Harvey's Garden

Antiplatelet agents

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Combination usage

  • The most common and important combination is DAPT (Aspirin + P2Y12 inhibitor) for ACS and coronary stents.
  • Adding an anticoagulant creates “Triple Therapy,” a necessary but high-risk strategy for pts with indications for both (e.g., Afib + stent).
  • GP IIb/IIIa inhibitors are potent IV “add-on” agents for high-risk PCI procedures.

Irreversible cyclooxygenase inhibitors

Agents

Acetylsalicylic acid (ASA, aspirin)

Mechanism of action

ASA covalently attaches an acetyl group to COX.

  • Irreversible COX-1 inhibition → inhibition of thromboxane (TXA2) synthesis in platelets → inhibition of platelet aggregation (antithrombotic effect)
    • Onset of antiplatelet action: within minutes
    • Duration of antiplatelet action: 7–10 days
  • Irreversible COX-1 and COX-2 inhibition → inhibition of prostacyclin and prostaglandin synthesis → antipyretic, anti-inflammatory, and analgesic effect
    • COX-2 is more resistant to inhibition than COX-1. Therefore, higher doses of aspirin are required to achieve the antipyretic, anti-inflammatory, and analgesic effects.

Effects

  • Low dose (below 300 mg/day): inhibition of platelet aggregation
  • Intermediate dose (300-2400 mg/day): antipyretic and analgesic effect
  • High dose (2400-4000 mg/day): antiinflammatory effect

ADP (P2Y12) Receptor Inhibitors

Agents

  • Irreversible Antagonists (Thienopyridines):
    • Clopidogrel: A prodrug activated by CYP2C19 (genetic variability in efficacy).
    • Prasugrel: More potent, more reliable activation than clopidogrel.
    • Ticlopidine: Rarely used due to severe side effects.
  • Reversible Antagonists:
    • Ticagrelor: Not a prodrug, faster onset.
    • Cangrelor: IV formulation, very short half-life.

Mechanism of action

  • Inhibit platelet aggregation by blocking the P2Y12 ADP receptor on the platelet surface.
  • Prevents ADP-mediated activation of the GpIIb/IIIa receptor complex.

Clinical Use

  • ACS, especially in combination with aspirin (Dual Antiplatelet Therapy - DAPT).
  • Prevention of thrombotic events in patients post-PCI (stenting) or with peripheral arterial disease.

Adverse Effects

  • Bleeding (major risk for all).
  • Ticlopidine: Neutropenia, agranulocytosis, TTP.
  • Prasugrel: Increased bleeding risk vs. clopidogrel; contraindicated in pts with prior stroke/TIA.
  • Ticagrelor: Dyspnea, ↑uric acid.

Glycoprotein (Gp) IIb/IIIa Inhibitors

Agents

  • Abciximab (Fab region fragments of monoclonal antibodies against glycoprotein IIb/IIIa receptors)
  • Eptifibatide
  • Tirofiban

Mechanism of action

  • Gp IIb/IIIa inhibitors bind to and block glycoprotein IIb/IIIa receptors (fibrinogen receptor) on the surface of activated platelets → prevention of platelets binding to fibrinogen → inhibition of platelet aggregation and thrombus formation

Indication

  • Prevention of thrombotic complications in high-risk patients with unstable angina/NSTEMI planned for PCI within 24 hours

Mnemonic

  • To remember that ABCiximab targets glycoproteins IIb/IIIa, think ABC rhymes with 123!
  • Eptifibatide and tirofiban are fibrinogen receptor blockers.

Phosphodiesterase (PDE) Inhibitors

  • Mechanism
    • Inhibit phosphodiesterase enzymes, leading to ↑ intracellular cAMP.
    • ↑ cAMP impairs platelet aggregation and also causes vasodilation.
  • Drugs
    • Dipyridamole: Often used with aspirin for secondary stroke prevention. Also used as a pharmacologic cardiac stress agent (vasodilatory properties).
    • Cilostazol: A PDE-3 inhibitor.
  • Clinical Use
  • Adverse Effects

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