This document provides information on various anticoagulant drugs including heparin, low molecular weight heparins, synthetic heparin derivatives like fondaparinux, direct thrombin inhibitors, and oral vitamin K antagonists like warfarin. It discusses their mechanisms of action, indications, dosing, advantages and disadvantages, interactions, and adverse effects. Key anticoagulants covered are heparin, enoxaparin, fondaparinux, dabigatran, rivaroxaban, and warfarin.

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.

2. Parenteral Anticoagulants
 Heparin
 Low Molecular Weight Heparins- Enoxaparin
Dalteparin, Tinzaparin, Ardeparin,
Nadroparin, Reviparin
 Synthetic Heparin Derivatives- Fondaparinux
 Thrombin Inhibitors-lepirudin, Bivalirudin,
Desirudin, Argatroban, Danaparoid,
Drotecogin Alfa (All Parentral), Rivaroxiban,
Dabigatran (Oral)

3.  Coumarin derivatives: warfarin,
acenocumarol, ethyl biscoumacetate and
dicumarol
 Indanedione group: phenindione and
Anisindione

4. Factor Name
I Fibrinogen
II Prothrombin
III Tissue Factor or thromboplastin
IV Ca++
V Proaccelerin
VII Proconvertin
VIII Antihemophilic A factor
IX Christmas factor or
X Stuart factor
XI Plasma thomboplastin antecedent
XII Hageman factor
XIII Fibrin stabilizing factor

6. INTRINSIC PATHWAY
All clotting factors are
within the blood vessels
 Clotting slower
 Activated partial
thromboplastin test (aPTT)
EXTRINSIC PATHWAY
Initiating factor is outside
the blood vessels - tissue
factor
 Clotting - faster - in
Seconds
 Prothrombin test (PT)

8.  Heparin is a non-uniform mixture of straight chain
mucopolysaccharide molecules
 The mean molecular weight of heparin is 15,000 D
 Strongest organic acid present in body
 Source- mast cells lung, liver, Int.mucosa
 Actions –acts both in-vivo and invitro
 Antithrombin III (ATIII) binding is necessary for its
anticoagulant activity

9.  Antithrombin III (ATIII) is a slow endogenous progressive
inhibitor of thrombin and other clotting enzymes.
 Higher doses inhibits
platelet aggregation and
Prolongs bleeding time.
 Lipaemia clearing

10.  Large, highly ionised molecule,
 Bioavailability- sc -variable, IV
 Does not cross –BBB or placenta
 Excreted in urine
 T1/2-1-4 hrs
 1000, 5000 u/ml 5ml vials
 Should not be mixed with penicillin,
tetracyclines.

11.  Bleeding: they both lead to bleeding but the
bleeding is less in LMWH
 To treat bleeding: inject antidote protamine sulphate
(1mg IV for each 100 units of UFH) (reversal effect)
 Thrombosis: heparin ↓ ATIII ↑risk of
thrombosis

12.  Thrombocytopenia: Heparin-induced thrombocytopenia
(HIT) is a life threatening immune reaction
 HIT ↑ platelet activation platelet aggregation
thrombosis.
 HIT endothelial damage
 HIT may occur in the early stages of treatment (within 5
days) but it’s non-immune reaction (not life threatening)
 LMWHs, though of lower risk, are contraindicated with
HIT.
 Osteoporosis, hyperkalemia, hypersensitivity

13.  Bleeding or hemophilia
 Severe hypertension
 Thrombocytopenia or purpura-HIT
 Intracranial hemorrhage
 Recent surgery-ocular, neuro, lumbar
 Hypersensitivity to heparin
 TB
 GIT ulcer
 Hepatic or renal disease, chronic alcoholics
 Use of digoxin

14.  M.Wt 2000-8000 Da ( avg 4500 Da )- prepared from SH by
fractionation & enzymatic degradation .
 Commercial preprn : Enoxaparin, Dalteparin, Ardeparin,
Tinzaparin, Reviparin, Nadroparin
 Routes : SC (OD)
 High anti-Xa and low anti-IIa activity↔ greater
antithrombotic and lower anticoag activity
 Low anti-IIa activity, hence, aPTT, TT are not ideal for
monitoring. Anti-Xa assay ideal
 Less complicated, dose independent clearance and more
predictable anticoagulant response than UFH.

15. 1. Heparin –IV -5000-10000 units
2. Low dose regimen-sc-DVT
LMWH-
1. Prophylaxis and trmt of DVT, pulm. Embolism-
enoxaparin -30mg sc
2. Unstable angina and MI-
3. To maintain patency of canula and shunts
4. RHD
5. Cerebrovascular diseases
6. DIC
7. Anticoagulation in pregnancy
8. Treatment of peripheral embolism

16.  Dabigatran etexilate is a new oral direct thrombin
inhibitor and the prodrug of Dabigatran
 Rivaroxaban is an orally available, small-molecule,
active site-directed factor Xa inhibitor
 Knee replacement surgeries
 Equivalent to LMWH

17.  first selective factor Xa inhibitor,
 55% better than enoxaparin (LMWH) at reducing risk
of VTE
 synthetic pentasaccharide: “represents the
oligosaccharide consensus sequence of heparin”
 Indirect inhibition: binds to antithrombin and
increases antithrombin’s affinity for factor Xa by
300-fold

18.  Fondaparinux is given –sc- once daily
 Long elimination t 1/2 (20 hrs). Renal clearance
Uses
1. Initial treatment of deep vein thrombosis (DVT)
2. pulmonary embolism (PE) and for
3. Venous thromboembolism prevention in patients
undergoing surgery for hip fracture or hip/knee
replacement

19.  Lepirudin (DTI) derived from hirudin from leech
salivary glands.
 -ischemic conditions associated with unstable angina
 Better in hepatic insufficiency patients
 Bivalirudin (DTI) approved for use during heparin-
induced thrombocytopenia (HIT) & percutaneous
coronary interventions
 Argatroban (DTI) can be used in patients with risk of
(HIT)
 Desirudin -DVT

20.  Danaparoid-84% heparan sulphate+12% dermatan
sulphate+ 4% chondroitin sulphate
 Drotrecogin Alfa
 Human recombinant activated protein C
 used in patients with sepsis; recombinant form of
activated protein C that inhibits f Va and f VIIIa

21. Vitamin K Antagonists (The Coumarins)
Vitamin K is co-factor for the hepatic
synthesis of clotting factors II, VII, IX & X
Warfarin inhibits Vit. K reductase 
no active form of Vit. K 
no synthesis of clotting factors
Clinical anticoagulant activity needs
several days to develop (due to the
already circulating clotting factors)
So the action of warfarin will appear
after the elimination of prior
clotting factors.

22.  Onset: starts after 12-16 hours
 lasts for 4-5 days
 Elimination time (factor II needs: 60 hours factor
X: 40 hours)
 Overlap heparin & warfarin therapy taken
together until the effect of warfarin appears
(after 5 days) then stop taking heparin.

23.  Warfarin has 100% oral bioavailability,
 plasma protein binding-99% &
 long plasma t1/2 of 36 hours
 A high loading dose followed by an adjusted
maintenance dose
Contraindicated with pregnancy -is teratogenic in
the first trimester & and induce intracranial
hemorrhage in the baby during delivery
 Warfarin is metabolized by hepatic Cytochrome
P450 enzymes with half-life of 40 hrs

24.  Dicumerol-bishydroxycoumarin-slowly,
unpredictably
 t1/2-prolonged GI-intolerance
Acenocumarol-t1/2 -8hrs active metabolite-24hrs
rapid action 1, 2, 4mg
Ethyl biscoumoacetate-rapid and brief action
Indandione derivative-Phenindione-S/E-leucopenia,
agranulocytosis, haemorrhage
Anisindione- S/E-vasculitis, haemorrhage, hematuria

25.  Prophylaxis and/or treatment of:
 Venous thrombosis and its extension-2-2.5
 Pulmonary embolism
 Thromboembolic complications associated with AF
and cardiac valve replacement-
 Post MI, to reduce the risk of death, recurrent MI,
and thromboembolic events such as stroke or
systemic embolization-3-3.5
 Prevention and treatment of cardiac embolism.

26.  INR= patients PT in seconds
 mean normal PT in seconds
ISI
INR = International Normalized Ratio
ISI = International Sensitivity Index

27.  Food and drug interactions
 Genetic variation in metabolism
 narrow therapeutic window
 slow onset of action
overlap with parenteral drugs
dosage adjustments &
freq. monitor with INR

28. 1. Induce microsomal enzymes (barbiturates,
meprobamate and other sedative-hypnotic drugs;
griseofulvin).
2. Inhibition of metabolism (e.g., allopurinol disulfiram.
3. Displaced from binding sites by phenylbutazone,
phenytoin, sulfinpyrazone, clofibrate, Salicylates,
Indomethacin, Oral Contraceptives
4. Acetaminophen inhibits warfarin degradation
5. Effect of anticoagulants on other drugs -Coumarin
agents prolong and intensify action of chlorpropamide,
tolbutamide, phenytoin and phenobarbital.