Abstract
Gastro-oesophageal reflux disease is a common condition with a complex pathophysiology. Despite the spectrum of abnormalities, gastric acid has a central role in mucosal damage, and the mainstay of medical treatment is suppression of gastric acid secretion. The results of antisecretory treatment as assessed by endoscopic healing are reviewed. H2 receptor antagonists give more rapid symptom relief than placebo and can produce endoscopic improvement in 31-88% of cases depending on the severity of oesophagitis. Complete healing, however, is seen only in 27-45% of patients and these have mainly grades I-II disease. Improved healing rates can be obtained by increasing the degree of acid suppression or the length of treatment. The addition of a prokinetic agent may be beneficial. Omeprazole heals 67-92% of patients overall and although most successful in the lower grades of oesophagitis, can also heal 48-62% of patients with grade IV disease. The degree and rate of healing seem to be related to the reduction in oesophageal acid exposure and thus may correlate with the degree and duration of acid suppression over 24 hours obtained by the various treatments. The underlying pathophysiology is unchanged, however, and long term treatment may be needed to maintain remission.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Archambault A. P., Farley A., Cleator I. G., Hershfield N. B., Navert H., Prokipchuk E. J., Thomson A. B. Cimetidine therapy for gastroesophageal reflux disease. West J Med. 1985 Nov;143(5):616–621. [PMC free article] [PubMed] [Google Scholar]
- Behar J., Brand D. L., Brown F. C., Castell D. O., Cohen S., Crossley R. J., Pope C. E., 2nd, Winans C. S. Cimetidine in the treatment of symptomatic gastroesophageal reflux: a double blind controlled trial. Gastroenterology. 1978 Feb;74(2 Pt 2):441–448. [PubMed] [Google Scholar]
- Behar J., Sheahan D. G., Biancani P., Spiro H. M., Storer E. H. Medical and surgical management of reflux esophagitis. A 38-month report of a prospective clinical trial. N Engl J Med. 1975 Aug 7;293(6):263–268. doi: 10.1056/NEJM197508072930602. [DOI] [PubMed] [Google Scholar]
- Borkent M. V., Beker J. A. Treatment of ulcerative reflux oesophagitis with colloidal bismuth subcitrate in combination with cimetidine. Gut. 1988 Mar;29(3):385–389. doi: 10.1136/gut.29.3.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bovero E., Cheli R., Barbara L., Baldi F., Boero A., Mura G. C., Camarri E., Corradini P., Dobrilla G., Piazzi L. Short-term treatment of reflux oesophagitis with ranitidine 300 mg nocte. Italian multicentre study. Hepatogastroenterology. 1987 Aug;34(4):155–159. [PubMed] [Google Scholar]
- Breen K. J., Desmond P. V., Whelan G. Treatment of reflux oesophagitis. A randomized, controlled evaluation of cimetidine. Med J Aust. 1983 Nov 26;2(11):555–558. [PubMed] [Google Scholar]
- Bright-Asare P., El-Bassoussi M. Cimetidine, metoclopramide, or placebo in the treatment of symptomatic gastroesophageal reflux. J Clin Gastroenterol. 1980 Jun;2(2):149–156. doi: 10.1097/00004836-198006000-00008. [DOI] [PubMed] [Google Scholar]
- Brown P. Cimetidine in the treatment of reflux oesophagitis. Med J Aust. 1979 Jul 28;2(2):96–97. doi: 10.5694/j.1326-5377.1979.tb112743.x. [DOI] [PubMed] [Google Scholar]
- Burget D. W., Chiverton S. G., Hunt R. H. Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression. Gastroenterology. 1990 Aug;99(2):345–351. doi: 10.1016/0016-5085(90)91015-x. [DOI] [PubMed] [Google Scholar]
- Carlsson E. A review of the effects of long-term acid inhibition in animals. Scand J Gastroenterol Suppl. 1989;166:19–23. doi: 10.3109/00365528909091238. [DOI] [PubMed] [Google Scholar]
- Caygill C. P., Hill M. J., Kirkham J. S., Northfield T. C. Mortality from gastric cancer following gastric surgery for peptic ulcer. Lancet. 1986 Apr 26;1(8487):929–931. doi: 10.1016/s0140-6736(86)91041-x. [DOI] [PubMed] [Google Scholar]
- Collen M. J., Lewis J. H., Benjamin S. B. Gastric acid hypersecretion in refractory gastroesophageal reflux disease. Gastroenterology. 1990 Mar;98(3):654–661. doi: 10.1016/0016-5085(90)90285-9. [DOI] [PubMed] [Google Scholar]
- Dehn T. C., Shepherd H. A., Colin-Jones D., Kettlewell M. G., Carroll N. J. Double blind comparison of omeprazole (40 mg od) versus cimetidine (400 mg qd) in the treatment of symptomatic erosive reflux oesophagitis, assessed endoscopically, histologically and by 24 h pH monitoring. Gut. 1990 May;31(5):509–513. doi: 10.1136/gut.31.5.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dent J. Recent views on the pathogenesis of gastro-oesophageal reflux disease. Baillieres Clin Gastroenterol. 1987 Oct;1(4):727–745. doi: 10.1016/0950-3528(87)90016-9. [DOI] [PubMed] [Google Scholar]
- Ferguson R., Dronfield M. W., Atkinson M. Cimetidine in treatment of reflux oesophagitis with peptic stricture. Br Med J. 1979 Aug 25;2(6188):472–474. doi: 10.1136/bmj.2.6188.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Festen H. P., Driessen W. M., Lamers C. B., Van Tongeren J. H. Cimetidine in the treatment of severe ulcerative reflux oesophagitis; results of an 8-week double-blind study and of subsequent long-term maintenance treatment. Neth J Med. 1980;23(6):237–240. [PubMed] [Google Scholar]
- Fiasse R., Hanin C., Lepot A., Descamps C., Lamy F., Dive C. Controlled trial of cimetidine in reflux esophagitis. Dig Dis Sci. 1980 Oct;25(10):750–755. doi: 10.1007/BF01345293. [DOI] [PubMed] [Google Scholar]
- Fielding J. F., Doyle G. D. Comparison between ranitidine and cimetidine in the treatment of reflux oesophagitis. Ir Med J. 1984 Nov;77(11):356–357. [PubMed] [Google Scholar]
- Galmiche J. P., Brandstätter G., Evreux M., Hentschel E., Kerstan E., Kratochvil P., Reichel W., Schütze K., Soule J. C., Vitaux J. Combined therapy with cisapride and cimetidine in severe reflux oesophagitis: a double blind controlled trial. Gut. 1988 May;29(5):675–681. doi: 10.1136/gut.29.5.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goy J. A., Maynard J. H., McNaughton W. M., O'Shea A. Ranitidine and placebo in the treatment of reflux oesophagitis. A double-blind randomized trial. Med J Aust. 1983 Nov 26;2(11):558–561. doi: 10.5694/j.1326-5377.1983.tb122676.x. [DOI] [PubMed] [Google Scholar]
- Graham D. Y., Smith J. L., Patterson D. J. Why do apparently healthy people use antacid tablets? Am J Gastroenterol. 1983 May;78(5):257–260. [PubMed] [Google Scholar]
- Greaney M. G., Irvin T. T. Cimetidine for the treatment of symptomatic gastro-oesophageal reflux. Br J Clin Pract. 1981 Jan;35(1):21–24. [PubMed] [Google Scholar]
- Grove O., Bekker C., Jeppe-Hansen M. G., Karstoft E., Sanchez G., Axelsson C. K., Nielsen H. O., Andersen B., Rask-Madsen J. Ranitidine and high-dose antacid in reflux oesophagitis. A randomized, placebo-controlled trial. Scand J Gastroenterol. 1985 May;20(4):457–461. doi: 10.3109/00365528509089680. [DOI] [PubMed] [Google Scholar]
- Guslandi M., Testoni P. A., Passaretti S., Masci E., Ballarin E., Comin U., Marchi R., Ronchi G., Tittobello A. Ranitidine vs metoclopramide in the medical treatment of reflux esophagitis. Hepatogastroenterology. 1983 Jun;30(3):96–98. [PubMed] [Google Scholar]
- Halvorsen L., Lee F. I., Wesdorp I. C., Johnson N. J., Mills J. G., Wood J. R. Acute treatment of reflux oesophagitis: a multicentre study to compare 150 mg ranitidine twice daily with 300 mg ranitidine at bedtime. Aliment Pharmacol Ther. 1989 Apr;3(2):171–181. doi: 10.1111/j.1365-2036.1989.tb00203.x. [DOI] [PubMed] [Google Scholar]
- Hameeteman W., v d Boomgaard D. M., Dekker W., Schrijver M., Wesdorp I. C., Tytgat G. N. Sucralfate versus cimetidine in reflux esophagitis. A single-blind multicenter study. J Clin Gastroenterol. 1987 Aug;9(4):390–394. doi: 10.1097/00004836-198708000-00007. [DOI] [PubMed] [Google Scholar]
- Harvey R. F., Gordon P. C., Hadley N., Long D. E., Gill T. R., Macpherson R. I., Beats B. C., Tottle A. J. Effects of sleeping with the bed-head raised and of ranitidine in patients with severe peptic oesophagitis. Lancet. 1987 Nov 21;2(8569):1200–1203. doi: 10.1016/s0140-6736(87)91332-8. [DOI] [PubMed] [Google Scholar]
- Havelund T., Laursen L. S., Skoubo-Kristensen E., Andersen B. N., Pedersen S. A., Jensen K. B., Fenger C., Hanberg-Sørensen F., Lauritsen K. Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial. Br Med J (Clin Res Ed) 1988 Jan 9;296(6615):89–92. doi: 10.1136/bmj.296.6615.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Havu N., Mattsson H., Ekman L., Carlsson E. Enterochromaffin-like cell carcinoids in the rat gastric mucosa following long-term administration of ranitidine. Digestion. 1990;45(4):189–195. doi: 10.1159/000200245. [DOI] [PubMed] [Google Scholar]
- Hetzel D. J., Dent J., Reed W. D., Narielvala F. M., Mackinnon M., McCarthy J. H., Mitchell B., Beveridge B. R., Laurence B. H., Gibson G. G. Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology. 1988 Oct;95(4):903–912. doi: 10.1016/0016-5085(88)90162-x. [DOI] [PubMed] [Google Scholar]
- Hine K. R., Holmes G. K., Melikian V., Lucey M., Fairclough P. D. Ranitidine in reflux oesophagitis. A double-blind placebo-controlled study. Digestion. 1984;29(2):119–123. doi: 10.1159/000199020. [DOI] [PubMed] [Google Scholar]
- Howden C. W., Hunt R. H. The relationship between suppression of acidity and gastric ulcer healing rates. Aliment Pharmacol Ther. 1990 Feb;4(1):25–33. doi: 10.1111/j.1365-2036.1990.tb00445.x. [DOI] [PubMed] [Google Scholar]
- Janisch H. D., Hüttemann W., Bouzo M. H. Cisapride versus ranitidine in the treatment of reflux esophagitis. Hepatogastroenterology. 1988 Jun;35(3):125–127. [PubMed] [Google Scholar]
- Johansson K. E., Boeryd B., Johansson K., Tibbling L. Double-blind crossover study of ranitidine and placebo in gastro-oesophageal reflux disease. Scand J Gastroenterol. 1986 Sep;21(7):769–778. doi: 10.3109/00365528609011116. [DOI] [PubMed] [Google Scholar]
- Johansson K. E., Tibbling L. Gastric secretion and reflux pattern in reflux oesophagitis before and during ranitidine treatment. Scand J Gastroenterol. 1986 May;21(4):487–492. doi: 10.3109/00365528609015167. [DOI] [PubMed] [Google Scholar]
- Johansson K. E., Tibbling L. Maintenance treatment with ranitidine compared with fundoplication in gastro-oesophageal reflux disease. Scand J Gastroenterol. 1986 Sep;21(7):779–788. doi: 10.3109/00365528609011117. [DOI] [PubMed] [Google Scholar]
- Jones D. B., Howden C. W., Burget D. W., Kerr G. D., Hunt R. H. Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs. Gut. 1987 Sep;28(9):1120–1127. doi: 10.1136/gut.28.9.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaul B., Petersen H., Erichsen H., Myrvold H. E., Grette K., Halvorsen T., Fjøsne U. Gastroesophageal reflux disease. Acute and maintenance treatments with cimetidine. Scand J Gastroenterol. 1986 Mar;21(2):139–145. doi: 10.3109/00365528609034638. [DOI] [PubMed] [Google Scholar]
- Klinkenberg-Knol E. C., Festen H. P., Meuwissen S. G. The effects of omeprazole and ranitidine on 24-hour pH in the distal oesophagus of patients with reflux oesophagitis. Aliment Pharmacol Ther. 1988 Jun;2(3):221–227. doi: 10.1111/j.1365-2036.1988.tb00691.x. [DOI] [PubMed] [Google Scholar]
- Klinkenberg-Knol E. C., Jansen J. M., Festen H. P., Meuwissen S. G., Lamers C. B. Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis. Lancet. 1987 Feb 14;1(8529):349–351. doi: 10.1016/s0140-6736(87)91726-0. [DOI] [PubMed] [Google Scholar]
- Larsson H., Carlsson E., Håkanson R., Mattsson H., Nilsson G., Seensalu R., Wallmark B., Sundler F. Time-course of development and reversal of gastric endocrine cell hyperplasia after inhibition of acid secretion. Studies with omeprazole and ranitidine in intact and antrectomized rats. Gastroenterology. 1988 Dec;95(6):1477–1486. doi: 10.1016/s0016-5085(88)80066-0. [DOI] [PubMed] [Google Scholar]
- Lehtola J., Niemelä S., Martikainen J., Krekelä I. Ranitidine, 150 mg three times a day, in the treatment of reflux oesophagitis. A placebo-controlled, double-blind study. Scand J Gastroenterol. 1986 Mar;21(2):175–180. doi: 10.3109/00365528609034643. [DOI] [PubMed] [Google Scholar]
- Lieberman D. A., Keeffe E. B. Treatment of severe reflux esophagitis with cimetidine and metoclopramide. Ann Intern Med. 1986 Jan;104(1):21–26. doi: 10.7326/0003-4819-104-1-21. [DOI] [PubMed] [Google Scholar]
- Lieberman D. A. Medical therapy for chronic reflux esophagitis. Long-term follow-up. Arch Intern Med. 1987 Oct;147(10):1717–1720. [PubMed] [Google Scholar]
- Nebel O. T., Fornes M. F., Castell D. O. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis. 1976 Nov;21(11):953–956. doi: 10.1007/BF01071906. [DOI] [PubMed] [Google Scholar]
- Northfield T. C., Hall C. N. Carcinoma of the gastric stump: risks and pathogenesis. Gut. 1990 Nov;31(11):1217–1219. doi: 10.1136/gut.31.11.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Offerhaus G. J., Tersmette A. C., Huibregtse K., van de Stadt J., Tersmette K. W., Stijnen T., Hoedemaeker P. J., Vandenbroucke J. P., Tytgat G. N. Mortality caused by stomach cancer after remote partial gastrectomy for benign conditions: 40 years of follow up of an Amsterdam cohort of 2633 postgastrectomy patients. Gut. 1988 Nov;29(11):1588–1590. doi: 10.1136/gut.29.11.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orr W. C., Robinson M. G., Humphries T. J., Antonello J., Cagliola A. Dose--response effect of famotidine on patterns of gastro-oesophageal reflux. Aliment Pharmacol Ther. 1988 Jun;2(3):229–235. doi: 10.1111/j.1365-2036.1988.tb00692.x. [DOI] [PubMed] [Google Scholar]
- Petrokubi R. J., Jeffries G. H. Cimetidine versus antacid in scleroderma with reflux esophagitis. A randomized double-blind controlled study. Gastroenterology. 1979 Oct;77(4 Pt 1):691–695. [PubMed] [Google Scholar]
- Powell-Jackson P., Barkley H., Northfield T. C. Effect of cimetidine in symptomatic gastro-oesophageal reflux. Lancet. 1978 Nov 18;2(8099):1068–1069. doi: 10.1016/s0140-6736(78)91802-0. [DOI] [PubMed] [Google Scholar]
- Quik R. F., Cooper M. J., Gleeson M., Hentschel E., Schuetze K., Kingston R. D., Mitchell M. A comparison of two doses of nizatidine versus placebo in the treatment of reflux oesophagitis. Aliment Pharmacol Ther. 1990 Apr;4(2):201–211. doi: 10.1111/j.1365-2036.1990.tb00465.x. [DOI] [PubMed] [Google Scholar]
- Robertson D. A., Aldersley M. A., Shepherd H., Lloyd R. S., Smith C. L. H2 antagonists in the treatment of reflux oesophagitis: can physiological studies predict the response? Gut. 1987 Aug;28(8):946–949. doi: 10.1136/gut.28.8.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruth M., Enbom H., Lundell L., Lönroth H., Sandberg N., Sandmark S. The effect of omeprazole or ranitidine treatment on 24-hour esophageal acidity in patients with reflux esophagitis. Scand J Gastroenterol. 1988 Nov;23(9):1141–1146. doi: 10.3109/00365528809090182. [DOI] [PubMed] [Google Scholar]
- Ryberg B., Carlsson E., Håkanson R., Lundell L., Mattsson H., Sundler F. Effects of partial resection of acid-secreting mucosa on plasma gastrin and enterochromaffin-like cells in the rat stomach. Digestion. 1990;45(2):102–108. doi: 10.1159/000200230. [DOI] [PubMed] [Google Scholar]
- Sandmark S., Carlsson R., Fausa O., Lundell L. Omeprazole or ranitidine in the treatment of reflux esophagitis. Results of a double-blind, randomized, Scandinavian multicenter study. Scand J Gastroenterol. 1988 Jun;23(5):625–632. doi: 10.3109/00365528809093923. [DOI] [PubMed] [Google Scholar]
- Sano C., Kumashiro R., Saito T., Inokuchi K. Promoting effect of partial gastrectomy on carcinogenesis in the remnant stomach of rats after oral administration of N-methyl-N'-nitro-N-nitrosoguanidine. Oncology. 1984;41(2):124–128. doi: 10.1159/000225806. [DOI] [PubMed] [Google Scholar]
- Schaub N., Meyrick Thomas J., Misiewicz J. J., Lovell D., Trotman I. F. Investigation of ranitidine 150 mg bd or 300 mg bd in the treatment of reflux disease. Hepatogastroenterology. 1986 Oct;33(5):208–213. [PubMed] [Google Scholar]
- Schotborgh R. H., Hameeteman W., Dekker W., vd Boomgaard D. M., Van Olffen G. H., Schrijver M., Vosmaer G. D., Tytgat G. N. Combination therapy of sucralfate and cimetidine, compared with sucralfate monotherapy, in patients with peptic reflux esophagitis. Am J Med. 1989 Jun 9;86(6A):77–80. doi: 10.1016/0002-9343(89)90163-0. [DOI] [PubMed] [Google Scholar]
- Sekiguchi T., Nishioka T., Kogure M., Kusano M., Horikoshi T., Sugiyama T., Kobayashi S. Once-daily administration of famotidine for reflux esophagitis. Scand J Gastroenterol Suppl. 1987;134:51–54. doi: 10.3109/00365528709090141. [DOI] [PubMed] [Google Scholar]
- Sherbaniuk R., Wensel R., Bailey R., Trautman A., Grace M., Kirdeikis P., Jewell L., Pare P., Levesque D., Farley A. Ranitidine in the treatment of symptomatic gastroesophageal reflux disease. J Clin Gastroenterol. 1984 Feb;6(1):9–15. [PubMed] [Google Scholar]
- Sontag S., Robinson M., McCallum R. W., Barwick K. W., Nardi R. Ranitidine therapy for gastroesophageal reflux disease. Results of a large double-blind trial. Arch Intern Med. 1987 Aug;147(8):1485–1491. [PubMed] [Google Scholar]
- Sölvell L. The clinical safety of omeprazole. Scand J Gastroenterol Suppl. 1989;166:106–113. doi: 10.3109/00365528909091255. [DOI] [PubMed] [Google Scholar]
- Temple J. G., Bradby G. V., O'Connor F. O., Panesar K. S., Mulligan T. O., Robinson T. J., Ward D. W. Cimetidine and metoclopramide in oesophageal reflux disease. Br Med J (Clin Res Ed) 1983 Jun 11;286(6381):1863–1864. doi: 10.1136/bmj.286.6381.1863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thanik K., Chey W. Y., Shak A., Hamilton D., Nadelson N. Bethanechol or cimetidine in the treatment of symptomatic reflux esophagitis: a double-blind control study. Arch Intern Med. 1982 Aug;142(8):1479–1481. [PubMed] [Google Scholar]
- Vantrappen G., Rutgeerts L., Schurmans P., Coenegrachts J. L. Omeprazole (40 mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagitis. Dig Dis Sci. 1988 May;33(5):523–529. doi: 10.1007/BF01798351. [DOI] [PubMed] [Google Scholar]
- Wesdorp E., Bartelsman J., Pape K., Dekker W., Tytgat G. N. Oral cimetidine in reflux esophagitis: a double blind controlled trial. Gastroenterology. 1978 May;74(5 Pt 1):821–824. [PubMed] [Google Scholar]
- Wesdorp I. C., Dekker W., Klinkenberg-Knol E. C. Treatment of reflux oesophagitis with ranitidine. Gut. 1983 Oct;24(10):921–924. doi: 10.1136/gut.24.10.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zeitoun P., Desjars De Keranroué N., Isal J. P. Omeprazole versus ranitidine in erosive oesophagitis. Lancet. 1987 Sep 12;2(8559):621–622. doi: 10.1016/s0140-6736(87)93005-4. [DOI] [PubMed] [Google Scholar]