Cholesterol fibrate drugs

Currently available treatments against atherosclerosis include cholesterol-lowering drugs such as statins, fibrates, nicotinic acid (NA) [8-13] and the cholesterol intestinal absorption inhibitor, ezetimibe (Fig. 1) [14]. 

Fibrate drugs are a class of lipid regulatory drugs. They are used to regulate blood lipid and cholesterol levels. They include drugs such as gemfibrozil, ciprofibrate, clofibrate, bezafibrate and fenofibrate (Fig. 1). As noted in Table 1, gemfibrozil (GEM) was identified in /xg/l concentrations in post-STP effluents collected from... 

B. Clinical Use Gemfibrozil and other fibrates are used to treat hypertriglyceridemia (Table 35-2). Because these drugs ha"e only modest effects on LDL cholesterol, they often are combined with other cholesterol-lowering drugs for treatment of patients with elevated concentrations of both LDL and VLDL. 

Combination drug therapy is an effective means to achieve greater reductions in LDL cholesterol (statin + ezetimibe or bile acid resin, bile acid resin + ezetimibe, or three-drug combinations) as well as raising HDL cholesterol and lowering serum triglycerides (statin + niacin or fibrate). 

Fibrates are the most effective triglyceride-lowering drugs and are used primarily in patients with elevated triglycerides and low HDL cholesterol. 

The fibrates are mainly used to treat two hyperlipi-demias, familial hypertriglyceridemia (type IV) and dysbetalipoproteinemia (type III). They are also useful in the treatment of hypertriglyceridemia associated with type II diabetes (secondary hyperlipidemia). The fibrates are the drugs of choice in treating hypertriglyceridemias, particularly those associated with low levels of HDL cholesterol. The fibrates additionally appear to... 

The fibrates potentiate the actions of the coumarin anticoagulants, such as warfarin, so care should be taken to reduce the dose of simultaneously administered anticoagulants, and plasma prothrombin should be frequently measured until the level stabilizes. As mentioned earlier, great care should be given to combining a statin with a fibrate, since this combination may increase the risk of myositis and perhaps rhabdomyolysis. Table 23.4 summarizes major interactions of drugs that lower cholesterol. 

These drugs should be avoided in patients with hepatic or renal dysfunction. There appears to be a modest increase in the risk of cholesterol gallstones, reflecting an increase in the cholesterol content of bile. Therefore, fibrates should be used with caution in patients with biliary tract disease or in those at high risk such as women, obese patients, and Native Americans. 

The fibrates are another class of antihyperlipidemic drug and are frequently coadministered with a statin. Fibrates act as agonists of the peroxisome proliferator-activated receptors (PPAR), particularly PPAR-a. PPARs are nuclear receptors that influence gene expression and lipid metabolism. Examples of fibrates include gemfibrozil (Lopid, A.110) and fenofibrate (Tricor, A.lll) (Figure A.30). Fenofibrate is hydrolyzed in the body to its active form, fenofibric acid (A.112). Fibrates do not decrease LDL levels as effectively as statins, but fibrates do elevate HDL cholesterol levels. 

Drugs used to increase HDL levels (fibrates, nicotinic acid, and statins) in otherwise normal people do not have the same effect in patients with Tangier disease. Therefore, it is necessary to identify and treat other risk factors associated with CAD. Exercise, weight reduction, dietary cholesterol and saturated fat reduction, and smoking cessation are the first line in management of low HDL cholesterol. Dietary management with low fat intake is beneficial in reducing the risk for CAD, as well... 

Low HDL cholesterol is a strong independent risk predictor of CHD. ATP III redefined low HDL cholesterol as <40 mg/dL but specified no goal for HDL cholesterol raising. In low HDL, the primary target remains LDL, but treatment emphasis shifts to weight reduction, increased physical activity, smoking cessation, and to fibrates and niacin if drug therapy is required. 

In general, drugs act to reduce the concentration of cholesterol within hepatocytes, causing a compensatory increase in low-density lipoprotein-receptors (LDL-R) on their surface, and increased uptake of cholesterol-rich LDL particles from the bloodstream (see Fig. 25.1). Statins decrease the synthesis of cholesterol and the secretion of VLDL and increase the activity of hepatic LDL-receptors. Bile-acidbinding resins deplete the bile acid and thus the cholesterol pool. Fibrates decrease the secretion of VLDL and increase the activity of lipoprotein lipase, thereby increasing the removal of tri-... 

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