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Ursodeoxycholic acid and its uses

Views: 9     Author: Site Editor     Publish Time: 2022-11-17      Origin: Site

Ursodeoxycholic acid:

Ursodeoxycholic acid (UDCA),also known as ursediol,is a secondary bile acid that is metabolized by gut bacteria in humans and most other species.It is synthesized in the liver of some species and was first found in the bile of Ursus bears,from which it is named.It is used in purified form for the treatment or prevention of a variety of liver or bile duct disorders.It is available as a generic medicine.Ursodeoxycholic acid is a bile acid used in the treatment of primary biliary cirrhosis (PBC), in dissolving clear gallstones in patients with a functioning gallbladder,and in the treatment of hepatobiliary disease associated with cystic fibrosis in pediatric patients.

Medical Use

UDCA has been used as a medicine to treat gallstone disease (cholelithiasis) and bile sludge. [8] [9] UDCA helps reduce cholesterol saturation in bile and causes gradual dissolution of cholesterol-rich gallstones.UDCA may be given after bariatric surgery to prevent cholelithiasis,which often occurs due to rapid weight loss leading to supersaturation of the biliary tract with cholesterol and hormonal changes secondary to biliary dyskinesia.

Primary biliary cholangitis Ursodeoxycholic acid-healthewaybio

UDCA is used to treat primary biliary cholangitis (PBC; formerly known as primary biliary cirrhosis), and it improves biomarkers.A meta-analysis confirmed conflicting results regarding mortality benefits.However, analyzes excluding trials of shorter duration (i.e. < 2 years) have demonstrated a survival benefit and are generally considered more clinically relevant.A 2012 Cochrane systematic review found no significant benefit in reducing mortality, liver transplantation rates, pruritus, or fatigue.Ursodiol and obeticholic acid are FDA-approved for the treatment of primary biliary cholangitis.

Primary sclerosing cholangitis

UDCA use was associated with improvements in serum liver function tests, which were not always associated with improvements in liver disease status.The World Health Organization Medicines Information advises against its use in primary sclerosing cholangitis at unapproved doses exceeding 13-15 mg/kg/day.

UDCA at doses of 28-30mg/kg/day was associated with a 2.3-fold increased risk of death and need for liver transplantation in patients with primary sclerosing cholangitis despite reduced liver enzymes.

Intrahepatic cholestasis of pregnancy

UDCA has been used in intrahepatic cholestasis of pregnancy.UDCA relieved itching in mothers and may reduce the number of preterm births.The effects on fetal distress and other adverse outcomes are unlikely to be large.

Cholestasis 

UDCA is not licensed for use in children because its safety and effectiveness have not been established.There is growing evidence that ursodeoxycholic acid is ineffective,unsafe, and its use is significantly associated with morbidity and mortality from neonatal hepatitis and neonatal cholestasis.

Other Conditions

UDCA is considered an adequate treatment for bile reflux gastritis.In cystic fibrosis, there is insufficient evidence to justify the routine use of UDCA,especially because of the lack of available data on long-term outcomes such as death or the need for liver transplantation.UDCA is also effective for nonalcoholic fatty liver disease and hepatic bile duct deficiency syndrome. Biliary obstruction such as biliary atresia is contraindicated. It is ineffective against liver allograft rejection and graft-versus-host disease involving the liver.

Side Effects

Diarrhea was the most common adverse event in the UDCA gallstone lysis trial, with an incidence of 2% to 9%, which was lower than that seen with chenodeoxycholic acid therapy.Bacterial conversion of UDCA to chenodeoxycholic acid may be the mechanism of this side effect Increased right upper quadrant pain and pruritus have occasionally been reported in trials in patients with PBC Other symptoms may include abdominal distension,weight gain,and occasionally hair thinning.

Mechanism

Choleretic Effect

Primary bile acids are produced by the liver and stored in the gallbladder.When secreted into the gut,primary bile acids can be metabolized by gut bacteria to secondary bile acids.Primary and secondary bile acids help the body digest fats.Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which cholesterol molecules are absorbed by the gut while breaking down the micelles that contain cholesterol.This drug reduces the absorption of cholesterol and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery.Cholestatic liver disease involves multiple mechanisms.

Immunomodulatory Effects

Ursodeoxycholic acid has also been experimentally shown to suppress immune responses, such as immune cell phagocytosis.Ursodeoxycholic acid may be toxic with prolonged exposure and/or systemic (throughout the body, not just in the digestive system) increased amounts.

Anti-inflammatory Effects

Ursodeoxycholic acid has been shown to exert anti-inflammatory and protective effects in human epithelial cells of the gastrointestinal tract.It has been implicated in the regulation of immunomodulatory responses through regulation of cytokines,antimicrobial peptide defenses, increased colonic wound recovery. Furthermore, the effects of UDCA have been shown to be extraepithelial.

While some bile acids are known to be colon tumor-promoting agents (e.g., deoxycholic acid), others, such as ursodeoxycholic acid, are thought to have chemopreventive effects, possibly by inducing cellular differentiation of colonic epithelial] cells and/or cellular senescence.


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