Gut dysmotility in functional gastrointestinal disorders. Potential for therapeutic adjustment in terms of clinical case management

Gastrointestinal motility disorders can be a leading pathogenetic factor contributing to the development of many common gastroenterological diseases. Motor disorders can be a pathogenetic mechanism of development of both organic pathology (developmental abnormalities, acquired diseases, etc.), and functional gastrointestinal diseases associated with impaired nervous, humoral, metabolic and local regulation. (the latter are quite common in clinical practice). Correction of digestive motility disorders is determined by an understanding of the mechanisms of its complex regulation, which allows you to find the necessary points of application of drugs and select the necessary therapy. The motility of the gastrointestinal tract is primarily affected by prokinetics. Opioids used for many years are considered to be one of the most promising groups of prokinetics with proven effectiveness, they can both enhance and weaken the motor. A mu-, kappa-, and beta-receptor agonist, trimebutin, which acts on all receptors at the same time, coordinates the work of the intestines, and normalizes motility by reducing visceral sensitivity. Trimebutin favorably affects both hyperkinetic and hypokinetic forms of disorders of the motor activity of the gastrointestinal tract. This mechanism of action of trimebutin allows its effective use in patients with functional diseases of the digestive system, including those with the syndrome of their intersection. Trimebutin may be the drug of choice for such a combined pathology as irritable bowel syndrome and functional dyspepsia, the use of which is presented in the article on a clinical example of these two diseases.

1. Drossman D.A., Hasler W.L. Rome IV - Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016;150(6):1257-1261. doi: 10.1053/j.gastro.2016.03.035.

2. Piessevaux H., De Winter B., Louis E., Muls V., De Looze D., Pelckmans P. et al. Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings. Neurogastroenterol Motil. 2009;21(4):378-388. doi: 10.1111/j.1365-2982.2009.01262.x.

3. Shadi S.Y., Christie J. Functional dyspepsia in review: Patho-physiology and challenges in the diagnosis and management due to coexisting gastroe-sophageal reflux disease and irritable bowel syndrome. Gastroenterol Res Pract. 2013;2013:ID351086. doi: 10.1155/2013/351086.

4. Hunt R., Quigley E., Abbas Z., Eliakim A., Emmanuel A., Goh K.-L. et al. WGO Global Guideline - Coping with common GI symptoms in the community. 2013. Available at: https://www.worldgastroenterology.org/ guidelines/global-guidelines/common-gi-symptoms/common-gi-symp-toms-english.

5. Takaki M. Gut pacemaker cells: the interstitial cells of Cajal (ICC). J Smooth Muscle Res. 2003;39(5):137-161. doi: 10.1540/jsmr.39.137.

6. . Newgreen D., Heather Y Enteric Nervous System: Development and Developmental Disturbances. Part 2. Pediatric and Developmental Pathology. 2002;5(3):329-349. doi: 10.1007/s10024-001-0142-y.

7. Klimov P.K., Ustinov V.N. Bioelectric activity of the smooth muscle of the gastrointestinal tract and its relationship to contractile activity. Uspekhi fiziologicheskikh nauk = Progress in Physiological Sciences. 1973;4(4):3-33.

8. Zai H., Kusano M. Investigation of gastric emptying disorders in patients with functional dyspepsia reveals impaired inhibitory gastric emptying regulation in the early postcibal period. Digestion. 2009;79(1):13-18. doi: 10.1159/000167861.

9. Kindt S., Dubois D., Van Oudenhove L., Caenepeel P., Arts J., Bisschops R., Tack J. Relationship between symptom pattern, assessed by the PAGI-SYM questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia. Neurogastroenterol Motil. 2009;21:1183-e1105. Available at: https://www.academia.edu/24803978/Relationship_between_symptom_pattern_assessed_by_the_PAGI-SYM_questionnaire_and_gastric_sensorimotor_dys-function_in_functional_dyspepsia.

10. Lee H.T., Kim B.J. Trimebutine as a modulator of gastrointestinal motility. Arch Pharm Res. 2011;34(6):861-864. doi: 10.1007/s12272-011-0600-7.

11. Yang YJ., Bang C.S., Baik G.H., Park T.Y., Shin S.P., Suk K.T., Kim DJ. Prokinetics for the treatment of functional dyspepsia: Bayesian network meta-analysis. BMC Gastroenterology. 2017;17(1):83. doi: 10.1186/s12876-017-0639-0.

12. Eamonn M.M. Quigley. Prokinetics in the Management of Functional Gastrointestinal Disorders. J Neurogastroenterol Motil. 2015;21(3):330-336. doi: 10.5056/jnm15094.

13. Roman FJ., Lanet S., Hamon J., Brunelle G., Maurin A., Champeroux P et al. Pharmacological Properties of Trimebutine and N-Monodesmethyltrime-butine. J Pharmacol Exp Ther. 1999;289(3):1391-1397. Available at: http//jpet.aspetjournals.org/content/289/3/1391.short.

14. Roman F., Pascaud X., Taylor J.E., Junien J.L. Interactions of trimebutine with guinea-pig opioid receptors. J Pharm Pharmacol. 1987;39(5):404-407. doi: 10.1111/j.2042-7158.1987.tb03409.x.

15. Borodulina E.V., Mareyev I.V., Kolokoltsova M.Yu., Samykina I.A., Udut V.V. Comparative efficiency of Neobutine® Retard, film-coated prolonged-release tablets 300 mg, and Trimedat®, tablets 200 mg, in patients with irritable bowel syndrome. Farmateka = Pharmateka. 2017;(S5-17):72-77. (In Russ.) Available at: https://pharmateca.ru/ru/archive/article/35740.

16. Minushkin O.N. Combined functional disorders (diseases) of the gastrointestinal tract. Diagnostic and treatment approaches. Meditsinskiy sovet = Medical Council. 2015;(13):20-25. (In Russ.) doi: 10.21518/2079-701X-2015-13-20-25.

17. Gwee K.A., Chua A.S.B. Functional dyspepsia and irritable bowel syndrome, are they different entities and does it matter. World J Gastroenterol. 2006;12(17):2708-2712. doi: 10.3748/wjg.v12.i17.2708.

18. Delvaux M., Wingate D. Trimebutine: mechanism of action, effects on gastrointestinal function and clinical results. J Int Med Res. 1997;25(5):225-246. doi: 10.1177/030006059702500501.

19. Aktas A., Caner B., Ozturk F., Bayhan H., Nazin Y., Mentes T. The effect of trimebutine maleate on gastric emptying in patients with non-ulcer dyspepsia. Ann Nucl Med. 1999;13(4):231-234. doi: 10.1007/bf03164897.

20. Butorova L.I., Tokmulina G.M., Plavnik T.E., Rassypnova L.I., Mamieva Z.A. Roman criteria IV irritable intestine syndrome: evolution of views on pathogenesis, diagnostics and treatment. Lechashchiy vrach = Attending physician. 2017;(3):61-64. (In Russ.) Available at: https://www.lvrach.ru/2017/03/15436690/.