Cytoprotection of gastroduodenal mucous membrane with analogues of prostaglandins

Abstract

Analogues of E-type prostaglandins, such as arbaprostil, enprostil, misoprostol, rioprostil, and trimoprostil, suppress gastric acid secretion and (like native E-type prostaglandins) the chemically modified analogues enhance a number of gastroduodenal mucosal defence factors. These include regulation of the thickness and the composition of the mucous layer at the epithelial surface; modulation of active bicarbonate secretion; hydrophobicity of the surface epithelium; rapid cell proliferation and differentiation after mucosal damage; maintenance of interstitial bicarbonate; and the integrity of the mucosal microcirculation. In theory, this bimodal action makes prostaglandin analogues ideal drugs for treating and preventing lesions of the gastroduodenal mucous membrane. In practice, however, these expectations remain unfulfilled. First, in doses lower than those required to decrease acid secretion, prostaglandin analogues retain cytoprotective properties but are no better than placebo in healing peptic ulcers. Second, in fully antisecretory doses some prostaglandin analogues accelerate ulcer healing compared with placebo and provide healing rates about as high cimetidine, but less than achieved with ranitidine. Third, despite the fact that high doses of some analogues are superior to placebo in alleviating pain associated with ulcer disease, these agents proved inferior to cimetidine and ranitidine in relieving pain in most comparative trials. Fourth, enprostil and misoprostol in doses which combine antisecretory with cytoprotective properties perform significantly poorer than ranitidine in preventing relapse of peptic ulcer disease. Fifth, although several uncontrolled observations have suggested a therapeutic benefit of prostaglandin analogues in gastroduodenal haemorrhage, placebo-controlled trials show no effect of arbaprostil in stopping bleeding and in preventing rebleeding.(ABSTRACT TRUNCATED AT 250 WORDS)