Phenprocoumon is the active ingredient in Marcumar. It is a chemical substance from the group of coumarins. Representatives of this class of substances have anticoagulant properties, so they are important as active pharmaceutical ingredients. They are used as a drug for thrombosis prophylaxis.
What is phenprocoumon?
Phenprocoumon is the active ingredient in Marcumar. It is used as a drug for thrombosis prophylaxis. In 1922, a cattle death caused by severe bleeding was reported in North America. Ten years later, the cause was found: Spoiled sweet clover contains dicumarol, a breakdown product of coumarin. Coumarin itself is not toxic. It is only in the rotting process or under the action of molds that it is converted into a highly potent derivative or dicumarol. Compounds derived from coumarin (coumarin derivatives) are similar in structure to vitamin K, which is involved in the activation of various coagulation factors. Factors II, VII, IX, and X are synthesized in the liver and subsequently converted to their coagulant form with the assistance of vitamin K
Pharmacologic action
In the presence of phenprocoumon, a coumarin derivative, the provision of these coagulation factors is inhibited. The situation resembles a deficiency of vitamin K.
This is referred to as an antagonistic effect to vitamin K. Therefore, phenprocoumon is suitable as an anticoagulant drug. Phenprocoumon is the most commonly used coumarin compound in Germany and is contained in the drugs Marcumar and Falithrom. When taken, phenprocoumon impedes clotting and thus prevents thrombosis. The clotting process, as a vital process, is optimally balanced in the healthy body. If this balance is disturbed, there is a risk that a thrombus (blood clot, blood clot) will block a blood vessel and thus cause thrombosis.
Medical application and use
Events that promote thrombosis include slowed blood flow, such as occurs with certain heart conditions or bedriddenness; damage to blood vessel walls, such as from medications or injury; and an increased tendency to clot. Phenprocoumon is administered for therapy in patients after a heart attack, in heart diseases with poor pump function, in atrial fibrillation, after insertion of artificial heart valves and after implantation of vascular prostheses. It is estimated that in Germany about 300 to 500 thousand patients are treated with phenprocoumon for life. The effect of phenprocoumon does not start immediately after ingestion, but only after 36-72 hours. After discontinuation of the drug, it again takes 36 to 48 hours for the blood to reach its complete clotting ability. Vitamin K is suitable for neutralizing phenprocoumon, but not in an emergency, because the effect would take too long. The only effective measure in such a case is the administration of blood or blood components containing vitamin K-dependent clotting factors. The responsiveness to phenprocoumon varies from patient to patient. In addition, the effect of phenprocoumon is influenced by other medications taken as well as by diet. The therapy must therefore be individually adapted and monitored by a physician. The level of anticoagulation is determined by a laboratory test. The International Normalized Ratio (INR) is determined. Healthy people have an INR of 1. The value increases when taking phenprocoumon and should be between two and 3.5, depending on the doctor’s prescription. There are now devices that patients can use to determine their own values at home after receiving training.
Interactions
Although vitamin K is known to be present in some foods, such as broccoli, cauliflower, spinach, and Brussels sprouts, it is not necessary to avoid them when taking phenprocoumon. More critical are drug interactions. Some reduce the effect, such as digitalis glycosides (heart preparations), anti-inflammatory drugs or diuretics (diuretics). Regular alcohol consumption also results in a reduced effect. Other factors lead to an increase in effect, such as acetylsalicylic acid (ASS, aspirin), allopurinol (for gout), various painkillers or broad-spectrum antibiotics. In any case, the package inserts should be studied and the intake coordinated with the attending physician.
Risks and side effects
The side effect resulting from the mode of action and thus the most common side effect during therapy with phenprocoumon is an increased tendency to bleed. It can often manifest itself in the form of increased bruising (bruises, hematomas), bloody urine, or frequent bleeding from the nose or gums. Less frequently, bleeding occurs in the gastrointestinal tract. In isolated cases, hives (urticaria), eczema, or reversible hair loss have been described as side effects. Phenprocoumon should not be taken if there is already an increased bleeding tendency or pregnancy. In addition, stroke (apoplexy), untreated hypertension, severe liver disease, and an increased tendency to fall because of the risk for extensive bruising are considered contraindications.
