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Table of Contents
Vol. 18, No. 2, 2000
Issue release date: 2000
Dig Dis 2000;18:93–102
(DOI:10.1159/000016970)

Pathophysiology and Pharmacological Treatment of Gastroesophageal Reflux Disease

Storr M. · Meining A. · Allescher H.-D.
Department of Internal Medicine II, Technical University of Munich, Germany

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Abstract

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in a gastroenterologist’s practice. Gastroesophageal reflux describes the retrograde movement of gastric contents through the lower esophageal sphincter (LES) to the esophagus. It is a common, normal phenomenon which may occur with or without accompanying symptoms. Symptoms associated with GERD include heartburn, acid regurgitation, noncardiac chest pain, dysphagia, globus pharyngitis, chronic cough, asthma, hoarseness, laryngitis, chronic sinusitis and dental erosions. The introduction of fiberoptic instruments and ambulatory devices for continuous monitoring of esophageal pH (24-hour pH monitoring) has led to great improvement in the ability to diagnose reflux disease and reflux-associated complications. The development of pathological reflux and GERD can be attributed to many factors. Pathophysiology of GERD includes incompetent LES because of a decreased LES pressure, transient lower esophageal sphincter relaxations (TLESRs) and deficient or delayed esophageal acid clearance. Uncomplicated GER may be treated by modification of life style and eating habits in an early stage of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H2 blockers, prokinetics and proton pump inhibitors. Although these drugs are effective, they do not necessarily influence the underlying causes of the disease by improving the esophageal clearance, increasing the LESP or reducing the frequency of TLESRs. The following article gives an overview regarding current concepts of the pathophysiology and pharmacological treatment of GERD.



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References

  1. Albibi R, McCallum RW: Metoclopramide: Pharmacology and clinical application. Ann Intern Med 1983;98:86–95.

    External Resources

  2. Allescher HD, Stoschus B, Wünsch E, Schusdziarra V, Classen M: Effect of human gastrin‐17 with and without acid suppression on human esophageal motility. Z Gastroenterol 1995;33:385–391.
  3. Baldi F, Ferrarini F, Longanesi A, Angeloni M, Ragazzini M, Miglioli M, Barbara L: Oesophageal function before, during, and after healing of erosive oesophagitis. Gut 1988;29:157–160.

    External Resources

  4. Bate C, Green J, Axon A, Murray F, Tildesley G, Emmas C, Taylor M: Omeprazole is more effective than cimetidine for the relief of all grades of GERD associated heartburn, irrespective of the presence or absence of endoscopic esophagitis. Aliment Pharmacol Ther 1997;11:755–763.
  5. Bate C, Keeling P, O’Morain C, Wilkinson S, Foster D, Mountford R, Temperley J, Harvey F, Thompson D, Davis M: Comparison of omeprazole and cimetidine in reflux esophagitis: Symptomatic. endoscopic and histological evaluations. Gut 1990;31:968–972.
  6. Beck I, Champion M, Lemire S, Thomson A, Anvari M, Armstrong D: The second Canadian consensus conference on the management of patients with gastroesophageal reflux disease. Can J Gastroenterol 1997;11:7–20.
  7. Champion G, Richter JE, Singh S, Schan C, Nellans H: Effects of oral erythromycin on esophageal pH and pressure profiles in patients with gastroesophageal reflux disease. Dig Dis Sci 1994;39:129–137.
  8. Champion MC: Domperidone. Gen Pharmacol 1988;19:499–505.
  9. Clarke DE, Craig DA, Fozard JR: The 5‐HT4 receptor: Naughty, but nice. Trends Pharmacol Sci 1989;10:385–386.
  10. Cohen M, Bloomquist W, Schaus J, Thompson T, Susemichel A: LY35344, a potent, orally effective, long acting 5HT4 receptor antagonist: Comparison to cisapride and RS23597‐190. J Pharmacol Exp Ther 1996;277:97–104.

    External Resources

  11. Corazziari E, Bontempo I, Anzini F: Effects of cisapride on distal esophageal motility in humans. Dig Dis Sci 1989;34:1600–1605.

    External Resources

  12. Dehn T, Shepherd H, Colin D, Kettlewell M, Carroll N: Double blind comparison of omeprazole versus cimetidine in the treatment of symptomatic erosive reflux esophagitis, assessed endoscopically, histologically and by 24 h pH monitoring. Gut 1990;31:509–513.
  13. Ehrenpreis ED: Alkali esophagitis and sucralfate. Am J Gastroenterol 1988;83:1187–1188.
  14. Galmiche JP, Barthelemy P, Hamelin B: Treating the symptoms of gastroesophageal reflux disease: A double‐blind comparison of omeprazole and cisapride. Aliment Pharmacol Ther 1997;11:765–773.
  15. Galmiche JP, Brandstatter G, Evreux M, Hentschel E, Kerstan E, Kratochvil P, Reichel W, Schutze K, Soule JC, Vitaux J: Combined therapy with cisapride and cimetidine in severe reflux oesophagitis: A double blind controlled trial. Gut 1988;29:675–681.

    External Resources

  16. Galmiche JP, Fraitag B, Filoche B, Evreux M, Vitaux J, Zeitoun P, Fournet J, Soule JC: Double‐blind comparison of cisapride and cimetidine in treatment of reflux esophagitis. Dig Dis Sci 1990;35:649–655.
  17. Gilbert RJ, Dodds WJ, Kahrilas PJ, Hogan WJ, Lipman S: Effect of cisapride, a new prokinetic agent, on esophageal motor function. Dig Dis Sci 1987;32:1331–1336.
  18. Greenwood B, Dieckman D, Kirst HA, Gidda JS: Effects of LY267108, an erythromycin analogue derivative, on lower esophageal sphincter function in the cat. Gastroenterology 1994;106:624–628.
  19. Hirsch DP, Holloway R, Tytgat GN, Boeckxstaens GE: Involvement of nitric oxide in human transient lower esophageal sphincter relaxations and esophageal primary peristalsis. Gastroenterology 1998;115:1374–1380.
  20. Holloway R, Penagini R, Ireland A: Criteria for objective definition of transient lower esophageal sphincter relaxation. Am J Physiol 1995;268:G128–G133.

    External Resources

  21. Inauen W, Emde C, Weber B, Armstrong D, Bettschen HU, Huber T, Scheurer U, Blum AL, Halter F, Merki HS: Effects of ranitidine and cisapride on acid reflux and oesophageal motility in patients with reflux oesophagitis: A 24 hour ambulatory combined pH and manometry study. Gut 1993;34:1025–1031.
  22. Janisch HD, Hutteman W, Bouzo MH: Cisapride versus ranitidine in the treatment of reflux esophagitis. Hepatogastroenterology 1988;35:125–127.

    External Resources

  23. Johnsson F, Weywadt I, Solhaug J, Hernqvist H, Bengtsson L: One‐week omeprazole treatment in the diagnosis of gastro‐esophageal reflux disease. Scand J Gastroenterol 1998;33:A20.
  24. Kao CH, Wang SJ, Pang DY: Effects of oral erythromycin on upper gastrointestinal motility in patients with non‐insulin‐dependent diabetes mellitus. Nucl Med Commun 1995;16:790–793.
  25. Katz PO, Geisinger KR, Hassan M, Wu WC, Huang D, Castell DO: Acid‐induced esophagitis in cats is prevented by sucralfate but not synthetic prostaglandin E. Dig Dis Sci 1988;33:217–224.
  26. Klauser A, Schindlbeck N, Müller‐Lissner S: Symptoms in gastro‐esophageal reflux disease. Lancet 1990;335:205–208.
  27. Klinkenberg‐Knol E, Festen H, Jansen J, Lamers C, Nelis F, Snel P, Lückers A, Dekkers C, Havu N, Meuwissen S: Long‐term treatment with omeprazole for refractory reflux esophagitis: Efficacy and safety. Ann Intern Med 1994;121:161–167.
  28. Klinkenberg‐Knol E, Jansen J, Lamers C, Nelis F, Meuwissen S: Temporary cessation of long‐term maintenance treatment with omeprazole in patients with H2 receptor antagonist resistant reflux esophagitis. Effects on symptoms, endoscopy, serum gastrin and gastric acid output. Scand J Gastroenterol 1990;25:1144–1150.
  29. Koelz HR: Treatment of reflux esophagitis with H2‐blockers, antacids and prokinetic drugs. An analysis of randomized clinical trials. Scand J Gastroenterol Suppl 1989;156:25–36.

    External Resources

  30. Lagergren J, Bergström R, Lindgren A, Nyren O: Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825–831.
  31. Lambert R: Current practice and future perspectives in the management of gastroesophageal reflux disease. Aliment Pharmacol Ther 1997;11:651–662.

    External Resources

  32. Lehmann A, Bremner M, Karrberg L, Hansson L: Baclofen stereospecifically inhibits transient lower esophageal sphincter relaxation in the dog. Gastroenterology 1999;116:A903 (abstract).
  33. Lundell L: The knife or the pill in long‐term treatment of gastroesophageal reflux disease. Yale J Biol Med 1994;67:233.

    External Resources

  34. Lundell L, Dalenbäck J, Hattlebakk J, Janatuinen E, Levander K, Miettinen P, Myrvold HE, Pedersen SA, Thor K, Junghard O, Andersson A: Outcome of open antireflux surgery as assessed in a Nordic multicenter prospective clinical trial. Nordic GORD‐Study Group. Eur J Surg 1998;164:751–757.
  35. Marshall RE, Anggiansah A, Manifold DK, Owen WA, Owen WJ: Effect of omeprazole 20 mg twice daily on duodenogastric and gastroesophageal bile reflux in Barrett’s esophagus. Gut 1998;43:603–606.
  36. McTavish D, Buckley M, Heel R: Omeprazole – An updated review of its pharmacology and therapeutic use in acid‐related disorders. Drugs 1991;42:138–170.
  37. Meining A, Classen M: Gastroösophageale Refluxkrankheit. Internist 1998;39:1215–1222.
  38. Mine Y, Yoshikawa T, Oku S, Nagai R, Yoshida N, Hosoki K: Comparison of effect of mosapride citrate and existing 5HT4 receptor agonists on gastrointestinal motility in vivo and in vitro. J Pharmacol Exp Ther 1997;283:1000–1008.
  39. Mittal R, Holloway R, Penagini R, Blackshaw LA, Dent J: Transient lower esophageal sphincter relaxation. Gastroenterology 1995;109:601–610.
  40. Mittal RK, Balaban DH: The esophagogastric junction. N Engl J Med 1997;336:924–932.
  41. Mittal RK, Chiareli C, Liu J, Shaker R: Characteristics of lower esophageal sphincter relaxation induced by pharyngeal stimulation with minute amounts of water. Gastroenterology 1996;111:378–384.
  42. Orr WC, Robinson MG, Humphries TJ, Antonello J, Cagliola A: Dose‐response effect of famotidine on patterns of gastro‐oesophageal reflux. Aliment Pharmacol Ther 1988;2:229–235.

    External Resources

  43. Pehl C, Pfeiffer A, Wendl B, Stelwag B, Kaess H: Effect of erythromycin on postprandial gastroesophageal reflux in reflux esophagitis. Dis Esophagus 1997;10:34–37.

    External Resources

  44. Penagini R, Bartesaghi B, Negri G, Bianchi PA: Effect of loperamide on lower oesophageal sphincter pressure in idiopathic achalasia. Scand J Gastroenterol 1994;29:1057–1060.
  45. Penagini R, Bianchi PA: Effect of morphine on gastroesophageal reflux and transient lower esophageal sphincter relaxation. Gastroenterology 1997;113:409–414.
  46. Penagini R, Picone A, Bianchi PA: Effect of morphine and naloxone on motor response of the human esophagus to swallowing and distension. Am J Physiol 1996;271:G675–G680.

    External Resources

  47. Pennathur A, Tran A, Cioppi M, Fayad J, Sieren GL, Little AG: Erythromycin strengthens the defective lower esophageal sphincter in patients with gastroesophageal reflux disease. Am J Surg 1994;167:169–172.
  48. Plein K, Hotz J, Wurzer H, Fumagalli I, Tenor H, Schneider A: Pantoprazole 20 mg is as effective as pantoprazole 40 mg in prevention of relapse of reflux esophagitis. Gastroenterology 1998;114:A259.
  49. Rampe D, Roy ML, Dennis A, Brown AM: A mechanism for the proarrhythmic effects of cisapride: High affinity blockade of the human cardiac potassium channel HERG. FEBS Lett 1997;417:28–32.
  50. Richter JE: Long‐term management of gastroesophageal reflux disease and its complications. Am J Gastroenterol 1997;92:30–34.
  51. Richter JE, Sabesin S, Kogut D, Kerr R, Wruble L, Collen M: Omeprazole versus ranitidine or ranitidine/metoclopramide in poorly responsive symptomatic GERD. Am J Gastroenterol 1996;91:1766–1772.

    External Resources

  52. Robertson CS, Evans DF, Ledingham SJ, Atkinson M: Cisapride in the treatment of gastro‐oesophageal reflux disease. Aliment Pharmacol Ther 1993;7:181–190.
  53. Ruth M, Hamelin B, Rohss K, Lundell L: The effect of mosapride, a novel prokinetic, on acid reflux variables in patients with gastro‐oesophageal reflux disease. Aliment Pharmacol Ther 1998;12:35–40.
  54. Schulze DK: Metoclopramide. Gatroenterology 1979;77:768–779.
  55. Seige M, Ott R, Allescher HD: Ösophagusmanometrie, 24‐Stunden‐pH‐Metrie und Provokationstests. Verdauungskrankheiten 1995;6:215– 229.
  56. Skoutakis V, Joe R, Hara D: Comparative role of omeprazole in the treatment of gastroesophageal reflux disease. Ann Pharmacother 1995;29:1252–1262.

    External Resources

  57. Stein H, De Meester T, Hinder R: Outpatient physiolocal resting and surgical management of foregut motor disorders. Curr Probl Surg 1992;24:415–455.
  58. Storr M, Allescher HD: Esophageal pharacology and treatment of primary motility disorders. Dis Esophagus 1999;12:241–257.
  59. Storr M, Geisler F, Neuhuber W, Allescher HD: Autonomic modulation of vagal input to the rat esophageal muscle – Influence of opiates. Neurogastroenterol Motil 1999;11:293.
  60. Storr M, Geisler F, Neuhuber W, Allescher HD: Characterisation of autonomic modulation of vagal input to the rat esophageal muscle. Gastroenterology 1999;116:A1088.
  61. Thomas AR, Chan LN, Bauman JL, Olopade CO: Prolongation of the QT interval related to cisapride‐diltiazem interaction. Pharmacotherapy 1998;18:381–385.

    External Resources

  62. Toussaint J, Gossuin A, Deruyttere M, Huble F, Devis G: Healing and prevention of relapse of reflux oesophagitis by cisapride. Gut 1991;32:1280–1285.
  63. Tsai SC, Kao CH, Pan DY, ChangLai SP, Wang SJ: Effects of oral erythromycin on esophageal motility in patients with noninsulin‐dependent diabetes mellitus. Kao Hsiung I Hsueh Ko Hseu Tsa Chih 1995;11:430–435.
  64. Tzovaras G, Xynos E, Chrysos E, Mantides A, Vassilakis JS: The effect of intravenous erythromycin on esophageal motility in healthy subjects. Am J Surg 1996;171:316–319.
  65. Vigneri G, Mela G, Pilotto A: A comparison of five maintenance therapies for reflux esophagitis. N Engl J Med 1995;333:1106–1110.
  66. Wallin L, Kruse AS, Madsen T, Boesby S: Effect of cisapride on the gastro‐oesophageal function in normal human subjects. Digestion 1987;37:160–165.

    External Resources

  67. Weihrauch TR, Forster CF, Krieglstein J: Evaluation of the effect of domperidone on human oesophageal and gastroduodenal motility by intraluminal manometry. Postgrad Med J 1979;55(suppl 1):7–10.
  68. Wienbeck M, Li Q: Cisapride in gastro‐oesophageal reflux disease: Effects on oesophageal motility and intra‐oesophageal pH. Scand J Gastroenterol Suppl 1989;165:13–18.

    External Resources

  69. Yoshida N, Kato S, Ito T: Mosapride citrate. Drugs Future 1993;18:513–515.
  70. Yoshida N, Omoya H, Kato S, Ito T: Pharmacological effects of the new gastroprokinetic agent mosapride citrate and its metabolites in experimental animals. Arzneimittelforschung 1993;43:1078–1083.
  71. Young M, Sanowski R, Talbert G, Harrison M, Walker B: Omeprazole administration as a test for gastroesophageal reflux. Gastroenterology 1992;102:192.
  72. Zerbib F, Bruley Des Varannes S, Scarpignato C, Leray V, D’Amato M, Rozé C, Galmiche JP: Endogenous cholecystokinin in postprandial lower esophageal sphincter function and fundic tone in humans. Am J Physiol 1998;275:G1266–G1273.

    External Resources



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