The observation that men with ED in general have greater LUTS suggests a common etiology.22 There are several mechanisms of PD-0332991 cost action supporting the utility of PDE5 inhibitors for the treatment of BPH. First, nitric oxide-staining nerves are abundant in the prostate and prostate smooth muscle tension is mediated by NO.23,24 Therefore, PDE5 inhibitors were initially investigated as a means to relax prostate smooth muscle. Alternative mechanisms of action summarized by Laydner and colleagues23 include endothelin inactivation, decrease in autonomic hyperactivity,
and reduction of pelvic ischemia. PDE5 inhibitors are Inhibitors,research,lifescience,medical the primary medical treatment option for ED: they are safe, efficacious, and Inhibitors,research,lifescience,medical easily administered. 25 Among the three commonly prescribed oral PDE5 inhibitors (sildenafil, tadalafil, and vardenafil), the only meaningful difference is the duration of action of tadalafil. Whereas vardenafil and sildenafil have a duration of action of 4 hours, tadalafil is active for as long as 36 hours (T1/2 = 17.5 h). Tadalafil, 5 mg, is the only drug approved for daily administration for the treatment of ED. This Inhibitors,research,lifescience,medical feature makes tadalafil the most promising commercially available PDE5 inhibitor as a once-daily treatment of BPH/LUTS. Initial data support the
clinical benefit of PDE5 inhibitors for the treatment of LUTS secondary to BPH. Four large, double-blind, placebo-controlled trials have examined the effectiveness of sildenafil, tadalafil, and vardenafil Inhibitors,research,lifescience,medical in men with LUTS and BPH.26–29 All of the studies consistently demonstrated that this class of drugs improves LUTS in men with BPH (Table 5). On the basis of risk/benefit, daily tadalafil, 5 mg, was thought to be its preferred dose.29 None of the studies showed meaningful changes in objective indices of outlet obstruction, including uroflowmetric parameters or postvoid residual volume. This very important observation provides validation that future treatments for LUTS secondary to BPH do not need to target prostate smooth
muscle Inhibitors,research,lifescience,medical relaxation or reduce prostate volume. Table 5 Randomized, Linifanib (ABT-869) Placebo-Controlled Trials of PDE5 Inhibitors for the Treatment of Clinical BPH Further investigations with PDE5 inhibitors in BPH/LUTS still need to be conducted; this includes assessments of primary treatment of BPH/LUTS in an unselected group of men with BPH, efficacy of combination treatment with an α-blocker and/or 5-ARI, and durability of effectiveness. Intraprostatic Botulinum Toxin Type A Botulinum toxin type A (BoNT-A) acts irreversibly at acetylcholinergic synapses to block the release of the neurotransmitter acetylcholine.30 This results in decrease of target muscle tone. Injection of BoNT-A is widely used for cosmetic purposes, as well as for treatment of various conditions, including strabismus, cervical dystonia, and esophageal achalasia.