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)