Pathophysiology of gastro-oesophageal reflux disease
Timmer, R.; Breumelhof, R.; Nadorp, J.H.; Smout, A.J.
Netherlands Journal of Medicine 44(1): 1-4
1994
ISSN/ISBN: 0300-2977 PMID: 8202199 Document Number: 3513
The key factor in the aetiology of GORD is constituted by insufficiency of the anti-reflux barrier provided by the lower oesophageal sphincter. The role of both a low resting tone and an increased incidence of spontaneous LOS relaxations in the pathogenesis of GORD has been well documented. In addition, failure of the crural diaphragm to act in concert with the LOS appears to play a role in patients with hiatal hernia. In patients with severe oesophagitis, delayed oesophageal acid clearance caused by failed and weakened peristalsis may contribute. Gastric hypersecretion is not a feature of GORD. Nevertheless, inhibitors of gastric acid secretion (histamine-2 receptor antagonists and Fr/K tATPase inhibitors) currently play a pivotal role in the treatment of the disease. Since GORD is primarily a motility disorder, it would be very logical to treat the disease with drugs that modify LOS pressure and/or oesophageal motility. However, drugs such as metoclopramide, domperidone and bethanechol have inconsistent therapeutic effects and are fraught with side effects. So far, cisapride is the most effective prokinetic agent studied for the treatment of GORD. Cisapride is superior to placebo in alleviating reflux symptoms and promoting healing of Grade I-II reflux oesophagitis, with few side effects or tachyphylaxis. The drug is also superior to placebo in preventing relapse of Grade 1 oesophagitis [25]. Ongoing clinical trials are assessing the role of motility-affecting agents such as clebopride, erythromycin, serotonin antagonists, and CCK antagonists in the management of GORD.
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