Q2i: MoA Anti-platelet drugs

Definition

Anti-platelet agents:  drugs which interfere with normal adhesion & aggregation of platelets

Classes of Antiplatelets

  1. COX inhibitors → aspirin
  2. ADP inhibitors → clopidogrel, ticagrelor
  3. IIb/IIIa inhibitors → tirofidan, abciximab
  4. Phosphodiesterase (PPD) inhibitors → dipyridamole

Cox Inhibitors

  • Arachidonic acid

↓ (COX)

Prostaglandin

↓ (thromboxane synthetase)

TXA2

  • MoA
    • TXA2 causes platelets to ∆shape, release granules & aggregate
    • Aspirin = irreversible acetylation of COX → inactivated
    • A-nucleus platelet undergo pr synthesis – COX inhibited for platelet lifespan (10 days)

ADP Inhibitors

  • Clopidogrel is a PRODRUG
  • Metabolised in liver → non-competitive antagonist of P2Y12 receptor (irreversible)
  • P2Y12 is a Gi GPCR
  • ∴Inhibits AC → ↓cAMP → ↓IIb/IIIa formation
  • P2Y12 is an ADP receptor → ADP activates platelets by binding & activating GP IIb/IIIa
ADP Inhibitors

Dipyridamole

Mechanism 1:

  • Inhibits phosphodiesterase enzyme which breaks down cAMP
  • ↑cAMP blocks platelet aggregation by ADP

Mechanism 2:

  • Inhibits reuptake of Adenosine by platelets

IIb/IIIA Inhibitors

  • Monoclonal Ab (Abciximab)
  • GP IIb/IIIa inhibitor
  • ∴prevents platelet aggregation by blocking platelet – platelet bridging by Fibrinogen