Pharmacological approach to the prevention of non-steroidal anti-inflammatory drug-induced gastropathy

Non-steroidal anti-inflammatory drugs can provoke gastric damage by multipl e interactive mechanisms These processes include topical irritant actions t hat disrupt the epithelial barrier which allows the back-diffusion of acid into the mucosa. The inhibition of the cyclo-oxygenase isoform, cyclo-oxyge nase-1 also promotes gastric injury, such effects involving the microcircul ation. These mechanisms of mucosal damage synergistically interact to cause more extensive injury, which can be attenuated by antisecretory agents or by mucosal protective agents such as the synthetic prostanoid, misoprostil. in addition, agents that release nitric oxide may prevent such mucosal dam age. However the development of the novel anti-inflammatory drugs, the cycl o-oxygenase-2 selective agents, that inhibit the formation of prostanoids a t inflammatory sites, but not the endogenous protective prostanoids in the stomach formed by cyclo-oxygenase-1, has provided a highly effective therap eutic approach to minimising of gastric damage.