Post on 16-Apr-2017
ORAL ANTICOAGULANTS
Dr. RENJU.S.RAVI MD
HEMOSTASIS
PLATELET PLUG FORMATION
COAGULATION CASCADE
ANTICOAGULANTSI) 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
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
WARFARIN Discovered after report of
hemorrhagic disorder in cattle ingested spoiled sweet clover (d/t dicoumarol) – Campbell & Link
Racemic mixture of R & S isomersf. II, VII, IX,X Carboxylated f.II,VII,IX,X
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
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
DRUG INTERACTIONS
Long acting sulfonamides, Phenytoin, Indomethacin, Probenecid, phenylbutazone displace warfarin from plasma protein binding
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
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
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but withdrawn d/t hepatotoxicity DABIGATRAN- recently approved in Europe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
ORAL FACTOR Xa INHIBITORRIVAROXIBAN
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