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The Pathophysiological and Pharmacological Basis of Peptic Ulcer Therapy

University of Connecticut Health Center, Farmington, Connecticut 06032

Both genetic and nongenetic factors predispose to ulcer diathesis. At the mucosal level ulcers result from an imbalance between aggressive factors and mucosal defense. Ulcer therapy reduces aggressive forces, bolsters defense, or both. Gastric acid, the major aggressive factor, may have its secretion inhibited or it may be partially neutralized by antacids. H2 receptor antagonists competitively block histamine occupancy of H2 receptors on parietal cells, thereby preventing stimulation of adenylate cyclase, cAMP rises, and activation of protein kinase and H⁺/K⁺ATPase. Prostaglandins inhibit acid secretion largely by preventing histamine-induced cAMP rises. Proton pump inhibitors bind H⁺/K⁺ATPase. Antimuscarinics inhibit acetylcholine receptors on the parietal cell, thereby blocking Ca²⁺ entry and subsequent activation of protein kinase and the proton pump. Mucosal defense is enhanced by certain prostaglandins, colloidal bismuth subcitrate and sucralfate. Prostaglandins stimulate secretion of bicarbonate and mucus, among other effects. Colloidal bismuth and sucralfate bind to proteins in the ulcer base and stimulate bicarbonate and mucus secretion, partially, in the case of sucralfate, by increasing endogenous prostanoid synthesis. Sucralfate also binds pepsin and bile acids. Colloidal bismuth temporarily eradicates mucosal colonization by Campylobacter pylori, another putative agent in ulcer diathesis.

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Toxicologic Pathology, Vol. 16, No. 2, 260-266 (1988)
DOI: 10.1177/019262338801600219


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Freston, J. W. Search for Related Content PubMed PubMed Citation Articles by Freston, J. W. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Peptic Ulcer Social Bookmarking                         What's this?