α1-Adrenoceptor selectivity and the treatment of benign prostatic hyperplasia and lower urinary tract symptoms

Abstract

The storage (irritative) and voiding (obstructive) symptoms associated with benign prostatic hyperplasia are generally attributed to prostate enlargement and increased prostatic smooth muscle tone mediated by the prevailing a 1 -adrenoceptors in the bladder neck and prostate. This results in obstruction and subsequent secondary changes to the bladder. However, there is growing evidence that many of these symptoms may be due to changes in extraprostatic a 1 -adrenoceptors, possibly a 1D -adrenoceptors. Findings from the VA cooperative trial challenge the current theory that the common side effects associated with these agents are due to vascular action of a 1 -adrenoceptor blockers. Prostate Cancer and Prostatic Diseases (2000) 3, 76±83.

Comparison of Different Alpha-blocker Combinations in Male Hypertensives with Refractory Lower Urinary Tract Symptoms

“…Therefore, the influence on these receptors by non-selective doxazosin can explain the more effective management of total voiding problems regardless of side effects. 18 On the other hand, tamsulosin selectively binds to alpha-1 A receptors abundant in prostate, and the high affinity to selective protein causes the drug to concentrate in the lower urinary tract rather than the central nervous system, comparing with doxazosin. This suggests that the two drugs are somewhat different in their action mechanisms due to different chemical structure categories.…”

“…This suggests that the two drugs are somewhat different in their action mechanisms due to different chemical structure categories. [18][19][20] However, it is generally accepted that many alpha-blockers have the same efficacy but only differ in terms of side effects. 4 Quinazoline family alpha-blockers such as terazosin, doxazosin, and alfuzosin were originally developed as anti-hypertensives.…”

Clinical ease of using doxazosin in BPH patients with and without hypertension

“…Another multicenter, community-based, 8-week, openlabel study (Hypertension and BPH Intervention Trial (HABIT)) evaluated the efficacy of doxazosin therapy in 491 patients with comorbid BPH and hypertension. 25 Because this was a community-based study, it approximated the experience encountered in everyday clinical practice.…”

“…7 Recent experimental data suggest the involvement of a central mechanism of action of a 1 -adrenoceptor antagonists in the mediation of LUTS relief, particularly with respect to storage symptoms. 8 In addition, results of an analysis of adverse event data from the Veterans Affairs cooperative study suggest that dizziness and asthenia associated with a 1 -adrenoceptor antagonists may not be due to vascular events. 9 As with BPH, blood pressure tends to increase with advancing age; 10,11 BPH and hypertension occur concomitantly in an estimated 25% of men older than 60 y of age.…”

A Study on Efficacy and Safety of Silodosin in Geriatric Patients with Benign Prostatic Hyperplasia

“…On the other hand, α1B-ARs are largely located on vascular smooth muscle which regulate the blood pressure and the contraction of peripheral vasculature [7,8]. Therefore, the drugs which are α1A-Adrenoreceptor selective are beneficial in treating BPH with fewer cardiovascular effects as seen in non selective α-blockers.…”