Selective Alpha-1a Antagonist


Selective Alpha-1a Antagonist, Selective Postsynaptic Alpha Adrenergic Antagonist

  1. Background
    1. Selective Alpha-1a Antagonist
      1. Selectively block alpha-1-Adrenergic Receptors in Smooth Muscle of the Bladder neck and Prostate
      2. Developed for specific Alpha-1a activity with minimal Antihypertensive effects
        1. However, even these selective agents have peripheral effects and risk of Orthostasis
    2. Older, Non-Selective Postsynaptic Alpha Adrenergic Antagonist (Terazosin, Doxazosin, Prazosin)
      1. Relatively weak Antihypertensives, were often used for BPH
  2. Rapid relaxation of Smooth Muscle tone and decreases Urethral obstruction and resistance
    1. Bladder neck
    2. Prostate Capsule
    3. Prostatic Urethra
  3. Relieves symptoms of urinary obstruction
    1. May see full effect within 2 weeks
  4. Does not effect size of Prostate (unlike Proscar)
  • Preparations
  • Selective Alpha-1a Antagonists (Prostate specific agents)
  1. Precautions
    1. Selective agents cause Orthostatic Hypotension, Fall Risk, Head Trauma and Fractures, despite selective nature
    2. Number needed to harm (NNH): 600 for fall-related hospitalizations, and 1600 for fall-related Fractures
    3. Welk (2015) BMJ 351:h5398 +PMID:26502947 [PubMed]
  2. Alfuzosin (Uroxatral, generic)
    1. Dose: 10 mg once daily
    2. Contraindicated in moderate to severe liver disease (and Exercise caution in renal disease)
    3. Alfuzosin ER is least likely to cause ejaculatory dysfunction of the selective alpha agents
  3. Silodosin (Rapaflo)
    1. Dose: 8 mg daily with food (4 mg daily if GFR 30-50 ml/min)
    2. Contraindicated when GFR <30 ml/min or severe liver disease (Child-Pugh Score 10 or more)
  4. Tamsulosin (Flomax, generic)
    1. Dose 0.4 mg orally daily (maximum 0.8 mg/day)
    2. Rare Sulfa Allergy cross-reactivity
  • Adverse Effects
  1. Postural Hypotension (esp. when combined with Antihypertensives)
  2. Dizziness
  3. Headache
  4. Ejaculatory dysfunction
  5. Floppy Iris Syndrome
    1. Risk with all Alpha Adrenergic Antagonists (selective or non-selective)
  • Safety
  1. Pregnancy Category B
  2. Avoid in Lactation
  • Drug Interactions
  1. Avoid all Selective Alpha-1a Antagonists with strong CYP3A4 inhibitors (e.g. Ketoconazole, Clarithromycin, Itraconazole, Ritonavir)
  2. Avoid Tamsulosin with strong CYP2D6 Inhibitors (e.g. Fluoxetine)
  3. Avoid Silodosin with strong P-Glycoprotein Inhibitors
  • References
  1. Hamilton (2020) Tarascon Pharmacopoeia, Jones and Bartlett, Boston
  2. Nachawati (2022) Alpha Blockers, StatPearls, Treasure Island, FL, accessed 12/25/2022