Lovastatin is a drug used to treat elevated cholesterol levels, heart attacks, acute coronary syndrome, and unstable angina. In the human body, it exerts its effects mainly on cholesterol formation and on the liver, which it stimulates to absorb more cholesterol from the blood.
What is lovastatin?
Lovastatin is a drug from the group of statins. As is typical for this type of medication, it is used in the treatment of elevated cholesterol levels (hypercholesterolemia), but it is also used after a heart attack, in acute coronary syndrome, and in unstable angina. Cholesterol is a blood fat that has a bad reputation because of its influence on the development of heart disease. However, the human organism needs it in normal quantities to produce various hormones, vitamin D, bile acid and cell membranes. Cholesterol belongs to the low-density lipoproteins (LDL). In 1987, lovastatin came on the market as the first statin to lower blood lipid levels. The molecular formula of the active ingredient, which is colorless by itself, is C24H36O5; the industry manufactures the drug with the help of the fungi Aspergillus terreus and Monascus ruber, with the microorganisms fermenting the starting materials in several process steps.
Pharmacological action
The mechanism of action of lovastatin is based on inhibition of the enzyme HMG-CoA reductase, which the human body needs to make cholesterol. At the same time, the drug stimulates the liver to absorb and break down more cholesterol. LDL receptors in the liver respond to blood fats like cholesterol: the LDL receptor binds to the molecule and takes it up into a depression in the cell membrane known as the spiny dimple. The occupied cavity then closes and in this way becomes a vesicle in the membrane. The trapped cholesterol is thus removed from the bloodstream. In addition, lovastatin inhibits the formation of new cholesterol. In normal cholesterol regulation, the enzyme HMG-COA reductase makes use of the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), which takes up the cleaved residues of the substrate in the biochemical reaction. In the body of a healthy person, cholesterol levels regulate themselves via thyroid hormones, insulin and glucagon as well as by the available amount of HMG-CoA reductase: As long as there is sufficient cholesterol, it binds to specific protein. However, if the cholesterol level drops, more and more of these binding proteins remain unoccupied and the activated proteins produce transcription factors, which in turn stimulate the synthesis of HMG-CoA reductase. Accordingly, the increasing number of enzymes leads to increased cholesterol formation, while conversely, rising cholesterol levels result in the automatic inhibition of synthesis. Lovastatin intervenes in this process by inhibiting HMG-CoA reductase, thereby curbing the formation of new cholesterol.
Medical application and use
Lovastatin finds use in the treatment of elevated blood cholesterol, among other conditions. This hypercholesterolemia is reflected in elevated LDL levels when the blood is tested in the laboratory. In a healthy person without risk factors, the value should not exceed 160 mg/dl; for patients with coronary heart disease or arteriosclerosis, the reference value is below 100 mg/dl. For these two diseases, an elevated cholesterol level is also a general risk factor. Arteriosclerosis is characterized by deposits in the blood vessels that can obstruct blood flow and consist of fat, thrombi, calcium or connective tissue. These can cause further complications and contribute, among other things, to the development of a heart attack, for the treatment of which the drug lovastatin is also indicated. In a heart attack or myocardial infarction, there is an interruption in the blood supply to the heart. Survivors are often given various medications after a heart attack to reduce the likelihood of another incident. Lovastatin is considered in this case, along with other statins, beta-blockers, ACE inhibitors, and other drugs, and in this role it has both a poststroke and preventive role. A less specifically delineated cardiac disease is acute coronary syndrome, in which various cardiac-related symptoms are present.The syndrome serves as a “working diagnosis” for physicians until they can precisely narrow down the actual disease. One of the possible causes of acute coronary syndrome is unstable angina pectoris, which results from a combination of arteriosclerosis and coronary heart disease. It may precede myocardial infarction and can also be treated with lovastatin.
Risks and side effects
Lovastatin is contraindicated in myopathy, biliary congestion (cholestasis), or elevated levels of liver enzymes. The most common side effects of the drug include headache, elevated liver enzymes, digestive problems, and myopathy. In this case, the latter belong to the toxic myopathies, as they are due to a drug and lead to the typical muscle weakness of the multiform clinical picture. Overall, muscle symptoms occur in 0.025% of patients taking lovastatin. In extreme cases, muscle fibers may disintegrate (rhabdomyolysis), leading to numerous other signs of disease: Muscle weakness and pain, edema in muscle tissue, fever, diarrhea, and vomiting are among the symptoms of rhabdomyolysis. Furthermore, blood uric acid levels may increase (hyperuricemia), the body may excrete greater amounts of the muscle pigment myoglobin (myoglobinuria), and electrolyte disturbances and consumption coagulopathy are possible in the setting of rhabdomyolysis. A patient’s risk of developing muscle fiber breakdown as a side effect of lovastatin increases when lovastatin is combined with fibrates: concomitant use of gemfibrozil and lovastatin, for example, causes the severe side effect in 1-5% of cases. In addition, various antibiotics and antifungals can promote side effects of lovastatin. Foods such as grapefruit juice may also cause this effect.
