2008B07 List the agents used therapeutically to reduce platelet function. Outline their mechanisms of action,
adverse effects, mode of elimination and duration of action.

Pharmacodynamics:

Mechanism of action (MoA)

Side effects (SE)

Pharmacokinetics:

Metabolism (M)

Excretion (E)

Duration (D)

Aspirin (irreversible)

·MoA: Irreversible COX1&2 acetylation

·↓TXA₂ production in platelet

·Minimal effect on endothelial PGI₂ at low dose

·SE: bleeding peptic ulcer, nausea, Reye’s syndrome, toxicity -> metabolic acidosis

·M: 80% (liver)

·E: 20% (kidney)

·D: 7 days (new platelets)

Dipyridamole

·MoA: PDE inhibition -> ↑cAMP

·MoA: potentiate PGI₂

·SEs: bleeding headache, hypotension

·M: live

·E: bile

·D: t_1/2β 10 hours -> BD dose

Clopidogrel

·Prodrug with active thiol metabolite

·MoA: irreversible P2Y₁₂ ADP receptor antagonist (ADPRA)

·SE: bleeding, risk of failure (2C19 polymorphism)

·M: 50% (2C19)

·E: 50% (renal)

·D: 7 days

Ticlopidine

·Prodrug

·MoA: irreversible P2Y₁₂ ADPRA

·SE: bleeding, TTP

·M: liver

·E: urine > bile

·D: 7 days

Ticagrelor

·MoA: Reversible P2Y₁₂ ADPRA

·Has an equipotent metabolite

·SE: bleeding, dyspnoea (esp if asthma)

·M: hepatic CYP3A4, 3A5

·E: bile > urine

·D: 2 days

Abciximab

·MoA: GPIIbIIIa mAb antagonist

·SE: bleeding, ↓plt

·M&E: reticulo-endothelial system

·D: 2 days (prolonged binding)

Tirofiban

·MoA: GPIIbIIIa inhibitor

·SE: bleeding, ↓plt

·M: nil

·E: 66% urine, 33% bile

·D: 8 hours

Prostacyclin

·MoA: G_s GPCR -> ↑cAMP -> inhibit activation

·M: liver, kidney, lung

·D: very short (t_1/2β 6 minutes)

Dextrans

·MoA: ↓von Willebrand factor

·SE: anaphylaxis, impair blood cross matching

·M: nil?

·E: renal

·Duration: 6-8 hours for volume expansion, ? antiplatelet duration