Description
ANTICOAGULANT
Drugs that prevent blood coagulation and stop the occurrence or expansion of a thrombus.
Classification:
1. Vitamin K antagonist – Warfarin.
2. Heparin and related drugs:
(a) Heparin.
(b) LMWH (Enoxaparin, Dalteparin, Tinzaparin).
(c) Synthetic heparin derivatives (Fondaparinux – longer acting).
3. Direct thrombin inhibitors:
(a) Parenteral → Hirudin, Lepirudin, Argatroban, Bivalirudin.
(b) Oral → Dabigatran.
4. Active factor Xa inhibitor → Rivaroxaban, Apixaban.
Warfarin:
• Competitively inhibits vitamin K epoxide reductase and inhibits the post-translational carboxylation of glutamate residues on vitamin K dependent coagulation factors II (prothrombin), VII, IX, and X.
anti-coagulants with examples. Write the mechanism of action of heparin.
Heparin:
• Antithrombin III-Irreversibly inactivates thrombin and factor Xa.
• Heparin potentiates anti-thrombin III activity.
Advantages of LMWH:
1. Can be administered s.c.
2. Effects are consistent and dosing less frequent (Long t1/2 and elimin. By 1st order kinetics).
3. Dose is given in mg (not in units) can be easily calculated on body weight basis.
4. Chance of haemorrhage is less.
5. Risk of osteoporosis is decreased.
Uses of anti-coagulants:
1. Myocardial infarction
2. Unstable angina
3. Rheumatic heart disease
4. Cerebrovascular disease
5. Haemodialysis
6. Defibrination syndrome (DIC)
Haemostasis (arrest of blood loss) and blood coagulation involve complex interactions between the injured vessels wall, platelets and coagulation factors.
Coagulants:
Vitamin K : K1 (from fat-soluble): phytonadione (phylloquinone)
: K3 (synthetic)
• Fat soluble (Menadione, Acetomenaphthone)
• Water soluble (Menadione sod. Bisulfite, Menadione sod. Diphosphate.
• Miscellaneous: Fibrinogen (human), Antihaemophilic factors, Desmopressin,
Adrenochrome monosemicarbazone, Rutin, Ethamsylate.
Vitamin K:
• Vit. K is a fat-soluble dietary principle required for the synthesis of clotting factors.
• Daily requirements: Vit. K2 produced by colonic bacteria and 3-10 µg/day external source may be sufficient. The total requirement of Vit. K for an adult has been estimated to be 50-100 µg/day.
Mechanism of Action:
• Vit. K acts as a cofactor at a late stage in the synthesis by liver of coagulation
proteins – prothrombin, factors VII, IX and X.
Vitamin K, produced by
the body, helps to form
blood-clotting proteins
Blood-clotting
proteins hold
blood cells
together to
form clots
Lower levels of clotting
proteins makes blood cells
Warfarin less likely to clot reduces the body’s ability to make vitamin K which
interferes with protein creation
Blood cell
Fig.: Role of Vitamin K in Blood Coagulation
