Possibilities of modern pharmacotherapy in patients with dysfunction of the sphincter of Oddi

Pain  in the  right  hypochondrium is one  of the  most  frequent  complaints  in patients with  diseases  of the  biliary system. According to statistics, every tenth  person experiences unpleasant sensations in the upper right abdomen  after drinking alcohol, fatty, fried or salty food, as well as after  psychoemotional and physical exertion. The most  common  of the  pathologies of the  biliary system  is the  sphincter  of Oddi dysfunction  (SOD). SOD is a clinical syndrome  caused  by a functional  disorder of sphincter  of Oddi (SO), which leads  to the  development of abdominal  pain syndrome, increased activity of liver and / or pancreatic enzymes, dilatation of the common bile duct and the main pancreatic duct. One of the methods of treatment of SOD is drug  therapy,  accompanied by the  following  groups  of drugs:  antispasmodics, nitrates,  choleretics,  antidepressants, etc. At the  same  time, many medications show low efficacy against  SOD, or cause  pronounced side  effects. At present,  for the treatment of sphincter  of Oddi dysfunction,  the  domestic  drug  from the  group  of myotropic  antispasmodics, hymecromon, Holicron, has the optimal  characteristics in terms  of price-quality  ratio in the Russian pharmacological market. The drug has a selective  antispasmodic effect  on SO, and also has a choleretic effect. Mechanism  of antispasmodic action  is an increase in the concentration of nitric oxide (II) and cyclic mononucleotides, which through  a cascade  of biochemical  reactions  leads to a decrease in the number of calcium ions in the cell and a decrease in the tone of smooth  myocytes of SO and gallbladder. The drug is absorbed  into the blood in a small amount, which excludes  its systemic effect and determines the selectivity of the effect on the biliary system. According to the results  of clinical testing  and consideration of a specific clinical case, it can be concluded that  the use of hymecromone (Holicron) reduces  the severity of pain syndrome  and reduces  dyspepsia  syndrome, good tolerability  and absence of side effects that  would require withdrawal  of the drug are also recorded.

1. Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta. 2013;1830(8):4117–4129. https://doi.org/10.1016/j.bbagen.2013.04.016.

2. Williamson JB. Effect of Morphine after Cholecystectomy. Br Med J. 1941;1:215. https://doi.org/10.1136/bmj.1.4179.215-a.

3. Smyth MJ. Exploration of the Common Bile Duct for Stone. Drainage with T-Tube and Cholangiography. Br Med J. 1941;1:111–126.4. https://doi.org/10.1136/bmj.1.4177.111.

4. Kegnæs M, Novovic S, Shabanzadeh DM. Dysfunction of Biliary Sphincter of Oddi – Clinical, Diagnostic and Treatment Challenges. J Clin Med. 2023;12(14):4802. https://doi.org/10.3390/jcm12144802.

5. Bueverov AО. Sphincter of Oddi dysfunction in the post-cholecystectomy period. Meditsinskiy Sovet. 2020;(15):90–95. (In Russ.) https://doi.org/10.21518/2079-701X-2020-15-90-95.

6. Ivashkin VT, Mayev IV, Shulpekova YuO, Baranskaya EK, Okhlobystin AV, Trukhmanov AS et al. Diagnostics and treatment of biliary dyskinesia: clinical guidelines of the Russian gastroenterological Association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018;28(3):63–80. (In Russ.) https://doi.org/10.22416/1382-4376-2018-28-3-63-80.

7. Boivineau G, Gonzalez JM, Gasmi M, Vitton V, Barthet M. Sphincter of Oddi dysfunction. J Visc Surg. 2022;159(1S):S16–S21. https://doi.org/10.1016/j.jviscsurg.2022.01.008.

8. Bordin DS, Dubtsova EA, Selezneva EYa, Kukoleva EO, Lashko ML, Chebotareva MV, Nikolskaya KA. Efficacy and safety of hymecromone various doses in patients who have undergone cholecystectomy. Effective Pharmacotherapy. 2021;17(39):34–38. (In Russ.) https://doi.org/10.33978/2307-3586-2021-17-39-34-38.

9. Bielefeldt K, Saligram S, Zickmund SL, Dudekula A, Olyaee M, Yadav D. Cholecystectomy for biliary dyskinesia: how did we get there? Dig Dis Sci. 2014;59(12):2850–2863. https://doi.org/10.1007/s10620-014-3342-9.

10. Cotton PB, Durkalski V, Romagnuolo J, Pauls Q, Fogel E, Tarnasky P et al. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014;311(20):2101–2109. https://doi.org/10.1001/jama.2014.5220.

11. Drossman DA, Hasler WL. Rome IV – Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016;150(6):1257–1261. https://doi.org/10.1053/j.gastro.2016.03.035.

12. Polunina TE. Biliary dysfunction. Rome consensus IV. Therapy. 2017;(6):100–112. (In Russ.) Available at: https://therapy-journal.ru/archive/article/35489.

13. Andreyev DN, Zaborovsky AV, Trukhmanov AS, Mayev IV, Ivashkin VT. Evaluation of the functional gastrointestinal diseases concept from stand-points of Rome IV (2016) diagnostic criteria (review). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2017;27(1):4–11. (In Russ.) https://doi.org/10.22416/1382-4376-2017-27-1-4-11.

14. Tsukanov VV, Tonkikh YuL, Vasyutin AV. Recommendations for the management of patients with functional disorders of the gall bladder and sphincter of Oddi. Meditsinskiy Sovet. 2017;(11):100–103. (In Russ.) https://doi.org/10.21518/2079-701X-2017-11-100-103.

15. Mekhtiev SN, Mekhtieva OA, Kulikova YuR. Oddi’s sphincter functional disorders in therapeutic practice. Lechaschi Vrach. 2017;(9):77–85. (In Russ.) Available at: https://www.lvrach.ru/2017/9/15436812.

16. Minushkin ON. Postcholecystectomy syndrome, dynamics of ideas, diagnostics, treatment. Meditsinskiy Sovet. 2021;(15):97–103. (In Russ.) https://doi.org/10.21518/2079-701X-2021-15-97-103.

17. Afghani E, Lo SK, Covington PS, Cash BD, Pandol SJ. Sphincter of Oddi Function and Risk Factors for Dysfunction. Front Nutr. 2017;4:1. https://doi.org/10.3389/fnut.2017.00001.

18. Rehman A, Affronti J, Rao S. Sphincter of Oddi dysfunction: an evidence-based review. Expert Rev Gastroenterol Hepatol. 2013;7(8):713–722. https://doi.org/10.1586/17474124.2013.849197.

19. Okhlobystin AV, Ufimtseva AK. Hymecromone in the treatment of biliary diseases: options and prospects. Pediatric Nutrition. 2020;18(5):66–74. (In Russ.) https://doi.org/10.20953/1727-5784-2020-5-66-74.

20. Baryshnikova NV, Sousova YaV. Effectiveness of hymecromone monotherapy in treatment of patients with various pathologies of biliary tract. Medical Alphabet. 2021;(40):14–20. (In Russ.) https://doi.org/10.33667/2078-5631-2021-40-14-20.

21. Kazyulin AN. Biliary pain: characteristics, causes, medical treatment. Experimental and Clinical Gastroenterology. 2015;(9):75–85. (In Russ.) Available at: https://www.elibrary.ru/umgwep.

22. Kazyulin AN. Mascs of functional disorders of the biliary tract. Experimental and Clinical Gastroenterology. 2015;(2):71–81. (In Russ.) Available at: https://www.elibrary.ru/thkcnx.

23. Selivanova GB, Poteshkina NG. Modern Approaches to the Treatment of Biliary Tract Disorders. Lechebnoe Delo. 2015;(1):55–60. (In Russ.) Available at: http://www.atmosphere-ph.ru/modules/Magazines/articles/delo/ld_1_2015_55.pdf.

24. Okhlobystin AV, Ufimtseva AK, Tatarkina MA, Okhlobystina OZ, Ivashkin VT. Efficacy of Hymecromone in Post-Cholecystectomy Patients. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(4):37–44. https://doi.org/10.22416/1382-4376-2021-31-4-37-44.