The therapeutic strategy for peptic ulcer disease.

Therapy of acid/peptic disease has evolved since the 1970s with development of: (i) more accurate endoscopes which permit precise examination and documentation of upper gastrointestinal lesions; and (ii) the histamine H2-receptor antagonists. As well, refined standards for clinical investigation have contributed to the clinical study of acid/peptide diseases. Initially, ulcer diseases were considered to be principally secondary to increased 'aggressive' factors (acid, pepsin) and the therapeutic focus was directed at antacids, the progressive evolution of additional histamine H2-receptor antagonists and recently the H+/K(+)-ATPase inhibitors. Later studies indicated efficacy of sucralfate, low dose antacids and prostaglandin analogues, drugs with either no or only modest antisecretory effect. This led to studies on the role of gastroduodenal mucosal defensive factors (mucus and bicarbonate secretion, blood flow, leucocyte adherence, cytokines, reactive oxygen radicals). The prominent role played by aspirin and other non-steroidal anti-inflammatory drugs (NSAID) in initiating and causing recurrence of peptic ulcer disease has been increasingly realized. Recognition of those most at risk for NSAID-induced complication has led to newer approaches to treatment and prevention. Since 1983, Helicobacter pylori has been incriminated as a major factor in the pathogenesis of ulcer disease, particularly ulcer recurrences. Treatment of such ulcers now includes antibiotics and bismuth compounds in order to eradicate H. pylori. This therapeutic regimen is in a state of flux ('triple therapy' vs a H+/K(+)-ATPase inhibitor plus antibiotic) as is the question of how to work up and treat patients initially presenting with ulcer symptoms.