Refractory peptic ulcers

Ulcers that do not heal after 8 weeks of treatment with standard-dose regimens of antiulcer drugs are considered refractory. Incidences of duodenal and gastric ulcers refractory to H2-receptor antagonists are 9% and 20%, respectively. When treated with a single daily dose of omeprazole 20 mg, duodenal ulcers have a refractory incidence of 3% and gastric ulcers, 11%. Omeprazole's benefit may result from its potent gastric antisecretory action. Acid hypersecretion is an important pathophysiologic factor associated with refractoriness to H2 antagonists. Some patients with refractory ulcer, however, have a normal pharmacologic response of decreasing intragastric acidity following administration of H2 antagonists. Two possible mechanisms may explain refractoriness in such cases: the relative preservation of daytime acidity, which is the usual pharmacologic response to standard doses of H2 antagonists, and excessive impairment of mucosal defense. The first possibility is consistent with the results that increased doses of H2 antagonists or more potent antisecretory drugs such as omeprazole do heal a subgroup of ulcers refractory to H2 antagonists. The second possibility is supported by reports that drugs that mainly enhance mucosal defense, such as misoprostol, sucralfate, and bismuth compounds, also effectively heal refractory ulcers, and that gastrointestinal prostaglandin levels are extremely low in the mucosa of such patients. Other reasons for refractoriness to omeprazole treatment include gastric hyperacidity and impaired gastric emptying that may disturb drug absorption. Infection with Helicobacter pylori might, to some extent, be involved in refractoriness to potent antisecretory drugs. Single daily doses of omeprazole 40 mg seem superior to omeprazole 20 mg or increased doses of H2 antagonists for maintenance therapy of H2 antagonist-refractory ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)