Reviews for Primary Care - Fall 2007 - (Page 4) Alpha Blockers for BPH Treatment continued study.32 Marco Caine and associates are to be commended for recognizing the importance of conducting randomized clinical trials in order to demonstrate a treatment-related effect in BPH. Validated symptom indices for quantifying changes in LUTS had not been developed at the time Caine reported this early study. Phenoxybenzamine was found to be superior to placebo at relieving LUTS and increasing peak flow rate. The primary limitation of phenoxybenzamine was its side effects, which included tiredness, dizziness, impaired ejaculation, nasal stuffiness, and hypotension. Selective Short-Acting Alpha 1 Blockers Prazosin was the first selective alpha 1 antagonist investigated for BPH. Several small, randomized, placebocontrolled trials suggested that prazosin exhibited comparable efficacy and better tolerability relative to phenoxybenzamine.33,34 Prazosin requires multiple daily dosing, and adverse events related to its blood pressure lowering properties remained problematic. Larger, multicenter, randomized clinical trials were never performed with prazosin, presumably due to the availability of generic prazosin and the general notion at the time that medical therapy would not be widely accepted by urologists for the treatment of BPH. Long-Acting Selective Alpha 1 Blockers Four long-acting alpha 1 blockers are approved by the Food and Drug Administration (FDA) for the treatment of symptomatic LUTS/BPH (Table 3). It is imperative when comparing different alpha 1 blockers to recognize that both efficacy and tolerability are dose dependent. Therefore, observed differences in both efficacy and toxicity may simply be due to different levels of alpha 1 blockade achieved and not to inherent advantages of the specific drug. It is therefore important to compare both efficacy and tolerability at various doses of drugs. Terazosin was the first selective long-acting alpha 1 blocker investigated for the treatment of BPH. Lepor and colleagues35 reported the first multicenter, randomized, placebocontrolled trial of any alpha blocker Table 3 Long-Acting Alpha Blockers Approved for the Treatment of Benign Prostatic Hyperplasia in the United States • Terazosin • Doxazosin • Tamsulosin • Alfuzosin that was properly powered to show that statistically significant changes in LUTS were also clinically significant. LUTS at baseline and throughout the study were ascertained using a quantitative symptom questionnaire. Statistically significant improvements were observed relative to placebo for both symptom scores and peak flow rate. Terazosin doses of 2 mg, 5 mg, or 10 mg were given once daily. Only 4% and 7% of the participants randomized to placebo and terazosin, respectively, withdrew from the 3-month study due to an adverse event. Two additional studies were part of the new drug application (NDA) submitted for Figure 1. The effect of terazosin on lower urinary tract symptoms and peak flow rate relative to placebo.38 Qmax, peak urinary flow. Terazosin Mean Change in Qmax (mL/s) 4 3.0* 2.9* 2.6* Mean Change in Symptom Score Placebo 0 1 1.1 2 3 4 5 6 Study 1 (12 week; 10 mg) 4.5* 5.3* Study 2 Study 3 (24 week; 2, 5, (24 week; 1, 10, 20 mg) 2, 5, 10 mg) N 1222 3 2 1.4 1 1.0 1.2 2.3 3.8 4.6* 0 Study 1 (12 week; 10 mg) Study 2 Study 3 (24 week; 2, 5, (24 week; 1, 10, 20 mg) 2, 5, 10 mg) *P .05 significantly more improvement than placebo. 4 VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE
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