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Reflux Inhibitors and Prokinetics

  • Woo-Jung Song
Chapter

Abstract

Gastro-oesophageal reflux disease (GORD) is a motility disorder that develops when reflux of stomach contents causes troublesome symptoms or complications [1]. This syndrome encompasses a broad range of pathological conditions in which reflux is the root cause of oesophageal or extra-oesophageal problems. Several factors are considered important in the pathophysiology of GORD, including the occurrence of reflux, refluxate constituents, clearance of refluxate, and oesophageal mucosal sensitivity [2]. The roles of each factor vary among individuals and respiratory conditions [3], and contribute to the heterogeneity of this syndrome.

References

  1. 1.
    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;101:1900–20.CrossRefPubMedGoogle Scholar
  2. 2.
    Kahrilas PJ, Boeckxstaens G. Failure of reflux inhibitors in clinical trials: bad drugs or wrong patients? Gut. 2012;61:1501–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Houghton LA, Lee AS, Badri H, DeVault KR, Smith JA. Respiratory disease and the oesophagus: reflux, reflexes and microaspiration. Nat Rev Gastroenterol Hepatol. 2016;13:445.CrossRefPubMedGoogle Scholar
  4. 4.
    Cazzola M, Segreti A, Calzetta L, Rogliani P. Comorbidities of asthma: current knowledge and future research needs. Curr Opin Pulm Med. 2013;19:36–41.CrossRefPubMedGoogle Scholar
  5. 5.
    Brown JP, Martinez CH. Chronic obstructive pulmonary disease comorbidities. Curr Opin Pulm Med. 2016;22:113–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Fahim A, Crooks M, Hart SP. Gastroesophageal reflux and idiopathic pulmonary fibrosis: a review. Pulm Med. 2011;2011:1.CrossRefGoogle Scholar
  7. 7.
    Morice A. The diagnosis and management of chronic cough. Eur Respir J. 2004;24:481–92.CrossRefPubMedGoogle Scholar
  8. 8.
    Morice AH. Airway reflux as a cause of respiratory disease. Breathe. 2013;9:256–66.CrossRefGoogle Scholar
  9. 9.
    Johnston N, Ondrey F, Rosen R, Hurley BP, Gould J, Allen J, DelGaudio J, Altman KW. Airway reflux. Ann N Y Acad Sci. 2016;1381:5–13.CrossRefPubMedGoogle Scholar
  10. 10.
    Komatsu Y, Hoppo T, Jobe BA. Proximal reflux as a cause of adult-onset asthma: the case for hypopharyngeal impedance testing to improve the sensitivity of diagnosis. JAMA Surg. 2013;148:50–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Lee AL, Goldstein RS. Gastroesophageal reflux disease in COPD: links and risks. Int J Chron Obstruct Pulmon Dis. 2015;10:1935–49.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Boeckxstaens G, El-Serag HB, Smout AJ, Kahrilas PJ. Symptomatic reflux disease: the present, the past and the future. Gut. 2014;63:1185–93.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Herregods TV, Pauwels A, Jafari J, Sifrim D, Bredenoord AJ, Tack J, Smout AJ. Determinants of reflux-induced chronic cough. Gut. 2017;66:2057.CrossRefPubMedGoogle Scholar
  14. 14.
    Kahrilas PJ, Howden CW, Hughes N, Molloy-Bland M. Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease. Chest. 2013;143:605–12.CrossRefPubMedGoogle Scholar
  15. 15.
    Holbrook JT, Wise RA, Gold BD, Blake K, Brown ED, Castro M, Dozor AJ, Lima JJ, Mastronarde JG, Sockrider MM. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA. 2012;307:373–81.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kiljander TO, Junghard O, Beckman O, Lind T. Effect of esomeprazole 40 mg once or twice daily on asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2010;181:1042–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Chan WW, Chiou E, Obstein KL, Tignor AS, Whitlock TL. The efficacy of proton pump inhibitors for the treatment of asthma in adults: a meta-analysis. Arch Intern Med. 2011;171:620–9.CrossRefPubMedGoogle Scholar
  18. 18.
    American Lung Association Asthma Clinical Research Centers. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360:1487–99.CrossRefPubMedCentralGoogle Scholar
  19. 19.
    Holloway RH, Hongo M, Berger K, McCallum RW. Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology. 1985;89:779–84.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhang Q, Lehmann A, Rigda R, Dent J, Holloway RH. Control of transient lower oesophageal sphincter relaxations and reflux by the GABAB agonist baclofen in patients with gastro-oesophageal reflux disease. Gut. 2002;50:19–24.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Brooks P, Glaum S, Miller R, Spyer K. The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro. J Physiol. 1992;457:115.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Page AJ, Blackshaw LA. GABAB receptors inhibit mechanosensitivity of primary afferent endings. J Neurosci. 1999;19:8597–602.CrossRefPubMedGoogle Scholar
  23. 23.
    Lidums I, Lehmann A, Checklin H, Dent J, Holloway RH. Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology. 2000;118:7–13.CrossRefPubMedGoogle Scholar
  24. 24.
    Cange L, Johnsson E, Rydholm H, Lehmann A, Finizia C, Lundell L, Ruth M. Baclofen-mediated gastro-oesophageal acid reflux control in patients with established reflux disease. Aliment Pharmacol Ther. 2002;16:869–73.CrossRefPubMedGoogle Scholar
  25. 25.
    Van Herwaarden MA, Samsom M, Rydholm H, Smout AJPM. The effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter function and reflux symptoms in patients with reflux disease. Aliment Pharmacol Ther. 2002;16:1655–62.CrossRefPubMedGoogle Scholar
  26. 26.
    Ciccaglione AF, Marzio L. Effect of acute and chronic administration of the GABAB agonist baclofen on 24 hour pH metry and symptoms in control subjects and in patients with gastro-oesophageal reflux disease. Gut. 2003;52:464–70.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Koek GH, Sifrim D, Lerut T, Janssens J, Tack J. Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors. Gut. 2003;52:1397–402.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    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.Google Scholar
  29. 29.
    Ertzgaard P, Campo C, Calabrese A. Efficacy and safety of oral baclofen in the management of spasticity: a rationale for intrathecal baclofen. J Rehabil Med. 2017;49:193–203.CrossRefPubMedGoogle Scholar
  30. 30.
    Lehmann A, Antonsson M, Holmberg AA, Blackshaw LA, Brändén L, Bräuner-Osborne H, Christiansen B, Dent J, Elebring T, Jacobson B-M. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action. J Pharmacol Exp Ther. 2009;331:504–12.CrossRefPubMedGoogle Scholar
  31. 31.
    Boeckxstaens G, Beaumont H, Mertens V, Denison H, Ruth M, Adler J, Silberg D, Sifrim D. Effects of lesogaberan on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease. Gastroenterology. 2010;139:409–17.CrossRefPubMedGoogle Scholar
  32. 32.
    Boeckxstaens GE, Beaumont H, Hatlebakk JG, Silberg DG, Björck K, Karlsson M, Denison H. A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial. Gut. 2011;60:1182–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Shaheen NJ, Denison H, Björck K, Karlsson M, Silberg DG. Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial. Gut. 2013;62:1248–55.CrossRefPubMedGoogle Scholar
  34. 34.
    Rydholm H, von Corswant C, Denison H, Jensen JM, Lehmann A, Ruth M, Soderlind E, Aurell-Holmberg A. Reducing adverse effects during drug development: the example of lesogaberan and paresthesia. Clin Ther. 2016;38:946–60.CrossRefPubMedGoogle Scholar
  35. 35.
    Lal R, Sukbuntherng J, Tai EH, Upadhyay S, Yao F, Warren MS, Luo W, Bu L, Nguyen S, Zamora J. Arbaclofen placarbil, a novel R-baclofen prodrug: improved absorption, distribution, metabolism, and elimination properties compared with R-baclofen. J Pharmacol Exp Ther. 2009;330:911–21.CrossRefPubMedGoogle Scholar
  36. 36.
    Lal R, Zomorodi K, Huff FJ, Luo W, Tovera J, Blumenthal R, Bian A, Cundy KC. Clinical pharmacokinetics and pharmacodynamics of arbaclofen placarbil, a novel reflux inhibitor, in subjects with GERD. Neurogastroenterol Motil. 2010;22:48.Google Scholar
  37. 37.
    Gerson LB, Huff FJ, Hila A, Hirota WK, Reilley S, Agrawal A, Lal R, Luo W, Castell D. Arbaclofen placarbil decreases postprandial reflux in patients with gastroesophageal reflux disease. Am J Gastroenterol. 2010;105:1266–75.CrossRefPubMedGoogle Scholar
  38. 38.
    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.CrossRefPubMedGoogle Scholar
  39. 39.
    Vakil NB, Huff FJ, Cundy KC. Randomised clinical trial: arbaclofen placarbil in gastro-oesophageal reflux disease—insights into study design for transient lower sphincter relaxation inhibitors. Aliment Pharmacol Ther. 2013;38:107–17.CrossRefPubMedGoogle Scholar
  40. 40.
    ClinicalTrials.gov. http://clinicaltrials.gov.
  41. 41.
    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;129:995–1004.CrossRefPubMedGoogle Scholar
  42. 42.
    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;58:1192–9.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Zerbib F, Bruley des Varannes S, Roman S, Tutuian R, Galmiche JP, Mion F, Tack J, Malfertheiner P, Keywood C. Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2011;33:911–21.CrossRefPubMedGoogle Scholar
  44. 44.
    Rouzade-Dominguez ML, Pezous N, David OJ, Tutuian R, Bruley des Varannes S, Tack J, Malfertheiner P, Allescher HD, Ufer M, Ruhl A. The selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056) reduces the incidence of reflux episodes in dogs and patients with moderate to severe gastroesophageal reflux disease. Neurogastroenterol Motil. 2017;29(8).  https://doi.org/10.1111/nmo.13058 Epub 2017 Mar 23.CrossRefGoogle Scholar
  45. 45.
    Xu XH, Yang ZM, Chen Q, Yu L, Liang SW, Lv HJ, Qiu ZM. Therapeutic efficacy of baclofen in refractory gastroesophageal reflux-induced chronic cough. World J Gastroenterol. 2013;19:4386–92.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Hunchaisri N. Treatment of laryngopharyngeal reflux: a comparison between domperidone plus omeprazole and omeprazole alone. J Med Assoc Thail. 2012;95:73–80.Google Scholar
  47. 47.
    Al-Biltagi M, Bediwy AS, Deraz S, Amer HG, Saeed NK. Esomeprazole, versus esomeprazole and domperidone in treatment of gastroesophageal reflux in children with difficult-to-treat asthma. Eur Respir J. 2013;42:P1138.Google Scholar
  48. 48.
    Chun BJ, Lee DS. The effect of itopride combined with lansoprazole in patients with laryngopharyngeal reflux disease. Eur Arch Otorhinolaryngol. 2013;270:1385–90.CrossRefPubMedGoogle Scholar
  49. 49.
    Canning BJ, Mori N, Lehmann A. Antitussive effects of the peripherally restricted GABA B receptor agonist lesogaberan in guinea pigs: comparison to baclofen and other GABA B receptor-selective agonists. Cough. 2012;8:7.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Tack J. Prokinetics and fundic relaxants in upper functional GI disorders. Curr Opin Pharmacol. 2008;8:690–6.CrossRefPubMedGoogle Scholar
  51. 51.
    Tonini M, Cipollina L, Poluzzi E, Crema F, Corazza G, De Ponti F. Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Aliment Pharmacol Ther. 2004;19:379–90.CrossRefPubMedGoogle Scholar
  52. 52.
    Barone JA. Domperidone: a peripherally acting dopamine2-receptor antagonist. Ann Pharmacother. 1999;33:429–40.CrossRefPubMedGoogle Scholar
  53. 53.
    Rao A, Camilleri M. Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther. 2010;31:11–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Richter JE, Sabesin SM, Kogut DG, Kerr RM, Wruble LD, Collen MJ. Omeprazole versus ranitidine or ranitidine/metoclopramide in poorly responsive symptomatic gastroesophageal reflux disease. Am J Gastroenterol. 1996;91:1766.PubMedGoogle Scholar
  55. 55.
    Maddern GJ, Kiroff GK, Leppard PI, Jamieson GG. Domperidone, metoclopramide, and placebo. All give symptomatic improvement in gastroesophageal reflux. J Clin Gastroenterol. 1986;8:135–40.CrossRefPubMedGoogle Scholar
  56. 56.
    Bellissant E, Duhamel JF, Guillot M, Pariente-Khayat A, Olive G, Pons G. The triangular test to assess the efficacy of metoclopramide in gastroesophageal reflux. Clin Pharmacol Ther. 1997;61:377–84.CrossRefPubMedGoogle Scholar
  57. 57.
    Hibbs AM, Lorch SA. Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review. Pediatrics. 2006;118:746–52.CrossRefPubMedGoogle Scholar
  58. 58.
    Bines JE, Quinlan JE, Treves S, Kleinman RE, Winter HS. Efficacy of domperidone in infants and children with gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 1992;14:400–5.CrossRefPubMedGoogle Scholar
  59. 59.
    Pritchard DS, Baber N, Stephenson T. Should domperidone be used for the treatment of gastro-oesophageal reflux in children? Systematic review of randomized controlled trials in children aged 1 month to 11 years old. Br J Clin Pharmacol. 2005;59:725–9.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Van Nueten J, Van Daele P, Reyntjens A, Janssen P, Schuurkes J. Gastrointestinal motility stimulating properties of cisapride, a non-antidopaminergic non-cholinergic compound. In: Gastrointestinal motility. Dordrecht: Springer; 1984. p. 513–20.CrossRefGoogle Scholar
  61. 61.
    Arabehety JT, Leitao OR, Fassler S, Olarte M, Serrano C. Cisapride and metoclopramide in the treatment of gastroesophageal reflux disease. Clin Ther. 1988;10:421–8.PubMedGoogle Scholar
  62. 62.
    Bravo Matus CA, Flores RM. Comparative study of cisapride and methoclopramide in newborns with gastroesophageal reflex. Invest Med Int. 1995;22:3–7.Google Scholar
  63. 63.
    Tack J, Camilleri M, Chang L, Chey W, Galligan J, Lacy B, Müller-Lissner S, Quigley E, Schuurkes J, Maeyer J. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35:745–67.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Yoshida N, Ito T. Mosapride citrate (AS-4370), a new gastroproltinetic agent, is a partial 5-HT4 receptor agonist in the gut. Neurogastroenterol Motil. 1994;6:197–204.CrossRefGoogle Scholar
  65. 65.
    Ruth M, Finizia C, Cange L, Lundell L. The effect of mosapride on oesophageal motor function and acid reflux in patients with gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol. 2003;15:1115–21.CrossRefPubMedGoogle Scholar
  66. 66.
    Miwa H, Inoue K, Ashida K, Kogawa T, Nagahara A, Yoshida S, Tano N, Yamazaki Y, Wada T, Asaoka D, Fujita T, Tanaka J, Shimatani T, Manabe N, Oshima T, Haruma K, Azuma T, Yokoyama T. Randomised clinical trial: efficacy of the addition of a prokinetic, mosapride citrate, to omeprazole in the treatment of patients with non-erosive reflux disease—a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;33:323–32.CrossRefPubMedGoogle Scholar
  67. 67.
    Hsu YC, Yang TH, Hsu WL, Wu HT, Cheng YC, Chiang MF, Wang CS, Lin HJ. Mosapride as an adjunct to lansoprazole for symptom relief of reflux oesophagitis. Br J Clin Pharmacol. 2010;70:171–9.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Shaheen NJ, Adler J, Dedrie S, Johnson D, Malfertheiner P, Miner P, Meulemans A, Poole L, Tack J, Thielemans L, Troy S, Vakil N, Zerbib F, Ruth M. Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy. Aliment Pharmacol Ther. 2015;41:649–61.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Tack J, Zerbib F, Blondeau K, Varannes S, Piessevaux H, Borovicka J, Mion F, Fox M, Bredenoord A, Louis H, Dedrie S, Hoppenbrouwers M, Meulemans A, Rykx A, Thielemans L, Ruth M. Randomized clinical trial: effect of the 5-HT4 receptor agonist revexepride on reflux parameters in patients with persistent reflux symptoms despite PPI treatment. Neurogastroenterol Motil. 2015;27:258–68.CrossRefPubMedGoogle Scholar
  70. 70.
    Kahrilas PJ, Quigley EMM, Castell DO, Spechler SJ. The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000;14:1503–9.CrossRefPubMedGoogle Scholar
  71. 71.
    Fox M, Menne D, Stutz B, Fried M, Schwizer W. The effects of tegaserod on oesophageal function and bolus transport in healthy volunteers: studies using concurrent high-resolution manometry and videofluoroscopy. Aliment Pharmacol Ther. 2006;24:1017–27.CrossRefPubMedGoogle Scholar
  72. 72.
    Rodriguez-Stanley S, Zubaidi S, Proskin H, Kralstein J, Shetzline M, Miner P. Effect of tegaserod on esophageal pain threshold, regurgitation, and symptom relief in patients with functional heartburn and mechanical sensitivity. Clin Gastroenterol Hepatol. 2006;4:442–50.CrossRefPubMedGoogle Scholar
  73. 73.
    Scarpellini E, Ang D, Pauwels A, De Santis A, Vanuytsel T, Tack J. Management of refractory typical GERD symptoms. Nat Rev Gastroenterol Hepatol. 2016;13:281.CrossRefPubMedGoogle Scholar
  74. 74.
    Kessing BF, Smout AJPM, Bennink RJ, Kraaijpoel N, Oors JM, Bredenoord AJ. Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects. Neurogastroenterol Motil. 2014;26:1079–86.CrossRefPubMedGoogle Scholar
  75. 75.
    Nennstiel S, Bajbouj M, Schmid RM, Becker V. Prucalopride reduces the number of reflux episodes and improves subjective symptoms in gastroesophageal reflux disease: a case series. J Med Case Rep. 2014;8:34.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Pitocco A, Grossi L, Di Berardino M, Ciccaglione AF, Marzio L. Prucalopride increases basal LES tone in patients with esophageal motility disorders. United European Gastroenterol J. 2015;3:A477.Google Scholar
  77. 77.
    Carbone F, Rotondo A, Andrews CN, Holvoet L, Van Oudenhove L, Vanuytsel T, Bisschops R, Caenepeel P, Arts J, Papathanasopoulos A, Tack J. Prucalopride improves symptoms and quality of life in a controlled cross-over trial in gastroparesis. Neurogastroenterol Motil. 2016;28:80.CrossRefGoogle Scholar
  78. 78.
    Vigone B, Caronni M, Severino A, Bellocchi C, Baldassarri AR, Montanelli G, Santaniello A, Beretta L. Efficacy of prucalopride in the treatment of systemic sclerosis-related intestinal involvement: results from an open label cross-over study. Arthritis Rheumatol. 2016;68:1128–9.CrossRefGoogle Scholar
  79. 79.
    Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C. A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med. 2006;354:832–40.CrossRefPubMedGoogle Scholar
  80. 80.
    Scarpellini E, Vos R, Blondeau K, Boecxstaens V, Farré R, Gasbarrini A, Tack J. The effects of itopride on oesophageal motility and lower oesophageal sphincter function in man. Aliment Pharmacol Ther. 2011;33:99–105.CrossRefPubMedGoogle Scholar
  81. 81.
    Kim YS, Kim TH, Choi CS, Shon YW, Kim SW, Seo GS, Nah YH, Choi MG, Choi SC. Effect of itopride, a new prokinetic, in patients with mild GERD: a pilot study. World J Gastroenterol. 2005;11:4210–4.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Dicpinigaitis PV. Effect of the GABA-agonist Baclofen on Bronchial Responsiveness in Asthmatics. Pulm Pharmacol Ther. 1999;12(4):257–60.CrossRefGoogle Scholar
  83. 83.
    Dicpinigaitis PV. Use of baclofen to suppress cough induced by angiotensin-converting enzyme inhibitors. Ann Pharmacother. 1996;30(11):1242–5.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Woo-Jung Song
    • 1
  1. 1.Department of Internal Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea

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