Action of Alpha Blockers
Alpha blockers work by selectively blocking alpha-1 adrenergic receptors in the smooth muscle of the prostate, prostatic capsule, bladder neck, and blood vessels, leading to relaxation of these tissues and reduction in urinary obstruction and blood pressure. 1, 2
Mechanism in Benign Prostatic Hyperplasia (BPH)
Primary Action on Urinary Tract
- Alpha-1 adrenoceptors are present in high density in the prostatic stroma, prostatic capsule, and bladder neck 2
- Blockade of these receptors decreases smooth muscle tone in the prostate and bladder neck, reducing urethral resistance 1, 2
- This relaxation relieves the dynamic (functional) component of bladder outlet obstruction, independent of prostate size 1, 3
- The result is improved urine flow and reduction in lower urinary tract symptoms (LUTS) 1
Clinical Efficacy in BPH
- Alpha blockers produce a 4-6 point improvement in the AUA Symptom Index on average, which patients perceive as meaningful 1, 4
- Urinary flow rate improves by 1-4.3 ml/s compared to baseline 3
- Symptom relief occurs in 20-65% of patients 3
- Clinical action is rapid, with treatment success typically assessed after 2-4 weeks 1, 4
Mechanism in Hypertension
Cardiovascular Effects
- Alpha blockers competitively antagonize alpha-1 (postjunctional) adrenergic receptors in vascular smooth muscle 2
- This blockade results in decreased systemic vascular resistance and lowered blood pressure 2
- Maximum blood pressure reductions occur 2-6 hours after dosing 2
- The effect is greater in the standing position, with a small increase in standing heart rate 2
Important Distinction: Uroselective vs Non-selective Agents
- Older agents (doxazosin, terazosin) block both prostatic and vascular alpha-1 receptors equally, causing significant blood pressure reduction 5, 6
- Newer "uroselective" agents (tamsulosin, alfuzosin) preferentially block prostatic alpha-1A and alpha-1D receptor subtypes while minimally affecting vascular alpha-1B receptors 6, 7
- Tamsulosin has higher affinity for prostatic than vascular alpha-1 receptors, resulting in minimal blood pressure effects in normotensive patients 5, 6
- Alfuzosin, while not receptor subtype selective, is clinically uroselective and does not significantly affect vascular receptors 7
Differential Effects Among Alpha Blockers
Cardiovascular Safety Profile
- Tamsulosin and alfuzosin have lower probability of orthostatic hypotension compared to doxazosin and terazosin 1, 4, 6
- In normotensive BPH patients, tamsulosin does not produce clinically significant blood pressure lowering 2, 5
- Doxazosin produces significant vascular alpha-1 blockade at therapeutic doses, unlike tamsulosin 5
Common Adverse Effects
- All alpha blockers can cause dizziness, asthenia (tiredness), and nasal congestion 1, 4
- Tamsulosin has higher probability of ejaculatory dysfunction but lower orthostatic hypotension risk 1, 4
- Orthostatic hypotension risk is highest with doxazosin and terazosin 1, 6
Critical Clinical Considerations
Hypertension Management Caveat
- In men with hypertension and cardiac risk factors, doxazosin monotherapy was associated with higher incidence of congestive heart failure than other antihypertensive agents 1
- Alpha blocker use for LUTS should not be assumed to constitute optimal management of concomitant hypertension—patients may require separate hypertension management 1
Surgical Risk
- All alpha blockers carry risk of intraoperative floppy iris syndrome (IFIS) during cataract surgery 4, 8
- Patients should inform their ophthalmologist about alpha blocker use before any eye surgery, even if no longer taking the medication 8
Onset and Duration Considerations
- Alpha blockers work rapidly (2-4 weeks), unlike 5-alpha reductase inhibitors which require 3-6 months 1, 4
- Effect is independent of prostate size, degree of obstruction, or symptom severity 3
- Alpha blockers do not alter disease progression or reduce long-term risk of acute urinary retention or surgery 4