Keywords
How to Cite
Abstract views: 642 PDF Downloads: 184
Abstract
Cholagogues are among the most popular in clinical practice, although only hymecromone (Biloddi) has an evidence base.
All cholagogues are divided into two categories: choleretics, which increase the liverʼs bile production, and cholekinetics, which increase the gallbladderʼs contractions and speed up the passage of bile from it into the duodenum. However, this division is arbitrary because cholagogues typically have both choleretic and cholekinetic effects, which are expressed to varying degrees in each drug and only prevail over each other. Hydrocholeretics are distinguished in the group of choleretics — drugs that increase bile secretion due to the water component.
The action of choleretics not only increases the liverʼs bile production volume, but also boosts the bileʼs bile salt content, thereby reducing its lithogenicity. The pancreas produces more lipase and bicarbonates, which can have both positive and negative effects. Additionally, it reduces the fermentation processes in the intestine, aiding in the correction of the intestinal floraʼs composition.
Cholekinetics usually act by increasing the production of cholecystokinin by the duodenal mucosa. As a result, gallbladder contractions increase, and the tone of Oddiʼs sphincter decreases. Cholekinetics include cholecystokinin octapeptide, polyhydric alcohols, sorbitol and xylitol, magnesium sulfate, Carlsbad salt, barberry preparations, and ceruletide. Cholekinetics are rarely administered for the planned treatment of hypokinetic dysfunction of the gallbladder. These drugs are usually used for diagnostic duodenal intubation as well as for non-tube duodenal tubage. A modern choleretic drug with hydrocholeretic properties and selective spasmolytic effect on the biliary sphincters, including the Oddi sphincter — hymecromone (Biloddi) — a synthetic analogue of the natural substance umbeliferone. The drug has an extensive evidence base and is registered in many countries of the European Union for the treatment of biliary dysfunctions, relief of biliary pain, and dyspeptic phenomena due to the choleretic effect and spasmolytic effect on the biliary sphincters in the absence of stimulation of gallbladder contraction. Hymecromone reduces the basal pressure of Oddiʼs sphincter and prolongs its opening time, thereby increasing (restoring) bile passage through the bile ducts. This is the only cholagogue that is not contraindicated in cholelithiasis.
References
Аршинов П. С., Коліуш О. І., Мухіна Е. П., Васильєва В. В. Терапія, що коригує дискінезії жовчовивідної системи при гепатиті А з тривалою реконвалесценцією. Вірусні хвороби, токсоплазмоз, хламідіоз. Матеріали науково-практичної конференції і пленуму Асоціації інфекціоністів України. Тернопіль: Б. в., 2004. С. 10–11.
Бабак О. Я., Соломенцева Т. А. Влияние комбинированной антигомотоксической терапии на состояние слизистых оболочек желудка и пищевода у больных хроническим гастритом и эзофагитом. Сучасна гастроентерологія. 2005. № 4. С. 67–70.
Боткин С. П. О желчной колике: Курс клиники внутренних болезней и клинические лекции. М.: Медгиз, 1950. Т. 2. (Клин. лекции). С. 467–505.
Губергриц Н. Б., Колкина В. Я. Эффективность антигомотоксической терапии при сочетании алкогольных заболеваний печени и поджелудочной железы. Сучасна гастроентерологія. 2004. № 1. С. 34–39.
Губергріц Н. Б., Колкіна В. Я. Антигомотоксична терапія в реабілітації хворих хронічним панкреатитом: метод. рекомендації МОЗ України. Київ, 2005. 32 с.
Звягинцева Т. Д., Гриднева С. В. Дисфункция сфинктера Одди и ее коррекция. Укр. мед. газета. 2006. № 1. С. 6–7.
Комплексные антигомотоксические препараты. Киев: Б. и., 2004. 279 с.
Крылова В. Ю. Применение антигомотоксических препаратов для устранения побочных эффектов при длительном приеме антиконвульсантов. Вісник епілептології. 2005. № 1. С. 83.
Никула Т. Д., Мойсеєнко В. О., Біякова О. В. Застосування комплексних антигомотоксичних препаратів при захворюваннях гепатобіліарної системи. Биол. терапия. 2003. № 1. С. 30–33.
Охлобыстин А. В., Уфимцева А. К. Применение гимекромона при заболеваниях желчевыводящих путей: возможности и перспективы. Вопросы детской диетологии. 2020. Т. 18, № 5. С. 66–74.
Скакун Н. М., Губергриц А. Я. Фармакотерапия заболеваний печени и желчных путей. Киев: Здоров’я, 1971. 148 с.
Терапия заболеваний желудочно-кишечного тракта с применением антигомотоксических препаратов: метод. рекомендации. Киев: Б. и., 2004. 120 с.
Циммерман Я. С. Гастроэнтерология. М.: ГЭОТАР-Медиа, 2015. 816 с.
Чекман І. С. Клінічна фітотерапія. Київ: ТОВ «РАДА», 2006. 655 с.
Abate A., Dimartino V., Spina P., Costa P. L., Lombardo C., Santini A., Del Piano M., Alimonti P. Hymecromone in the treatment of motor disorders of the bile ducts: a multicenter, double-blind, placebo-controlled clinical study. Drugs Exp. Clin. Res. 2001. Vol. 27, No 5–6. P. 223–231.
Aguilar K., Sharma A. K., Yang T., Mehta D., Panda C. S., Lokeshwar V. B. Teaching an Old Drug a New Trick: Targeting Treatment Resistance in Genitourinary Cancers. J. Cell. Signal. 2024. Vol. 5, No 2. P. 51–56.
Draese K., Hirche H. Pharmakologische Beeinflussung der Sphincter Oddi-Motorik. Postoperative Elektromanometrie der Gallenwege [Pharmacological effects on the motor activity of Oddi’s sphincter. Postoperative electromanometric measurements of the bile ducts]. Fortschr. Med. 1980. Vol. 98, No 39. P. 1529–1533. German.
Fang Y., Wang H., Zhu W., Wang L., Liu H., Xu X., Yin W., Sima Y., Xu S. Antioxidative properties of 4-methylumbelliferone are related to antibacterial activity in the silkworm (Bombyx mori) digestive tract. J. Comp. Physiol. B. 2014. Vol. 184, No 6. P. 699–708.
Fischer D., Krumme H. Vergleich der Wirksamkeit von 4-Methylumbelliferon und Hyoscin-N-butylbromid in der Therapie nach Gallenwegseingriffen [Comparison of effectiveness of 4-methylumbelliferone and hyoscine-N-butylbromide in therapy following biliary tract surgery]. Med. Welt. 1980. Vol. 31, No 23. P. 894–897. German.
Garrett E. R., Venitz J., Eberst K., Cerda J. J. Pharmacokinetics and bioavailabilities of hymecromone in human volunteers. Biopharm. Drug Dispos. 1993. Vol. 14, No 1. P. 13–39.
Heistermann H. P., Krawzak H. W., Andrejeweski K., Hohlbach G. Pharmakologische Beeinflussung der postprandialen Gallengangskinetik —Sonographische Lumenmessung des Gallenganges [Pharmacologic modification of postprandial bile duct kinetics — ultrasound measurement of the lumen of the bile duct]. Ultraschall. Med. 1997. Vol. 18, No 2. P. 84–87. German.
Hoffmann R. M., Schwarz G., Pohl C., Ziegenhagen D. J., Kruis W. Gallensäure-unabhängige Wirkung von Hymecromon auf die Gallesekretion und die Motilität der Gallenwege [Bile acid-independent effect of hymecromone on bile secretion and common bile duct motility]. Dtsch. Med. Wochenschr. 2005. Vol. 130, No 34–35. P. 1938–1943. German.
Krawzak H. W., Heistermann H. P., Andrejewski K., Hohlbach G. Postprandial bile-duct kinetics under the influence of 4-methylumbelliferone (hymecromone). Int. J. Clin. Pharmacol. Ther. 1995. Vol. 33, No 10. P. 569–572.
Lopez-Gonzalez J. S., Prado-Garcia H., Aguilar-Cazares D., Molina-Guarneros J. A., Morales-Fuentes J., Mandoki J. J. Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines. Lung Cancer. 2004. Vol. 43, No 3. P. 275–283.
Mühlig J. Hymecromone in postoperative therapy after choledochotomy. MMW, Munchener medizinische Wochenschrift. 1983. Vol. 125, No 16. P. 345–347.
Nagy N., Kaber G., Sunkari V. G., Marshall P. L., Hargil A., Kuipers H. F., Ishak H. D., Bogdani M., Hull R. L., Grandoch M., Fischer J. W., McLaughlin T. L., Wight T. N., Bollyky P. L. Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes. Matrix Biol. 2023. Vol. 123. P. 34–47.
Nagy N., Kuipers H. F., Frymoyer A. R., Ishak H. D., Bollyky J. B., Wight T. N., Bollyky P. L. 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer. Front. Immunol. 2015. Vol. 6. P. 123.
Nersesov A. V., Kaybullaeva D. A., Rakhmetova V. S., Lozinskaya I. A., Kurmangalieva A. K., Ahyupova V. S., Orazbaeva A. B., Kanabaeva A. K., Shulpekova Yu. O. Hymecromone Administration in Real Clinical Practice: Results of the Prospective Multicentre Observational Study in the Republic of Kazakhstan. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021. Vol. 31, No 5. P. 34–50.
Okhlobystin A., Budzinsky S., Okhlobystina O., Ponkratova N., Ivashkin V. Impact of Biliary Sludge to Development of Chronic Pancreatitis. Pancreatology. 2017. Vol. 17, No 3, Suppl. P. S74–75.
Petrioli G. Perorale Hymecromon-Behandlung bei Patientinnen unter langjähriger Psychopharmaka-Therapie [Peroral hymecromone treatment of female patients under long term therapy with psychopharmaceuticals]. Fortschr. Med. 1979. Vol. 97, No 25–26. P. 1174–1178. German.
Piccioni F., Fiore E., Bayo J., Atorrasagasti C., Peixoto E., Rizzo M., Malvicini M., Tirado-González I., García M. G., Alaniz L., Mazzolini G. 4-methylumbelliferone inhibits hepatocellular carcinoma growth by decreasing IL-6 production and angiogenesis. Glycobiology. 2015. Vol. 25, No 8. P. 825–835.
Quaranta S., Rossetti S., Camarri E. Studio clinico in doppia cecità tra imercromone e placebo nei disordini motori delle vie biliari dopo colecistectomia [Double-blind clinical study on hymecromone and placebo in motor disorders of the bile ducts after cholecystectomy]. Clin. Ter. 1984. Vol. 108, No 6. P. 513–517. Italian.
Ramesh B., Pugalendi K. V. Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats. J. Med. Food. 2006. Vol. 9, No 4. P. 562–566.
Sim M. O., Ham J. R., Lee H. I., Seo K. I., Lee M. K. Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice. Chem. Biol. Interact. 2014. Vol. 216. P. 9–16.
Stacchino C., Spanò R., Pettiti A. Spasmolytic activity of some 4-methylumbelliferone derivatives. Boll. Chim. Farm. 1983. Vol. 122, No 3. P. 158–160.
Staritz M. Pharmacology of the sphincter of Oddi. Endoscopy. 1988. Vol. 20, Suppl. 1. P. 171–174.
Štěpánková K., Mareková D., Kubášová K., Sedláček R., Turnovcová K., Vacková I., Kubinová Š., Makovický P., Petrovičová M., Kwok J. C. F., Jendelová P., Machová Urdzíková L. 4-Methylumbeliferone treatment at a dose of 1.2 g/kg/day is safe for long-term usage in rats. Int. J. Mol. Sci. 2023. Vol. 24, No 4. P. 3799.
Takeda S., Aburada M. The choleretic mechanism of coumarin compounds and phenolic compounds. J. Pharmacobiodyn. 1981. Vol. 4, No 9. P. 724–734.
Tanayama S., Kanai Y. Studies on increased bile formation produced by polyoxybenzenes in rats. Jpn. J. Pharmacol. 1977. Vol. 27, No 1. P. 71–78.
Ursofalk: primary biliary cirrhosis, dyspeptic complaints, cholesterol gallstones. Freiburg, 2005. 199 p.
Walter P., Seidel W. Untersuchungen über die Wirkung von-4-Methyl-umbelliferon (Hymecromon) bei Patienten nach operativer Revision der Gallenwege [Studies on the effect of 4-methyl-umbelliferon (Hymecromone) in patients following surgical revision of the biliary pathways]. Chirurg. 1979. Vol. 50, No 7. P. 436–440. German.
Yang S., Ling Y., Zhao F., Li W., Song Z., Wang L., Li Q., Liu M., Tong Y., Chen L., Ru D., Zhang T., Zhou K., Zhang B., Xu P., Yang Z., Li W., Song Y., Xu J., Zhu T., Shan F., Yu W., Lu H. Hymecromone: a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression. Signal. Transduct. Target. Ther. 2022. Vol. 7, No 1. P. 91.
Yoshida E., Kudo D., Nagase H., Shimoda H., Suto S., Negishi M., Kakizaki I., Endo M., Hakamada K. Antitumor effects of the hyaluronan inhibitor 4-methylumbelliferone on pancreatic cancer. Oncol. Lett. 2016. Vol. 12, No 4. P. 2337–2344.