A 58-year-old man from Delhi presents with a 3-month history of nocturia (×4 per night), hesitancy, and weak urinary stream. Digital rectal examination reveals a firm, enlarged prostate. PSA is 4.2 ng/mL. He is started on an alpha blocker for symptomatic relief. Two weeks later, he reports dizziness on standing and a syncopal episode after his morning dose. Blood pressure supine: 145/92 mmHg; standing: 118/70 mmHg. Which alpha blocker is most likely responsible, and what is the mechanism of this adverse effect?

Explanation

## Mechanism of Orthostatic Hypotension with Non-Selective Alpha Blockers **Key Point:** Non-selective α1 blockers (doxazosin, terazosin, prazosin) block α1-adrenergic receptors on both vascular smooth muscle and urinary sphincters, causing peripheral vasodilation and orthostatic hypotension—a well-recognized and dose-limiting side effect. ### Pathophysiology Alpha-1 adrenergic receptors are distributed in: - **Vascular smooth muscle** (α1A and α1B subtypes): mediate vasoconstriction and maintain blood pressure - **Urinary bladder neck and proximal urethra** (α1A subtype): mediate smooth muscle contraction Non-selective α1 blockers inhibit both, resulting in: 1. Peripheral vasodilation → reduced systemic vascular resistance 2. Impaired baroreceptor-mediated compensatory vasoconstriction on postural change 3. Net result: orthostatic hypotension, syncope, and dizziness ### Clinical Presentation in This Case The patient's **orthostatic vital signs** (drop of 27 mmHg systolic on standing) and **syncope after morning dose** are classic for non-selective α1 blockade. The timing (2 weeks into therapy) reflects drug accumulation and dose-dependent effect. ### Comparison of Alpha Blockers by Selectivity | Agent | α1A Selectivity | Vascular Effects | Orthostatic Hypotension | BPH Efficacy | First-Dose Effect | |-------|-----------------|------------------|------------------------|--------------|-------------------| | **Doxazosin** | Non-selective | Marked | **High** | Good | **Severe** | | **Terazosin** | Non-selective | Marked | **High** | Good | **Severe** | | **Prazosin** | Non-selective | Marked | **High** | Moderate | **Severe** | | **Tamsulosin** | α1A-selective | Minimal | Low | Good | Minimal | | **Alfuzosin** | α1A-selective | Minimal | Low | Good | Minimal | | **Silodosin** | α1A-selective | Minimal | Low | Excellent | Minimal | **High-Yield:** Doxazosin and terazosin are non-selective and cause the most orthostatic hypotension. They are rarely used for BPH monotherapy in India due to this risk; tamsulosin and alfuzosin are preferred. ### Management Strategy ```mermaid flowchart TD A["Non-selective α1 blocker side effect: orthostatic hypotension"]:::outcome --> B{"Severity?"}:::decision B -->|"Mild: dizziness only"| C["Dose reduction + counseling"]:::action B -->|"Moderate: presyncope"| D["Switch to α1A-selective agent"]:::action B -->|"Severe: syncope/fall risk"| E["Discontinue + switch to α1A-selective"]:::urgent C --> F["Monitor orthostatic vitals"]:::action D --> F E --> F ``` **Clinical Pearl:** The "first-dose effect" (severe orthostatic hypotension after the first dose) is most pronounced with non-selective agents. Patients should take the first dose at bedtime and be counseled to rise slowly from supine/sitting positions. **Warning:** ~~Tamsulosin and alfuzosin cause orthostatic hypotension~~ — they are α1A-selective and have minimal vascular effects. This is a common exam trap. [cite:KD Tripathi 8e Ch 12]