Pathogenesis and therapy of peptic ulcer disease

The epithelial cells of the stomach and duodenum are normally protected from the damaging effects of acid and pepsin by a balancing mechanism of mucosal resistance. If an imbalance occurs, peptic ulcer may result. Traditional teaching has emphasized the importance of acid (and pepsin) as the cause of this imbalance; however, it is clear that acid and pepsin are not the only important factors in the pathogenesis of peptic ulcer. More recent investigative efforts have been directed at what constitutes mucosal resistance and how it can be disrupted to product, in the presence of gastric acid, a peptic ulcer. Depletion of endogenous prostaglandins and Helicobacter pylori gastritis have emerged as prominent theories. As evidence exists both to support and refute these theories in humans, any definitive conclusions cannot be made at this time. The acute management of peptic ulcer disease is directed at relieving pain, accelerating ulcer healing, and preventing complications. Peptic ulcers can be healed with antisecretory agents (i.e., H₂-receptor antagonists, omeprazole), antacids, prostaglandins, and sucralfate. Because they are effective, safe, and convenient, the H₂-receptor antagonists are the most widely used agents for the management of peptic ulcer disease. Because the H₂-receptor antagonist agents are equally effective in their indicated uses and are equally safe based on scientifically valid data, selection should be based primarily on cost. Omeprazole is the newest antisecretory agent: a single morning dose of 20 mg suppresses acid secretion for 24 h. The agent offers little advantage over H₂-receptor antagonists for the majority of patients with peptic ulcer. Rather, its major role will probably be in patients with hypersecretory states, refractory peptic ulcer, and gastroesophageal reflux disease. Antacids are effective in ulcer healing; however, in high doses, they are costly, often unpalatable, and cause diarrhea. Low-dose antacids may work as well without the side effects, although studies are not available from the United States. Sucralfate offers effective acute therapy for duodenal ulcer but has not been approved for gastric ulcer or maintenance therapy. Prostaglandins must be given in acid-reducing doses to heal ulcers, and studies to date are unimpressive. Misoprostol is approved for prevention of NSAID-induced gastric ulcers, but who should receive the drug is poorly defined. Bismuth subcitrate (not available in the United States) promotes both duodenal and gastric ulcer healing, and may result in prolonged remission. Although an effect on H. pylori has been suggested as the explanation for long remission, this remains to be proven conclusively.