What are Alpha (α) Adrenergic Receptors?

From the Guidelines

Alpha adrenergic receptor antagonists, such as doxazosin, tamsulosin, alfuzosin, and terazosin, are the most effective treatment options for patients with Lower Urinary Tract Symptoms (LUTS) secondary to Benign Prostatic Hyperplasia (BPH). These medications work by inhibiting the alpha1-adrenergic-mediated contraction of prostatic smooth muscle, resulting in relief of bladder outlet obstruction 1. The use of these alpha blockers has been extensively investigated, and meta-analyzed data suggest that they are similarly effective in partially relieving symptoms, producing on average a 4-to-6 point improvement in the AUA Symptom Index 1.

Key Points to Consider

• The primary adverse events reported with alpha-blocker therapy are orthostatic hypotension, dizziness, tiredness, ejaculatory problems, and nasal congestion 1.
• Tamsulosin appears to have a lower probability of orthostatic hypotension but a higher probability of ejaculatory dysfunction than the other alpha blockers 1.
• Patients with hypertension may require separate management of their hypertension, as the use of an alpha blocker to manage LUTS should not necessarily be assumed to constitute optimal management of concomitant hypertension 1.
• The maximum tolerable and effective doses of alpha blockers have not been defined, but reported clinical data support the efficacy and safety of titrating patients to 8 mg of doxazosin, to 0.8 mg of tamsulosin, and to 10 mg of terazosin 1.

Treatment Recommendations

• Alfuzosin, doxazosin, tamsulosin, and terazosin are appropriate treatment options for patients with LUTS secondary to BPH 1.
• Prazosin and phenoxybenzamine are not recommended as treatment options for LUTS secondary to BPH due to insufficient data and potential adverse effects 1.

From the FDA Drug Label

The dynamic component is a function of an increase in smooth muscle tone in the prostate and bladder neck leading to constriction of the bladder outlet Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha 1 adrenoceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. At least three discrete alpha 1 adrenoceptor subtypes have been identified: alpha 1A, alpha 1B, and alpha 1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha 1 receptors in the human prostate are of the alpha 1A subtype.

The alpha adrenergic receptors involved in the pathology of BPH are alpha 1 adrenoceptors, with three subtypes: alpha 1A, alpha 1B, and alpha 1D. The alpha 1A subtype is the most abundant in the human prostate, making up approximately 70% of the alpha 1 receptors. The blockade of these alpha 1 adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH 2.

From the Research

Alpha Adrenergic Receptors

• Alpha adrenergic receptors play a critical role in the pathophysiology of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) 3.
• There are three receptor subtypes of alpha1-adrenergic receptors in humans, with different distributions between urinary tract and cardiovascular tissues 3.
• The alpha1aAR and alpha1dAR subtypes are involved in the symptoms of BPH, and drugs with high selectivity for these subtypes have been developed to treat LUTS associated with BPH 3, 4.

Treatment of BPH-Related LUTS

• Alpha1-adrenergic-receptor antagonists (alpha1-blockers) are the standard of care for the medical management of BPH-related LUTS 4.
• Tamsulosin and alfuzosin are newer "uroselective" alpha1-blockers that have a decreased potential for cardiovascular adverse effects compared to older agents 4.
• These agents are efficacious in relieving LUTS and have a decreased potential for cardiovascular adverse effects such as postural hypotension 4, 5.

Interaction with Antihypertensive Therapy

• Many alpha blockers used to treat BPH also decrease blood pressure, and can interact with antihypertensive therapy 6, 5.
• The selective alpha1A blocker tamsulosin does not appear to have significant cardiovascular side effects and produces minimal blood pressure reductions, making it a suitable option for patients with hypertension and BPH 5.
• Alpha blockers can be used to treat both hypertension and BPH, or to treat BPH without interacting with antihypertensive therapy 5.

Medical Treatment of BPH

• Medical treatment of BPH includes 5 alpha-reductase inhibitors and alpha-adrenergic antagonists, which have different mechanisms of action but are both effective in treating BPH 7.
• Alpha-adrenergic antagonists decrease the smooth muscle tone of the bladder neck, prostatic adenoma, and prostatic capsule, relieving obstructive voiding symptoms 7.
• The use of medical therapies for BPH has expanded the role of internists and primary-care physicians in the care of patients with BPH, and requires collaboration with urologists to serve the needs of patients with prostatism 7.