What are examples of selective α‑1 adrenergic antagonists used to relax the bladder neck and proximal urethra to improve voiding, and what are their usual starting doses?

Selective α-1 Adrenergic Antagonists for Bladder Neck and Urethral Relaxation

The selective α-1 adrenergic antagonists used to relax the bladder neck and proximal urethra include tamsulosin, alfuzosin, doxazosin, terazosin, and silodosin. 1

Specific Agents and Starting Doses

First-Generation Selective α-1 Blockers

• Terazosin: Start at 1 mg orally once daily at bedtime, then titrate upward to 5 mg daily as tolerated 2, 3

  • Requires dose titration due to cardiovascular effects
  • Effective for reducing bladder outlet resistance in both men and women 2

• Doxazosin: Similar titration schedule to terazosin, starting at low doses and increasing gradually 1, 3

  • Used extensively in benign prostatic hyperplasia but applicable to functional bladder outlet obstruction 1

Newer Selective α-1 Blockers (Uroselective)

• Tamsulosin: Standard dose is 0.4 mg orally once daily 1, 4

  • Does not typically require dose titration
  • Higher selectivity for α-1A receptors in the prostate and bladder neck 3
  • Most commonly associated with ejaculatory dysfunction among α-1 blockers 1

• Alfuzosin: 10 mg orally once daily (extended-release formulation) 5, 3

  • Selective for α-1 adrenoreceptors in the lower urinary tract 5
  • Causes smooth muscle relaxation in bladder neck and prostate, improving urine flow 5

• Silodosin: 8 mg orally once daily 6

  • Highest selectivity for α-1A receptor subtype 6
  • Binds with high affinity to α-1A adrenoceptors located in prostate, bladder base, bladder neck, and prostatic urethra 6

Mechanism of Action

• All selective α-1 blockers antagonize post-synaptic α-1 adrenergic receptors concentrated at the bladder neck and proximal urethra 7, 5, 6
• This antagonism produces smooth muscle relaxation and lowers outlet resistance, facilitating bladder emptying 7, 5
• The introduction of selective α-1 blockers in the 1980s markedly reduced the incidence of hypotension and dizziness compared with earlier non-selective agents 7

Clinical Application

• α-1 blockers are first-line pharmacological treatment for male lower urinary tract symptoms and can facilitate bladder emptying in functional bladder outlet obstruction 1, 7
• These agents may be used off-label in women with functional bladder outlet obstruction, though evidence is more limited 2, 8
• The uroselective compounds (tamsulosin, alfuzosin, silodosin) have improved tolerability profiles compared to older agents 3

Important Caveats

• All α-1 blockers carry some risk of orthostatic hypotension, though selective agents have reduced this risk 1, 7, 9
• Ejaculatory dysfunction is significantly more common with selective α-1 blockers, particularly tamsulosin and silodosin 1, 6
• Patients undergoing cataract surgery face increased risk of intraoperative floppy iris syndrome 1
• Use in children and for certain voiding dysfunction indications remains off-label 7