TRC: Vitamin K antagonists

Oral anticoagulants

Vitamin K antagonists (oral anticoagulants)

Vitamin K antagonists or coumarin derivatives diminish the availability of vitamin K. Synthesis of various coagulation factors in the liver is dependent on vitamin K. During carboxylation of glutamic acid residues (Glu) of these factors into gamma-carboxyglutamic acid (Gla) residues reduced vitamin K (hydroquinone) acts as a co-factor and is oxidized to vitamin K epoxide. Subsequently, vitamin K epoxide is reduced again in two steps to vitamin K hydroquinone. Coumarin derivatives inhibit the enzymes responsible for the reduction process (vitamin K epoxide reductase or VKOR), resulting in less available reduced vitamin K, decreased gamma-carboxylation and impaired function of these coagulation factors. The Gla-residues are necessary for binding calcium ions resulting in conformational change and binding to phospholipid surfaces through which the efficacy of the coagulation process is increased.

Coumarin derivatives (acenocoumarol, fenprocoumon) are widely used for the prevention and treatment of arterial and venous thromboembolism (deep vein thrombosis, pulmonary embolism, atrial fibrillation, artificial heart valves). Bleeding is the major adverse effect of coumarin treatment. Coumarins have important interactions with many other drugs. Examples of drugs that potentiate the action of coumarins are amiodarone, miconazol, metronidazole, and thyroxin. Other drugs inhibit the action of coumarins (aminoglutethimide, barbiturates, carbamazepin, phenytoin, rifampicin).

What is true about acenocoumarol?

Extra info: Acenacoumarol is contraindicated during the first 13 weeks of pregnancy and should be used with care during the rest of the pregnancy. Rash is not an important side effect of acenocoumarol. Thromb-embolic problems are the main indication.

Option explanation:

it may not be used during pregnancy after 13 weeks

it is metabolized in the liver

after bleeding, rash is the main adverse effect

it has arterial thrombosis as main indication

What is true about acenocoumarol?

Extra info: Its effect only becomes obvious 48 hours after the first dose. This is because the clotting factors present in the circulation need to be eliminated first. The half-life of acenocoumarol is 12 hours. It is well absorbed from the GI tract. Therefore, C is the correct answer and is the reason that we directly measure the effect of anticoagulants by monitoring the PT and INR.

Option explanation:

the effect of anticoagulation occurs within the first 12 hours after the first dose

it has a half-life of about 72 hours

there is no correlation between plasma concentration and PT

it is not absorbed from the gastrointestinal system

The monitoring of the effect of coumarins is best done by

Extra info: Coumarins do have a direct effect on the prothrombin time (PT), however, because the laboratory standards change from batch to batch and laboratory to laboratory, the International Normalized Ratio (INR) is used.

Oral anticoagulants

Vitamin K antagonists (oral anticoagulants)

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