antiplatelet drugs

1. ANTI-PLATELET DRUGS

2. Role of platelets in thrombosis
• In arterial thrombi, platelets are the main constituents.
• Platelets first stick to damaged vessel wall and aggregation
occurs which lead to release of ADP, TXA2, serotonin other
substances which promote further aggregation by activation of
Gp IIb/IIIa on surface of the platelets.
• Vascular PGI2 is potent inhibitor of platelet aggregation.

3. Antiplatelet Drugs
1)COX inhibitors Aspirin
2)ADP Receptor
blockers
Irreversible Ticlopidine,
Clopidogrel, Prasugrel
Reversible Ticagrelor, Cangrelor
3)GP llb/llla inhibitors Monoclonal antibody Abciximab
Synthetic molecules Eptifibatide, Tirofiban
4)PDE inhibitors Dipyridamole,
Cilostazol
5) Thrombin Receptor
inhibitor
Vorapaxar

4. Platelet adhesion and aggregation

5. • GPVI and GPIb are platelet receptors that bind to collagen and
vWF, causing platelets to adhere to the subendothelium of a
damaged blood vessel.
• TxA2 is the major product of COX-1 involved in platelet
activation.
• Prostacyclin (PGI2), synthesized by endothelial cells, inhibits
platelet activation.

6. • PAR-1 and PAR-4 are PARs that respond to thrombin (IIa)
• P2Y1 and P2Y12 are receptors for ADP; when stimulated by
agonists, these receptors activate the fibrinogen-binding
protein GPIIb/IIIa and COX-1 to promote platelet aggregation
and secretion.

7. Sites of action of antiplatelet drugs

8. Aspirin
• Aspirin inhibits TxA2 synthesis by irreversibly acetylating
COX-1.
• Reduced TxA2 release attenuates platelet activation and
recruitment to the site of vascular injury.
• Therapeutic Uses-Acute myocardial infarction or acute
ischemic stroke & Secondary prevention in patients with
stroke, coronary artery disease, or peripheral artery disease.

9. • COX-1 inhibitor(selectivity>100x over COX-2)
• Antithrombotic effect achieved with low doses(<100 mg daily)
• Reduced toxicity with lower doses
• Higher doses do not improve efficacy and potentially are less
efficacious because of inhibition of prostacyclin production,
which can be largely spared by using lower doses of aspirin.

10. • Adverse effects- Risk of gastrointestinal adverse events (ulceration
and bleeding)
• Lack of response in some patients (aspirin resistance)
• Nonsteroidal anti-inflammatory drugs that are reversible inhibitors
of COX-1 have not been shown to have antithrombotic efficacy.
• May even interfere with low-dose aspirin regimens.
• Hence concomitant use with aspirin should be avoided.

11. ADP Receptor blockers
• Ticlopidine, clopidogrel, and prasugrel irreversibly block
P2Y12, a key ADP receptor on the platelet surface
• Cangrelor and ticagrelor are reversible inhibitors of P2Y12.
• Clopidogrel therapeutic uses-Acute coronary syndrome &
Secondary prevention in patients with myocardial infarction,
stroke, or peripheral artery disease

12. • Prasugrel, Ticagrelor & Cangrelor used after percutaneous
coronary intervention for acute coronary syndrome
• Adverse effects- increases the risk of bleeding, particularly
intracranial bleeding,

13. GP llb/llla inhibitors
• Abciximab, eptifibatide, and tirofiban inhibit the final common
pathway of platelet aggregation by blocking fibrinogen and
vWF from binding to activated GPIIb/IIIa.
• Therapeutic uses-Coronary intervention for acute coronary
syndrome
• Adverse Effects- The major side effect is bleeding.
Thrombocytopenia occurs in 0.5%–2% of patients.

14. Dipyridamole
• Interferes with platelet function by increasing the intracellular
concentration of cyclic AMP, mediated by inhibition of
phosphodiesterase or by blockade of uptake of adenosine,
thereby increasing the dwell time of adenosine at cell surface
adenosine A2 receptors that link to the stimulation of platelet
adenylyl cyclase.
• Therapeutic uses-secondary prevention of stroke when
combined with aspirin.

15. Thrombin Receptor Inhibitor
• Vorapaxar inhibits thrombin-mediated platelet activation by
targeting PAR-1(Protease activated receptor), the major
thrombin receptor on platelets.
• Therapeutic uses-Secondary prevention in patients with a
history of myocardial infarction or peripheral artery disease
• Adverse Effects- increases the risk of bleeding and is
contraindicated in patients with a history of intracranial
bleeding, stroke, or transient ischemic attack.

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