Gastrointestinal motor disorders: treatment with prokinetics
DOI: 10.32364/2587-6821-2022-6-5-252-258
V.A. Akhmedov Omsk State Medical University, Omsk, Russian Federation
Abstract
Prokinetic agents, or prokinetics, are medications that increase and coordinate muscle contractions in the gastrointestinal (GI) tract, including the coordination between various segments of the intestine, and thereby promote the transport of intraluminal content. This paper reviews the current approaches to the use of prokinetics for GI motor disorders. The author addresses the studies on various classes of drugs with prokinetic action that target different pathological mechanisms (including abnormalities of anthro-duodenal coordination manifesting with subjective symptoms and objective delay in stomach emptying). Meanwhile, to date, many of these medications are not approved in the Russian Federation. Domperidon, a drug that is currently used in routine practice and approved in Russia, still proves to be relevant. In functional dyspepsia, gastroparesis, and gastroesophageal reflux disease, this medication is recommended in combination with proton pump inhibitors. Domperidon provides an antiemetic effect and has a favorable safety profile when used for approved indications.
Keywords: functional dyspepsia, gastroesophageal reflux disease, gastroparesis, prokinetics, delay in stomach emptying, anthro-duodenal coordination, antiemetic effect.
For citation: Akhmedov V.A. Gastrointestinal motor disorders: treatment with prokinetics. Russian Medical Inquiry. 2022;6(5):252–258 (in Russ.). DOI: 10.32364/2587-6821-2022-6-5-252-258.
About the author:
Vadim A. Akhmedov — Dr. Sc. (Med.), Professor, Head of the Department of Medical Rehabilitation, Omsk State Medical University; 12, Lenin str., Omsk, 644099, Russian Federation; ORCID iD 0000-0002-7603-6093. Contact information: Vadim A. Akhmedov, e-mail: v_akhmedov@mail.ru.
Financial Disclosure: author has no financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 04.04.2022.
Revised 27.04.2022.
Accepted 26.05.2022.
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26. Van der Ploeg L., Laken H., Sharma S. et al. Preclinical gastrointestinal prokinetic efficacy and endocrine effects of the ghrelin mimetic RM-131. Life Sci. 2014;109(1):20–29. DOI: 10.1016/j.lfs.2014.06.003.
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34. Tack J., Janssen P., Bisschops R. et al. Influence of tegaserod on proximal gastric tone and on the perception of gastric distention in functional dyspepsia. Neurogastroenterol Motil. 2011;23(2):e32–e39. DOI: 10.1111/j.1365-2982.2010.01613.x.
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2. Sarosiek I., Van Natta M., Parkman H.P. et al. Effect of Domperidone Therapy on Gastroparesis Symptoms: Results of a Dynamic Cohort Study by NIDDK Gastroparesis Consortium. Clin Gastroenterol Hepatol. 2022;20(3):e452–e464. DOI: 10.1016/j.cgh.2021.05.063.
3. Chedid V., Halawi H., Brandler J. et al. Gastric accommodation measurements by single photon emission computed tomography and two-dimensional scintigraphy in diabetic patients with upper gastrointestinal symptoms. Neurogastroenterol Motil. 2019;31(6):e13581. DOI: 10.1111/nmo.13581.
4. Bouras E.P., Delgado-Aros S., Camilleri M. et al. SPECT imaging of the stomach: comparison with barostat, and effects of sex, age, body mass index, and fundoplication. Single photon emission computed tomography. Gut. 2002;51(6):781–786. DOI: 10.1136/gut.51.6.781.
5. Carbone F., Tack J., Hoffman I. The Intragastric Pressure Measurement: A Novel Method to Assess Gastric Accommodation in Functional Dyspepsia Children. J Pediatr Gastroenterol Nutr. 2017;64(6):918–924. DOI: 10.1097/MPG.0000000000001386.
6. Tack J., Caenepeel P., Piessevaux H. et al. Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia. Gut. 2003;52(9):1271–1277. DOI: 10.1136/gut.52.9.1271.
7. Orthey P., Dadparvar S., Parkman H.P., Maurer A.H. Enhanced Gastric Emptying Scintigraphy to Assess Fundic Accommodation Using Intragastric Meal Distribution and Antral Contractility. J Nucl Med Technol. 2019;47(2):138–143. DOI: 10.2967/jnmt.118.215566.
8. Mounsey A., Barzin A., Rietz A. Functional Dyspepsia: Evaluation and Management. Am Fam Physician. 2020;101(2):84–88. PMID: 31939638.
9. Cangemi D.J., Lacy B.E. Gastroparesis and functional dyspepsia: different diseases or different ends of the spectrum? Curr Opin Gastroenterol. 2020;36(6):509–517. DOI: 10.1097/MOG.0000000000000677.
10. Nelson A.D., Camilleri M., Acosta A. et al. Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers. Neurogastroenterol Motil. 2016;28(11):1705–1713. DOI: 10.1111/nmo.12870.
11. Vosoughi K., Ichkhanian Y., Jacques J. et al. Role of endoscopic functional luminal imaging probe in predicting the outcome of gastric peroral endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2020;91(6):1289–1299. DOI: 10.1016/j.gie.2020.01.044.
12. Tack J., Camilleri M., Chang L. et al. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35(7):745–767. DOI: 10.1111/j.1365-2036.2012.05011.x.
13. Carbone F., Van den Houte K., Clevers E. et al. Prucalopride in Gastroparesis: A Randomized Placebo-Controlled Crossover Study. Am J Gastroenterol. 2019;114(8):1265–1274. DOI: 10.14309/ajg.0000000000000304.
14. Kuo B., Barnes C.N., Nguyen D.D. et al. Velusetrag accelerates gastric emptying in subjects with gastroparesis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 study. Aliment Pharmacol Ther. 2021;53(10):1090–1097. DOI: 10.1111/apt.16344.
15. Chedid V., Brandler J., Arndt K. et al. Randomised Study: Effects of the 5-HT4 Receptor Agonist Felcisetrag vs Placebo on Gut Transit in Patients with Gastroparesis. Aliment. Pharmacol. Ther. 2021;53(9):1010–1020. DOI: 10.1111/apt.16304.
16. Chapman M.J., Jones K.L., Almansa C. et al. Blinded, Double-Dummy, Parallel-Group, Phase 2a Randomized Clinical Trial to Evaluate the Efficacy and Safety of a Highly Selective 5- Hydroxytryptamine Type 4 Receptor Agonist in Critically Ill Patients with Enteral Feeding Intolerance. JPEN J Parenter Enteral Nutr. 2021;45(1):115–124. DOI: 10.1002/jpen.1732.
17. Beattie D.T., Armstrong S.R., Vickery R.G. et al. The Pharmacology of TD-8954, a Potent and Selective 5-HT(4) Receptor Agonist with Gastrointestinal Prokinetic Properties. Front Pharmacol. 2011;2:25. DOI: 10.3389/fphar.2011.00025.
18. Beattie D.T., Higgins D.L., Ero M.P. et al. An In Vitro Investigation of the Cardiovascular Effects of the 5- HT(4) Receptor Selective Agonists, Velusetrag and TD-8954. Vascul Pharmacol. 2013;58(1–2):150–156. DOI: 10.1016/j.vph.2012.11.002.
19. Stakenborg N., Labeeuw E., Gomez-Pinilla P.J. et al. Preoperative administration of the 5-HT4 receptor agonist prucalopride reduces intestinal inflammation and shortens postoperative ileus via cholinergic enteric neurons. Gut. 2019;68(8):1406–1416. DOI: 10.1136/gutjnl-2018-317263.
20. Kuo B., Scimia C., Dukes G. et al. Randomised Clinical Trial: Safety, Pharmacokinetics and Pharmacodynamics of Trazpiroben (TAK-906), a Dopamine D 2/D 3 Receptor Antagonist, in Patients with Gastroparesis. Aliment Pharmacol Ther. 2021;54(3):267–280. DOI: 10.1111/apt.16451.
21. Pasricha P.J., Yates K.P., Sarosiek I. et al. Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders. Gastroenterology. 2018;154(1):65–76.e11. DOI: 10.1053/j.gastro.2017.08.033.
22. Jacob D., Busciglio I., Burton D. et al. Effects of NK1 receptors on gastric motor functions and satiation in healthy humans: results from a controlled trial with the NK1 antagonist aprepitant. Am J Physiol Gastrointest Liver Physiol. 2017;313(5):G505–G510. DOI: 10.1152/ajpgi.00197.2017.
23. Carlin J.L., Lieberman V.R., Dahal A. et al. Efficacy and Safety of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Randomized, Placebo-Controlled Trial. Gastroenterology. 2021;160(1):76–87.e4. DOI: 10.1053/j.gastro.2020.07.029.
24. Tack J., Depoortere I., Bisschops R. et al. Influence of ghrelin on interdigestive gastrointestinal motility in humans. Gut. 2006;55(3):327–333. DOI: 310.1136/gut.2004.060426.
25. Camilleri M., Papathanasopoulos A., Odunsi S.T. Actions and therapeutic pathways of ghrelin for gastrointestinal disorders. Nat Rev Gastroenterol Hepatol. 2009;6(6):343–352. DOI: 10.1038/nrgastro.2009.72.
26. Van der Ploeg L., Laken H., Sharma S. et al. Preclinical gastrointestinal prokinetic efficacy and endocrine effects of the ghrelin mimetic RM-131. Life Sci. 2014;109(1):20–29. DOI: 10.1016/j.lfs.2014.06.003.
27. Shin A., Camilleri M., Busciglio I. et al. Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics. Diabetes Care. 2013;36(1):41–48. DOI: 10.2337/dc12-1128.
28. Nelson A.D., Camilleri M., Acosta A. et al. Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers. Neurogastroenterol Motil. 2016;28(11):1705–1713. DOI: 10.1111/nmo.12870.
29. Thielemans L., Depoortere I., Perret J. et al. Desensitization of the human motilin receptor by motilides. J Pharmacol Exp Ther. 2005;313(3):1397–1405. DOI: 10.1124/jpet.104.081497.
30. Parkman H.P., Pagano A.P., Vozzelli M.A., Ryan J.P. Gastrokinetic effects of erythromycin: myogenic and neurogenic mechanisms of action in rabbit stomach. Am J Physiol. 1995;269(3 Pt 1):G418–G426. DOI: 10.1152/ajpgi.1995.269.3.G418.
31. Ray W.A., Murray K.T., Meredith S. et al. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351(11):1089–1096. DOI: 10.1056/NEJMoa040582.
32. Kusunoki H., Haruma K., Manabe N. et al. Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: randomized controlled study evaluation by real-time ultrasonography. Neurogastroenterol Motil. 2012;24(6):540–545, e250–1. DOI: 10.1111/j.1365-2982.2012.01897.x.
33. Matsueda K., Hongo M., Tack J. et al. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut. 2012;61(6):821–828. DOI: 10.1136/gutjnl-2011-301454.
34. Tack J., Janssen P., Bisschops R. et al. Influence of tegaserod on proximal gastric tone and on the perception of gastric distention in functional dyspepsia. Neurogastroenterol Motil. 2011;23(2):e32–e39. DOI: 10.1111/j.1365-2982.2010.01613.x.
35. Wang X.J., Burton D.D., Breen-Lyles M., Camilleri M. Gastric accommodation influences proximal gastric and total gastric emptying in concurrent measurements conducted in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2021;320(5)G759–G767. DOI: 10.1152/ajpgi.00008.2021.
36. Hasler W.L., Wilson L.A. Nguyen L.A. et al. Opioid Use and Potency Are Associated With Clinical Features, Quality of Life, and Use of Resources in Patients With Gastroparesis. Clin Gastroenterol Hepatol. 2019;17(7):1285–1294.e1. DOI: 10.1016/j.cgh.2018.10.013.
37. Camilleri M., Sanders K.M. Opiates, the Pylorus, and Gastroparesis. Gastroenterology. 2020;159(2):414–421. DOI: 10.1053/j.gastro.2020.04.072.
38. Coleski R., Anderson M.A., Hasler W.L. Factors associated with symptom response to pyloric injection of botulinum toxin in a large series of gastroparesis patients. Dig Dis Sci. 2009;54(12):2634–2642. DOI: 10.1007/s10620-008-0660-9.
39. Arts J., Holvoet L., Caenepeel P. et al. Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis. Aliment Pharmacol Ther. 2007;26(9):1251–1258. DOI: 10.1111/j.1365-2036.2007.03467.x.
40. Tonini M., Cipollina L., Poluzzi E. et al. Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Aliment Pharmacol Ther. 2004;19(4):379–390. DOI: 10.1111/j.1365-2036.2004.01867.x.
41. Camilleri M., Parkman H.P., Shafi M.A. et al. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108(1):18–37; quiz 38. DOI: 10.1038/ajg.2012.373.
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