Rationale for high-dose H2-receptor blockade in the treatment of gastro-oesophageal reflux disease.

Chronic gastro-oesophageal reflux disease is a common clinical problem. The underlying pathophysiology is considered to be acid injury to the oesophageal mucosa secondary to reflux of gastric contents across an incompetent lower oesophageal sphincter. Evidence suggests that gastro-oesophageal reflux disease is primarily a motility disorder, possibly the combined effect of decreased lower oesophageal sphincter pressure, abnormal oesophageal peristalsis, and, perhaps, delayed gastric emptying. The rationale for the use of acid-suppressing drugs in chronic gastro-oesophageal reflux disease is based on control of the known destructive role of acid and pepsin. Recent evidence indicates, however, that standard doses of H2-receptor blockers are often inadequate to control gastric acid-induced injury in many patients with chronic reflux. Long-term maintenance therapy with standard doses of these drugs has proved unsuccessful in approximately 50% of patients. More recent studies show that greater symptom relief and improved healing can be achieved with the use of larger doses of H2-receptor antagonists. This has been shown particularly with ranitidine at a dosage of 300 mg four times daily.