Pharmacologic Treatment of GERD

Part of the Respiratory Medicine book series (RM, volume 2)


Gastroesophageal reflux disease (GERD) is extremely common, affecting 7–10 % of the adult population in the United States on a daily basis [1]. GERD has been found to have a greater negative impact on quality of life for a patient than more severe chronic diseases, including hypertension, heart failure, and angina [2]. The clinical range of GERD has expanded from classic esophageal symptoms of heartburn and regurgitation to now include symptoms and disease outside the esophagus, namely, the entire aerodigestive tract. Treatment of the spectrum of reflux diseases, be it isolated to the esophagus or proximal disease of the oropharynx or lungs, shares a common pathophysiology, and therefore, similar treatment strategies can be implemented with only slight variations. There is a range of effective pharmacologic treatment options for patients with reflux disease: acute symptoms of classic reflux may simply require over-the-counter (OTC) acid-neutralizing medications, while other individuals with more persistent, recurring symptoms need a more directed, long-term strategy requiring systemic medications. The nature of the disease is one of chronicity. Thus, a majority of patients started on acid-suppressant medications will have symptoms that require long-term pharmacologic treatment. With the high prevalence of reflux disease, the spectrum of reflux manifestations, and the array of products available to treat reflux, the clinical and financial burden of treating reflux patients is high. This chapter focuses on the pharmacologic treatment for reflux disease.


Pharmacologic treatment Gastroesophageal reflux disease (GERD) Treatment strategies Reflux-moderating agents Acid-suppressing agents Prokinetic medications 


  1. 1.
    Richter J. Surgery for reflux disease: reflections of a gastroenterologist. N Engl J Med. 1992;326(12):825–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Dimenas E. Quality of life in patients with upper gastrointestinal symptoms. Scand J Gastroenterol. 1993;28:681–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Tsuzuki T, Yamamoto K, et al. Proton pump inhibitor step-down therapy for GERD: a multicenter study in Japan. World J Gastroenterol. 2011;17(11):1480–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Marrewijk CJ, et al. Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary care-based randomized controlled trial. Lancet. 2009;373:215–25.PubMedCrossRefGoogle Scholar
  5. 5.
    Castell DO, Dalton CB, Becker D, et al. Alginic acid decreases postprandial upright gastroesophageal reflux. Comparison with equal strength antacid. Dig Dis Sci. 1992;37:589–93.PubMedCrossRefGoogle Scholar
  6. 6.
    Graham DY, Patterson DJ. Double-blind comparison of liquid antacid and placebo in the treatment of symptomatic reflux esophagitis. Dig Dis Sci. 1983;28:559–63.PubMedCrossRefGoogle Scholar
  7. 7.
    Tran T, Lowry A, El-Serag H. Meta-analysis: the efficacy of over-the-counter gastro-­oesophageal reflux disease drugs. Aliment Pharmacol Ther. 2007;25:143–53.PubMedGoogle Scholar
  8. 8.
    Stanciu C, Bennett JR. Alginate/antacids in the reduction of gastroesophageal reflux. Lancet. 1974;1:109–11.PubMedCrossRefGoogle Scholar
  9. 9.
    Bell NJV, Burget D, Hunt RH, et al. Appropriate acid suppression for the management of gastro-esopageal reflux disease. Digestion. 1992;51:59–67.PubMedCrossRefGoogle Scholar
  10. 10.
  11. 11.
    Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology. 2000;119:9–31.CrossRefGoogle Scholar
  12. 12.
    Silver MT, Murdock RH, Sue SO. Ranitidine 300 mg twice daily and 150 mg four times daily are effective in healing erosive esophagitis. Aliment Pharmacol Ther. 1996;10:373.PubMedCrossRefGoogle Scholar
  13. 13.
    Peghini PL, Katz PO, Castell DO. Ranitidine controls nocturnal gastric acid breakthrough on Omeprazole: a controlled study in normal subjects. Gastroenterology. 1998;115:1335–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Mainie I, Tutian R, Castell DO. Addition of a H2 receptor antagonist to PPI improved acid control and decreased nocturnal acid breakthrough. Clin Gastroenterol. 2008;42:676–9.CrossRefGoogle Scholar
  15. 15.
    Ours T, Fackler WK, Vaezi MF. Nocturnal acid breakthrough: clinical significance and correlation with esophageal acid exposure. Am J Gastroenterol. 2003;98:545–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Tutuian R, Katz PO, Castell DO. Nocturnal acid breakthrough: pH, drugs and bugs. Eur J Gastroenterol Hepatol. 2004;16:441–3.PubMedCrossRefGoogle Scholar
  17. 17.
    Schindlbeck NE, Klauser AG, Berghammer G, Londong W, Muller-Lissner SA. Three year follow up of patients with gastroesophageal reflux disease. Gut. 1992;33:1016–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Lipsy RJ, Fennerty B, Fagan TC. Clinical review of histamine 2 receptor antagonists. Arch Intern Med. 1990;150:745.PubMedCrossRefGoogle Scholar
  19. 19.
    Yu EW, Bauer DC. Acid suppression medications and bone loss and fracture in older adults. Calcif Tissue Int. 2008;83:251–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology. 1997;112(6):1798–810.PubMedCrossRefGoogle Scholar
  21. 21.
    Robinson M, Hom J. Clinical pharmacology of proton pump inhibitors: what the practicing physician need to know. Drugs. 2003;63:2739–54.PubMedCrossRefGoogle Scholar
  22. 22.
    Lew EA. Review article: pharmacokinetic concerns in the selection of anti-ulcer therapy. Aliment Pharmacol Ther. 1999;13:11–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Klotz U. Pharmacokinetic considerations in the eradication of H. pylori. Clin Pharmacokinet. 2000;38:243–70.PubMedCrossRefGoogle Scholar
  24. 24.
    Shi S, Klotz U. Proton pump inhibitors: an update on their clinical use and pharmacokinetics. Eur J Clin Pharmacol. 2008;64:935–51.PubMedCrossRefGoogle Scholar
  25. 25.
    Mossner J, Caca K. Developments in the inhibition of gastric acid secretion. Eur J Clin Invest. 2005;35:469–75.PubMedCrossRefGoogle Scholar
  26. 26.
    Havelund T, et al. Omeprazole and Ranitidine in treatment of reflux esophagitis: double blind comparative trial. Br Med J. 1988;296:89.CrossRefGoogle Scholar
  27. 27.
    Kuo B, Castell DO. Optimal dosing of omeprazole 40 mg daily: effects on gastric and esophageal pH and serum gastrin in healthy controls. Am J Gastroenterol. 1996;91:1532.PubMedGoogle Scholar
  28. 28.
    Mulder CJ, Dekker W, Gerretsen M. Lansoprazole 30 mg vs. Omeprazole 40 mg in the treatment of reflux esophagitis. Eur J Gastroenterol Hepatol. 1996;8:1101.PubMedCrossRefGoogle Scholar
  29. 29.
    Lind T, Rydberg L, Kyleback A, et al. Esomeprazole provides improved acid control vs Omeprazole in patients with symptoms of gastro-esophageal reflux disease. Aliment Pharmacol Ther. 2000;14:861–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Yang YX, Lewis JD, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947–53.PubMedCrossRefGoogle Scholar
  31. 31.
    Gray SL, Zhao C, et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density on postmenopausal women. Arch Intern Med. 2010;170:765–71.PubMedCrossRefGoogle Scholar
  32. 32.
    Yu EW, Bauewr SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011;124:519–26.PubMedCrossRefGoogle Scholar
  33. 33.
    Targownik LE, Lix LM, Leung S. Chronic proton pump inhibitor use is not associated with and increased risk of osteoporosis. Gastroenterology. 2009;136:1–70.CrossRefGoogle Scholar
  34. 34.
    Targownik LE, Lix L, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179:319–26.PubMedCrossRefGoogle Scholar
  35. 35.
    Richards JB, Goltzman D. Proton pump inhibitors: balancing the benefits and potential fracture risks. CMAJ. 2008;179:306–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Dial S, Alrasadi K, Manoukian C, Huang A, Menzies D. Risk of clostridium difficile diarrhea among hospital inpatients prescribed PPIs: cohort and case-control studies. CMAJ. 2004;171:33–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Linsky A, Gupta K, Lawler E, et al. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med. 2010;170(9):772–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Naggie S, Woods CW, et al. A case-control study of community associated Clostridium difficile infection: no role for proton pump inhibitors. Am J Med. 2011;124:276.PubMedCrossRefGoogle Scholar
  39. 39.
    Rassen JA, Choudhry NK, Avorn J, Schneeweiss S. Cardiovascular outcomes and mortality in patients using clopidogrel with PPI after percutaneous coronary intervention or acute coronary syndrome. Circulation. 2009;120:2322–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Li XQ, Weidolf L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004;32:821–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Bhatt DL. COGENT: a prospective randomized, placebo-controlled trial of omeprazole in patients receiving aspirin and clopidogrel. Presented at the Transcatheter Cardiovascular Therapeutics, San Francisco, CA, 24 Sep 2009.Google Scholar
  42. 42.
    Aihara H, et al. Effect of individual proton pump inhibitors on cardiovascular events in patients treated with Clopidogrel following coronary stenting. Cath Cardiovasc Interv. October 1, 2012, Vol 80, Issue 4, pp 556–563Google Scholar
  43. 43.
    Kwok CS, Loke YK. Effects of proton pump inhibitors on platelet function in patients receiving clopidogrel: as systematic review. Drug Saf. 2012;35(2):127–39.PubMedCrossRefGoogle Scholar
  44. 44.
    Toussant J, Gossium A, Deruyttere M, et al. Healing and prevention of relapse of reflux esophagitis by cisapride. Gut. 1991;32:1280–5.CrossRefGoogle Scholar
  45. 45.
    Zhang Q, Lehmann A, Rigda R, et al. Control of transient lower esophageal sphincter relaxations and reflux by the GABA agonist baclofen in patients with GERD. Gut. 2002;50:19–24.PubMedCrossRefGoogle Scholar
  46. 46.
    Vakil NB, Huff FJ, Bian A, Jones DS, Stamler D. Arbaclofen placarbil in GERD: a randomized double-blind, placebo-controlled study. Am J Gastroenterol. 2011;106:1427–38.PubMedCrossRefGoogle Scholar
  47. 47.
    Boeckxstaens GE, et al. Effect of lesogaberan on transient lower esophageal relaxations in male subjects. Aliment Pharmacol Ther. 2010;31:1208–17.PubMedCrossRefGoogle Scholar
  48. 48.
    Vigneri S, Davi G, et al. A comparison of five maintenance therapies for reflux esophagitis. New Engl J Med. 1995;333:1106–10.PubMedCrossRefGoogle Scholar
  49. 49.
    Van der Velden A, de Wit NJ, Quartero AO, Grobbee DE, Numans ME. Pharmacological dependency in chronic treatment of GERD: a randomized controlled clinical trial. Digestion. 2010;81:43–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Division of Gastroenterology, Department of Medicine, School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of MedicineUniversity of Wisconsin HospitalMadisonUSA

Personalised recommendations