• Platelets are the initial hemostatic plug after vascular injury in the arteries 
• Platelets also participate in the pathological processes of atherosclerosis + thrombosis (especially arterial thrombi)
• Arachidonate pathway causes the production of TXA2 and PG
• TXA2:  Induces platelet aggregation + vasoconstriction 

• Platelet aggregation
• Platelet shape change 
• Platelet granule release
• Vasoconstriction 

• Inhibition of platelet aggregation 
• Inhibition of platelet secretion 
• Vasodilation 

MOA of aspirin (acetylsalicylic acid-ASA)

High dose effects of aspirin

Low dose effects of aspirin

• ASA interferes with hemostasis 
• ASA inhibits COX-1 by covalently binding to enzyme
• Low dose:  Inhibition of COX-1 at low doses is going to cause decreased conversion of cyclooxygenase to TXA2 which is going to decrease platelet aggregation + decrease vasoconstriction 
• High dose:  Inhibition of COX-1 at high doses is going to cause a decrease of cyclooxygenase to PGI2 which is going to INCREASE platelet aggregation and vasoconstriciton 

• Aspirin at low doses ONLY affect the non-nucleated platelet COX-1 enzyme and inhibit production of TXA2
• Since platelets are non-nucleated they cannot produce more COX-1 and are thus inhibited for the life of the platelet (7-10 days) 

• Unlike at low doses that only affect the platlets, high dose aspirin causes inhibition of COX-1 in the endothelial cells
• Inhibition of COX-1 at endothelial cells causes a decrease in PGI-2 which causes increased platelet aggregation and vasoconstrction 
• This is why there are cardiac-mortalities associated with COX-2 inhibitors 
• Essentially, higher doses of aspirin do NOT improve efficacy but instead increase toxicity especially bleeding 

• Acute phase of evolving MI:  Should be administered routinely to virtually all patients with evolving MI
• Secondary prevention of MI and stoke:  Long-term aspirin has shown a benefit on risk of sbusequent MI, stroke, vascular death in patients with CV disease 
• Primary prevention of CV disease:  Inconclusive 
• Additional benefits:  Reduction of thromboembolic complications in artifical HRT valves, decrease thrombotic occlusion of uremic patients undergoing hemodialysis, increase patency of coronary bypass graft 

• 81-325 mg
• Baby aspirin = 81 mg 
• Single aspirin tablet = 325 mg

• Severe anemia
• History of blood coagulation defects
• GI ulcers 
• Take anticoagulants

• Intake of aspirin might reduce the risk of cancer 

• Anti-platelet formation
• Prodrug 
• Inhibits platelet fibrinogen binding by selectively + IRREVERSIBLLY inhibiting the fucntion of platelet ADP receptors.  Which inhibit the formation of IIb/IIIa complex 
• ADP receptors are required for the activation of glycoprotein IIb/IIIa complex aand subsequent platelet aggregation 
• Platelets are affected for the remainder of their life-span b/c this process is irreversible and platelets cannot synthesize new receptors b/c they are anuclear 

• Activation: Clopidogrel is a prodrug that needs to be activated by the liver 
• Used for: prophylaxis of stroke + MI + peripheral arterial disease + ACS
• Potential problem:  In patients with hepatic problems b/c cannot convert to active drug 

• Anti-platelet drug
• Inhibits cAMP phosphodiesterase-III to suppresses cAMP degradation
• This increased intracellular cAMP:

               1)  Inhibits platelet aggregation 

               2)  Increases vasodilation 

• Reduction of symptoms of intermittent claudications (indicated by increased walking distance) 
• However, the efficacy for improvement of intermittent claudication is not impressive 

• Patients with CHF of ANY severity 

• Increases cAMP by inhibiting phosphodiesterase
• Increases cAMP by increasing adenosine levels which may stimulate cAMP synthesis 

• Prosthetic heart valves 
• Alternative to aspirin for 2ndary prevention of acute MI, prevent stroke in patients with ischemic attacks, maintain patency of coronary bypass graft 

• Anti-platelet drug 
• This is a monoclonal antibody 
• Binds to glycoprotein IIb/IIIa receptor to inhibit platelet aggregation 

• Has greater anti-thrombotic activity than aspirin or heparin 
• High-risk angioplasty 
• ACS 

What is going to be used to prevent restenosis of the artery after an angioplasty procedure?

What is the MOA?

Untoward effect?

Effectiveness of anti-platelet activity? 

***Eptifibatide + tirofiban***

Used during percutaneous transluminal coronary angioplasty procedures

These two drugs have > antiplatelet activity than clopidogrel

• MOA:  Peptide analogs of fibrinogen that inhibit platelet aggregation by blocking ligand binding to IIb/IIIa receptor 
• Untowrd effect:  Bleeding is a significant SE