HMG-CoA reductase inhibitors

HMG-CoA reductase inhibitors

HMG-CoA reductase inhibitors (also known as the statins) lowerlipid levels by interfering with cholesterol synthesis. These drugs include atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvas-tatin, and simvastatin.

Pharmacokinetics

Each drug has slightly different pharmacokinetic properties. With the exception of pravastatin, all are highly bound to plasma pro-teins and undergo extensive first-pass metabolism. However, plas-ma levels don’t correlate with the drugs’ abilities to lower choles-terol.

Pharmacodynamics

HMG-CoA reductase inhibitors inhibit the enzyme responsible for the conversion of HMG-CoA to mevalonate, an early step in the synthesis of cholesterol.

Pharmacotherapeutics

Statins are used primarily to reduce LDL cholesterol and total blood cholesterol levels. These agents also produce a mild in-crease in HDL cholesterol levels.

Statins are used to treat primary hypercholesterolemia (types IIa and IIb). Because of their effect on LDL and total cholesterol, these drugs are also used to reduce the risk of CAD and to prevent MI or stroke in patients with high cholesterol levels.

Drug interactions

Taking a statin drug with amiodarone, clarithromycin, cy-closporine, erythromycin, fluconazole, gemfibrozil, itraconazole, ketoconazole, or niacin increases the risk of myopathy or rhab-domyolysis (a potentially fatal breakdown of skeletal muscle, causing renal failure).

·                 Lovastatin, rosuvastatin and simvastatin may increase the risk of bleeding when administered with warfarin.

·                 All of these drugs should be administered 1 hour before or 4 hours after the administration of bile-sequestering drugs (cholestyramine, colesevelam, and colestipol). (See Adverse reac-tions to HMG-CoA reductase inhibitors.)