Which of the following adverse effects is MOST characteristic of non-selective alpha blockers like prazosin and doxazosin, and occurs especially with the first dose?

Explanation

## First-Dose Syncope with Non-Selective Alpha Blockers **Key Point:** Non-selective α1 antagonists (prazosin, doxazosin, terazosin) cause **first-dose syncope** — a sudden, severe drop in blood pressure and syncope that occurs within 30–90 minutes of the first dose or after dose escalation. **High-Yield:** Mechanism and management: 1. **Mechanism:** Sudden blockade of vascular α1B receptors → profound vasodilation → acute reduction in peripheral vascular resistance and venous return → syncope. 2. **Prevention:** Always start with a low dose (prazosin 0.5–1 mg) at bedtime; warn patients not to drive or stand suddenly after the first dose. 3. **Why uroselective agents avoid this:** Tamsulosin and alfuzosin selectively block α1A (prostatic), sparing α1B (vascular), so first-dose syncope is rare. ### Timeline and Risk Factors | Factor | Details | | --- | --- | | **Onset** | 30–90 minutes after first dose or dose escalation | | **Severity** | Can be profound — patient may lose consciousness | | **Risk factors** | Volume depletion, concurrent antihypertensives, rapid dose escalation | | **Prevention** | Low starting dose (prazosin 0.5 mg), bedtime administration, patient counseling | | **Management** | Lie flat, elevate legs; usually resolves in minutes | **Clinical Pearl:** Patients often describe "fainting" or "blacking out" shortly after taking the first dose — this is pathognomonic for non-selective α-blocker initiation and should prompt a history of recent drug start. **Warning:** ~~Retrograde ejaculation~~ is a side effect of **all** alpha blockers (selective and non-selective) due to relaxation of the bladder neck smooth muscle, not specific to first-dose syncope.