This document discusses anticoagulants, focusing on warfarin. It classifies anticoagulants as in vitro, parenteral, and oral. It describes warfarin's mechanism of action as inhibiting vitamin K epoxide reductase, interfering with the regeneration of vitamin K's active form and the carboxylation of clotting factors. The document outlines warfarin's pharmacokinetics including its oral bioavailability, plasma protein binding, metabolism, and drug interactions. It notes warfarin's therapeutic uses for conditions like deep vein thrombosis and prophylaxis. The document also covers warfarin's adverse drug reactions and contraindications.

1. Anticoagulants
Warfarin
Dr. Archana Dhavalshankh
Pro & Head, Dept of Pharmacology
D Y Patil Medical College, Kolhapur

2. Classification of Anticoagulants : Warfarin
In Vitro
Heparin
Sod. Citrate – used in blood blank to store blood.
Sod. Oxalate & Sod. Edetate – used as an anticoagulant in laboratory
Parenteral
• Heparin
• Low mole wt. Heparins: Enoxaparin,
Dalteparin, Tinzaparin, Neviparin
• Synthetic: Fondaparinux
• Direct thrombin inhibitors: Lepirudin,
Bivaluridin, Argatroban
Oral
Coumarin Derivatives : Warfarin, Dicumarol
Indandione Derivatives: Phenindione
Direct thrombin inhibitors: Dabigatran
In Vivo

3. Vitamin K epoxide (Inactive form)
Vitamin K reduced (Active Form)
Inactive factors Active form
II, VII. IX, X II, VII. IX, X
Mechanism of Action : Warfarin
• All oral anticoagulants are Vit K antagonists
• They act indirectly by inhibiting with the synthesis
of Vit k dependent clotting factors in liver.
• They apparently behave as a competitive antagonist
of vit K & lower the plasma levels of functional
clotting factors.
• Warfarin inhibit Vit K epoxide reductase enzyme
• so regeneration of active form from epoxide form of
Vit K is interfered & active form is important for
carboxylase enzyme to convert descarboxy factors
(inactive) II, VII,IV & X to convert in active form.

4. Pharmacokinetics : Warfarin
• When warfarin is given
Factor VII level falls first (has shortest t ½ - 6 hrs)
Then factor IX --- then factor X & lastly factor II prothrombin.
• Synthesis of clotting factors diminishes within 2-4 hrs after warfarin
administration
But anticoagulant effect develops gradually over next 1-3 days.
(time taken to decline level of clotting factors present already in plasma.)
Th. Effect occurs only when synthesis of clotting factors is reduced by 40-50 %

5. Pharmacokinetics : Warfarin
Oral bioavailibity – 100 %
Plasma protein binding – 90 %
Volume of distribution avd- 7.7 L
Lorger t ½ - 36 hrs
Drug interactions – due to displacement
Metabolism – Liver conjugation with glucuronic acid & enterohepatic circulation.
Excretion – Urine
Cross- Placenta

6. Drug Interactions : Warfarin
↑ Activity ↓ Activity
Enzyme inducers : barbiturates
rifampicin, carbamazepine
Enzyme inhibitors: chlorpromazine,
disulfiram, erythromycin
Bind with cholestyramine Displacement : by probenecid,
phenytoin
Decrease absorption: sucralfate
Increase synthesis of clotting factors
– estrogen and OCP
Vit K deficiency : Liq. Paraffin cause
emulsification and excretion of Vit K

7. ADR & CI : Warfarin
Adverse Drug Reactions
Hemorrhage
Teratogenicity
Transient alopecia
Dermatitis
Diarrhea.
Contraindication
Pregnancy : Abortion Birth defects.

8. Therapeutic Uses : Warfarin
• Do not dissolve clot but prevent thrombosis extension
• Reduce rate of thrombus formation
• Reduce rate of thrombus recurrence
• Reduce rate of thrombus embolic complications.
Therapy Heparin + Warfarin Start concurrently
↓ ↓
Stop after Take full therapeutic effect
5-7 days

9. Therapeutic Uses : Warfarin
1. Deep vein thrombosis : for venous thrombi as they are fibrin thrombi
2. Prophylactic use : bed ridden patients after hip or leg fracture
10-15 mg orally
↓ Monitor prothrombin time
5-7 mg/day
3. MI- arterial thrombi (platelet thrombi) – Antiplatelet are given.
Unstable angina
Rheumatic heart disease.