 |
| 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:
 |
| 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.
Side effect of warfarin:
➜ 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.
