Simvastatin is a classic statin and is used as a cholesterol-lowering agent. It was approved in 1990 and is used relatively frequently.
What is simvastatin?
Simvastatin, chemically (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl-2,2-dimethylbutanoate, is a drug used primarily as a cholesterol-lowering agent. Simvastatin is structurally derived from the naturally occurring monacolin K, also known as lovastatin. Simvastatin is partially synthetically produced from lovastatin. In 1990, simvastatin was approved in Germany. In 2003, the patent expired – since then, numerous generics have been available on the market in addition to the original preparation. The molecular formula of simvastatin is C25H38O5. It belongs to the class of statins and acts as an HMG-CoA reductase inhibitor. Simvastatin is present in the solid state. The molar mass is 418.57 g x mol^-1. The melting point of the substance is 127 to 132 degrees Celsius. The lethal dose 50 (LD50) of the substance in the rat after oral administration is 4438 mg kg^-1.
Pharmacological effects on body and organs
Simvastatin, as a classic representative of statins, has a lowering effect on blood cholesterol levels and is therefore classified as a cholesterol-lowering agent. It does so by inhibiting HMG-CoA reductase. This enzyme is responsible for the synthesis of cholesterol in the liver. The enzyme is therefore of central importance in cholesterol biosynthesis. If the activity of the enzyme is inhibited, the cholesterol level decreases because less new cholesterol can be synthesized. In addition, it causes increased LDL receptor synthesis. As a result, more LDL cholesterol is stored in the liver. This storage in turn causes less LDL cholesterol to reach the periphery – so blood cholesterol levels continue to fall. Simvastatin is metabolized mainly by cytochrome P450 3A4. Thus, metabolization takes place in the liver. For this reason, drugs and foods that inhibit cytochrome 3A4 should be avoided whenever possible, as this slows the breakdown of simvastatin, which in turn increases the risk of side effects. Inhibition of cytochrome 3A4 is caused, for example, by clarithromycin, itraconazole, ketoconazole, or grapefruit juice.
Medical use and use for treatment and prevention.
As mentioned above, simvastatin finds medical use as a cholesterol-lowering agent. Thus, the use of simvastatin is indicated primarily for elevated cholesterol levels. Furthermore, simvastatin is used in acute coronary syndrome, unstable angina, and myocardial infarction. The term acute coronary syndrome does not clearly denote a disease. Acute coronary syndrome is to be understood as a working diagnosis under which several cardiovascular diseases, which cannot be distinguished with certainty clinically, are grouped together. These are namely unstable angina pectoris, non-transmural infarction without ST elevations but with elevation of troponin T/1, transmural infarction with ST elevations in the fresh stage of infarction and elevation of troponin T/1, and sudden cardiac death. Angina pectris (“chest tightness”) refers to a frequent, seizure-like chest pain caused by a lack of blood supply (ischemia) to the heart. In unstable angina, symptoms are not constant but change. However, there are no signs of a heart attack (myocardial infarction). First-onset angina, angina occurring in the first two weeks after a myocardial infarction, and angina occurring at rest are also referred to as unstable. In myocardial infarction, heart muscle tissue perishes due to a local disturbance of blood flow. The reason for the local circulatory disturbance is a reduction in the diameter (lumen) of a branch of the coronary arteries (coronary vessels).
Risks and side effects
Simvastatin may also cause side effects. They include nonspecific headache, elevation of liver enzymes, gastrointestinal discomfort, and toxic myopathies (muscle disorders without a neuronal cause), up to and including rhabdomyolysis, the breakdown of muscles or muscle fibers. This side effect occurs primarily with concomitant administration of gemfibrozil.Simvastatin is contraindicated in cholestasis (bile stasis), elevated liver enzymes, myopathies, during pregnancy and lactation, and in hypersensitivity to any of the ingredients. As mentioned above, simvastatin should not be taken with medications or foods that inhibit cytochrome 3A4. In addition, simvastatin should not be given with fibrates (e.g., gemfibrozil) because of the increased risk of muscle damage. Contraindicated are the drugs gemfibrozil, ciclosporin and danazol. For further information, contact the treating physician.
