What are alpha (α) adrenergic blockers?

From the Guidelines

Alpha adrenergic blockers, such as alfuzosin, doxazosin, tamsulosin, and terazosin, are effective treatment options for patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) 1. These medications work by blocking alpha-1 receptors, causing smooth muscle relaxation in the prostate, leading to improved urinary flow.

• Common alpha blockers include:
  • Doxazosin (Cardura)
  • Terazosin (Hytrin)
  • Tamsulosin (Flomax)
  • Alfuzosin (Uroxatral)
• For BPH, tamsulosin 0.4mg or alfuzosin 10mg daily are commonly prescribed, with the option to titrate doses as needed and tolerated, up to 8mg of doxazosin, 0.8mg of tamsulosin, and 10mg of terazosin 1.
• Patients should be aware of potential side effects, including dizziness, headache, fatigue, nasal congestion, and retrograde ejaculation, and take the first dose at bedtime to minimize orthostatic hypotension risk.
• Alpha blockers may interact with PDE-5 inhibitors like sildenafil, potentially causing significant hypotension, so spacing these medications is important 1.
• The use of alpha blockers is based on the hypothesis that clinical BPH is partly caused by alpha1-adrenergic-mediated contraction of prostatic smooth muscle, resulting in bladder outlet obstruction, and they have been shown to provide a 4-to-6 point improvement in the AUA Symptom Index, which is perceived as a meaningful change by patients 1.

From the FDA Drug Label

The signs and symptoms of orthostasis (postural hypotension, dizziness, and vertigo) were detected more frequently in Tamsulosin Hydrochloride Capsules -treated patients than in placebo recipients. As with other alpha adrenergic blocking agents there is a potential risk of syncope [ see Adverse Reactions (6. 1) ]. Tamsulosin Hydrochloride Capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [ see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. Tamsulosin Hydrochloride Capsules should be used with caution in combination with moderate inhibitors of CYP3A4 (e.g., erythromycin), in combination with strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, in patients known to be CYP2D6 poor metabolizers particularly at a dose higher than 0. 4 mg (e.g., 0.8 mg) [ see Drug Interactions (7.1)and Clinical Pharmacology (12.3)]. Caution is advised when alpha adrenergic blocking agents, including Tamsulosin Hydrochloride Capsules, are co-administered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [ see Drug Interactions (7.3)and Clinical Pharmacology (12. 3)].

Alpha Adrenergic Blockers are a class of medications that can cause orthostatic hypotension, dizziness, and vertigo. They should be used with caution in combination with other medications that can lower blood pressure, such as PDE5 inhibitors.

• Contraindications: Strong inhibitors of CYP3A4 (e.g., ketoconazole)
• Precautions: Moderate inhibitors of CYP3A4 (e.g., erythromycin), strong or moderate inhibitors of CYP2D6 (e.g., paroxetine, terbinafine), and PDE5 inhibitors
• Adverse reactions: Orthostatic hypotension, dizziness, vertigo, syncope, and priapism 2 2 Key points:
• Alpha adrenergic blockers can cause orthostatic hypotension and syncope
• They should be used with caution in combination with other medications that can lower blood pressure
• Patients should be advised to avoid situations in which injury could result should syncope occur 3

From the Research

Alpha Adrenergic Blockers

• Alpha adrenergic blockers are used to treat benign prostatic hyperplasia (BPH) and hypertension [(4,5,6)].
• These blockers can be used to treat both BPH and hypertension, but may have significant cardiovascular side effects, such as asthenia/fatigue, postural hypotension, and dizziness 4.
• Selective alpha1A blockers, such as tamsulosin, have minimal blood pressure reductions and do not appear to have significant cardiovascular side effects [(4,7)].

Treatment of BPH and Hypertension

• Alpha blockers can be used as a treatment for both BPH and hypertension, especially in patients with coexisting conditions [(5,6)].
• Long-acting alpha1-blockers, such as doxazosin and terazosin, can be used to treat hypertension, but require careful initial bedtime dosing and avoiding overdosing to minimize orthostatic hypotension 5.
• Combination therapy using alpha-1-adrenergic antagonists and 5-alpha-reductase inhibitors can be effective in managing BPH, especially in patients at risk of clinical progression 8.

Side Effects and Considerations

• Alpha adrenergic blockers can cause orthostatic hypotension, especially in the elderly, and require careful dosing [(5,7)].
• Fluid retention is a potential concern with the use of alpha1-blockers, which can be overcome by combining with a diuretic 5.
• Common adverse events with alpha1-blockers include dizziness and asthenia 7.