α-Adrenoceptor antagonists in the treatment of benign prostatic hyperplasia

Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) have a significant impact on the lifestyle of older men. Transurethral resection of the prostate (TURP) is the most effective surgical therapy for this condition but an increasing number of patients are electing conservative medical therapy. Alpha-Adrenoceptor antagonists and 5alpha-reductase inhibitors are the 2 categories of drug therapy currently available for BPH. Use of alpha-adrenoceptor antagonists in the treatment of BPH is based on their ability to prevent the neural stimulation which induces prostate smooth muscle contraction, producing lower urinary tract symptoms. Several studies have demonstrated that alpha-receptors predominate in the prostatic stroma, capsule and bladder neck. Initial work focused on the use of phenoxybenzamine, a nonspecific alpha-blocker, in the treatment of BPH. While results were promising, significant adverse effects and concern over potential mutagenicity have resulted in a lack of use of this medication for this indication. Subsequent attention was directed towards the short-acting alpha-specific antagonist prazosin. Results conflicted regarding whether an actual sustained improvement in lower urinary tract symptoms could be achieved with this medication, and because of twice daily dosing compliance issues were a drawback. Thus, the mainstay in pharmacological treatment of BPH over the past decade has been 2 once-a-day alpha-specific antagonists, doxazosin and terazosin. Over 75% of all prescriptions written for BPH are for one of these 2 medications. Despite their tremendous success in both decreasing urinary symptoms and increasing urinary flow rates, systemic adverse effects can be bothersome. Recently, efforts have focused on use of alpha1A-urospecific antagonists such as tamsulosin and alfuzosin in an attempt to achieve similar clinical results as doxazosin and terazosin without systemic adverse effects. Thus far, results are promising, but long term studies must be done to determine whether pharmacological uroselectivity is actually clinically relevant.