Bile acid sequestrant
The bile acid sequestrants are a group of resins used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption from the gut. In general, they are classified as hypolipidemic agents, although they may be used for purposes other than lowering cholesterol. They are used in the treatment of chronic diarrhoea due to bile acid malabsorption.
Since bile acids are biosynthesized from cholesterol, disruption of bile acid reabsorption will decrease cholesterol levels, in particular, low-density lipoprotein (commonly known as "bad cholesterol"). Therefore, they may be used for the treatment of hypercholesterolemia and dyslipidemia.
In chronic liver diseases such as cirrhosis, bile acids may deposit in the skin, causing pruritus (itching). Hence, bile acid sequestrants may be used for the prevention of pruritus in patients with chronic liver disease.
In addition, diarrhea may be caused by excess bile salts entering the colon rather than being absorbed at the end of the small intestine (the ileum). The condition of bile acid malabsorption occurs after surgery to the ileum, in Crohn's disease, with a number of other gastro-intestinal causes, or is commonly a primary, idiopathic condition. The SeHCAT test can be used for diagnosis. Bile salt diarrhea is a side-effect of gallbladder removal. Bile acid sequestrants may reduce diarrhea in these patients.
Bile acid sequestrants may also be used to treat hyperthyroidism as an adjunct therapy. By inhibiting the enterohepatic circulation, more L-thyroxine will be lost through defecation, thus lowering body thyroxine levels.
Use of these agents as hypolipidemic agents has decreased markedly since the introduction of the statins, which are more efficacious than bile acid sequestrants at lowering LDL. They are occasionally used as an adjunct to the statins (as an alternative to the fibrates (another major group of cholesterol-lowering drugs), which are thought to increase the risk of rhabdomyolysis when used with statins.
Because bile acid sequestrants are not well-absorbed from the gut, they are generally regarded as safe in pregnant women. However, by interfering with vitamin absorption, they may cause vitamin deficiencies that may affect the fetus. Hence, vitamin supplementation may be warranted, with appropriate intervals between dosing of the vitamins and bile acid sequestrants.
Bile acid sequestrants are the principal therapy for the diarrhea found in bile acid malabsorption. Cholestyramine, colestipol and colesevelam have all been used. Doses may not need to be as high as those previously used for hyperlipidemia. Many patients find them hard to tolerate, as although the diarrhea may improve, bloating and abdominal pain can worsen.1
Cholestyramine is used in the treatment of Clostridium difficile infections, in order to absorb toxins A and B.
Since bile acid sequestrants are designed to stay in the gut, they, in general, do not have systemic side-effects. However, they may cause problems in the gastrointestinal tract (GI tract), such as constipation, diarrhea, and flatulence. Some patients complain of the bad taste.
In addition to bile acids, bile acid sequestrants may also bind drugs in the GI tract, preventing their absorption into the bloodstream. For this reason, it is generally advised that bile acid sequestrants be spaced several hours apart from other drugs.
Bile acid sequestrants are polymeric compounds that serve as ion-exchange resins. Bile acid sequestrants exchange anions such as chloride ions for bile acids. By doing so, they bind bile acids and sequester them from enterohepatic circulation.
Since bile acid sequesterants are large polymeric structures, they are not well-absorbed from the gut into the bloodstream. Thus, bile acid sequestrants, along with any bile acids bound to the drug, are excreted via the feces after passage through the gastrointestinal tract.2
Three drugs are members of this class; all are synthetic polymeric resins:
- Cholestyramine (Questran)
- Colesevelam3 (Cholestagel in Europe, Welchol in the USA)
- Colestipol (Colestid)Colestipid
- Walters, JR; Pattni, SS (2010). "Managing bile acid diarrhoea". Therapeutic advances in gastroenterology 3 (6): 349–57. doi:10.1177/1756283X10377126. PMC 3002596. PMID 21180614.
- FDA Heart Health Online - Bile Acid Sequestrants
- Wong NN (2001). "Colesevelam: a new bile acid sequestrant". Heart disease (Hagerstown, Md.) 3 (1): 63–70. PMID 11975771.