It belongs to a class of drugs called HMG CoA reductase inhibitors. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (commonly known as statins) lower elevated LDL-C, resulting in a substantial reduction in coronary events and death from CHD. They are considered first-line treatment for patients with elevated risk of ASCVD. Therapeutic benefits include plaque stabilization, improvement of coronary endothelial function, inhibition of platelet thrombus formation, and anti-inflammatory activity. The value of lowering LDL-C with statins has been demonstrated in patients with and without established CHD.
Mechanism of action:
Simvastatin, including Lovastatin, pravastatin , atorvastatin, fluvastatin, pitavastatin, and rosuvastatin are competitive inhibitors of HMG CoA reductase, the rate-limiting step in cholesterol synthesis. By inhibiting de novo cholesterol synthesis, they deplete the intracellular supply of cholesterol. Depletion of intracellular cholesterol causes the cell to increase the number of cell surface LDL receptors that can bind and internalize circulating LDLs. Thus, plasma cholesterol is reduced, by both decreased cholesterol synthesis and increased LDL catabolism. Pitavastatin, rosuvastatin, and atorvastatin are the most potent LDL cholesterol–lowering statins, followed by simvastatin, pravastatin, and then lovastatin and fluvastatin. [Note: Because these agents undergo a marked first-pass extraction by the liver, their dominant effect is on that organ.] The HMG CoA reductase inhibitors also decrease triglyceride levels and may increase HDL cholesterol levels in some patients.
These drugs are effective in lowering plasma cholesterol levels in all types of hyperlipidemias. However, patients who are homozygous for familial hypercholesterolemia lack LDL receptors and, therefore, benefit much less from treatment with these drugs.
Simvastatin is lactone that is hydrolyzed to the active drug. Absorption of the statins is variable (30% to 85%) following oral administration. All statins class drugs are metabolized in the liver, with some metabolites retaining activity. Excretion takes place principally through bile and feces, but some urinary elimination also occurs. Their half-lives are variable.
Elevated liver enzymes may occur with Simvastatin therapy. Therefore, liver function should be evaluated prior to starting therapy and if a patient has symptoms consistent with liver dysfunction. [Note: Hepatic insufficiency can cause drug accumulation.] Myopathy and rhabdomyolysis (disintegration of skeletal muscle; rare) have been reported. In most of these cases, patients usually had renal insufficiency or were taking drugs such as erythromycin, gemfibrozil, or niacin. Simvastatin is metabolized by cytochrome P450 3A4, and inhibitors of this enzyme may increase the risk of rhabdomyolysis. Plasma creatine kinase levels should be determined in patients with muscle complaints. Simvastatin may also increase the effect of warfarin. Thus, it is important to evaluate international normalized ratio (INR) frequently. Simvastatin and other drugs in this class are contraindicated during pregnancy and lactation.