Why proton pump inhibition should heal and protect against nonsteroidal anti-inflammatory drug ulcers.
Several lines of evidence provide support for the potential of gastric acid-inhibitory therapy in the management of nonsteroidal anti-inflammatory drug (NSAID)-associated gastroduodenal injury. Studies on the rat stomach have shown that the acute mucosal injury produced by both aspirin and indomethacin can be prevented by elevation of the pH of the gastric contents of >4.0. The pH-dependent pattern of mucosal injury is best explained by the very low activity of gastric pepsin above pH 4.0. This view is supported by studies of experimental esophagitis, which indicate that the pH-activity curve of gastric pepsin approximates the aggressiveness of acid-pepsin mixtures to the esophageal mucosa. Healthy human volunteer studies have shown that elevation of intragastric pH with omeprazole greatly reduces, or abolishes, aspirin-associated gastric microbleeding. A small amount of clinical data also support the view that elevation of gastric pH with acid-inhibitory therapy is a promising option for both the treatment of established NSAID-associated chronic peptic ulcer, even during continued NSAID use, and for prophylaxis against the develop of chronic gastric and duodenal ulcers during NSAID therapy. These data indicate consistently that the benefits from gastric acid-inhibitory therapy are proportional to the degree of elevation of gastric pH by therapy. This dose-response relationship suggests that proton pump inhibition has the potential to achieve superior results in patients who have, or who are at risk of, NSAID-associated peptic ulcer, when compared with agents that inhibit gastric acid secretion to lower levels than seen with proton pump inhibition.
Dent
J
J
Department of Gastrointestinal Medicine, Royal Adelaide Hospital, North Terrace, Australia.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D006801:Humans; D010437:Peptic Ulcer / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D054328:Proton Pump Inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054328:Proton Pump Inhibitors