Pharmacopeia

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Field ASPIRIN
Haematology · Haematology · Level 2
TICAGRELOR
Haematology · Haematology · Level 2
PRASUGREL
Haematology · Haematology · Level 2
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)

Allosteric, reversible antagonist at P2Y12-R (an ADP receptor), preventing activation of glycoprotein IIb/IIIa→ prevents platelet crosslinking

Irreversibly binds the P2Y12-R (an ADP receptor), preventing activation of glycoprotein IIb/IIIa→ prevents platelet crosslinking

Absorption

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

BA=40%

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Protein binding

85% protein binding, pKa 3

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Volume of distribution

Vd 10L

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Metabolism

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

Metabolized by CYP3A4

Prodrug- 1 step metabolism
Less susceptible to CYP polymorphism and CYP inhibition or induction than Clopidogrel

Excretion

- Renal as salicylate

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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)

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Adverse Effects Toxicity

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

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Class Group

Antiplatelet

Antiplatelet

Antiplatelet

Introduction

COX inhibitor

ADP Receptor Antagonist - Thienopyridine

ADP Receptor Antagonist - Thienopyridine

Prodrug

Legacy Cicm Level

Level 1

Level 3

Level 3

Main Action

Platelet inhibition

Platelet inhibition

Platelet inhibition