Reviews for Primary Care - Fall 2007 - (Page 5) Alpha Blockers for BPH Treatment Table 4 Terazosin: Adverse Effects38 Terazosin (n 636) Asthenia/fatigue Postural hypotension Dizziness Somnolence Nasal congestion/rhinitis Impotence 7.4% 3.9% 9.1% 3.6% 1.9% 1.6% Placebo (n 360) 3.3% 0.8% 4.2% 1.9% 0.0% 0.6% terazosin’s FDA approval for the treatment of symptomatic BPH.36,37 All of the terazosin studies included a dose titration study design beginning at 1 mg in order to avoid the firstdose effect. The treatment-related efficacy and adverse events of terazosin are shown in Figure 1 and Table 4, respectively. Doxazosin was the second alpha 1 blocker approved by the FDA for the treatment of symptomatic BPH. Two pivotal multicenter, randomized clinical trials were performed comparing various doses of doxazosin with placebo.39,40 The potential advantage of doxazosin was its longer half life tolerability. The treatment-related efficacy and side effects are shown in Figure 2 and Table 5. Both doxazosin studies included a dose titration design in order to avoid the first-dose effect related to efficacy or tolerability. Based on its efficacy and tolerability comparable with terazosin, doxazosin’s longer half life did not appear to confirm any clinical advantage. Both terazosin and doxazosin exhibited lowering of blood pressure only in those men who were hypertensive at baseline.41-43 The effect on blood pressure was interpreted as a desirable outcome because 2 common conditions (BPH and hypertension) in the aging male could be treated effectively with a single agent. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack trial (ALLHAT) subsequently demonstrated that alpha blockers were inferior to other classes of drugs as firstline therapy for the treatment of hypertension.44 This led many to conclude that in men with both BPH and hypertension, the 2 disease entities should be treated independently with the best available agents. Tamsulosin was the third alpha 1 blocker to be approved for the treatment of BPH. Tamsulosin was brought to market as the first subtype selective alpha 1 antagonist for the treatment of BPH. Tamsulosin alpha 1 subtype selective was supported by binding studies, which showed that tamsulosin was approximately tenfold more selective for the alpha 1a versus alpha 1b subtype.45,46 There was no demonstrable subtype selectivity of tamsulosin for the alpha 1a versus alpha Figure 2. The effect of doxazosin on lower urinary tract symptoms and peak flow rate relative to placebo.41 Qmax, peak urinary flow. Doxazosin 4 mg Mean Change in Qmax (mL/s) 4 3.3† 3 2.3* 2 Doxazosin 8 mg Mean Change in Symptom Score 0 1 2 3 4 Placebo 2.5 1 0.1 0 Study 2 Fixed-Dose (14 week) 4.2* 5 6 Study 2 Fixed-Dose (14 week) N 609 5.0† *P †P .05 Compared with placebo. .01 Compared with placebo. VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE 5
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