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.
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
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
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withdrawn d/t hepatotoxicity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