Prazosin causes first-dose hypotension primarily because it selectively blocks which adrenoceptor subtype at post-synaptic vascular smooth muscle while sparing the presynaptic autoreceptor that limits noradrenaline release?

• A Alpha-2 receptors
• B Beta-1 receptors
• C Beta-2 receptors
• D Alpha-1 receptors ✓

Explanation

Prazosin selectively blocks postsynaptic alpha-1 adrenoceptors on vascular smooth muscle, causing vasodilation and hypotension. Unlike non-selective alpha blockers (e.g., phentolamine), prazosin spares presynaptic alpha-2 autoreceptors, which normally provide negative feedback limiting noradrenaline release — thus the reflex tachycardia is less severe. The pronounced first-dose hypotension occurs because the initial blockade is not compensated rapidly enough, especially in volume-depleted patients.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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