Cholestyramine with statins

The primary goal of therapy is the control of the hypercholesterolemia and prevention of atherosclerotic cardiovascular disease. Patients with heterozygous FH can usually be successfully treated with medications to lower the LDL cholesterol to acceptable levels (Table 14-2). They are generally responsive to treatment with statins, alone or in combination with other drugs, such as bile acid sequestrants (such as cholestyramine) or cholesterol absorption inhibitors (such as ezetimibe) that act additively to upregulate the expression of the functioning LDL receptor as described in the Biochemical Perspectives section. In a few cases, a more aggressive treatment with LDL apheresis (discussed in this section) may have to be considered in order to reach acceptable LDL cholesterol levels. 

Ann Jeina was treated with a statin (pravastatin) and cholestyramine, a bile acid sequestrant. With the introduction of the cholesterol absorption blocker ezetimibe, the use of cholestyramine with its high level of gastrointestinal side effects may decline. Ezetimibe reduces the percentage of absorption of free cholesterol present in the lumen of the gut and hence the amount of cholesterol available to the enteroc5de to package into chylomicrons. This, in turn, reduces the amount of cholesterol returning to the liver in chylomicron remnants. The net result is a reduction in the cholesterol pool in hepatocytes. The latter induces the synthesis of an increased number of LDL receptors by the hver cells. As a consequence, the capacity of the liver to increase hepatic uptake of LDL from the circulation leads to a decrease in serum LDL levels. 

In addition to treatment with the statins, hypercholesterolemia is sometimes treated with the use of nonabsorbable anion-exchange resins like cholestyramine (5.13) and colestipol, which sequester bile acid in the intestine, excrete them, and thus increase their synthesis in the liver by a feedback mechanism. Increased bile acid synthesis increases cholesterol metabolism and also decreases LDL concentrations. Unfortunately, these resins interfere with the absorption of other fats and fat-soluble vitamins (A, D, E, and K). They... 

A patient has been on combination statin and cholestyramine therapy to lower his serum cholesterol levels. Prior to any surgery, this patient would be weU advised to be supplemented with which of the foUowing ... 

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. 

The reduction in IDL-C by resins is dose-dependent. Doses of 8-12 g of cholestyramine or 10-15 g of colestipol are associated with 12-18% reductions in LDL-C. Maximal doses (24 g of cholestyramine, 30 g of colestipol) may reduce LDDC by as much as 25%, but will cause GI side effects that are poorly tolerated by most patients. One to two weeks is sufficient to attain maximal LDDC reduction by a given resin dose. In patients with normal triglyceride levels, triglycerides may increase transiently and then return to baseline. HDL-C levels increase 4-5%. Statins plus resins or niacin plus resins can reduce LDL-C by as much as 40-60%. Colesevelam, in doses of 3-3.75 g, reduces LDL-C levels by 9-19%. 

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