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but withdrawn d/t hepatotoxicity DABIGATRAN- recently approved in Europe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