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14-September-2008 10:43:22 - Bile acid sequestrant The bile acid sequestrants are a group of medications used for binding certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of 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. Contents 1 Mechanism of action 2 Indications 3 Examples of bile acid sequestrants 4 Side effects 5 Drug interactions 6 Role in clinical use 7 References Mechanism of action Bile acid sequestrants are polymeric compounds which 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 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.1 Indications 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 hypercholesterolemia and dyslipidemia. In chronic liver diseases such as cirrhosis, bile acids may deposit in the skin, causing pruritus itching. Hence, bile acid sequenstrants may be used for the prevention of pruritus in patients with chronic liver disease. Additionally, diarrhea may 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 gallbladder removal. 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 polymeric resins: Cholestyramine Questran Colesevelam2 Cholestagel in Europe, WelcholTM in the USA Colestipol Colestid Side effects 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. Drug interactions 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 rhabdomyolysis when 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. References ^ 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. v d e Lipid modifying agents C10 Statins HMG-CoA reductase Atorvastatin Cerivastatin‡ Fluvastatin Lovastatin Mevastatin Pitavastatin Pravastatin Rosuvastatin Simvastatin Fibrates PPAR Clofibrate‡ Bezafibrate Aluminium clofibrate Gemfibrozil Fenofibrate Simfibrate Ronifibrate Ciprofibrate Etofibrate Clofibride Clinofibrate Bile acid sequestrants Colestyramine Colestipol Colestilan Colextran Colesevelam Niacin and derivatives Niceritrol Niacin Nicofuranose Aluminium nicotinate Nicotinyl alcohol Acipimox CETP inhibitors Anacetrapib† Torcetrapib§ Combinations Niacin/lovastatin Niacin/simvastatin Ezetimibe/simvastatin Other Dextrothyroxine Probucol Tiadenol Benfluorex Meglutol Omega-3-triglycerides Magnesium pyridoxal 5-phosphate glutamate Policosanol Ezetimibe Lapaquistat§ †Undergoing clinical trials. ‡Withdrawn from market. §Development terminated. Retrieved from http://en..org/wiki/Bile_acid_sequestrant Categories: Hypolipidemic agents | Hepatology Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Português ไทย This page was last modified on 2 September 2008, at 07:53
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