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Acenocoumarol: mechanism of action and interactions

Acenocoumarol is the active ingredient of the drug marketed under the name Sintrom. It is a medicine with anticoagulant properties , prescribed to prevent the formation of blood thrombi. Its mechanism of action is based on acting against vitamin K, essential to start up the coagulant mechanisms.

It is virtually identical to warfarin ( Coumadin ), since both belong to the group of coumarin anticoagulants. Its use is more widespread in Anglo-Saxon countries, while Sintrom is the most used anticoagulant in our environment.

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How does blood coagulate?

Acenocoumarol: mechanism of action and interactions

Under normal conditions, the coagulation is started before a hemorrhage , avoiding the loss of blood. In this way, before an aggression, for example, a wound, a series of mechanisms that slow down the hemorrhage are activated.

These mechanisms can be divided into primary mechanisms and secondary mechanisms depending on the moment in which they act. Thus, the primary ones act practically immediately after the aggression, while the secondary ones take a little longer.

After the assault, the walls of the blood vessel that has been injured are narrowed. This process is called vasospasm, and its goal is to limit the amount of blood that passes through the damaged vessel, to prevent its loss. Next, the platelet plug is formed. The platelets adhere, on the one hand, to the collagen in the damaged vessel; and, on the other hand, each other.

After this first phase, the coagulation cascade is started. The final result is the formation of a fibrin clot, firm and insoluble , which prevents bleeding. For this, a series of sequential reactions are produced in which the main protagonists are the coagulation factors.

What are the coagulation factors?

  These are 13 molecules of a protein nature, which intervene in the cascade of coagulation reactions , activating each other until, in the final step, fibrinogen is converted into fibrin and the clot is formed.

Some of them need vitamin K to activate , and therefore, exercise their function. Activation is performed in the liver, through a process called gammacarboxylation. Factors II, VII, IX and X and proteins C and S are vitamin K dependent.

Mechanism of action of acenocoumarol

Acenocoumarol: mechanism of action and interactions

Acenocoumarol acts as “antivitamin K”. Thus, it inhibits a process that takes place in the liver, called gammacarboxylation, for which this vitamin is essential. If this is not done, the coagulation factors that depend on vitamin K are not activated. With the dependent vitamin K coagulation factors in a non-active state, the coagulation cascade can not be performed, whereby the blood remains in the liquid state.

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When is acenocoumarol prescribed?

It is the drug of choice for the treatment and prophylaxis of thrombotic diseases. Likewise, in many cases it is prescribed in a preventive manner after surgical interventions, especially after an intervention in traumatology (knee, hip operations …). Some examples of diseases treated with acenocoumarol are:

  • Prevention of thrombus formation in “hypercoagulable states” in people who have already had a thrombotic accident before. Hypercoagulability states are pathologies that predispose people to blood clot and form a thrombus.
  • In young patients who suffer recurrent thrombosis in which there are no known risk factors.
  • Prevention of thrombus formation and a consequent embolism in cardiac diseases . In this context, prevention of atrial fibrillation and valve diseases is especially important. In addition, people with valvular prostheses or who have undergone cardioversion should also be treated.

When is it contraindicated to take acenocoumarol?

Acenocoumarol: mechanism of action and interactions

Acenocoumarol is contraindicated, basically, in any situation where there is a high risk of hemorrhaging:

  • In cases of gastric ulcer and active diverticulitis.
  • In people with a dissecting aortic aneurysm .
  • When there is a recent history of cerebral hemorrhage or recent ocular or cerebral surgical intervention.  
  • In cases of severe hypertension or renal or hepatic failure.
  • People with urological, pulmonary or digestive cancer.

Interactions

In a very simple way, the taking of other medicines together with acenocoumarol can alter the effects of this. There are medications that can enhance their effects, while there are others that can decrease them.

Some examples of medications that can potentiate their effects are:

  • Anabolic steroids (the popular “anabolic”) and androgynous hormones (hormone replacement treatments)
  • Some antiarrhythmics, such as amiodarone or quinidine.
  • Some antibiotics, such as erythromycin or tetracyclines.
  • Clofibic acid and its derivatives.
  • Thyroid hormones used in substitution treatments.

Some examples of medications that can reduce their effects are:

  • Oral contraceptives

Likewise, acenocoumarol can also potentiate or decrease the effects of other medications. For example, the joint intake of acenocoumarol and hydantoin derivatives increases the blood concentration of the latter, thereby enhancing its effect. Some hydantoin derivatives are phenytoin (anticonvulsant), or dantrolene, used to treat malignant hyperthermia.

Other drugs that potentiate their effects are oral antidiabetics . In these cases, the seriousness lies in the fact that the hypoglycaemic effect is enhanced, with which the “sugar drop” is greater.

The excessive consumption of alcohol is also totally contraindicated , since the effects of this interaction can not be known in advance. Likewise, the joint taking of the drug with San Juan herb is discouraged. If the doctor has prescribed acenocoumarol, or has informed you that it is going to be done, be sure to tell him or her about any medications you may be taking. Also, if you have had surgery on your stomach or intestine, you should also inform them.

Acenocoumarol overdose: hemorrhage

Acenocoumarol: mechanism of action and interactions

The result of an overdose for this drug is, as would be expected, the appearance of hemorrhages . To stop them, it is usually enough to remove acenocoumarol. In the most severe cases, vitamin K will be administered in progressively higher doses until it is controlled.

Bibliography

  1. Vademecum (internet). Available at:
  1. World Federation of Hemophilia (internet). Available at:
  1. Sanchez Guijo F, Rational Basic Manual of Hematology. 4th Ed. Elsevier Salamanca.

Acenocoumarol: mechanism of action and interactions

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