Ticagrelor, unlike clopidogrel, does not require metabolic activation. Beyond this, which pharmacological property of ticagrelor is responsible for its adverse effect of dyspnoea not seen with clopidogrel?
- A Off-target P2Y11 receptor blockade in pulmonary vasculature causing bronchoconstriction
- B Inhibition of adenosine reuptake via equilibrative nucleoside transporter-1 (ENT-1), increasing plasma adenosine ✓
- C Weak COX-1 inhibition reducing PGI2 in pulmonary endothelium causing platelet-mediated vasoconstriction
- D Direct stimulation of carotid body chemoreceptors via P2Y13 receptor agonism
Explanation
Ticagrelor, in addition to reversibly blocking P2Y12 receptors, inhibits the equilibrative nucleoside transporter-1 (ENT-1) responsible for adenosine uptake into cells. This increases plasma and interstitial adenosine concentrations. Adenosine stimulates A2A receptors on pulmonary vagal C-fibre afferents, triggering a reflex sensation of dyspnoea and sometimes transient respiratory pauses. This is a class effect of ticagrelor but not clopidogrel or prasugrel, which do not inhibit ENT-1. The dyspnoea from ticagrelor is usually benign but is the most common cause of discontinuation. Elevated adenosine also contributes to some of ticagrelor's pleiotropic cardioprotective effects.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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