Coumadine

Question 1

Mechanism of action?

Answer 1

Coumadine inhibits vitamine K dependent coagulation factors &cofactors. For the synthesis of the coagulation factors, vit K needs to be in its reduced form. Vit K is then oxidized during the synthetic process, and is reduced again by the vit K epoxide reductase. Coumadine inhibits this enzyme, preventing the reactivation of vit K &the synthesis of the coagulation factors.

Question 2

Indications?

Answer 2

• VTE = PE + DVT : to prevent clot extension &recurrence.
• AF : to prevent embolic complications.
• Heart valve replacements : to prevent embolic complications; stroke.

Question 3

Is Warfarin used for preventing ARTERIAL thrombosis?

Answer 3

No, as this is driven by platelet aggregation &prevented by anti-platelet agents : Aspirin, Clopidogrel.

Question 4

AE?

Answer 4

bleeding : a slight excess of warfarin increases the risk of bleeding from existing abnormalities, as well as following minor traumas (existing as peptic ulcers). Large excess of warfarin induces spontaneous hemorrhage : epistaxis &retroperitoneal hemorrhage.

Question 5

cautions?

Answer 5

DO NOT USE in first term or towards the end of pregnancy.

Question 6

interactions?

Answer 6

• P450 cytochrome inhibitors decrease warfarin metabolism &increase bleeding risk (fluconazole, macrolides, protease inhibitors)
• P450 cytochrome inducers increase warfarin metabolism &increase risk of clots (phenytoine, carbamazepine, rifampicine)
• many antibiotics destruct gut flora that synthesize vit K &thus; increase the risk of bleeding.

Question 7

How is warfarin taken?

Answer 7

Orally, generally once a day, at 18h for consistent effects on INR taken the following morning, with lower doses for : elderly &patients with increase risk of bleeding, on other medicines). Patients needing immediate anticoagulation are put on heparin for rapid onset &warfarin, heparin is continued for 5-7days &withdrawn when full anticoagulation with warfarin is achieved. 3-6months on warfarin in a single episode of VTE, lifelong warfarin (may be required) in recurrent VTE or cardiac disease.

Question 8

List Novel Oral AntiCoagulants, similar efficacy to warfarin, slightly safer profiles &less intensive monitoring required? NACO (Nouvaux AntCoagulants Oraux)

Answer 8

Dabigatran, Rivaroxaban, Apixaban, Edoxaban.

Question 9

Noms generiques?

Answer 9

SINTROM Acenocoumarol
PREVISCAN Fluindione (derivé de l’indanedione)
COUMADINE/WARFARINE Coumadine

PRADAXA Dabigatran
XARELTO Rivaroxiban
LIXIANA Edoxaban
ELIQUIS Apixaban

Question 10

Surveillance de l’heparine (HNF) &le Warfarine?

Answer 10

HNF par le TCA (en cas de HIT : numeration plaquettaire)

Warfarine par le INR