Prazosin causes a first-dose hypotension more pronounced than that of doxazosin at equivalent doses. The pharmacokinetic basis for this differential effect is best explained by:
- A Prazosin's higher bioavailability leading to higher peak plasma concentrations
- B Prazosin's shorter half-life and rapid Cmax due to lack of extended-release formulation compared to doxazosin's intrinsically longer t1/2 ✓
- C Doxazosin's more selective α1A over α1B subtype blockade, sparing vascular tone
- D Prazosin's active metabolite causing additional sympatholysis
Correct answer: B. Prazosin's shorter half-life and rapid Cmax due to lack of extended-release formulation compared to doxazosin's intrinsically longer t1/2
Explanation
Prazosin has a half-life of 2–3 hours and a rapid absorption profile, generating a high peak concentration shortly after the first dose and causing pronounced reflex hypotension. Doxazosin has a half-life of 20–22 hours with a much slower rise to Cmax, reducing the magnitude of first-dose hypotension; this is why doxazosin is titrated more gently. Neither drug has a clinically significant α1A preference distinguishing them in vascular smooth muscle.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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