Role and safety of prokinetic drugs in the treatment of upper gastrointestinal motility disorders: an Indian perspective
DOI:
https://doi.org/10.18203/2320-6012.ijrms20233067Keywords:
Prokinetics, Functional GI disorders, Motility, ItoprideAbstract
Upper gastrointestinal (GI) motility disorders such as functional dyspepsia (FD), gastroesophageal reflux disease, and gastroparesis are associated with symptoms such as acid reflux, regurgitation, bloating, and heartburn. This review summarizes the prevalence, diagnosis and management of upper GI motility disorders in clinical practice in India, with focus on the use of prokinetics. Lifestyle and dietary modifications, psychotherapy, and pharmacotherapy form the armamentarium for management of motility disorders. Among pharmacotherapies, prokinetics increase gastric emptying and provide symptomatic relief. However, neurological and cardiovascular safety issues are associated with commonly prescribed prokinetics making it important to judiciously select an appropriate drug after weighing out its risk-benefit profile. While metoclopramide, domperidone, and levosulpiride are widely prescribed prokinetics in Indian clinical practice, they are associated with adverse effects such as extrapyramidal symptoms (EPS) and cardiovascular side effects. Itopride, which is a prokinetic with dual mechanism of action, has been found to have equivalent efficacy to other prokinetics and has shown significant improvement in quality of life and symptoms in randomized controlled trials in patients with FD. It acts as a D2 receptor antagonist and acetylcholinesterase inhibitor. Both these actions cause increase in acetylcholine levels, which increases gastric motility. Itopride also has negligible cardiac and neurological safety concerns. Thus, it is a relatively safer molecule compared with other prokinetics, with no EPS or cardiotoxicity concerns and can be used for the long-term management of upper GI motility disorders in a wide pool of patient groups either alone or in combination with other drug classes.
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Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterol. 2006;130(5):1377-90.
Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterol. 2016;19:S0016-5085.
Sperber AD, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, Tack J et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome foundation global study. Gastroenterol. 2021;160(1):99-114.
Nirwan JS, Hasan SS, Babar Z-U-D, Conway BR, Ghori MU. Global prevalence and risk factors of gastro-oesophageal reflux disease (GORD): systematic review with meta-analysis. Sci Rep. 2020;10(1):5814.
Lacy BE, Weiser K. Gastrointestinal motility disorders: an update. Dig Dis. 2006;24(3-4):228-42.
Singh R, Zogg H, Ghoshal UC, Ro S. Current treatment options and therapeutic insights for gastrointestinal dysmotility and functional gastrointestinal disorders. Front Pharmacol. 2022;13.
Ghoshal UC, Singh R. Frequency and risk factors of functional gastro-intestinal disorders in a rural Indian population. Gastroenterol. 2016;32(2):378-87.
Goyal O, Nohria S, Dhaliwal AS, Goyal P, Somi RK, Chhina et al. Prevalence, overlap, and risk factors for Rome IV functional gastrointestinal disorders among college students in northern India. Ind J Gastroenterol. 2021;40(2):144-53.
Quigley EMM, Lacy BE. Overlap of functional dyspepsia and GERD-diagnostic and treatment implications. Nat Rev Gastroenterol Hepat. 2013;10:175-86.
Yarandi SS, Christie J. Functional dyspepsia in review: pathophysiology and challenges in the diagnosis and management due to coexisting gastroesophageal reflux disease and irritable bowel syndrome. Gastroenterol Res Pract. 2013;351086.
Jehangir A, Parkman HP. Rome IV diagnostic questionnaire complements patient assessment of gastrointestinal symptoms for patients with gastroparesis symptoms. Dig Dis Sci. 2018;63:2231-43.
Harer KN, Hasler WL. Functional dyspepsia: a review of symptoms, evaluation, and treatment options. Gastroenterol Hepatol. 2020;16(2):66-74.
Rome IV Diagnostic Criteria for FGIDs. Available at: https://theromefoundation.org/rome-iv/rome-iv-criteria/. Accessed on 27 April, 2023.
Vakil N, Halling K, Ohlsson L, Wernersson B. Symptom overlap between postprandial distress and epigastric pain syndromes of the Rome III dyspepsia classification. Am J Gastroenterol. 2013;108(5):767-74.
Van den Houte K, Scarpellini E, Verbeure W, Mori H, Schol J, Masuy I et al. The role of GI peptides in functional dyspepsia and gastroparesis: a systematic review. Front Psychiatr. 2020;11:172.
Venerito M, Kandulski A, Malfertheiner P. Functional (Nonulcer) Dyspepsia. In: Dyspepsia in Clinical Practice. Springer New York Dordrecht Heidelberg London. 2011;43-52.
Pittayanon R, Yuan Y, Bollegala NP, Khanna R, Leontiadis GI, Moayyedi P. Prokinetics for functional dyspepsia. Cochrane Database Syst Rev. 2018;10(10):CD009431.
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(8):832-40.
Talley NJ. Functional dyspepsia: advances in diagnosis and therapy. Gut Liver. 2017;11(3):349-57.
Geeraerts A, Houtte BV, Clevers E, Geysen H, Vanuytsel T, Tack J et al. Gastroesophageal reflux disease-functional dyspepsia overlap: do birds of a feather flock together? Am J Gastroenterol. 2020;115(8):1167-82.
Quach DT, Ha QV, Nguyen CT-N, Le QD, Nguyen DT-N, Vu NT-H et al. Overlap of gastroesophageal reflux disease and functional dyspepsia and yield of esophagogastroduodenoscopy in patients clinically fulfilling the Rome IV criteria for functional dyspepsia. Front Med. 2022;9:910929.
Heading RC. Proton pump inhibitor failure in gastro-oesophageal reflux disease: a perspective aided by the Gartner hype cycle. Clin Med (London). 2017;17(2):132-6.
Ren L-H, Chen W-X, Qian L-J, Li S, Gu M, Shi R-H. Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis. World J Gastroenterol. 2014;20(9):2412-9.
Aswath GS, Foris LA, Ashwath AK, Patel K. Diabetic gastroparesis. StatPearls. 2022.
Anudeep V, Vinod KV, Pandit N, Sharma VK, Dhanapathi H, Dutta TK et al. Prevalence and predictors of delayed gastric emptying among Indian patients with long-standing type 2 diabetes mellitus. Indian J Gastroenterol. 2016;35(5):385-92.
Sturm A, Holtmann G, Goebell H, Gerken G. Prokinetics in patients with gastroparesis: a systematic analysis. Digestion. 1999;60:422-7.
Gupta S, Kapoor V, Kapoor B. Itopride: a novel prokinetic agent. JK Science. 2004;6(2):105-8.
Rai RR, Choubal CC, Agarwal M, Khaliq AM, Farishta FJ, Harwani YP et al. A prospective multicentric postmarketing observational study to characterize the patient population with reduced gastrointestinal motility among Indian diabetic patients receiving itopride: the Progress study. Int J Appl Basic Med Res. 2019;9(3):148-53.
Peghini P, Katz PO, Bracy NA, Castell DO. Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors. Am J Gastroenterol. 1998;93(5):763-67.
Katz PO, Anderson C, Khoury R, Castell DO. Gastro-oesophageal reflux associated with nocturnal gastric acid breakthrough on proton pump inhibitors. Ailment Pharmacol Ther. 1998;12(12):1231-4.
Hatlebakk JG, Katz PO, Kuo B, Castell DO. Nocturnal gastric acidity and acid breakthrough on different regimens of omeprazole 40 mg daily. Ailment Pharmacol Ther. 1998;12(12):1235-40.
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. Dis Esophagus. 2017;30(5):1-9.
Cellek S, John AK, Thangiah R, Dass NB, Bassil AK, Jarvie EM et al. 5-HT4 receptor agonists enhance both cholinergic and nitrergic activities in human isolated colon circular muscle. Neurogasterenterol Motil. 2006;18(9):853-61.
Spiller R. Serotonergic modulating drugs for functional gastrointestinal diseases. Br J Clin Pharmacol. 2002;54(1):11-20.
Quigley EMM. Prokinetics in the management of functional gastrointestinal disorders. J Neurogastroenterol Motil. 2015;21(3):330-36.
Broad J, Sanger GJ. The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin. Br J Pharmacol. 2013;168(8):1859-67.
Vitola J, Vukanovic J, Roden DM. Cisapride-induced torsades de pointes. J Cardiovasc Electrophysiol. 1998;9(10):1109-13.
Mendzelevski B, Ausma J, Chanter DO, Robinson P, Kerstens R, Vandeplassche L et al. Assessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double-blind, placebo- and positive-controlled thorough QT study. Br J Clin Pharmacol. 2012;73(2):203-9.
Claasssen S, Zunkler BJ. Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacol. 2005;74(1):31-6.
Bor S, Demir M, Ozdemir O, Yuksel K. A meta-analysis on the cardiac safety profile of domperidone compared to metoclopramide. United European Gastroenterol J. 2018;6(9):1331-46.
Miller LG, Jankovic J. Metoclopramide-induced movement disorders. Clinical findings with a review of the literature. Arch Intern Med. 1989;149(11):2486-92.
Chaudhary R, Malla G, Kadayat M. Metoclopramide-induced acute dystonic reactions: a case report. J Med Case Rep. 2021;520.
Corazza GR, Biagi F, Albano O, Porro GB, Cheli R, Mazzacca G et al. Levosulpiride in functional dyspepsia: a multicentric, double-blind, controlled trial. Ital J Gastroenterol. 1996;28(6):317-23.
Radhakrishnan D, Goyal V. Levosulpiride induced movement disorder: 7 cases. International Congress, International Parkinson and Movement Disorder Society. 2018.
Shin H-W, Kim MJ, Kim JS, Lee MC, Chung SJ. Levosulpiride-induced movement disorders. Mov Disord. 2009;24(15):2249-53.
Van der Meer YG, Venhuizen WA, Heyland DK, van Zanten ARH. Should we stop prescribing metoclopramide as a prokinetic drug in critically ill patients? Critical Care. 2014;18.
Ganzini L, Casey DE, Hoffman WF, McCall AL. The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. Arch Intern Med. 1993;153(12):1469-75.
Joe J. Levosulpiride-induced neurological adverse effects: a prospective study from a tertiary care center. Ann Indian Acad Neurol. 2020;23(2):174-6.
Hong S-W, Shin H-W. Mosapride-induced movement disorders. J Mov Disord. 2022;15(3):273-6.
Dhakal OP, Dhakal M, Bhandari D. Domperidone-induced dystonia: a rare and troublesome complication. BMJ Case Rep. 2014;bcr2013200282.
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