The pathophysiological and pharmacological basis of peptic ulcer therapy.
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.
D000863:Antacids / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology; D010276:Parasympatholytics / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D011453:Prostaglandins / Q000627:therapeutic use
D000863:Antacids; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010276:Parasympatholytics; D011453:Prostaglandins