Ursodiol
Encyclopedia
Ursodiol, also known as ursodeoxycholic acid and the abbreviation
UDCA, is one of the secondary bile acid
s, which are metabolic byproducts of intestinal bacteria.
and stored in the gall bladder. When secreted into the colon, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest
fat
s. Ursodeoxycholic acid helps regulate cholesterol
by reducing the rate at which the intestine
absorbs cholesterol molecules while breaking up micelle
s containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat (cholesterol) gallstone
s non-surgically.
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.
it is marketed in capsules of 250 mg under the name Coric by Mexican
pharmaceutical Landsteiner Scientific.
Ursodeoxycholic acid can be chemically synthesized and was brought to market by the Montreal-based Axcan Pharma
in 1998, which continues to market the drug.
The drug reduces cholesterol
absorption and is used to dissolve (cholesterol) gallstone
s in patient
s who want an alternative to surgery
. The drug is very expensive, however, and if the patient stops taking it, 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
.
It is the only FDA approved drug to treat primary biliary cirrhosis
.
A Cochrane review to evaluate if ursodeoxycholic acid has any beneficial effect in primary biliary cirrhosis patients included 16 randomized clinical trials with a total of 1447 patients. The primary outcome measures were mortality and mortality or liver transplantation. Although treatment with ursodeoxycholic acid showed a reduction in liver biochemistry, jaundice, and ascites, it did not decrease mortality or liver transplantation.
In absence of biochemical response to 13-15mg/kg/day ursodeoxycholic acid, the 15 year incidence of hepatocellular carcinoma in patients with primary biliary cirrhosis is 20%.
In children, its use is not licensed, as its safety and effectiveness are not established.
In double the recommended daily dose ursodeoxycholic acid reduces elevated liver enzyme levels in patients 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). After adjustment for baseline stratification characteristics, the risk was 2.1 times greater for death,transplantation, or minimal listing criteria in patients on ursodeoxycholic acid than for those on placebo (P = 0.038). Serious adverse events, were more common in the ursodeoxycholic acid group than the placebo group (63% versus 37% [P < 0.01])).
Research by the Imperial College London
has produced promising results in the treatment of arrhythmia, both in patients who have suffered a heart attack and in foetuses, by using ursodiol to change the electrical properties of myofibroblast
cells. Myofibroblasts disrupt the transmission of electrical signals controlling heart rhythm.
s are kept on farms in China, Vietnam and South Korea for the purpose of harvesting ursodeoxycholic acid. Ursodeoxycholic acid is found in large quantities in bear bile.
Abbreviation
An abbreviation is a shortened form of a word or phrase. Usually, but not always, it consists of a letter or group of letters taken from the word or phrase...
UDCA, is one of the secondary bile acid
Bile acid
Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...
s, which are metabolic byproducts of intestinal bacteria.
Endogenous effects
Primary bile acids are produced by the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and stored in the gall bladder. When secreted into the colon, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest
Digestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....
fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
s. Ursodeoxycholic acid helps regulate cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
by reducing the rate at which the intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
absorbs cholesterol molecules while breaking up micelle
Micelle
A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single tail regions in the micelle centre. This phase is...
s containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat (cholesterol) gallstone
Gallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...
s non-surgically.
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
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.
Ursodeoxycholic acid has also been shown experimentally to suppress immune response
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
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.
As a pharmaceutical
Ursodeoxycholic acid goes by the trade names Actigall, Ursosan, Egyurso( Egyphar Egypt), Urso, and Urso Forte. In Italy and Switzerland, it is marketed under the name Deursil. In MexicoMexico
The United Mexican States , commonly known as Mexico , is a federal constitutional republic in North America. It is bordered on the north by the United States; on the south and west by the Pacific Ocean; on the southeast by Guatemala, Belize, and the Caribbean Sea; and on the east by the Gulf of...
it is marketed in capsules of 250 mg under the name Coric by Mexican
Mexican people
Mexican people refers to all persons from Mexico, a multiethnic country in North America, and/or who identify with the Mexican cultural and/or national identity....
pharmaceutical Landsteiner Scientific.
Ursodeoxycholic acid can be chemically synthesized and was brought to market by the Montreal-based Axcan Pharma
Axcan Pharma
Axcan Pharma Inc. is a privately held, Birmingham, Alabama-based, specialty pharmaceutical company that develops, manufactures, markets and distributes a broad line of gastrointestinal products primarily in North America and Europe. Formerly traded publicly on NASDAQ, Axcan was acquired by TPG...
in 1998, which continues to market the drug.
The drug reduces cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
absorption and is used to dissolve (cholesterol) gallstone
Gallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...
s in patient
Patient
A patient is any recipient of healthcare services. The patient is most often ill or injured and in need of treatment by a physician, advanced practice registered nurse, veterinarian, or other health care provider....
s who want an alternative to surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
. The drug is very expensive, however, and if the patient stops taking it, 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
Cholecystectomy
Cholecystectomy is the surgical removal of the gallbladder. It is the most common method for treating symptomatic gallstones. Surgical options include the standard procedure, called laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.-Open surgery:A...
.
It is the only FDA approved drug to treat primary biliary cirrhosis
Primary biliary cirrhosis
Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...
.
A Cochrane review to evaluate if ursodeoxycholic acid has any beneficial effect in primary biliary cirrhosis patients included 16 randomized clinical trials with a total of 1447 patients. The primary outcome measures were mortality and mortality or liver transplantation. Although treatment with ursodeoxycholic acid showed a reduction in liver biochemistry, jaundice, and ascites, it did not decrease mortality or liver transplantation.
In absence of biochemical response to 13-15mg/kg/day ursodeoxycholic acid, the 15 year incidence of hepatocellular carcinoma in patients with primary biliary cirrhosis is 20%.
In children, its use is not licensed, as its safety and effectiveness are not established.
In double the recommended daily dose ursodeoxycholic acid reduces elevated liver enzyme levels in patients 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). After adjustment for baseline stratification characteristics, the risk was 2.1 times greater for death,transplantation, or minimal listing criteria in patients on ursodeoxycholic acid than for those on placebo (P = 0.038). Serious adverse events, were more common in the ursodeoxycholic acid group than the placebo group (63% versus 37% [P < 0.01])).
Research by the Imperial College London
Imperial College London
Imperial College London is a public research university located in London, United Kingdom, specialising in science, engineering, business and medicine...
has produced promising results in the treatment of arrhythmia, both in patients who have suffered a heart attack and in foetuses, by using ursodiol to change the electrical properties of myofibroblast
Myofibroblast
A Myofibroblast is a cell that is in between a fibroblast and a smooth muscle cell in differentiation.-Developmental origin:There are many possible ways of myofibroblast development:#Partial smooth muscle differentiation of a fibroblastic cell...
cells. Myofibroblasts disrupt the transmission of electrical signals controlling heart rhythm.
Production
The drug is generally not derived from animals. However, it is believed more than 12,000 bile bearBile bear
Bile bear, or battery bear, refers to Asiatic black bears kept in captivity in China and Vietnam to harvest bile, a digestive juice produced by the liver and stored in the gall bladder. When extracted, the bears’ bile is a valuable commodity for sale as an ingredient in traditional Chinese medicine...
s are kept on farms in China, Vietnam and South Korea for the purpose of harvesting ursodeoxycholic acid. Ursodeoxycholic acid is found in large quantities in bear bile.
External links
- Ursodeoxycholic acid information at MedlinePlusMedlinePlusMedlinePlus is a free Web site that provides consumer health information for patients, families, and Health care providers. The site brings together information from the United States National Library of Medicine, the National Institutes of Health , other U.S. government agencies, and...