oral and parenteral anticoagulants

1. WAQAS AHMED
KHAN

2.  Use of pharmacologic agents which inhibit
blood clotting , for the treatment and
prevention of venous and arterial
thromboembolism

3. 1. To prevent recurrence, extension and
embolization of thrombi
2. To reduce risk of post-thrombotic syndrome

4. Atrial
Fibrillation
Coronary artery
disease
Ischemic stroke
Deep vein
thrombosis
Pulmonary
embolism
Hypercoagulable
states
Bedridden
patients

5. 1.Heparin and related compounds
UFH,LMWH,Fondaparinux
2.Vitamin K Antagonists
Warfarin
3.Direct factor Xa inhibitors
Rivaroxaban, apixaban
4.Direct thrombin inhibitors
Lepirudin, Bivalirudin, Dabigatran, Argatroban

10. Fondaparinux
LMWH (Enoxaparin)
Unfractionated
heparin

11.  Unfractionated heparin is a large molecule
 Pentasaccharide binding site attaches to
antithrombin III which inhibits thrombin and
factor Xa
 It increases antithrombin effect by 1000x
 UFH is given IV or SC
 LMWH are produced by enzymatic breakdown
of UFH

12.  LMWH block factor Xa but not thrombin
 Fondaparinux is a synthetic compound and is
composed of only the pentasaccharide unit of
heparin
 LMWH/Fondaparinux is given SC

13. UFH LMWH Fondaparinu
x
Size 15k to 20k Da 2k to 6k Da tiny
Mode of
administration
S/C , I/V S/C S/C
Mechanism Inhibits Xa ,
Thrombin
Inhibits Xa Inhibits Xa
Duration
Adverse Effect More common Less common Less common
Reversal by
antidote
Complete Partial Partial

14.  Bleeding (intracranial hemorrhage, GI
bleeding)
 Thrombocytopenia
 Osteoporosis
These adverse effects are less common with
LMWH and Fondaparinux

15.  Antidote to over dosage of heparin
 Completely reverses the heaprin effects
 LMWH/Fondaparinux effects are only
partially reversed by protamine sulphate

16. X
ll
IX
VII
Pr
C,S
reductase
enzyme (VKOR) Vit K

17.  Inhibits reductase enzyme (VKOR) with
normally regenerates vitamin K
 Inhibit Vitamin K dependant factors
II,VII,IX,X,proteins C and S
 Oral administration for long term use
 Monitored by INR

18.  Warfarin is used for chronic anticoagulation
Atrial fibrillation
DVT/PE
Mechanical heart valves
 Monitoring is required
 Target INR 2-3 (may vary)

19.  Bleeding
 Skin necrosis (early in the therapy)
 Osteoporosis
 Purple toe syndrome
 Calcification of valves and arteries

20.  Contraindicated
 Teratogenic
 Spontaneous abortion, still birth or preterm
birth
 1st trimester: Fetal Warfarin Syndrome FWS
 Later : CNS and eye defects
Heparin (LMWH) can be used in pregnancy

21. Cytochrome p450 inhibitors reduce
warfarin clearance and increase its
anticoagulant effect
SSRIs , amiodarone, cimetidine
Cytochrome p450 inducing drugs
increase warfarin clearance and hence
reduces its anticoagulant effects
barbiturates, carbamazepine,
phenytoin,rifampin

22.  Vitamin K… takes 6-24 hours
 FFP.. that contains normal clotting factors
 Prothrombin complex concentrate.. Contains
factors II, VII, IX, X

23.  Directly bind to thrombin active site and
inactivates it
 Alternatives to heparin esp. in patients with
HIT
 Monitored by aPTT
• Lepirudin , bivalirudin,
argatroban are
administered parenterally
• Dabigatran is an oral
DTI

24.  Bleeding
 Anaphylactic reactions

25.  Directly bind to activated factor X and
inactivates it
 Substitutes for warfarin and heparin
 Prevention of stroke in AF
 Prevention of VTE
Rivaroxaban, epixaban are administered
orally

26.  Oral administration
 Rapid onset and offset of action
 Once daily dosing
 Do not need monitoring
 Low risk of intracranial bleeds

28.  LMWH (Enoxaparin) can be used alongwith
thrombolytics (for 2-8 days)
 Fondaparinux
 Heparin + GPIIb/IIIa inhibitors can be used
during angioplasty and coronary stenting
 In case of large anterior wall MI consider
warfarin for 3 months as prophylaxis against
systemic thromboembolism from LV mural
thrombus

29.  To prevent embolization and Stroke
 Based on CHADS2VASc score
 If CHADS2VASc score is more >1,
anticoagulation must be considered
 Warfarin
 Dabigatran

30.  LMWH and warfarin should be started
simultaneously
 Daily INR for 5 days
 Stop heparin after 5 days or once INR >2 for 2
days
 Continue warfarin for 3 months
 INR should be measured on alternate days
until stable, then weekly, and then less often