Abstract
Gastroesophageal reflux disease (GERD) is common. Many patients with recurring or troublesome symptoms are referred for endoscopic examination. Patients seen in secondary care usually have failed OTC or primary care anti-reflux therapy. Acid suppression is the mainstay of healing and maintenance therapy. Increasingly proton pump inhibitors (PPIs) are preferred above H2 receptor antagonists (H2RAs), not only for the more severe end of the GERD spectrum but also for patients with mild degrees of esophagitis. Not all patients respond symptomatically to acid suppression, not even with high dose PPI. Prokinetics are mainly useful in the milder degrees of GERD. It is still not clear whether a particular symptom cluster can be recognized for which prokinetics are especially useful. The concept of "step-up versus step-down" approach remains in need for proper validation. Switching from PPIs to cisapride for "step-down" maintenance appears inadequate in practice. All current therapies have shortcomings; H2RAs insufficiently block meal-stimulated acid secretion; long-term strong acid suppression worsens Helicobacter pylori-associated inflammation in the corpus and may accelerate development of atrophy; PPI-potency is substantially weaker in non-H. pylori infected individuals. Optimization of individualized therapy will require more potent and more precisely targeted motility modulating drugs and superior acid/peptic inhibiting pharmaceuticals.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bell N. J., Hunt R. H. Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease. Gut. 1992 Jan;33(1):118–124. doi: 10.1136/gut.33.1.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boeckxstaens G. E., Hirsch D. P., Fakhry N., Holloway R. H., D'Amato M., Tytgat G. N. Involvement of cholecystokininA receptors in transient lower esophageal sphincter relaxations triggered by gastric distension. Am J Gastroenterol. 1998 Oct;93(10):1823–1828. doi: 10.1111/j.1572-0241.1998.00527.x. [DOI] [PubMed] [Google Scholar]
- Carlsson R., Galmiche J. P., Dent J., Lundell L., Frison L. Prognostic factors influencing relapse of oesophagitis during maintenance therapy with antisecretory drugs: a meta-analysis of long-term omeprazole trials. Aliment Pharmacol Ther. 1997 Jun;11(3):473–482. doi: 10.1046/j.1365-2036.1997.00167.x. [DOI] [PubMed] [Google Scholar]
- Carlsson R., Galmiche J. P., Dent J., Lundell L., Frison L. Prognostic factors influencing relapse of oesophagitis during maintenance therapy with antisecretory drugs: a meta-analysis of long-term omeprazole trials. Aliment Pharmacol Ther. 1997 Jun;11(3):473–482. doi: 10.1046/j.1365-2036.1997.00167.x. [DOI] [PubMed] [Google Scholar]
- Chiba N., De Gara C. J., Wilkinson J. M., Hunt R. H. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology. 1997 Jun;112(6):1798–1810. doi: 10.1053/gast.1997.v112.pm9178669. [DOI] [PubMed] [Google Scholar]
- DeVault K. R., Castell D. O. Guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Practice Parameters Committee of the American College of Gastroenterology. Arch Intern Med. 1995 Nov 13;155(20):2165–2173. [PubMed] [Google Scholar]
- Driman D. K., Wright C., Tougas G., Riddell R. H. Omeprazole produces parietal cell hypertrophy and hyperplasia in humans. Dig Dis Sci. 1996 Oct;41(10):2039–2047. doi: 10.1007/BF02093608. [DOI] [PubMed] [Google Scholar]
- Ellis K. K., Oehlke M., Helfand M., Lieberman D. Management of symptoms of gastroesophageal reflux disease: does endoscopy influence medical management? Am J Gastroenterol. 1997 Sep;92(9):1472–1474. [PubMed] [Google Scholar]
- Galmiche J. P., Barthelemy P., Hamelin B. Treating the symptoms of gastro-oesophageal reflux disease: a double-blind comparison of omeprazole and cisapride. Aliment Pharmacol Ther. 1997 Aug;11(4):765–773. doi: 10.1046/j.1365-2036.1997.00185.x. [DOI] [PubMed] [Google Scholar]
- Hatlebakk J. G., Berstad A. Gastro-oesophageal reflux during 3 months of therapy with ranitidine in reflux oesophagitis. Scand J Gastroenterol. 1996 Oct;31(10):954–958. doi: 10.3109/00365529609003113. [DOI] [PubMed] [Google Scholar]
- Hendel J., Hendel L., Hage E., Hendel J., Aggestrup S., Nielsen O. H. Monitoring of omeprazole treatment in gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol. 1996 May;8(5):417–420. [PubMed] [Google Scholar]
- Hunt R. H. The relationship between the control of pH and healing and symptom relief in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 1995;9 (Suppl 1):3–7. doi: 10.1111/j.1365-2036.1995.tb00777.x. [DOI] [PubMed] [Google Scholar]
- Klinkenberg-Knol E. C., Festen H. P., Jansen J. B., Lamers C. B., Nelis F., Snel P., Lückers A., Dekkers C. P., Havu N., Meuwissen S. G. Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med. 1994 Aug 1;121(3):161–167. doi: 10.7326/0003-4819-121-3-199408010-00001. [DOI] [PubMed] [Google Scholar]
- Leite L. P., Johnston B. T., Just R. J., Castell D. O. Persistent acid secretion during omeprazole therapy: a study of gastric acid profiles in patients demonstrating failure of omeprazole therapy. Am J Gastroenterol. 1996 Aug;91(8):1527–1531. [PubMed] [Google Scholar]
- Lind T., Havelund T., Carlsson R., Anker-Hansen O., Glise H., Hernqvist H., Junghard O., Lauritsen K., Lundell L., Pedersen S. A. Heartburn without oesophagitis: efficacy of omeprazole therapy and features determining therapeutic response. Scand J Gastroenterol. 1997 Oct;32(10):974–979. doi: 10.3109/00365529709011212. [DOI] [PubMed] [Google Scholar]
- McDougall N. I., Watson R. G., Collins J. S., McFarland R. J., Love A. H. Maintenance therapy with cisapride after healing of erosive oesophagitis: a double-blind placebo-controlled trial. Aliment Pharmacol Ther. 1997 Jun;11(3):487–495. doi: 10.1046/j.1365-2036.1997.00176.x. [DOI] [PubMed] [Google Scholar]
- Mittal R. K., Balaban D. H. The esophagogastric junction. N Engl J Med. 1997 Mar 27;336(13):924–932. doi: 10.1056/NEJM199703273361306. [DOI] [PubMed] [Google Scholar]
- Mittal R. K., Holloway R. H., Penagini R., Blackshaw L. A., Dent J. Transient lower esophageal sphincter relaxation. Gastroenterology. 1995 Aug;109(2):601–610. doi: 10.1016/0016-5085(95)90351-8. [DOI] [PubMed] [Google Scholar]
- Schoeman M. N., Tippett M. D., Akkermans L. M., Dent J., Holloway R. H. Mechanisms of gastroesophageal reflux in ambulant healthy human subjects. Gastroenterology. 1995 Jan;108(1):83–91. doi: 10.1016/0016-5085(95)90011-x. [DOI] [PubMed] [Google Scholar]
- Tytgat G. N., Blum A. L., Verlinden M. Prognostic factors for relapse and maintenance treatment with cisapride in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 1995 Jun;9(3):271–280. doi: 10.1111/j.1365-2036.1995.tb00381.x. [DOI] [PubMed] [Google Scholar]
- Tytgat G. N., Janssens J., Reynolds J. C., Wienbeck M. Update on the pathophysiology and management of gastro-oesophageal reflux disease: the role of prokinetic therapy. Eur J Gastroenterol Hepatol. 1996 Jun;8(6):603–611. doi: 10.1097/00042737-199606000-00020. [DOI] [PubMed] [Google Scholar]
- Tytgat G. N. Long-term therapy for reflux esophagitis. N Engl J Med. 1995 Oct 26;333(17):1148–1150. doi: 10.1056/NEJM199510263331711. [DOI] [PubMed] [Google Scholar]
- Venables T. L., Newland R. D., Patel A. C., Hole J., Wilcock C., Turbitt M. L. Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice. Scand J Gastroenterol. 1997 Oct;32(10):965–973. doi: 10.3109/00365529709011211. [DOI] [PubMed] [Google Scholar]
- Waldum H. L., Arnestad J. S., Brenna E., Eide I., Syversen U., Sandvik A. K. Marked increase in gastric acid secretory capacity after omeprazole treatment. Gut. 1996 Nov;39(5):649–653. doi: 10.1136/gut.39.5.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- el-Omar E., Banerjee S., Wirz A., Penman I., Ardill J. E., McColl K. E. Marked rebound acid hypersecretion after treatment with ranitidine. Am J Gastroenterol. 1996 Feb;91(2):355–359. [PubMed] [Google Scholar]
