Please find the power point on Pharmacology of Anticoagulants, antiplatelets . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you

1. Sunil Kumar Daha

2. Coagulation Cascade

4. Basic Pharmacology
• Anticoagulants
• limit the ability of the blood to clot
• venous thrombosis  fibrin rich
• Antiplatelet drugs
• limit the migration or aggregation of platelets
• arterial thrombosis  platelet rich
• Thrombolytics / Fibrinolytics
• drugs act to dissolve clots after they have formed
• venous thrombosis  fibrin rich

5. Anticoagulant drugs
Oral anticoagulants
• Vitamin K antagonism : Warfarin/coumarins
• Direct thrombin inhibition : Dabigatran
• Direct Xa inhibition : Rivaroxaban, Apixaban
Injectable anticoagulants
• Antithrombin-dependent inhibition of thrombin and Xa: Heparin
• Antithrombin-dependent inhibition of Xa :Fondaparinux, Idraparinux
• Direct thrombin inhibition ::Lepirudin, Argatroban,
Bivalirudin

6. Heparin
• MOA: promotes the action of antithrombin III to inactivate thrombin and
factor Xa and suppresses coagulation. Affects factor IIa, IXa, Xa, Xia,XIIa and
VIIa
• Uses: pulmonary embolism, DVT
• Mode of administration: only IV or deep s.c.
• Adverse effect
Hemorrhage
Heparin-induced thrombocytopenia
Hypersensitivity reaction
Osteoporosis(long term use)
Safe in pregnency

8. • Contraindication
- Active bleeding
- Hypertension
- Tuberculosis
- Renal disease
- Recent surgery of brain, spinal cord, eye.
- Ulcerative lesions in GIT
• Half life 1-5 hrs
• Antidote: protamine sulfate

10. Warfarin

11. Warfarin
• Clearance is slow = 36 hrs
• Delayed onset
• Oral Administration
• 5-10 mg daily
• Antidote
• Vitamin K infusion
• Can cross placenta
• do not use during late pregnancies

12. Monitoring of Warfarin Therapy
• INR ( International Normalized Ratio )
• INR=(PT patient/PT normal)ISI
• Target INR= 2.0 TO 3.0
• Every 2-3 weeks

13. Adverse effects of Warfarin
• Bleeding
• Skin necrosis
• Fetal abnormalities, bleeding

14. Contraindications to Anticoagulant use
• Previous Heparin-induced thrombocytopenia syndrome (HITS)
• Coagulopathies
• Hemophilia
• thrombocytopenia
• Active bleeding
• intracranial hemorrhage
• gastrointestinal (GI) ulcers
• certain cancers

15. Antiplatelet
1. Aspirin
MOA:
• Cause irreversible acetylation of COX enzyme and inhibit Thromboxane A2
formation in platelet thus inhibit platelet aggregation.
• Also inhibit release of ADP
Dose: 75-325 mg daily
• At high dose prostacyclin production which promotes platelet aggregation.
• High dose- more A/E and toxicity

17. 2. Dipyridamole (vasodilator)
• Inhibits phosphodiesterase enzyme and block uptake of adenosine –
increase cAMP - potentiate PGI2 – inhibit platelet aggregation.
• Act on platelet on the vessel wall rather than on circulating one.
Dose: 150-300 mg/day
• Used with aspirin reduces thrombus
• Used with warfarin reduce incidence of thromboembolism.

18. 3. Ticlopidine/clopidogrel/prasugrel
• Inhibits the binding of ADP to platelet- inhibit activation of GPIIb/IIIa receptor required
for platelet to bind with fibrinogen or each other.
Dose: Clopidogrel- 75 mg OD
Ticlopidine- 250 mg BD
A/E: Ticlopidine: diarrhoea, vomiting, rash,
neutropenia, bleeding
Clopidogrel: better tolerated, rarely associated with
neutropenia

19. 4. Abciximab/eptifibatide/tirofiban
• Glycoprotein IIb/IIIa receptor antagonists
• Inhibit platelet aggregation
Adverse effect
Hemorrhage
Thrombocytopenia
Constipation
Arrythmia

20. Uses of antiplatelet
• Coronary artery disease
MI
Unstable angina
• Cerebrovascular disease
Transeint ischemic attack
• Coronary bypass implant

21. Thrombolytics/fibrinolytics
• These are drugs used to lyse thrombi/ clot to recanalize occluded
blood vessels (mainly coronary artery)
• work by activating the natural fibrinolytic system
• Clinically important fibrinolytics are
Streptokinase
Urokinase
Alteplase (rt-P A), Reteplase, Tenecteplase

22. Fibrinolytics: MOA

23. Streptokinase
• Side effects:
 it is antigenic
 rash, fever, hypotension and arrhythmia
• Indication and dosage
For MI: 7.5-15 lac IV infused i.v. over 1 hr.
For deep vein thrombosis and pulmonary embolism: 2.5 lac IU
loading dose over 1/2-1 hr, followed by 1 lac IU/hr for 24 hr.

24. Urokinase
• Indication:
patients in whom streptokinase has been used for an earlier
episode
• Side effects
Fever(common), hypotenssion and allergic reaction are rare.
• Indications and dosages
For MI: 2.5 lac IU iv. over 10 min followed by 5 lac IU over next 60
min (stop in between if full recanalization occurs) or 6000 IU/min
for upto 2 hr.
For venous thrombosis and pulmonary embolism: 4400 IU/kg over
10 min iv. followed by 4400 IU/kg/hr for 12 hr.

25. Alteplase
• recombinant tissue plasminogen activator (rt-PA)
• short halflife: 4-5min
• Side effects: nausea,fever, mild hypotension
• Indications and dosages
For MI: 15 mg iv. bolus injection followed by 50 mg over 30 min,
then 35 mg over the next 1 hr.
For pulmonary embolism: 100 mg i.v. infused over 2 hr.

26. References
• Harrison’s Principle of Medicine, 18th ed.
• Davidson’s Principle and Practice of Medicine, 21st ed.
• Katzung’s Basic and Clinical Pharmacology, 12th ed.

27. Thank You