Anticoagulants
Name: Suhena Shirin Barbhuiya
Roll No: 08
Class: M. Pharm 1st Semester
Institute Name: NETES Institute of Pharmaceutical Science
Subject: Advance Pharmacology – I
ANTICOAGULANTS
Anticoagulants are the drugs that is used to reduce the
coagulability of blood.
Coagulation will occur instantaneously once a blood vessel has
been severed.
Blood begins to solidify to prevent excessive blood loss and to
prevent invasive substances from entering the blood stream.
CLASSIFICATION OF ANTICOAGULANTS
Anticoagulant
Used in vivo
Parentral
Used in vitro
Oral
Heparin
Sodium
Citrate
Sodium
Oxalate
Sodium
edetate
Parenteral
Anticoagulants
Indirect thrombin inhibitor
Direct thrombin inhibitors
* Unfractionated heparin(UFH)
* Low molecular weight heparin(LMWH)
* Fondaparinux
* Danaparoid
* Bivalirudin
* Argatroban
* Desirudin
Oral
Anticoagulants
Vit. K Anatagonists
* Warfarin
* Acenocoumarol
Direct Factor Xa inhibitor
* Rivaroxaban
* Apixaban
Oral direct thrombin
inhibitors
* Dabigatran
Unfractionated heparin(UFH)
 Normally occurs as a macromolecule in mast cells with histamine.
 Commercial preparations extracted from beef lung or pig intestine.
Mechanism of Action
 Heparin binds to antithrombin 3 to bring about conformational changes,that makes it
faster in binding to thrombin.
 Then leaves the cpmplex in thrombin bonded to its inhibitor anti thrombin, to again
bind to another anti thrombin 3.
 And the Cycle continues eventually decreasing blood coagulability.
Pharmacokinetics of heparin
 It needs to be given intravenously as oral administration makes it unabsorbable because
of tis high negative charge and molecular size.
 It works immediately after administation.
 And connot cross blood brin barrier or placental barrier making its use safe during
pregnancy.
 As the heparin reaches live, it immediately gets inactivated and metabolites are
excreted into urine.
Adverse effects (ADR)
 Bleeding (Major ADR)
 Heparine induced thrombocytopenia.
 Hypersensitivity reactions like skin rashes, urticaria, fever etc.
 Osteoporosis.
Low Molecular Weight Heparine (LMWH)
 Heparine has been fractionated into LMW form ( MW 3000-7000) by different techniques.
 LMW Heparines have a different anticoagulant profile i.e., they selectively inhibit factor Xa
with little effect on factor IIa.
Mechanism of action
 It increase the action of antithrombin-III on factor Xa (inhibit factor X) but there is no action
on thrombin because the molecules are too small to bind to both enzymes and inhibitors.
Advantages
 They have a higher bioavailability and longer T1/2
 Have more predictable anticoagulant response because of reduced binding toplasma protein,
platelets and osteoblast.
 There is a lower incidence of thrombocytopenia and osteoporosis as compared to UFH.
 They are used increasingly in place of UFH
 ADVERSE EFFECTS AND CONTRAINDICATIONS ARE SAME AS OTHER
ANTICOAGULENTS
Fondaparinux
 It is a synthetic parentral anticoagulant.
 It binds to antithrombin and selectively inactivates factor Xa
without an effect on thrombin.
 It is administered subcutaneously.
 It is useful inn pulmonary embolism and deep vein thrombosis.
 It does not require routine laboratory monitoring
 It should not be administered in patients with renal failure.
Parenteral Direct Thrombin Inhibitor
 They bind directly to thrombin and in activate it.
 They do not bind to antithrombin-III.
 Lepirudin inhibits thrombin irreversibly.
 Argatroban and Bivalirudin inhibit thrombin reversibly.
 They are used as anticoagulant in patients who are at risk of heparine
induced thrombocytopenia.
 The main adverse effect is bleeding.
Vitamin k Antagonist
Coumarin (warfarin)
Mechanism of action
 Inhibits the synthesis of biologically active forms of vitamin K dependent
coagulation factors that are factor 2,7,9,10.
 As well as anticoagulant proteins.
 Warfarin interferes with natural process of vitamin k regeneration by
inhibiting vitamin k epoxide reductase.
Pharmacokinetics
 It is almost completely absorbed after oral administration.
 It is highly bound to plasma proteins and can cross placental barrier.
 Metabolized in liver and excreted in urine and stool.
Adverse effects
 Bleeding: Most important and common side effect.
 Teratogenic effect: Warfarin is contraindicated during pregnancy.
 Skin necrosis: Rare complication that occurs within the 1st week of
therapy.
 Other rare side effects: Diarrhoea, dermatitis, abdominal cramp etc
Therapeutic Uses
Venous thromboembolism.
Atrial fibrillation.
Myocardial Infarction.
Drug Interactions
 Medications that decrease the effect of anticoagulants thus
increasing the chance of blood clots
---- vit k
---Haloperidol
----Rifampin
---Phenobarbitol
 Medications that increase the effect of anticoagulants thus increasing
the chance of bleeding
---Allopurinol
---Ciprofloxacin
---Aspirin
---Diclofenac
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