This document discusses oral anticoagulants, including coumarin derivatives like warfarin, and newer oral anticoagulants. It provides details on warfarin such as its discovery, pharmacokinetics, interactions, side effects and monitoring. Newer oral anticoagulants discussed include direct thrombin inhibitors like dabigatran and factor Xa inhibitors like rivaroxiban which have advantages over warfarin like predictable pharmacokinetics and no need for routine monitoring. Overall the document reviews both traditional and newer oral anticoagulant options.

1. ORAL ANTICOAGULANTS
Dr. RENJU.S.RAVI MD

2. HEMOSTASIS

3. PLATELET PLUG FORMATION

4. COAGULATION CASCADE

5. ANTICOAGULANTS
I) USED INVIVO
PARENTERAL
 Unfractionated heparin (UFH)
 Low molecular weight heparin(LMWH) – Enoxaparin,
Dalteparin, Ardeparin, Nadroparin, Pamparin, Reviparin,
Tinzaparin
 Heparinoids- heparan sulfate, danaproid, ancrod
 Fondaparinux
 Direct thrombin inhibitor – lepirudin, argatroban
bivalirudin
 Drotrecogin Alfa – human recombinant activated
protein C

6. ORAL
 Coumarin derivatives-
bishydroxycoumarin, Warfarin,
acenocoumarol, ethylbiscoumacetate
 Indanedione derivative- Phenindione
II)USED INVITRO
 Heparin- 150 U for 100 ml blood
 Calcium complexing agents – sodium
citrate, sodium oxalate, sodium edetate

7. WARFARIN
 Discovered after report of hemorrhagic
disorder in cattle ingested spoiled sweet
clover (d/t dicoumarol) – Campbell & Link
 Racemic mixture of R & S isomers
f. II, VII, IX,X Carboxylated f.II,VII,IX,X

8. WARFARIN
 Rapid, complete absorption from GIT
 Plasma half life 36-42 hrs
 >97% PPB
 S isomer oxidative metabolised by CYP2C9
 2 variants CYP2C9*2,CYP2C9*3 – reduced
activity

9. WARFARIN cont…
 Crosses placenta
 Resistance with advanced GI Cancer
& hereditary
 Started at 5-10 mg dose along with
parenteral anticoagulant for 5 days
 Monitored by PT with target INR 2-3;
2.5 – 3.5 in pts with mechanical
prosthetic valves

10. DRUG INTERACTIONS

11.  Long acting sulfonamides, Phenytoin,
Indomethacin, Probenecid,
phenylbutazone displace warfarin
from plasma protein binding

12. SIDE EFFECTS
 BLEEDING
withhold drug - INR 3.5-4.5 asymptomatic
S/L vit K - INR > 4.5
1 mg vit K - INR 4.9 – 9
2 -3 mg vit K - INR >9
10 mg slow IV along with FFP if excessively
high
 SKIN NECROSIS – in pts with cong or acq def
of protein C/S
 TERATOGENIC EFFECTS – nasal hypoplasia,
stippled epiphysis

13. OTHER COUMARIN DERIVATIVES
 Bishydroxy coumarin (Dicoumarol)
Slowly absorbed, poor GI tolerance
 Acenocoumarol
half life 24 hrs, acts rapidly
S/E – spontaneous haemorrhage,
stomatitis, dermatitis, alopecia
 Ethyl biscoumacetate (Tromexane)
Rapid & brief action, difficult to
maintain
S/E - spontaneous haemorrhage, alopecia

14. ORAL DTI
 Advantages incl predictable PK, so fixed dosing
can be given and routine monitoring unnecessary
 Do not interact with P450 interacting drugs
 Rapid onset & offset of action
 XIMELAGATRAN – first oral DTI approved but
withdrawn d/t hepatotoxicity
 DABIGATRAN- recently approved in Europe for Px
of VTE in pts undergone hip, knee surgery
Equivalent efficacy & safety to LMWH
No routine monitoring required

15. ORAL FACTOR Xa INHIBITOR
RIVAROXIBAN
 First oral factor Xa inhibitor to reach phase III
trial
 Safety & efficacy atleast equivalent or better
to LMWH for preventing DVT
 NO routine monitoring necessary
 Also in trial for Rχ of Venous
thromboembolism & prevention of stroke in AF