Ursodeoxycholic acid

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Ursodeoxycholic acid (INN, BAN and AAN), also known as ursodiol (USAN) and the abbreviation UDCA, from the root-word for bear urso, as bear bile contains the substance, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria.

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Endogenous effects

Primary bile acids are produced by the liver and stored in the gall bladder. When secreted into the intestine, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest fats. Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol molecules while breaking up micelles containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat (cholesterol) gallstones non-surgically. It is also used to relieve itching in pregnancy for some women who suffer obstetric cholestasis.

While some bile acids are known to be colon tumor promoters (e.g. deoxycholic acid), others such as ursodeoxycholic acid are thought to be chemopreventive, perhaps by inducing cellular differentiation and/or cellular senescence in colon epithelial cells.

It is believed to inhibit apoptosis.

Ursodeoxycholic acid has also been shown experimentally to suppress immune response such as immune cell phagocytosis. Prolonged exposure and/or increased quantities of systemic (throughout the body, not just in the digestive system) ursodeoxycholic acid can be toxic.

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Medical uses

An incomplete list of the current uses is as follows:

• Reduction in gallstone formation, either in patients with gallstones unfit for cholecystectomy, or obese patients undergoing rapid weight loss to prevent gallstone formation.
• For the treatment of primary biliary cholangitis (also known as primary biliary cirrhosis, PBC).
• To aim to improve bile flow in patients with cystic fibrosis (controversial)
• In newborn infants with impaired bile flow
• After bariatric surgery, to prevent cholelithiasis due to the rapid weight loss with biliary cholesterol oversaturation and also biliary diskinesia secondary to abnormalities in cholecystokinin and biliary enervation.

Meta-analyses have borne out conflicting results on the mortality benefit of UDCA in PBC, however analyses that exclude trials of short duration (i.e. < 2 years) have demonstrated a survival benefit and are generally considered more clinically relevant. A Cochrane systematic review in 2012 found no significant benefit in reducing mortality, the rate of liver transplantation, pruritus or fatigue. Ursodiol is the only FDA approved drug to treat PBC but many patients do not respond; other treatments are under study.

Ursodiol may be used to treat intrahepatic cholestasis of pregnancy, to relieve the symptoms of itching, to decrease infant mortality rate, and to decrease bile absorption. Ursodiol is not believed to reduce maternal mortality from hemorrhage in such cases.

In children, ursodeoxycholic acid use is not licensed, as its safety and effectiveness have not been established. Evidence is accumulating that ursodeoxycholic acid is ineffective and unsafe in neonatal hepatitis and neonatal cholestasis.

There is insufficient evidence to justify routine use of ursodeoxycholic acid in cystic fibrosis, especially that available data for analysis of long-term outcomes such as death or need for liver transplantation is lacking.

In double the recommended daily dose, ursodeoxycholic acid reduces elevated liver enzyme levels in those with primary sclerosing cholangitis, but its use was associated with an increased risk of serious adverse events (the development of cirrhosis, varices, death or liver transplantation) in patients who received ursodeoxycholic acid compared with those who received placebo. Serious adverse events were more common in the ursodeoxycholic acid group than the placebo group. The risk was 2.1 times greater for death, transplantation, or minimal listing criteria in patients on ursodeoxycholic acid than for those on placebo.

It is concluded that ursodeoxycholic acid use is associated with improved serum liver tests that do not always correlate with improved liver disease status. WHO Drug Information advises against its use in primary sclerosing cholangitis in unapproved doses beyond 13-15 mg/kg/day.

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Mechanism of action

The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery. If the patient stops taking the drug the gallstones tend to recur if the condition that gave rise to their formation does not change. For these reasons, it has not supplanted surgical treatment by cholecystectomy.

Ursodeoxycholic acid has been shown to exert anti-inflammatory and protective effects in human epithelial cells of the gastrointestinal tract. It has been linked to regulation of immunoregulatory responses via regulation of cytokines, antimicrobial peptides defensins, and take an active part in increased restitution of wound in the colon. Moreover, UDCA's effects has been shown to have exert actions outside the epithelial cells.

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Trade names

Ursodeoxycholic acid can be chemically synthesized and is marketed under multiple trade names, including Actibile, Actigall, Biliver, Deursil, Egyurso, Udcasid, Udiliv, Udoxyl, Urso, Urso Forte, Ursocol, Ursoliv, Ursofalk, Ursosan, Ursoserinox, Udimarin, Ursonova, and Stener.

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See also

• Chenodeoxycholic acid--an epimer
• Hyodeoxycholic acid--an isomer

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References

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External links

• Ursodeoxycholic acid information at MedlinePlus
• Ursodeoxycholic acid in the British National Formulary

Source of article : Wikipedia