Gastric Acid-Dependent Diseases: A Twentieth-Century Revolution

Excerpt

Until recently, peptic ulcer disease (PUD) has been a major scourge to humanity, associated with high incidence of morbidity and mortality, the latter due primarily to foregut perforation or hemorrhage. Advancements in the understanding of the pathophysiology and treatment of PUD have included the discovery of gastric HCl secretion by Prout [1], and the realization that PUD only occurred in the presence of gastric acid [2], leading to the pronouncement “no acid, no ulcer.” Apart from a strict bland diet [3], only surgery, ranging from partial or total gastrectomy to vagotomy and to selective or highly selective vagotomy successfully reduced gastric acid secretion [4, 5]. In the last quarter of the twentieth century, three major advances took place, completely altering the treatment of gastric acid-related diseases: (1) the development of histamine₂ receptor antagonists (H₂RA) as a result of rational drug design; (2) the development of proton pump inhibitors (PPIs), in part serendipitous but also followed by rational drug design; and (3) recognition that infection by Helicobacter pylori (Hp) is a major causative factor in peptic ulcer disease and even of gastric cancer [6, 7]. In the last two decades, PUD has been replaced by gastro-esophageal reflux disease (GERD) as the major reason for physician consultation due to foregut-related symptoms. …