1. ANTICOAGULANT, THROMBOLYTICS & ANTIPLATELET DRUGS.
BLOOD COAGULATION,
ANTICOAGULANT, THROMBOLYTICS & ANTIPLATELET DRUGS.
PRESENTED BY:-
DR. MARWA SHAALAN
PHARM-D

2. Physiology and Pathophysiology of Coagulation
Hemostasis
Stage 1—formation of platelet plug
Platelet aggregation
Stage 2—coagulation
Intrinsic coagulation pathway
Extrinsic coagulation pathway
Keeping hemostasis under control
Physiologic removal of clots
Thrombosis
Arterial thrombosis
Venous thrombosis .

3. A Blood Clot Consists of platelets meshed into fibrin
A web-like accumulation of strands with RBCs
There are two major facets of the clotting mechanism – the platelets, and the thrombin system
Causes a plug for bloodstream

4. Anticoagulants – General Overview
Drugs that help prevent the clotting (coagulation) of blood
Coagulation will occur instantaneously once a blood vessel has been hurt.
Blood begins to solidify to prevent
excessive blood loss and to prevent
invasive substances from entering
the bloodstream

5. MECHANISM OF PLATELET AGGREGPATION
. Mechanism of platelet aggregation and actions of antiplatelet drugs
MECHANISM OF PLATELET AGGREGPATION

6. Mechanism of platelet aggregation and actions of antiplatelet drugs.

7. Anticoagulant Use
Anticoagulant drugs help prevent the development of harmful clots in the blood vessels by lessening the blood's ability to cluster together
The function of these drugs is often misunderstood because they are sometimes referred to as blood thinners; they do not in fact thin the blood
These drugs will not dissolve clots that already have formed, but it will stop an existing clot from becoming worse and prevent future clots

8. 1-Anticoagulant Drugs
Heparin and warfarin are the two traditional anticoagulants
Anticoagulants are used for acute coronary syndromes, deep-vein thrombosis (DVT), pulmonary embolism (PE), and heart surgery
Thrombus - A blood clot that forms abnormally within the blood vessels
Embolus - When a blood clot becomes dislodged from the vessel wall and travels through the bloodstream
It is also given to certain people at risk for forming blood clots, such as those with artificial heart valves or who have atrial fibrillation (AF)
intravascular coagulation of the blood in any part of the circulatory system, as in the heart, arteries, veins, or capillaries

9. A-Parenteral Anticoagulants 1-Heparin and Related Drugs
1-Heparin (unfractionated)
Sources
Lungs of cattle
Intestines of pigs
Rapid-acting anticoagulant
Uses
Pulmonary embolism (PE)
Stroke evolving
Massive deep venous thrombosis (DVT) .

10. A-Parenteral Anticoagulants I: 1-Heparin and Related Drugs (cont’d)
Adverse effects
– Hemorrhage
– Heparin-induced thrombocytopenia
– Hypersensitivity reactions
Protamine Sulfate[ antidote]
Activated partial thromboplastin time (APTT) for monitoring.

11. 2-Low-Molecular-Weight Heparins
Heparin preparations composed of molecules that are shorter than those found in unfractionated heparin as ENOXAPARIN.
Therapeutic use
Prevention of DVT following surgery
Treatment of established DVT
Prevention of ischemic complications
Adverse effects and interactions
Bleeding
Immune-mediated thrombocytopenia
Cost .

12. 3-Fondaparinux [Arixtra]
Synthetic anticoagulant
Selective inhibition
Therapeutic use
Prevention of DVT following surgery
Treatment of acute PE (in conjunction with warfarin)
Treatment of acute DVT (in conjunction with warfarin)
Adverse effects
Bleeding
Patients weighting less than 50 kg
Thrombocytopenia
Spinal or epidural hematoma

13. 4-Direct Thrombin Inhibitors
Bivalirudin [Angiomax], Lepirudin
Argatroban
Desirudin
Therapeutic use
Prevent clot formation (combined with aspirin)
Mechanism of action
Facilitates the actions of antithrombin
Prevents the conversion of fibrinogen into fibrin
Prevents the activation of factor XIIIa
Adverse effects
Back pain
Nausea
Headache

14. B-Oral Anticoagulant 1-WARFARIN
Antagonist to vitamin K
Blocks the biosynthesis of factors VII, IX, X, and prothrombin
Therapeutic uses
Long-term prophylaxis of thrombosis
Prevention of venous thrombosis and associated pulmonary embolism
Prevention of thromboembolism (in patients with prosthetic heart valves)
Prevention of thrombosis during atrial fibrillation

15. Warfarin, an Oral Anticoagulant (cont’d)
Adverse effects
Hemorrhage
Fetal hemorrhage and teratogenesis from use during pregnancy
Not to be Used during lactation WARNING? .

16. Warfarin, an Oral Anticoagulant (cont’d)
Drug interactions
Drugs that increase anticoagulant effects[ CYT P450 inhibitors as cimetidine]
Drugs that promote bleeding
Drugs that decrease anticoagulant effects[CYT P 450 INDUCERS AS PHENYTOIN]
Heparin
Aspirin
Acetaminophen

17. 2-Dabigatran etexilate
Dabigatran etexilate is a new oral direct thrombin inhibitor and the prodrug of dabigatran
Dabigatran is a small molecule that reversibly inhibits both free and clot-bound thrombin by binding to exosite 1 and/or the active site of thrombin

18. The future for anticoagulants
Molecular targets are factor IIa (thrombin) and factor Xa
The two candidate compounds, one direct thrombin inhibitor (dabigatran etexilate) and one direct factor Xa inhibitor (rivaroxaban) are hoping to be approved as new oral anticoagulants in the near future

19. 2-Antiplatelet Drugs Aspirin (ASA) Inhibition of cyclooxygenase
Adverse effect
Increase risk of GI bleeding
Ticlopidine [Ticlid]
Inhibits ADP-mediated aggregation
Adverse effects
Hematologic effects
Clopidogrel [Plavix]
ADP receptor antagonist

20. Antiplatelet Drugs (cont’d)
Glycoprotein (GP) IIb/IIIa receptor antagonists
Most effective antiplatelet drugs esp. in acute coronary syndromes.
Reversible blockade of platelet GP IIb/IIIa receptors
EXAMPLE: ABCIXIMAB

21. 3-Thrombolytic Drugs Drugs that break down, or lyse, preformed clots
Older drugs
streptokinase and urokinase
Newer drugs
Tissue plasminogen activator (t-PA)
Anisoylated plasminogen-streptokinase activator complex (APSAC)

22. Thrombolytic Drugs (cont’d)
Streptokinase
Binds plasminogen
Uses
Myocardial infarction
Deep vein thrombosis
Massive pulmonary emboli
Adverse effects
Bleeding
– Antibody production
Hypotension
Fever

23. Thrombolytic Drugs (cont’d) NEW COMPOUNDS
anistreplase (Eminase)
alteplase (t-PA, Activase)
reteplase (Retavase)
tenecteplase (TNKase)

24. Thrombolytic Drugs Indications
Acute MI
Arterial thrombolysis
DVT
Occlusion of shunts or catheters
Pulmonary embolus
Acute ischemic stroke

25. Thrombolytic Drugs: Adverse Effects
Bleeding
Internal
Intracranial
Superficial
Other effects
Nausea, vomiting, hypotension, anaphylactic reactions
Cardiac dysrrhythmias; can be dangerous

26. Thank you !