Key concepts

O The lower urinary tract symptoms (LUTS) and signs of benign prostatic hyper-plasia (BPH) are due to static, dynamic, or detrusor factors. The static factor refers to anatomic obstruction of the bladder neck caused by an enlarged prostate gland. The dynamic factor refers to excessive stimulation of a-adrenergic receptors in the smooth muscle of the prostate, urethra, and bladder neck. The detrusor factor refers to irritability of hypertrophied detrusor muscle as a result of longstanding bladder outlet obstruction.

01 Drug treatment goals for BPH include relieving obstructive and irritative voiding symptoms, preventing complications of disease, and reducing the need for surgical intervention.

Watchful waiting is indicated for patients with mild symptoms that are not bothersome.

Single-drug treatment with an a-adrenergic antagonist is preferred for patients with moderate or severe symptoms of BPH. Single-drug treatment with a 5a-re-ductase inhibitor should be reserved for patients with moderate or severe symptoms and significantly enlarged prostates of at least 30 g (1.05 oz).

® Surgical intervention should be reserved for patients with severe LUTS due to BPH and those with complications of disease, such as recurrent urinary tract infections, recurrent severe gross hematuria, renal failure, and bladder calculi.

a-Adrenergic antagonists reduce the dynamic factor. They competitively antagonize a-adrenergic receptors, thereby causing relaxation of the bladder neck, prostatic urethra, and prostate smooth muscle. They do not shrink an enlarged prostate. The onset of action is days to weeks, depending on the need for up-titration of the daily dose to achieve a therapeutic response. Dose limiting adverse effects include hypotension and syncope. In addition, delayed or retrograde ejaculation has been reported. Combined use with antihypertensives, diuretics, or phosphodiesterase inhibitors can increase the risk of hypotensive episodes.

Among the a-adrenergic antagonists, modified-release alfuzosin is considered functionally uroselective because usual therapeutic doses produce relaxation of the bladder neck and prostatic smooth muscle with minimal peripheral vascular relaxation. Although alfuzosin appears to produce less hypotension than immediate-release formulations of terazosin and doxazosin, it is not clear if it has the same cardiovascular profile as tamsulosin. Although not uroselective, controlled-release doxazosin produces less hypotension than the immediate release formulation. Tamsulosin and silodosin are pharmacologically uroselective and exert greater antagonism of a1A- and a1D-receptors, which predominate in prostatic and bladder detrusor muscle, respectively, as compared to vascular a1B-receptors. Therefore, tamsulosin and silodosin can be initiated with a full therapeutic dose, which achieves peak effects sooner than with immediate-release formulations of terazos-

in and doxazosin, which must be up-titrated. Tamsulosin appears to have the lowest potential to cause hypotension. In various clinical trials, tamsulosin is well tolerated in the elderly and in patients taking diuretics and antihypertensives. It is also commercially available in a controlled-release dosage formulation. Therefore, with chronic use, tamsulosin can be taken once daily at the patient's convenience.

® 5«-Reductase inhibitors shrink enlarged prostates, reducing symptoms caused by the static factor. They do so by inhibiting 5a-reductase that is responsible for intraprostatic conversion oftestosterone to dihydrotestosterone, the active androgen that stimulates prostate tissue growth. The onset of action is slow with peak shrinkage of the prostate taking up to 6 months. Unlike treatment with a-adrener-gic antagonists, 5a-reductase inhibitors have been shown to reduce the incidence of acute urinary retention and need for prostate surgery in patients with significantly enlarged prostate glands (more than 30 g), and those with prostate-specific antigen (PSA) serum levels of 1.5 ng/mL (1.5 mcg/L) or more. Because 5a-reductase inhibitors do not produce cardiovascular adverse effects, they are preferred for treatment of moderate to severe symptoms of BPH when the patient is at risk ofhypotension, but wants to be treated medically. Adverse effects include gynecomastia, decreased libido, erectile dysfunction, and ejaculation disorders. Drug interactions are uncommon.

O When monitoring efficacy of drug treatment for BPH, subjective end points include relief of obstructive and irritative voiding symptoms. Objective end points include improvements of urinary flow rates, decreased postvoid residual urinary volume, and decreased complications of disease.

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