Ulcerogenic drugs and antiulcer compounds: effects on gastroduodenal mucosa

Nonsteroidal antiinflammatory drugs (NSAID) and steroids are ulcerogenic to the gastroduodenal mucosa in man although the exact incidence of drug-induced lesions is unknown. It is assumed that NSAID are ulcerogenic because they block the biosynthesis of prostaglandins, thereby reducing the mucosal resistance to acid peptic digestion. NSAID inhibit recognized mucosal defense factors, such as bicarbonate transport and mucus glycoprotein production and release; they reduce the thickness of the pH-mucus barrier, interfere with cytoprotection and have antitrophic actions. Prostaglandins reverse the inhibition of defense factors by NSAID and prevent their ulcerogenic actions; they stimulate secretion of bicarbonate and glycoproteins and have trophic and cytoprotective properties. Challenge of the mucosa stimulates defense factors and prostaglandin formation in parallell; pretreatment with NSAID impairs the defensive response and reduces local prostaglandin formation. Mucosal lesions, produced by NSAID may be prevented by agents that neutralize or inhibit gastric acid, such as H2-receptor blockers, antacids and acid antisecretory prostaglandins. Compounds, which stimulate--or simulate--mucosal defense factors are also effective such as sucralfate, colloidal bismuth and prostaglandins devoid of acid antisecretory properties. Of these, several may work by increasing local prostaglandin concentration.