 1). Prostaglandins are involved in many homeostatic processes and are important mediators of inflammation. COX is a bifunctional enzyme which catalyses both the oxidation of arachidonic acid to the cyclic endoperoxide PGG2 and the peroxidative reduction of PGG2 to PGH2. PGH2 is then converted to a variety of prostaglandins and other compounds by cellular synthetases. Inhibition of cyclooxygenase can explain all of the pharmacological and most of the adverse effects of NSAIDs. The arachidonic cascade. The sites where NSAIDs inhibit COX-1 and COX-2 are shown. KeywordsArachidonic AcidFamilial Adenomatous PolyposisGastric Mucosal LesionSpinal Fusion SurgeryConventional NSAIDThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.