Core pharmacology

Class Group

Antiplatelet

Legacy Cicm Level

Level 1

Introduction

COX inhibitor

Main Action

Platelet inhibition

Mechanism of action

Non-specific Irreversible platelet cyclooxygenase inhibitor
(COX-1 and 2) via acetylation of serine residues → ↓formation PG precursors.
- Inhibits formation of thromboxane (TXA) → inhibit aggregation
- At higher doses prostacyclin (PFI2) synthesis also inhibited → vasoconstriction (but endothelium can regenerate COX)

Adverse Effects Toxicity

Bleeding
Bronchospasm, Renal toxicity
Reye’s Syndrome, GI ulceration
Caution with other anticoagulants

Absorption

- PO. BA. 50%.
- 300mg Loading. 100mg maint.

Protein binding

85% protein binding, pKa 3

Volume of distribution

Vd 10L

Metabolism

- Converted to salicylic acid in GI mucosa and liver
- Hepatic conjugation (saturable)

Excretion

- Renal as salicylate

Half-life

- T1/2b 15~20 mins when first order
- Dur: 4-6 hrs. (Effect on platelet aggregation will last life of current cohort of platelets (7-10 days)