Prostaglandins: mucosal protection and peptic ulceration

Endogenous and exogenous prostaglandins mobilize gastroduodenal mucosal defenses which are compromised by inhibition of prostaglandin synthesis with non-steroidal anti-inflammatory drugs (NSAIDS). There is some evidence, conversely, that stimulation of endogenous prostaglandin synthesis by increasing precursor availability by dietary enrichment or by provoking its release may increase mucosal integrity. However, there are also non-prostaglandin defense mechanisms which can be elicited even when prostaglandin synthesis is profoundly depressed. Most (but not all) evidence suggests that gastric ulcer patients have deficient prostaglandin synthesis, though it is not clear whether this is a primary or secondary defect and the evidence on duodenal ulcer patients is incoherent. Prostaglandin analogues heal both gastric ulcers and duodenal ulcers, mainly as a result of acid inhibition. There is suggestive, but not conclusive, evidence that subsequent relapse may be retarded. Misoprostol has obtained a licensed indication for the prevention of NSAID-induced peptic ulcer on the basis of studies showing a reduced development of peptic ulcers and erosions over 4-8 weeks, implying that deficient endogenous prostaglandin levels can be replaced by exogenous administration.