1. ANTIPLATELETES AGENTS
BY :DR. ISRAA OMAR

2. The role of platelets
Platelets play a critical role in thromboembolic disease like ischemic heart disease and stroke
Platelets adhere to the diseased or damaged areas and become activated, exposing phospholipids and GPIIb/IIIa receptors.
Platelet change their shape to stellate form
Activate platelets also synthesize and release mediators like TXA2 and ADP, which stimulate other platelets to aggregate and eventually fibrin formation and thrombosis.
Platelet aggregation is inhibited by prostaglandin I2
TXA2 production is reduced by cAMP

3. Aspirin( Acetylsalicylic acid )
Aspirin inhibits COX-1 irreversibly, this will lead to inhibition of synthesis of thromboxane A2 which in turn lead to inhibition of platelet activation and aggregation.

4. Aspirin (Acetylsalicylic acid) – mechanism of action
Antithrombotic drugs
Aspirin (Acetylsalicylic acid) – mechanism of action
September 2007

5. Acetylsalicylic acid – (Aspirin) mechanism of action
Antithrombotic drugs
Acetylsalicylic acid – (Aspirin) mechanism of action
September 2007

6. (Acetylsalicylic acid – (Aspirin mechanism of action
Antithrombotic drugs
(Acetylsalicylic acid – (Aspirin mechanism of action
September 2007

7. (Aspirin )Acetylsalicylic acid – mechanism of action
Antithrombotic drugs
(Aspirin )Acetylsalicylic acid – mechanism of action
September 2007

8. (Aspirin) Acetylsalicylic acid – mechanism of action
Antithrombotic drugs
(Aspirin) Acetylsalicylic acid – mechanism of action
September 2007

9. Aspirin– pharmacokinetics
Antithrombotic drugs
Aspirin– pharmacokinetics
Rapid absorption of aspirin occurs in the stomach and upper intestine, with the peak plasma concentration being achieved minutes after administration
The peak inhibitory effect on platelet aggregation is apparent approximately one hour post- administration
Aspirin produces the irreversible inhibition of the enzyme cyclooxygenase and therefore causes irreversible inhibition of platelets for the rest of their lifespan (7 days)
Reference:
Patron C. Aspirin as an antiplatelet drug. N Engl J Med 1994;330:1287–94.
September 2007

10. Acetylsalicylic acid – major use
Antithrombotic drugs
Acetylsalicylic acid – major use
Secondary prevention of transient ischaemic attack (TIA), ischaemic stroke and myocardial infarction
Prevention of ischaemic events in patients with angina pectoris
Prevention of coronary artery bypass graft (CABG) occlusion
September 2007

11. (Aspirin )– major drawbacks
Antithrombotic drugs
(Aspirin )– major drawbacks
Risk of gastrointestinal adverse events (ulceration and bleeding)
Allergic reactions
Is not a very effective antithrombotic drug but is widely used because of its ease of use
Lack of response in some patients (aspirin resistance)
The irreversible platelet inhibition
September 2007

12. 2. Clopidogrel and Ticlodipine (Thienopyridines )
It inhibits platelets aggregation by irreversibly binding for ADP receptors on the surface of platelets.
This will lead to reduce mobilization of calcium from intracellular stores and reduces the expression of glycoprotein receptors on the platelets surface

13. ADP-receptor antagonists – mechanism of action
Antithrombotic drugs
ADP-receptor antagonists – mechanism of action
September 2007

14. ADP-receptor antagonists – mechanism of action
Antithrombotic drugs
ADP-receptor antagonists – mechanism of action …
September 2007

15. ADP-receptor antagonists – mechanism of action
Antithrombotic drugs
ADP-receptor antagonists – mechanism of action
September 2007

16. ADP-receptor antagonists – mechanism of action
Antithrombotic drugs
ADP-receptor antagonists – mechanism of action .
September 2007

17. ADP-receptor antagonists – pharmacokinetics
Antithrombotic drugs
ADP-receptor antagonists – pharmacokinetics
Both currently available ADP-receptor antagonists are thienopyridines that can be administered orally, and absorption is approximately 80-90%
Thienopyridines are pro-drugs that must be activated in the liver
September 2007

18. ADP-receptor antagonists – major use
Antithrombotic drugs
ADP-receptor antagonists – major use
Secondary prevention of ischaemic complications after myocardial infarction, ischaemic stroke and established peripheral arterial disease
Secondary prevention of ischaemic complications in patients with acute coronary syndrome (ACS) without ST-segment elevation
September 2007

19. ADP-receptor antagonists – major drawbacks
Antithrombotic drugs
ADP-receptor antagonists – major drawbacks
Clopidogrel is only slightly more effective than aspirin
As with aspirin, clopidogrel binds irreversibly to platelets
In some patients there is resistance to clopidogrel treatment
September 2007

20. GPIIb/IIIa-receptor antagonists
Abciximab is a monoclonal antibody with Fc region removed to prevent immunogenicity .
It bind irreversibly to GPIIb/IIIa receptors and prevent its binding to fibrinogen .
It can reduce the platelets aggregation by more than 90% .

21. GPIIb/IIIa-receptor antagonists – mechanism of action
Antithrombotic drugs
GPIIb/IIIa-receptor antagonists – mechanism of action
September 2007

22. GPIIb/IIIa-receptor antagonists – mechanism of action
Antithrombotic drugs
GPIIb/IIIa-receptor antagonists – mechanism of action .
September 2007

23. GPIIb/IIIa-receptor antagonists – mechanism of action
Antithrombotic drugs
GPIIb/IIIa-receptor antagonists – mechanism of action
September 2007

24. GPIIb/IIIa-receptor antagonists – mechanism of action
Antithrombotic drugs
GPIIb/IIIa-receptor antagonists – mechanism of action
September 2007

25. GPIIb/IIIa-receptor antagonists – mechanism of action
Antithrombotic drugs
GPIIb/IIIa-receptor antagonists – mechanism of action
September 2007

26. GPIIb/IIIa-receptor antagonists – major use
Antithrombotic drugs
GPIIb/IIIa-receptor antagonists – major use
Prevention of ischaemic cardiac complications in patients with acute coronary syndrome (ACS) without ST-elevation and during percutaneous coronary interventions (PCI), in combination with aspirin and heparin
September 2007

27. Dipyramole It is a phosphodiaestrase inhibitor .
It increases intracellular cyclic AMP, thus reducing TXA2 synthesizes and also potentiate the prostacyclin effect on platelets making them less sticky and therefore making them less adhesive to thrombogenic surface .
It is ineffective when used alone; should be used with aspirin
It reduces the risk of stroke .
Unlike aspirin it does not increase the risk of bleeding

28. Thank you

29. Referrences:
Lippincottes pharmacology
Rang and dale pharmacology