A Comprehensive Review of Gastroesophageal Reflux Disease (GERD) Treatment and its Clinical Perspectives

DOI:

https://doi.org/10.37285/ijpsn.2023.16.6.9

Authors

  • AVIJIT MAZUMDER Noida Institute of Engineering & Technology (Pharmacy Institute); https://orcid.org/0000-0002-3053-8106
  • NAVEEN KUMAR Noida Institute of Engineering & Technology (Pharmacy Institute)
  • SAUMYA DAS Noida Institute of Engineering & Technology (Pharmacy Institute)

Abstract

Gastroesophageal reflux disease (GERD) occurs by regurgitation of food in the stomach. Aggressive factors increase GERD whereas defensive factors decrease GERD progression. GERD if mild can be put under control by lifestyle modification and giving non-pharmacological treatment methods to patients however if the disease progresses non-pharmacological methods are ineffective. Drugs reduce GERD progression and also maintain the pH of the stomach to a normal level and prevent abnormal acid exposure to the oesophagus. Antacids and alginate protect oesophagus by reducing acidity and increasing viscosity. Proton pump inhibitors and histamine 2 receptor antagonists reduce acid secretion by inhibiting its secretion. Prokinetic agents increase the motility of the stomach and reduce obesity. Metabotropic glutamate receptors, gamma-aminobutyric acid receptor agonists, and cannabinoid receptors are receptor-specific drugs that act on receptors underlying the gastrointestinal tract and alter the function of receptors which increases reflux disease. Combination of antacid and alginate, domperidone and omeprazole, omeprazole and baclofen, aluminum hydroxide, magnesium, and simethicone are frequently given in GERD to expedite the healing rate and reduce acid secretion. Combinations of suitable medications reduce the adverse effects of a single medication and also make it therapeutically more effective than using monotherapy drugs. The pharmacological method is safe and effective and treats GERD completely.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Keywords:

Combination therapy, metabotropic, mono-therapy, mucosal, regurgitate, glutamate receptor

Published

2023-11-15

How to Cite

1.
MAZUMDER A, KUMAR N, DAS S. A Comprehensive Review of Gastroesophageal Reflux Disease (GERD) Treatment and its Clinical Perspectives. Scopus Indexed [Internet]. 2023 Nov. 15 [cited 2024 May 4];16(6):7093-10. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/2467

References

Maret-Ouda J, Markar SR, Lagergren J. Gastroesophageal reflux disease: a review. JAMA. 2020;324(24):2536-47.

Vakil N, Van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;3:1900-20.

Tack J, Pandolfino JE. Pathophysiology of gastroesophageal reflux disease. Gastroenterology. 2018;154(2):277-88.

Mittal R, Vaezi MF. Esophageal motility disorders and gastroesophageal reflux disease. N Engl J Med. 2020;383(20):1961-72.

Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am Gastroenterol. 2013;108(3): 308-28.

Herregods TVK, Bredenoord AJ, Smout AJPM. Pathophysiology of gastroesophageal reflux disease: new understanding in a new era. Neurogastroenterol Motil. 2015;27(9):1202-13.

Hershcovici T, Mashimo H, Fass R. The lower esophageal sphincter. Neurogastroenterol Motil. 2011;23(9):819-30.

Mikami DJ, Murayama KM. Physiology and pathogenesis of gastroesophageal reflux disease Surgery. Am Gastroenterol. 2015;5:515-25.

Dent J, Becher A, Sung J, Zou D, Agréus L, Bazzoli F. Systematic review: patterns of reflux-induced symptoms and esophageal endoscopic findings in largescale surveys. Clin Gastroenterol Hepatol. 2012;10(8):863-873.e3.

Bethesda (MD). Drugs and lactation database (LactMed) Internet. National Library of Medicine; 2006; 2021.

MacFarlane B. Management of gastroesophageal reflux disease in adults: a pharmacist’s perspective. Integr Pharm Res Pract. 2018;7: 41-52.

Chuang TW, Chen SC, Chen KT. Current status of gastroesophageal reflux disease: diagnosis and treatment. Acta Gastroenterol Belg. 2017;80(3):396-404.

Salisbury BH, Terrell JM. Antacids. StatPearls Internet. 2020;Jan:2021.

Katz PO, Castell DO. Editorial: simultaneous prolonged monitoring of the acid pocket and oesophageal reflux. Aliment Pharmacol Ther. 2020 [editorial];52(2):397-8.

Mitchell DR, Derakhshan MH, Robertson EV, McColl KEL. The role of the acid pocket in gastroesophageal reflux disease. J Clin Gastroenterol. 2016;50(2):111-9.

Chawla S. Chawla S, Seth D, Mahajan P, Kamat D. Gastroesophageal reflux disorder: a review for primary care providers. Clin Pediatr. 2006;45(1): 7-13.

Kellerman R, Kintanar T. Gastroesophageal reflux disease. Prim Care. 2017;44(4):561-73.

Savarino E, De Bortoli N, Zentilin P. Alginate controls heartburn in patients with erosive and non-erosive reflux disease. World J Gastroenterol. 2012;18(32):4371-8.

Mandel KG, Daggy BP, Brodie DA, Jacoby I. Review article: alginate-raft formulations in the treatment of heartburn and acid reflux: review: barrier treatments in acid reflux disorders. Aliment Pharmacol Ther. 2000;14(6):669-90.

Leiman DA, Riff BP, Morgan S, Metz DC, Falk GW, French B et al. Alginate therapy is effective treatment for GERD symptoms: a systematic review and meta-analysis. Diseases of the Esophagus. 2017;30(5):1-9.

Bor S, Kalkan İH, Çelebi A, Dinçer D, Akyüz F, Dettmar P et al. Alginates: from the ocean to gastroesophageal reflux disease treatment. Turk J Gastroenterol. [Bretagne JF, Honnorat C, Richard-Molard B (2008)]. Management of gastroesophageal reflux disease by primary care physicians and gastroenterologists: a prospective study of patients’ records. Gastroenterol Clin Biol 32. 2019;30:109-136:995-1000.

Sontag S trugala V, Avis J, Jolliffe IG. Johnstone LM, Dettmar PW. J Pharm Pharmacol. 2009. The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease;61:1021-38.

Wang WH, Huang JQ, Zheng GF, Wong WM, Lam SK, Karlberg J et al. Is proton pump inhibitor testing an effective approach to diagnose gastroesophageal reflux disease in patients with noncardiac chest pain: a meta-analysis. Arch Intern Med. 2005;165(11):1222-38.

Fass R. Therapeutic options for refractory gastroesophageal reflux disease. J Gastroenterol Hepatol. 2012;27:3-7.

Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C et al. De prescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3(3):CD011969.

Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15.

Iwakiri K. Treatment strategy for standard-dose proton pumps inhibitor-resistant reflux esophagitis. J Nippon Med Sch. 2017;84(5):209-14.

Graham DY, Tansel A. Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterological Assoc. 2018;16(6):800-808.e7.

Bruley des Varannes S, Lofman HG, Karlsson M. Cost and burden of gastroesophageal reflux disease among patients with persistent symptoms despite proton pump inhibitor therapy: an observational study in France. BMC Gastroenterol. 2013;28:13-39.

Savarino V, Di Mario F, Scarpignato C. Proton pump inhibitors in GORD. An overview of their pharmacology, efficacy and safety. Pharmacol Res. 2009;159:135-53.

McRorie JW, Gibb RD, Miner PB. Evidence-based treatment of frequent heartburn: the benefits and limitations of over-the-counter medications. J Am Assoc Nurse Pract. 2014;26(6):330-9.

Dean BB, Gano AD Jr, Knight K, Ofman JJ, Fass R. Effectiveness of proton pump inhibitors in non-erosive reflux disease. Clin Gastroenterol Hepatol. 2004;2(8):656-64.

Hungin APS, Hill C, Molloy-Bland M, Raghunath A. Systematic review: patterns of proton pump inhibitor use and adherence in gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2012;10(2):109-16.

Gunaratnam NT, Jessup TP, Inadomi J, Lascewski DP. Sub-optimal proton pump inhibitor dosing is prevalent in patients with poorly controlled gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2006;23(10):1473-7.

Kushner PR, Peura DA. Review of proton pump inhibitors for the initial treatment of heartburn: is there a dose ceiling effect? Adv Therapy. 2011;28(5):367-88.

Chen J, Yuan YC, Leontiadis GI, Howden CW. Recent safety concerns with proton pump inhibitors. J Clin Gastroenterol. 2012;46(2):93-114.

Kung YM, Hsu WH, Wu MC, Wang JW, Liu CJ, Su YC et al. Recent advances in the pharmacological management of gastroesophageal reflux disease. Dig Dis Sci. 2017;62(12):3298-316.

Zhao F, Wang S, Liu L, Wang Y. Comparative effectiveness of histamine-2 receptor antagonists as short-term therapy for gastro-esophageal reflux disease: a network meta-analysis. Int J Clin Pharmacol Ther. 2016;54(10):761-70.

Nakano M, Kitano S, Nanri M, Kiniwa M. Lafutidine, a unique histamine H2-receptor antagonist, inhibits distention-induced gastric acid secretion through an H2 receptor-independent mechanism. Eur J Pharmacol. 2011;658(2-3):236-41.

Akiba Y, Kaunitz JD. Lafutidine, a protective H₂ receptor antagonist, enhances mucosal defense in rat esophagus. Dig Dis Sci. 2010;55(11):3063-9.

Nakano M, Ajioka H, Abe M, Kiniwa M. Possible involvement of host defense mechanism in the suppression of rat acute reflux esophagitis by the particular histamine H2 receptor antagonist lafutidine. Pharmacology. 2012;90(3-4):205-11.

Hom C, Vaezi MF. Extra-esophageal manifestations of gastroesophageal reflux disease diagnosis and treatment. Drugs. 2013;73(12):1281-95.

Savarino E, Zentilin P, Marabotto E, Bodini G, Della Coletta M, Frazzoni M et al. A review of pharmacotherapy for treating gastroesophageal reflux disease (GERD). Expert Opin Pharmacother. 2017;18(13):1333-43.

Kroch DA, Madanick RD. Medical treatment of gastroesophageal reflux disease. World J Surg. 2017;41(7):1678-84.

Glicksman JT, Mick PT, Fung K, Carroll TL. Prokinetic agents and laryngopharyngeal reflux disease: prokinetic agents and laryngopharyngeal reflux disease: a systematic review. Laryngoscope. 2014;124(10):2375-9.

Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013;108(5):679-92.

Ren LH, Chen WX, Qian LJ. Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis. World J Gastroenterol. 2014;20(9):2412-9.

Ferguson DD, DeVault KR. Medical management of gastroesophageal reflux disease. Expert Opin Pharmacother. 2007;8(1):39-47.

Yamashita H, Kanamori A, Fukuchi T, Tsujimae M, Koizumi A, Iwatsubo T et al. Novel prokineticacotiamide reduces transient lower esophageal sphincter relaxation in healthy subjects. Digestion. 2015;92(2):90-8.

Ishimura N, Mori M, Mikami H, Shimura S, Uno G, Aimi M et al. Effects of acotiamide on esophageal motor function and gastroesophageal reflux in healthy volunteers. BMC Gastroenterol. 2015;15(1):117-29.

Tominaga K, Kato M, Takeda H. A randomized, placebo controlled, double-blind clinical trial of rikkunshito for patients with non-erosive reflux disease refractory to proton-pump inhibitor: the G-PRIDE study. J Gastroenterol. 2014;49:1392-405.

Rawla P, Sunkara T, Ofosu A, Gaduputi V. Potassium-competitive acid blockers – are they the next generation of proton pump inhibitors. World J Gastrointest Pharmacol Ther. 2018;9(7):63-8.

Inatomi N, Matsukawa J, Sakurai Y, Otake K. Potassium-competitive acid blockers: advanced therapeutic option for acid-related diseases. Pharmacol Ther. 2016;168:12-22.

Sugano K. Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date. Ther Adv Gastroenterol. 2018;11:1756283X17745776.

Echizen H. The first-in-class potassium-competitive acid blocker, VonoprazanFumarate: pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet. 2016;55(4):409-18.

Jenkins H, Sakurai Y, Nishimura A, Okamoto H, Hibberd M, Jenkins R et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2015;41(7):636-48.

Simon WA, Herrmann M, Klein T, Shin JM, Huber R, Senn-Bilfinger J et al. Soraprazan: Setting New Standards in Inhibition of Gastric Acid Secretion. J Pharmacol Exp Ther. 2007;321(3):866-74.

Mermelstein J, Mermelstein AC, Chait MM. Tegoprazan to treat gastroesophageal reflux disease. Drugs Today (Barc). 2020;56:715-21.

Takahashi N, Take Y. Tegoprazan, A novel potassium-competitive acid blocker to control gastric acid secretion and motility. J Pharmacol Exp Ther. 2018;364(2):275-86.

Surdea-Blaga T, Băncilă I, Dobru D, Drug V, Frățilă O, Goldiș A et al. Mucosal protective compounds in the treatment of gastroesophageal reflux disease. A position paper based on evidence of the Romanian society of neurogastroenterology. J Gastrointest Liver Dis. 2016;25(4):537-46.

Ricky Wayne M. The role for pre-polymerized sucralfate in management of erosive and non-erosive gastroesophageal reflux disease – high potency sucralfate-mucin barrier for enteric cytoprotection. Acad. J Gastroenterol Hepatol. 2020;2. AJGH MS. ID.000531.

Smits M, Benninga MA. Mucosal protective agent: sucralfate in the treatment of gastroesophageal reflux disease in children. Esophageal Gastric Disord Infancy Child. 2017:979-81.

Sugiyama T. Mucosal protective drugs. Nihon Rinsho. 2015;73:1147-52.

VanHoeij FB, Weijenborg PW, van den Bergh Weerman MA. Mucosal integrity and sensitivity to acid in the proximal oesophagus in patients with gastroesophageal reflux disease. Am J Physiol Gastrointest Liver Physiol. 2016;311:G117-22.

Nishio H, Terashima S, Nakashima M, Aihara E, Takeuchi K. Involvement of prostaglandin E receptor EP2 subtype and prostacyclin IP receptor in decreased acid response in damaged stomach. J Physiol Pharmacol. 2007;58:407-21.

Martin GR, Wallace JL. Gastrointestinal inflammation: a central component of mucosal defense and repair. Exp Biol Med (Maywood). 2006;231(2):130-7.

Bolaños-Díaz R. Efficacy of drugs used in gastro-oesophageal reflux: network meta-analysis. Pharmacol Pharm. 2013;4:201-8.

Lehmann A, Jensen JM, Boeckxstaens GE. GABAB receptor agonism as a novel therapeutic modality in the treatment of gastroesophageal reflux disease. Adv Pharmacol. 2010;58:287-313.

Koek GH, Sifrim D, Lerut T, Janssens J, Tack J. Effect of the GABA (B) agonist Baclofen in patients with symptoms and duodenogastrooesophageal reflux refractory to proton pump inhibitors. Gut. 2003;52:1397-402.

Lehmann A, Antonsson M, Aurell Holmberg A, Blackshaw LA. Peripheral GABAB receptor agonism as a potential therapy for gastroesophageal reflux disease. J Pharmacol Exp Ther. 2009;331:504-12.

Brändén L, Fredriksson A, Harring E, Jensen J, Lehmann A. The novel, peripherally restricted GABAB receptor agonist lesogaberan (AZD3355) inhibits acid reflux and reduces esophageal acid exposure as measured with 24-h PH metry in dogs. Eur J Pharmacol. 2010;634(1-3):138-41.

Li S, Shi S, Chen F, Lin J. The effects of Baclofen for the treatment of gastroesophageal reflux disease: a meta-analysis of randomized controlled trials. Gastroenterol Res Pract. 2014;2014:1-8.

Hershcovici T, Mashimo H, Fass R. The lower esophageal sphincter. Neurogastroenterol Motil. 2011;23(9):819-30.

Akiyama J, Kuribayashi S, Baeg MK, de Bortoli N, Valitova E, Savarino EV et al. Current and future perspectives in the management of gastroesophageal reflux disease. Ann N Y Acad Sci. 2018;1434(1):70-83.

Sharkey KA, Wiley JW. The role of the endocannabinoid system in the brain-gut axis. Gastroenterology. 2016;151(2):252-66.

Goyal H, Singla U, Gupta U, May E. Role of cannabis in digestive disorders. Eur J Gastroenterol Hepatol. 2017;29(2):135-43.

Badillo R, Francis D. Diagnosis and treatment of gastroesophageal reflux disease. World J Gastrointest Pharmacol Ther. 2014;5(3):105-12.

Camilleri M. Cannabinoids and gastrointestinal motility: pharmacology, clinical effects, and potential therapeutics in humans. Neurogastroenterol Motil. 2018;30(9):e13370.

Hazekamp A, Ware MA, Müller-Vahl KR, Abrams D, Grotenhermen F. The medicinal use of cannabis and cannabinoids an international cross-sectional survey on administration forms. J Psychoact Drugs. 2013;45(3):199-210.

Ferrigno A, Berardo C, Di Pasqua LG, Siciliano V, Richelmi P, Vairetti M. Localization and role of metabotropic glutamate receptors subtype 5 in the gastrointestinal tract. World J Gastroenterol. 2017;23(25):4500-7.

Rohof WO, Lei A, Hirsch DP, Ny L, Astrand M, Hansen MB et al. The effects of a novel metabotropic glutamate receptor 5 antagonist (AZD2066) on transient lower oesophageal sphincter relaxations and reflux episodes in healthy volunteers. Aliment Pharmacol Ther. 2012;35(10):1231-42.

Lindsley CW, Bates BS, Menon UN, Jadhav SB, Kane AS, Jones CK et al. (3-Cyano-5-fluorophenyl)biaryl Negative Allosteric Modulators of mGlu 5: Discovery of a new tool compound with activity in the OSS mouse model of addiction. ACS Chem Neurosci. 2011;2(8):471-82.

Frisby CL, Mattsson JP, Jensen JM, Lehmann A, Dent J, Blackshaw LA. Inhibition of transient lower esophageal sphincter relaxation and gastroesophageal reflux by metabotropic glutamate receptor ligands. Gastroenterology. 2005;129(3):995-1004.

Keywood C, Wakefield M, Tack J. A proof-of-concept study evaluating the effect of ADX10059, a metabotropic glutamate receptor-5 negative allosteric modulator, on acid exposure and symptoms in gastro-oesophageal reflux disease. Gut. 2009;58(9):1192-9.

Zerbib F, Bruley des Varannes S, Roman S, Tutuian R, Galmiche J-P, Mion F et al. Randomised clinical trial: effects of monotherapy with ADX10059, an mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2011;33(8):911-21.

De Ruigh RS, Chen J, Pandolfino JE, Kahrilas PJ. Gaviscon double action liquid (antacid and alginate) is more effective than antacid in controlling postprandial oesphageal acid exposure in GERD patients: a double-blind crossover-study. Aliment Pharmacol Ther. 2014;40:531-47.

Dettmar PW, Gil-Gonzalez D, Fisher J, Flint L, Rainforth D, Moreno-Herrera A et al. A comparative study on the raft chemical properties of various alginate antacid raft-forming products. Drug Dev Ind Pharm. 2018;44(1):30-9.

Zhao CX, Wang JW, Gong M. Efficacy and safety of alginate formulations in patients with gastroesophageal reflux disease: A systematic review and meta-analysis of randomized controlled trials. Eur Rev Med Pharmacol Sci. 2020;24:11845-57.

Wilkinson J, Wade A, Thomas SJ, Jenner B, Hodgkinson V, Coyle C. Randomized clinical trial: a double-blind, placebo-controlled study to assess the clinical efficacy and safety of alginate-antacid (Gaviscon Double Action) chewable tablets in patients with gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol. 2019;31(1):86-93.

Shaw M, Dent J, Beebe T, Junghard O, Wiklund I, Lind T et al. The Reflux Disease Questionnaire: a measure for assessment of treatment response in clinical trials. Health Qual Life Outcomes. 2008;6(1):31-53.

Zhang YF, Chen XY, Dai XJ. Influence of omeprazole on pharmacokinetics of domperidone given as free base and maleate salt in healthy Chinese patients. Acta Pharmacol Sci. 2007;28:1243-6.

Sontag S, Robinson M, Roufail W. Daily omeprazole is needed to maintain healing in erosive esophagitis: a US, multicenter, double blind study. Am J Gastroenterol. 1992;87:A1258.

Moroshek AA, Burmistrov MV. An integrated approach to treatment of patients with complicated forms of gastroesophageal reflux disease. Kazan Med J. 2020;101(4):595-602.

Abbasinazari M, Panahi Y, Mortazavi SA, Fahimi F. Effect of combinations of omeprazole plus sustained release Baclofen versus omeprazole alone on symptoms of patients with gastroesophageal reflux disease (GERD). Iran J Pharm Res. 2014;13:1221-36.

Chahuan J, Rey P, Monrroy H. Rumination syndrome. A review article. Rev Gastroenterol Mex (Engl Ed). 2021;86(2):163-71.

Bethesda (MD). Drugs and lactation database (LactMed) Internet. National Library of Medicine; 2006; 2021.

Ummarino D, Miele E, Martinelli M, Scarpato E, Crocetto F, Sciorio E et al. Effect of magnesium alginate plus simethicone on gastroesophageal reflux in infants. J Pediatr Gastroenterol Nutr. 2015;60(2):230-5.