Thebile acid sequestrants are a group of resins used to bind certain components ofbile in thegastrointestinal tract. They disrupt theenterohepatic circulation ofbile acids by combining with bile constituents and preventing their reabsorption from the gut. In general, they are classified ashypolipidemic agents, although they may be used for purposes other than lowering cholesterol. They are used in the treatment ofchronic diarrhea due tobile acid malabsorption.[1]
Bile acid sequestrants arepolymeric compounds that serve asion-exchange resins. Bile acid sequestrants exchangeanions such aschloride ions for bile acids. By doing so, they bind bile acids and sequester them from the enterohepatic circulation. The liver then produces more bile acids to replace those that have been lost. Because the body uses cholesterol to make bile acids, this reduces the level of LDL cholesterol circulating in the blood.[2]
Bile acid sequestrants are large polymeric structures, and they are not significantly 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.[3]
As bile acids are biosynthesized fromcholesterol, disruption of bile acid reabsorption will decrease cholesterol levels, in particular,low-density lipoprotein (commonly known as "bad cholesterol") in blood. Consequently, these drugs have been used for the treatment ofhypercholesterolemia anddyslipidemia.[4][5][6]
Use of these agents ashypolipidemic agents has decreased markedly since the introduction of thestatins, which are more efficacious than bile acid sequestrants at loweringLDL. They are occasionally used as an adjunct to the statins as an alternative to thefibrates (another major group of cholesterol-lowering drugs), which are thought to increase the risk ofrhabdomyolysis when used with statins. The bile-acid-binding resins can raise triglycerides modestly (about 5%) and cannot be used if the triglycerides are elevated.
Chronic diarrhea may be caused by excess bile salts entering the colon rather than being absorbed at the end of the small intestine (theileum). This condition ofbile acid malabsorption occurs after surgery to theileum, inCrohn's disease, with a number of other gastrointestinal causes, or is commonly a primary, idiopathic condition. TheSeHCAT test can be used for diagnosis. Bile salt diarrhea can also be a side-effect ofgallbladder removal.[1]
Bile acid sequestrants are the principal therapy for bile acid-induced diarrhea.[7][1]Cholestyramine,colestipol andcolesevelam 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.[8][9]
In chronicliver diseases such ascirrhosis, bile acids may deposit in the skin, causingpruritus (itching). Hence, bile acid sequestrants may be used for the prevention ofpruritus in patients with chronic liver disease.[10]
Bile acid sequestrants may also be used to treathyperthyroidism as an adjunct therapy. By inhibiting the enterohepatic circulation, more L-thyroxine will be lost through defecation, thus lowering bodythyroxine levels.
Cholestyramine has been used in the treatment ofClostridioides difficile infections, in order to absorb toxins A and B.
As bile acid sequestrants are designed to stay in the gut; in general, they do not have systemic side effects. However, they may cause problems in thegastrointestinal tract, such asconstipation,diarrhea,bloating, andflatulence. Some patients complain of the bad taste.
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 (see below), they could cause vitamin deficiencies that may affect the fetus. So, vitamin supplementation may be considered, with appropriate intervals between dosing of the vitamins and bile acid sequestrants.
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.[8]
They can also bindfat-soluble vitamins, such asvitamin A,vitamin D,vitamin E, andvitamin K. This effect could result in a vitamin deficiency, and so checking blood levels and possible supplementation has been suggested.[8]
Three drugs are members of this class; all are syntheticpolymeric resins:[1]
