Lipoproteins, differentiated on the basis of density, size, and protein content, are essential for the biogenesis of plasma membrane and maintenance of its integrity; they also serve as sources of energy, hormone precursors, and signaling molecules.3 In blood, lipoproteins transport cholesterol and triglycerides. Abnormalities of lipoprotein metabolism appear to be the result of genetic factors, which modify the sensitivity of individuals to adverse dietary habits and to sedentary lifestyles.
Elevated cholesterol-rich low-density lipoproteins (LDLs) and lipoproteins that are rich in triglycerides (TGs), and decreased levels of high-density lipoproteins (HDLs) are strongly associated with atherosclerosis.3 Diet and exercise can reduce total plasma cholesterol concentrations by as much as 25%. If this approach is insufficient to normalize lipid levels drug therapy is initiated. Drugs in the top 300 that regulate lipoprotein metabolism (Table 1) fall into six major classes.2,3,10
Table 1. Drugs that Affect Cholesterol and Lipoprotein Metabolism.2,3,10
Drugs
Mechanisms of Action
Common Indications
Inhibitors of cholesterol synthesis
Atorvastatin
Simvastatin
Pravastatin
Rosuvastatin
Lovastatin
Inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis
Decrease LDL
Decrease TG
Increase HDL
Hypercholesterolemia
Prophylaxis for coronary atherosclerosis
Inhibitors of bile acid absorption
Colestipol
Bind to bile acids and prevent enterohepatic circulation
Decrease LDL
Increase HDL
Hypercholesterolemia
Inhibitors of cholesterol absorption
Ezetimibe
Ezetimibe w/simvastatin
Decrease cholesterol transport into enterocytes
Decrease LDL
Decrease TG
Increase HDL
Hypercholesterolemia
Fibrates
Fenofibrate
Gemfibrozil
Agonists of peroxisome proliferator-activated receptor α (PPARα) in hepatocytes
Decrease TG
Decrease LDL
Increase HDL
Hypertriglyceridemia
Niacin
Niacin
Niacin w/simvastatin
Reduces free fatty acid release from adipose tissue
Decreases TG
Decreases LDL
Increases HDL
Hypertriglyceridemia
Hypercholesterolemia
Omega-3 fatty acids
Omega-3-acid ethyl ester
Regulate hepatic nuclear transcription factors to reduce TG synthesis and increase fatty acid oxidation