A 58-year-old man with benign prostatic hyperplasia (BPH) presents with lower urinary tract symptoms (LUTS) including nocturia (×4/night), weak stream, and post-void residual urine of 80 mL. He is started on an alpha blocker. After 2 weeks of therapy, he reports dizziness on standing and a syncopal episode while getting out of bed in the morning. Blood pressure supine: 145/92 mmHg; standing: 110/68 mmHg. Which of the following alpha blockers would be the LEAST likely to cause this adverse effect?

Explanation

## Selectivity and Orthostatic Hypotension in Alpha Blockers ### Mechanism of Orthostatic Hypotension **Key Point:** Non-selective α₁ blockers cause vasodilation of both vascular and urethral smooth muscle, leading to significant orthostatic hypotension. Selective α₁A blockers preferentially block urethral receptors with minimal vascular effects. ### Alpha Blocker Selectivity Profile | Drug | α₁A Selectivity | Vascular Effect | Urethral Effect | Orthostatic Risk | |------|-----------------|-----------------|-----------------|------------------| | **Tamsulosin** | **High (>100-fold)** | **Minimal** | **Strong** | **Very Low** | | Doxazosin | Non-selective | Strong | Strong | High | | Terazosin | Non-selective | Strong | Strong | High | | Prazosin | Non-selective | Strong | Strong | High | ### Clinical Distinction **High-Yield:** Tamsulosin is a **uroselective α₁A antagonist** — it binds preferentially to α₁A receptors in the prostate urethra and bladder neck, sparing α₁B receptors in blood vessels. This selectivity dramatically reduces orthostatic hypotension and syncope. **Clinical Pearl:** The patient's presentation (supine hypertension with standing hypotension, syncope on positional change) is the classic first-dose effect or cumulative orthostatic hypotension from non-selective α₁ blockade. ### Why Tamsulosin Differs 1. **Tissue selectivity:** ~160-fold selectivity for α₁A over α₁B receptors 2. **Vascular sparing:** Minimal effect on α₁B-mediated vasoconstriction 3. **Dosing:** Once-daily fixed dose (0.4 mg) — no titration needed, further reducing orthostatic risk 4. **Clinical outcome:** Orthostatic hypotension incidence <2% vs. 10–15% with non-selective agents **Warning:** Doxazosin and terazosin require dose titration starting at 0.5–1 mg, which increases first-dose syncope risk. Prazosin, though older, is also non-selective and carries high orthostatic risk. ### Management Principle ```mermaid flowchart TD A["Patient with BPH + LUTS"]:::outcome --> B{"Risk of orthostatic hypotension?"}:::decision B -->|"Yes: elderly, hypotensive, on antihypertensives"| C["Use uroselective α₁A blocker<br/>Tamsulosin preferred"]:::action B -->|"No: young, normotensive"| D["Non-selective α₁ blocker acceptable<br/>Doxazosin, terazosin, prazosin"]:::action C --> E["Minimal vascular side effects"]:::outcome D --> F["Monitor for orthostatic hypotension"]:::action ``` [cite:KD Tripathi 8e Ch 6]