Reviews for Primary Care - Fall 2007 - (Page 8) Alpha Blockers for BPH Treatment continued episode of acute urinary retention.56 An episode of acute urinary retention is no longer an absolute indication for surgical intervention. Alpha blockers are a very reasonable initial option for managing acute urinary retention. Summary All the alpha blockers evaluated for the treatment of symptomatic BPH have comparable effectiveness. Over the past 30 years, the evolution of alpha blocker therapy for BPH has dysfunction represents a step forward in the development of alpha blockers for the treatment of LUTS/BPH. Many consider alfuzosin 10 mg to be the superior alpha blocker currently available for treating BPH because it achieves clinically significant improvements in LUTS and has no significant effects on dizziness, asthenia, and ejaculatory dysfunction. Alpha 1a Subtype Selective Agents As previously discussed, there is increasing evidence that alpha blockers Without a doubt, minimizing the effect on ejaculatory dysfunction represents a step forward in the development of alpha blockers for the treatment of LUTS/BPH. focused primarily on improving convenience and tolerability. All of the long-acting alpha 1 blockers are well tolerated, but only tamsulosin and alfuzosin SR are administered without the requirement for dose titration. The advantage of alfuzosin over tamsulosin is the lower incidence of ejaculatory dysfunction. Without a doubt, minimizing the effect on ejaculatory relieve LUTS through mechanisms other than prostate smooth-muscle relaxation.4 It is universally agreed that prostate smooth-muscle contraction is mediated by the alpha 1a subtype,30 but the specific alpha 1 subtype mediating LUTS is unknown. There is also increasing evidence that adverse events associated with alpha blocker therapy, including asthenia and dizziness, are not due to blood pressure lowering.57 Therefore, developing a drug that preferentially relaxes prostate smooth muscle without affecting vascular smooth muscle will not necessarily yield a more effective drug with fewer side effects. Several alpha 1a subtype selective drugs entered the developmental phase at different pharmaceutical companies. All of these drug development programs were discontinued because of failure to relieve LUTS despite increasing peak urinary flow rate. The clinical outcomes with alpha 1a subtype selective drugs provide compelling evidence that the improvement in LUTS is not related to relief of BOO. Understandably, there are presently few active development programs to bring subtype selective alpha blocker drugs to market. It is unlikely that an alpha 1 blocker more effective or better tolerated than alfuzosin will be developed in the future. Efforts should be directed toward unraveling the pathophysiology of LUTS instead of pursuing subtype selective alpha 1 Main Points • The indications for treating benign prostatic hyperplasia (BPH) include reversing signs and symptoms (lower urinary tract symptoms [LUTS], incomplete bladder emptying, urinary tract infections, urinary retention, urosepsis, chronic renal insufficiency, and hematuria) or preventing progression of the disease. • Four long-acting alpha 1 blockers are approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, and alfuzosin. When comparing them, it is imperative to recognize that both efficacy and tolerability are dose dependent. • Both terazosin and doxazosin lower blood pressure, but other classes of drugs are superior to alpha blockers as first-line therapy for hypertension, leading many to conclude that it should be treated independently in men with BPH. • The ability of the 0.4 mg tamsulosin dose to achieve a clinically significant effect without the requirement for dose titration represented a unique advantage over the other approved alpha blockers, but this convenience came at the expense of ejaculatory dysfunction. • The American Urological Association Guidelines Committee concluded that alfuzosin has comparable clinical efficacy to tamsulosin and the other approved alpha blockers but does not cause ejaculatory dysfunction. • An episode of acute urinary retention is no longer an absolute indication for surgical intervention. Alpha blockers are a very reasonable initial option for managing acute urinary retention. 8 VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE
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