Bile acid sequestrating agents

Dosingof selected agents by class fibrate (gemfibrozil 600 mg twice a day) niacin (1.5-3 g/day of immediate-release product) statin (simvastatin 10-40 mg/day if glomerular filtration rate [GFR] <30 mL/min, 20-80 mg/day if GFR >30 mL/min) bile acid sequestrant (cholestyramine 4-16 g/day). 

AccessMedicine Print Chapter 35. Agents Used in Dyslipidemia Bile acid sequestrants... 

Cholesterol-Reducing Agents. Hypercholesterolemia is well known as a major risk factor for coronary heart disease. In clinical practice, two main hypocholestrolemic agents are commonly used. One is the 3-hy-droxy-3-methylgrutaryl coenzyme A (HMG-CoA) reductase inhibitors (such as Lipitor) another is the bile acid sequestrants, such as cholestyramine and colestipol (97), which bind bile acid in the intestinal lumen and thus increase their excretion. The main drawback of... 

Thiazide diuretics may diminish the effects of anticoagulants, uricosuric agents used to treat gout, sulfonylureas, and insulin and increase the effects of anesthetics, diazoxide, cardiac glycosides, hthium, loop diuretics, and vitamin D. The effectiveness of thiazide diuretics may be reduced by NSAlDs and bile acid sequestrants (reduced absorption of thiazides). Amphotericin B and corticosteroids increase the risk of hypokalemia induced by thiazide diuretics. 

The two established bUe-acid sequestrants or resins (cholestyramine and colestipol) are most often used as second agents if statin therapy does not lower LDL-C levels sufficiently. When used with a statin, cholestyramine and colestipol usually are prescribed at submaximal doses. Maximal doses can reduce LDL-C by up to 25% but are associated with unacceptable gastrointestinal (GI) side effects (bloating and constipation) that limit compliance. Colesevelam is a newer bile-acid sequestrant that is prepared as an anhydrous gel and taken as a tablet. It lowers LDL-C by 18% at its maximum dose. The safety and efficacy of colesevelam have not been studied in children or pregnant women. 

Bile Acid Sequestrants Polymeric Drugs as Cholesterol-Lowering Agents... 

Key randomized clinical trials employing niacin with cardiovascular and clinical endpoints are summarized in Table 39.2. Most of the trials used niacin in combination with other agents—bile acid sequestrants, fibrates or statins. 

Drug interactions The extent to which vitamin D supplementation alters drug effectiveness and toxicity in humans has been systematically reviewed. Bile acid sequestrants and lipase inhibitors were found to inhibit the absorption of vitamin D from the gut. Statins, rifampicin, isoniazid, hydroxychloroquine, antiepileptics, corticosteroids, immimo-suppressive and chemotherapeutic agents, antiretroviral drugs and H2 receptor antagonists interfered with vitamin D metabolism. The interaction between vitamin D and thiazide diuretics could result in hypercalcaetnia. Vitamin D supplementation decreases concentrations of atorvastatin, and could cause hypercalcaetnia in elderly individuals or tixose with compromised renal function or hyperparathyroidism [84 ]. 

Bile acid sequestrants are charged resins that are ingested in a liquid suspension. They bind to bile acids in the intestine and prevent their reabsorption. Since bile acids normally feed back on their own synthesis from cholesterol, these agents evoke a compensatory increase in bile acid synthesis. The diversion of liver cholesterol for bile acid production leads to an upregulation of the LDL receptor and thus a reduction in LDL levels. Because bile acid sequestrants increase cholesterol catabolism and statins decrease cholesterol synthesis, the two agents together act synergistically. 

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