mechanism of action warfarin #simple and easy way

mechanism-of-action-warfarin-#simple-and-easy-way
warfarin mechanism of action


Warfarin is used as an anticoagulant drug. they prevent the coagulation of blood. Reduce the clot formation and thrombosis. It’s called a “blood thinner”

It prevents blood stroke in heart patients because it is reducing the blood clot in the vein and arteries. They inhibit the coagulation factors as well as vitamin K. that’s why called a vitamin K antagonist.

Here, further, discuss the detailed mechanism of action warfarin, pharmacokinetics, adverse effect, drug interaction, and its factor. So, stay tuned.

Overview of warfarin drugs:

Points

Warfarin

Sources

Synthetically
Chemistry

Coumarin derivatives
Route of administration

Oral administration
Duration of action

3 to 6 days
Onset of action

1 to 3 days (delayed)
Mechanism of action warfarin
Vitamin K antagonists and inhibit clotting factors.
Teratogenic effect
Cross the placental barrier and has a teratogenic potential
Drug interaction

Most significantly, except for some drugs
Use

For prevent the formation of clot and thrombus
Cost

Inexpensive


Mechanism of action warfarin:

mechanism-of-action-warfarin
warfarin mechanism of action



It works as a competitive antagonist of vitamin K. Because it is indirectly affecting the vitamin K depended on clotting factors in the liver (clotting factors 2,7,9 & 10).

They inhibit the vitamin K epoxide reductase and inhibit the conversion of inactivating vitamin K to activate vitamin K.

Active vitamin K is a useful conversion of inactivating clotting factors to activate clotting factors. Whenever active clotting factors are increasing its increase the coagulation of blood is increase.


 VITAMIN K INHIBIT ® CLOTTING FACTORS (2,7,9 & 10) DECREASE ® DECREASE COAGULATION


Coagulation factors:

Factors 1        

Fibrinogen
Factor 2

Prothrombin
Factor 3

Tissue thromboplastin
Factor 4

Ionized calcium
Factor 5

Proaccelerin or labile factor
Factor 6

Unassigned
Factor 7

Proconvertin or stable factor
Factor 8

Antihemophilic factor
Factor 9
Christmas factor or plasma thromboplastin component
Factor 10

Stuart – power factor
Factor 11

Plasma thromboplastin antecedent
Factor 12

Hageman factor
Factor 13

Fibrin stabilizing factor

The clotting factor is rich in glutamic acid residues and it’s carbonylated in the liver where active vitamin K acts as a coenzyme.

The carboxylation of glutamic acid is necessary for the coagulation to bind the calcium ion. That is an important role produce in the coagulation.

Also, a vitamin K is converted to its inactivated vitamin K epoxide by the oxidation and it's regenerated to the active form by epoxide reductase enzyme.

The structure of warfarin is similar to vitamin K.

That’s why warfarin competitively inhibits the vitamin K dependent coagulation factors like 2, 7,9, and 10. Thus, that produces an anticoagulant effect.

The onset and duration of action of warfarin are depended on the half-life of coagulation factors.


Coagulation factors

Half-life (t½)
Factors 2

50 hr
Factors 7

6 hr
Factors 9

24 hr
Factors 10

40 hr

So, the synthesis of the clotting factors is the decline within the 2 to 4 hours of warfarin is administration. Its anticoagulant effect developed produce within 2 to 5 days. Also, a produce a delayed action.

Which condition warfarin (anticoagulant) action increase

Hyperthyroidism. In this condition clotting factors degraded itself.

Liver disease and chronic alcoholism. to clotting factors synthesis may be deficient.

Malnutrition, malabsorption, and debility. in this condition vitamin K supply to the liver is decreased.  

New-borns. low level of vitamin K and other clotting factors.  


Which condition warfarin (anticoagulant) action decrease

Pregnancy. in pregnancy condition plasma level of the clotting factor is increasing. So, decrease the warfarin effect.

Nephrotic syndrome. Drug bound to the plasma protein is lost in the urine.

Genetic warfarin resistance. To the affinity of warfarin to bind with reductase enzyme and produce vitamin K epoxide is a decrease or low.

The above condition might chance to change the warfarin action.


Racemic warfarin sodium

Mechanism of action warfarin, warfarin sodium is the most popular oral anticoagulant. Commercial preparation of the warfarin is a mixture of R (dextrorotatory) and S (laevorotatory) enantiomers.

S enantiomers are more potent than R enantiomers. R enantiomers are less potent.

R and S enantiomers are partially conjugated with the glucuronic acid and finally, its excreted in the urine.

It’s completely absorbed from the intestine and 99% plasma proteins are bound. it secreted in milk to cross the placenta.

It is completely absorbed through oral administration. Bound to the plasma protein and cross the placental barrier. It is metabolized in the liver and excreted through stool and urine. 

Half-life is long like (40 hours) and the duration of action is almost 2 to 5 days.

Use of warfarin

Generally, warfarin medication is used for maintenance therapy. Whenever heparin medication discontinued then warfarin and other anticoagulants continued. (here, in this article complete details of heparin - heparin)

Heparin is used for 3 to 8 days and warfarin treatment used for 3 months. (as per your doctor suggestion)

➜ Thrombosis and embolism. The main aim of warfarin drugs is to prevent thrombosis and embolism by decreasing the fibrin formation rate. 

Thrombus formation. The use of warfarin (anticoagulant therapy) is to prevent the clot and thrombus formation in the vein and artery. They do not break the already formed clot or thrombus.

    Myocardial infarction and stroke. Anticoagulant is indirectly preventing stroke and myocardial infarction. Specially used to combine with a low dose of aspirin.

      clotting factor. It is also useful in the selected cases to decrease the consumption of the clotting factors.

        ➜ Thromboembolism. Warfarin is required for vascular surgery & prosthetic heart valve to prevent thromboembolism.

          hemodialysis. Oral anticoagulant is used in hemodialysis to prevent the thrombosis in the blood circuit.

          Side effect of warfarin:

          ➜ The most common side effect is produced is bleeding. 

          ➜ Gi tract bleeding, skin bleeding, pulmonary bleeding and urinary tract bleeding produced.

          ➜ Bleeding is controlled by parental vitamin K1.

          ➜ It is contraindicated during pregnancy. May cause hypoplasia, CNS abnormality, abortion, CNS abnormalities, and intrauterine death.

          ➜ In case, it given in early pregnancy, they increase the birth defect (skeletal abnormalities).

          ➜ Within the first of therapy warfarin produce a skin lesion on abdomen, things, buttocks and breast.

          ➜ Some other side effect produced like diarrhea, urticaria, dermatitis, abdominal cramps, alopecia and anorexia.

          Drug interaction of warfarin

          ·        Warfarin with cholestyramine. cholestyramine is bind to the warfarin and reduces the absorption of warfarin in the gut. it reduces the bioavailability of the warfarin drugs and the anticoagulant effect decreases.

          ·        Warfarin with broad-spectrum antibiotics. they inhibit the microbial gut flora and they reduce the vitamin K production and potentiate the anticoagulant effect.

          ·        Warfarin with tetracycline. tetracycline is the suppress the bacterial flora and reduce the formation of vitamin K. hence, that is potential an anticoagulant effect.

          ·        Warfarin with ceftriaxone and cefoperazone. due to hypoprothrombinaemia severe blood loss.

          ·        Warfarin with erythromycin and metronidazole. It is decreasing the metabolic clearance of warfarin and increase the warfarin activity.

          ·        Warfarin with sulphonamide and phenytoin. it can increase the free plasma concentration of warfarin. And enhance the warfarin effect.

          ·        Warfarin with aspirin and other NSAIDs. NSAIDs have an antiplatelet effect and thus, potential the warfarin effect.  

          ·        Warfarin with paraffin. they reduce the vitamin K absorption.

          ·        Warfarin with barbiturates (not benzodiazepines). they increase the metabolism of the oral anticoagulant.

          ·        Warfarin with oral contraceptives. they increase the activated clotting factors and reduce the warfarin effect.


          Conclusion: in this article, you find the mechanism of action warfarin, side effect, drug interaction, uses, and other details. if you like this comment out.


          TAGS: Mechanism of action warfarin, side effect of warfarin, use of warfarin, drug interaction of warfarin