Synonyms in a broader sense
- Phenprocoumon (active ingredient name)
- Coumarins
- Vitamin K antagonists (inhibitors)
- Anticoagulants
- Anticoagulant
Marcumar® belongs to the group of indirectly acting blood coagulation inhibitors (medically: indirect anticoagulants). In demarcation to the directly acting anticoagulants like the heparin intervening directly into the blood coagulation the mechanism of action of the Cumarine consists of an inhibition of the formation of blood clotting factors necessary for the clotting (see below). Their effect was discovered by chance in Canada: In the 1920s it could be proven that the frequent occurrence of heavy, often fatal bleeding in cattle and sheep was due to their consumption of rotting clover, which contained large quantities of the coumarin Dicoumarol, which is produced during fermentation. The disease, previously feared as Sweet Clover Disease, thus enabled the treatment of the first patients with dicoumarol only a few years later and was recommended since 1944 for preventive treatment after a heart attack.
Trade names
Marcumar ®
Chemical name
PhenprocoumonMarcumar® is used in the following clinical pictures, among others: Coumarine/Marcumar® are used to treat leg vein clots (thrombosis) and pulmonary embolism. Pulmonary embolism occurs when a clot in the leg veins dissolves, enters the pulmonary artery via the inferior vena cava, atrium and ventricle of the right heart and blocks the vessel. This can happen, for example, after prolonged immobility such as air travel or after operations followed by bed-ridden patients.
The typical symptoms of pulmonary embolism, 10% of which are fatal within the first hour, are In severe cases of pulmonary embolism (so-called “fulminant” pulmonary embolism), a sudden drop in blood pressure with dizziness or unconsciousness can also occur: The right heart, which is responsible for supplying blood to the lungs, tries to pump blood into the lungs against the increased resistance in the downstream vessel caused by the clogged clot, but as a pump designed for low pressures it is overtaxed and becomes insufficient. The significance of the coumarineMarcumar® tablets (medical: oral) in the treatment of pulmonary embolism is primarily in the prevention of further pulmonary embolisms. The mechanism consists in the inhibition of the formation of blood coagulation factors II, VII, IX, and X, which are necessary for blood coagulation.
The enzyme (protein) required for production is irreversibly (irrevocably) inactivated by Marcumar®. Enzymes are biological catalysts that accelerate chemical reactions in the body. The task of the enzyme inhibited by Marcumar® is to accelerate the regeneration of vitamin K, which is required for the synthesis of the above-mentioned blood clotting factors and is “consumed” in the process.
The significance of the coumarineMarcumar® tablets (medical: oral) taken as Marcumar® tablets in the treatment of pulmonary embolism consists primarily in the prevention of further pulmonary embolisms. The mechanism consists in the inhibition of the formation of blood coagulation factors II, VII, IX, and X, which are necessary for blood coagulation. The enzyme (protein) required for production is irreversibly (irrevocably) inactivated by Marcumar®.
Enzymes are biological catalysts that accelerate chemical reactions in the body. The task of the enzyme inhibited by Marcumar® is to accelerate the regeneration of vitamin K, which is required for the synthesis of the above-mentioned blood clotting factors and is “consumed” in the process.
- Thrombosis
- Pulmonary Embolism
- Atrial fibrillation
- Artificial heart valves
- Heart attack prophylaxis
- Sudden shortness of breath (medical term: dyspnoea) or accelerated breathing (tachypnoea)
- Stabbing pain in the thorax (thorax)
- And characteristic blood picture changes (in 95% of all embolisms so-called D-dimers are detectable in the blood, which are fragments of the body’s own protein fibrin.
The D-dimers are created as a natural defence reaction of the body against excessive blood clotting leading to clot formation.
A lack of vitamin K (the K stands here for “coagulation”, medically for “blood clotting”) therefore has the same effect as taking coumarins. In response the blood clotting inhibition can be terminated at any time by the income of Vitamin K (z.B. if bleeding occurs as an undesirable side effect, see below), as this is then again available for the synthesis of blood clotting factors.
Coagulation improves again within a few hours with the administration of Marcumar®. For dissolving existing clots (thrombosis), however, so-called fibrinolytics are indicated instead of coumarine/Marcumar®. These are enzymes that break down the fibrin formed during the coagulation reaction.
Urokinase, alteplase and streptokinase derived from bacteria are examples of such fibrinolytics that are administered acutely in the intensive care unit as a first measure. CumarineMarcumar® are also used for the prevention of clot formation in atrial fibrillation (VHF). In this most common persistent cardiac arrhythmia, 80% of which is asymptomatic, the atria contract up to 400 times per minute, resulting in insufficient ejection into the ventricles and, as a consequence, a slowing of the blood flow (medical term: stasis) and increased risk of clot formation (thrombosis).
The reason for this is that the shear forces of the flowing blood stimulate the vessel walls to release endogenous, anticoagulant substances. If the stimulation fails to take place, a vaso-occlusive thrombus forms. The anticoagulants formed by intact vessel walls, such as nitric oxide (NO), can also be administered therapeutically in order to dilate the coronary vessels in the event of an angina pectoris attack (angina pectoris medically means “chest tightness” and refers to the feeling of tightness in the chest caused by a lack of oxygen supply to the heart.
The cause is almost always atherosclerosis of the coronary arteries, known as coronary heart disease, or CHD for short, i.e. the deposition of fatty particles in the vessel wall, which causes inflammation with the immigration of immune cells and release of vascular-damaging substances. The deposits in the vessel reduce its diameter so much that not enough blood can flow through it to supply the heart muscle. For the treatment of this illness, which is mainly caused by too high blood cholesterol levels, cigarette smoking and high blood pressure, besides the already mentioned NO, see above, so-called beta-blockers are also available, which reduce the oxygen demand by lowering the heart rate and the heart’s power.
In addition, beta-blockers prolong the duration of the disease, for example the frequently administered drugs metoprolol and bisoprolol (trade names: Belok zok® and bisoprolol), which prolong the relaxation phase of the heart known as diastole, in which the coronary vessels are passively filled with oxygen-rich blood following a contraction of the subsequently flaccid heart muscle. In this way, beta-blockers improve the oxygen supply to the heart not only by reducing the demand but also by increasing the supply of oxygen). Studies with many patients have shown that coumarineMarcumar® improves the prognosis of existing coronary heart disease in the long term, since the anticoagulation inhibition leads less frequently to e.g. complete blockage of the coronary arteries and death of heart muscle cells (heart attack). Such anticoagulation is also necessary after operations involving the replacement of heart valves, since artificial heart valves, as a foreign material, increasingly activate the coagulation system, even though attempts are being made to minimize this risk by using new materials coated with anticoagulant substances. A further application of CoumarinenMarcumar® is the prevention of relapses (medically: recurrence prophylaxis) after heart attacks.
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