Active Ingredients

Simvastatin – Effect, Application & Risks

Simvastatin

Simvastatin is a classic statin and is used to lower cholesterol. It was approved in 1990 and is used relatively frequently.

What is Simvastatin?

Simvastatin chemical (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 that is mainly used as a cholesterol-lowering agent. Simvastatin is structurally derived from the naturally occurring monacolin K, also known as lovastatin .

Simvastatin is made semi-synthetically from lovastatin. Simvastatin was approved in Germany in 1990. The patent expired in 2003 – 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 drug class of statins and acts as an HMG-CoA reductase inhibitor. Simvastatin is in the solid state. The molar mass is 418.57 gx mol^-1. The melting point of the substance is 127 to 132 degrees Celsius. The lethal dose 50 (LD50) of the substance in rats after oral administration is 4438 mg kg^-1.

Pharmacological effect on body & organs

As a classic representative of the statins, simvastatin has a lowering effect on the cholesterol level in the blood , so it can be assigned to the cholesterol-lowering drugs. This happens via inhibition of 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 drops because less new cholesterol can be synthesized.

In addition, increased LDL receptor synthesis is brought about. As a result, more LDL cholesterol is stored in the liver. This storage in turn means that less LDL cholesterol reaches the periphery – so the cholesterol level in the blood continues to drop.

Simvastatin is primarily metabolised by cytochrome P450 3A4. The metabolism therefore takes place in the liver. For this reason, drugs and foods that inhibit cytochrome 3A4 should be avoided as far as possible, as this slows down the breakdown of simvastatin, which in turn increases the risk of side effects . Cytochrome 3A4 inhibition is caused, for example, by clarithromycin , itraconazole , ketoconazole or grapefruit juice.

Medicinal Application & Use for Treatment & Prevention

As already mentioned, simvastatin is used medicinally as a cholesterol-lowering agent. The use of simvastatin is therefore indicated above all in the case of elevated cholesterol levels. Furthermore, simvastatin is used in acute coronary syndrome , unstable angina pectoris and myocardial infarction .

The term acute coronary syndrome does not denote a clear disease. The acute coronary syndrome is to be understood as a working diagnosis under which several cardiovascular diseases that cannot be clinically distinguished with certainty are summarized. These are in particular unstable angina pectoris, a non-transmural infarction without ST elevations but with an increase in troponin T/1, a transmural infarction with ST elevations in the fresh stage of the infarction and an increase in troponin T/1, and sudden cardiac death .

Angina pectris (“chest tightness”) describes a frequent, paroxysmal pain in the chest caused by a lack of blood supply ( ischemia ) to the heart . In unstable angina pectoris, the symptoms are not constant but change. However, there are no signs of a heart attack (myocardial infarction). Angina pectoris occurring for the first time, angina pectoris in the first two weeks after a myocardial infarction and angina pectoris occurring at rest are also described as unstable.

In myocardial infarction, myocardial tissue perishes due to a local circulatory disorder . The reason for the local circulatory disorder lies in the reduction in the diameter (lumen) of a branch of the coronary arteries (coronary vessels).

Risks & side effects

Simvastatin can also cause side effects. They include non-specific headaches , an increase in liver enzymes , gastrointestinal complaints and toxic myopathies (muscle disorders without a neuronal cause) through to rhabdomyolysis , the breakdown of muscles or muscle fibers . This side effect mainly occurs when gemfibrozil is administered at the same time .

Simvastatin is contraindicated in cholestasis (bile stasis), increased liver enzymes, myopathies, during pregnancy and lactation , as well as hypersensitivity to any of the ingredients.

As previously mentioned, simvastatin should not be taken with drugs or foods that inhibit cytochrome 3A4. In addition, simvastatin should not be given together with fibrates (eg gemfibrozil), since the risk of muscle damage is increased. The drugs Gemfibrozil, Ciclosporin and Danazol are contraindicated . The doctor treating you will provide further information.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.