Examples: Lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), and atorvastatin (Lipitor), rosuvastation (Crestor).
First choice drugs: These are the most effective drugs for lowering LDL-cholesterol levels and cause few adverse effects.
Mechanism of Action: Statins inhibit the liver enzyme HMG CoA reductase (hydroxymethylglutaryl-Coenzyme A reductase). This enzyme controls the rate at which cholesterol is synthesized in the liver. Cholesterol levels decrease in the liver, and the liver tries to raise the cholesterol levels by increasing the number of LDL receptors present on the hepatocytes. These receptors will take up the LDL-cholesterol from the plasma and bring it into the liver. The net effect is to lower LDL-cholesterol in the plasma.
- Pharmacokinetics: Administered orally. Most of absorbed dose is extracted from the blood on its first pass through the liver.
- Lovastatin and simvastatin undergo extensive first-pass metabolism by CYP3A4 and their serum concentrations can be dramatically increased by CYP3A4 inhibitors such as the antifungal drugs itraconazole, ketoconazole, and the antibiotic erythromycin or grapefruit juice.
- Crosses placenta and blood-brain barrier (contraindicated for pregnancy and nursing).
- Most effective when taken at dinner or bedtime when the liver increases its synthesis of cholesterol.
- Lovastatin, pravastatin and simvastatin must be taken with food.
- Adverse Effects:
- Minor: headache, rash or GI disturbances
- Major: Hepatotoxicity (use with extreme caution for alcoholics and those with liver damage.
- Myopathy: Highest risk with lovastatin, particularly if combines with other lipid lowering drugs such as gemfibrozil or nicotinic acid