Safety and efficacy of silodosin for the treatment of benign prostatic hyperplasia

Clinical Interventions in Aging Dovepress open access to scientific and medical research Review Open Access Full Text Article Clinical Interventions in Aging downloaded from https://www.dovepress.com/ by 79.137.96.48 on 12-Jul-2018 For personal use only. Safety and efficacy of silodosin for the treatment of benign prostatic hyperplasia This article was published in the following Dove Press journal: Clinical Interventions in Aging 21 June 2011 Number of times this article has been viewed Masaki Yoshida 1 Junzo Kudoh 2 Yukio Homma 3 Kazuki Kawabe 4 Department of Medical Informatics, Department of Urology, Japan Labor Health and Welfare Organization, Kumamoto Rosai Hospital, Kumamoto, Japan; 3Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 4 Tokyo Teishin Hospital, Tokyo, Japan 1 2 Benign prostatic hyperplasia Correspondence: Masaki Yoshida Department of Medical Informatics, Japan Labor Health and Welfare Organization, Kumamoto Rosai Hospital 3-30-34-1402 Suizenji, Kumamoto 862-0950, Japan Tel +81 96 382 9215 Fax +81 96 382 9215 Email submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/CIA.S13803 Powered by TCPDF (www.tcpdf.org) Abstract: Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the α1-adrenergic receptor antagonists. Silodosin is a new α1-adrenergic receptor antagonist that is selective for the α1A-adrenergic receptor. By antagonizing α1A-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the α1A-adrenergic receptor than for the α1B-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by α1B-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective α1A-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH. Keywords: α1A-adrenoceptor antagonist, silodosin, selective, benign prostatic hyperplasia, lower urinary tract symptoms Benign prostatic hyperplasia (BPH) is a common progressive disease among men, with an incidence that is age-dependent. Histological BPH, which typically develops after the age of 40 years, ranges in prevalence from .50% at 60 years to as high as 90% by 85 years of age.1–3 BPH contributes to, but is not the single cause of, bothersome lower urinary tract symptoms (LUTS) that may affect quality of life. The prevalence of troublesome symptoms increases with age, with symptoms typically occurring in men aged $50 years.3 Histologically, BPH is characterized by a progressive increase in the number of epithelial and stromal cells, that develops initially in the periurethral area of the prostate gland.1,4,5 This cellular proliferative process increases prostatic smooth muscle tone, resulting in urethral constriction.6 Benign prostatic enlargement may also result from the proliferation of epithelial and stromal cells, and may further contribute to constriction of the urethra, leading to bladder outlet obstruction. Benign prostatic enlargement and bladder outlet obstruction do not occur in all men with Clinical Interventions in Aging 2011:6 161–172 161 © 2011 Yoshida et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Clinical Interventions in Aging downloaded from https://www.dovepress.com/ by 79.137.96.48 on 12-Jul-2018 For personal use only. Yoshida et al h istopathological BPH/LUTS, and the presence of benign prostatic enlargement does not necessarily mean that bladder outlet obstruction will develop.5 Approximately 50% of patients with histological BPH report moderate to severe LUTS,2 consisting of storage and voiding symptoms.2,3 Commonly reported storage-related symptoms include urinary frequency, urgency, and nocturia. Voiding symptoms, typically attributable to urethral obstruction, consist of decreased and intermittent force of the urinary stream and the sensation of incomplete bladder emptying.1 Although bothersome LUTS may affect quality of life by altering normal daily activities and sleep patterns, mortality associated with BPH is rare.1,7 Although uncommon, serious complications of BPH may occur, including acute urinary retention, renal insufficiency, urinary tract infections, hematuria, bladder stones, and renal failure.6,8 These complications may be triggered or worsened by inadequate management of BPH. The incidence of acute urinary retention in untreated patients ranges from 0.3% to 3.5% per year; the risk of developing other long-term complications is unclear.8 The management of patients with BPH includes nonpharmacological, pharmacological, and surgical options, with the choice of therapy typically depending on the presence and severity of symptoms.1,9 Watchful waiting is the preferred management strategy for patients with mild LUTS and those who do not perceive their symptoms to be particularly bothersome. Pharmacological treatments include α1-adrenergic receptor antagonists (or blockers) and 5α-reductase inhibitors, which are recommended for use alone or in combination in patients with bothersome moderate to severe LUTS. Currently, adrenergic receptor antagonists are commonly used as the first-line treatments for LUTS associated with BPH.3,6 α1-Adrenergic receptors Adrenergic receptors were originally divided into α-adrenergic receptor and β-adrenergic receptor categories,8 but application of molecular biological methods has conf irmed nine adrenergic receptor subtypes: α1A (formerly named α1C), α1B, α1D, α2A, α2B, α2C, b1, b2, and b3.10–12 All three α1-adrenergic receptor subtypes exist in a wide range of human tissues.13,14 In terms of male LUTS, α1-adrenergic receptor expression in the prostate, urethra, spinal cord, and bladder is important. Molecular and contraction studies in human prostate tissue demonstrate that the α1A-adrenergic receptor subtype predominates (70%–100%) in prostate stroma.15,16 Because baseline tone is present in prostate smooth muscle 162 Powered by (...truncated)