- Bile acid sequestrant
The bile acid sequestrants are a group of medications used for binding certain components of
bilein the gastrointestinal tract. They disrupt the enterohepatic circulationof bile acids by sequestering them and preventing their reabsorption from the gut. They are generally classified as hypolipidemic agents, although they may be used for purposes other than lowering cholesterol.
Mechanism of action
Bile acid sequestrants are
polymeric compounds which serve as ion exchange resins. Bile acid sequestrants exchange anions such as chlorideions for bile acids. By doing so, they bind bile acids and sequester them from enterohepatic circulation.
Since bile acid sequestrants 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. [ [http://www.fda.gov/hearthealth/treatments/medications/bileacid.html FDA Heart Health Online - Bile Acid Sequestrants ] ]
Since bile acids are biosynthesized from
cholesterol, the disruption of bile acid reabsorption will decrease cholesterol levels, particularly low density lipoprotein(commonly known as "bad cholesterol"). Therefore, they may be used for the treatment of hypercholesterolemiaand dyslipidemia.
liverdiseases such as cirrhosis, bile acids may deposit in the skin, causing pruritus(itching). Hence, bile acid sequenstrants may be used for the prevention of pruritusin patients with chronic liver disease.
diarrheamay be caused by excess bile salts entering the colon rather than being absorbed at the end of the small intestine, typically shortly after eating. Bile salt diarrhea is a possible side-effect of gallbladderremoval. Bile acid sequestrants may reduce diarrhea in these patients.
Bile acid sequetrants may also be used to treat hyperthyroidism as an adjunct therapy. By inhibiting the enterohepatic circulation, more L-thyroxine will be lost through defecation and thus lowers body thyroxine levels.
Examples of bile acid sequestrants
Three drugs are members of this class; all are synthetic
Colesevelamcite journal |author=Wong NN |title=Colesevelam: a new bile acid sequestrant |journal=Heart disease (Hagerstown, Md.) |volume=3 |issue=1 |pages=63–70 |year=2001 |pmid=11975771 |doi=] (Cholestagel in Europe, WelcholTM in the USA)
Since bile acid sequestrants are designed to stay in the gut, they generally 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.
They may also bind fat-soluble
vitamins, such as vitamin A, vitamin D, vitamin E, and vitamin K. This effect may result in a vitamin deficiency. Hence, vitamin supplementation may be warranted.
Role in clinical use
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; this is because the fibrates (another major group of cholesterol-lowering drugs) are thought to increase the risk of rhabdomyolysiswhen used with statins, and so this otherwise expectable combination is frequently avoided.
Additionally, because bile acid sequestrants are not well-absorbed from the gut, they are generally regarded as being 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.
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