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Lecture Notes on Antiplatelet agents

Overview of the Topics
Antiplatelet Drugs (Click Here)

Antiplatelet drugs

- Platelet aggregation occurs in response to vascular injury
- The aggregation of platelets  in the coronary artery can lead to the development of atherosclerotic plaque
- It may precipitate coronary vasospasm, myocardial infarction, and stroke

Clinical Indication
- Prophylaxis of arterial thrombosis
- Therapeutic management of myocardial infarction and stroke
- Should be infused within 2 hours of myocardial infarction or stroke for significant benefit

Clinically Important Antiplatelet Agents
- Thromboxane A2 pathway, ADP pathway & GPIIb/IIIa receptors are the therapeutic targets to prevent platelet activation and aggregation. The drugs include
- Aspirin
- Clopidogrel
- Abciximab

Aspirin

- Aspirin inhibits platelet aggregation and prolongs bleeding time 
- Aspirin irreversibly inhibits an enzyme cycloxygenase (COX-1) in platelets and prevents the formation of thromboxane A2
- In endothelial cells, aspirin inhibits the synthesis of prostacyclin (PGI2)
- The selective inhibition of thromboxane A2  inhibits platelet activation (See figure above)
- Aspirin shows drug interaction with ibuprofen, ibuprofen lowers the effect of aspirin by decreasing the availability of COX for acetylation.

Clopidogrel

-Clopidogrel and structurally related drugs irreversibly inhibit specific purinergic receptors and interfere with ADP and receptor binding
- This results in decreased ADP induced expression of platelet membrane GPIIb/IIIba and fibrinogen binding to platelets
- Often used for prevention of thrombotic stroke in patients that cannot tolerate aspirin 

Abciximab
- Chimeric monoclonal antibody Abciximab binds to the GPIIb/IIIa complex  
- inhibits the interaction of fibrinogen and von Willebrand's factor with the integrin receptor
- decreases the platelet aggregation

For more information on Antiplatelet medications visit: https://www.ncbi.nlm.nih.gov/books/NBK537062/, https://www.ncbi.nlm.nih.gov/books/NBK470539/


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