Medication Summary
The goals of pharmacotherapy for benign prostatic hypertrophy (BPH) are to reduce morbidity and to prevent complications. The agents used include the following, alone or in combination:
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Alpha-adrenergic blockers
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5-Alpha-reductase inhibitors
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Phosphodiesterase-5 enzyme inhibitors
Alpha-Adrenergic Blockers
Class Summary
These agents block effects of postganglionic synapses at the smooth muscle and exocrine glands.
Phenoxybenzamine (Dibenzyline)
Phenoxybenzamine is a nonselective alpha-adrenergic receptor blocker that antagonizes both alpha-1 and alpha-2 receptors. This nonselectivity leads to a higher incidence of adverse effects, which has led to decreased use of this agent in clinical settings. Phenoxybenzamine induces subjective improvement in urinary flow rates when compared with placebo. It may improve daytime and nighttime urinary frequency. Symptoms improve in 75% of patients.
Prazosin (Minipress)
Prazosin is currently approved for the treatment of hypertension. Prazosin improves urine flow rates by relaxing smooth muscle. Relaxation is produced by blocking alpha-1 adrenoreceptors in the bladder neck and prostate. The advantage of prazosin over nonselective alpha-adrenergic blockers includes a lower incidence of adverse effects. Because of availability of longer-acting, once-daily selective agents, however, the clinical utility of prazosin for BPH has been reduced.
Prazosin improves urinary flow rate and frequency of micturition. Subjective improvement is observed in 82% of patients treated. When increasing dosages, administer the first dose of each increment at bedtime to reduce syncopal episodes. Although doses above 20 mg/d do not usually increase efficacy, some patients may benefit from up to 40 mg/d.
Alfuzosin (UroXatral)
Alfuzosin is indicated for the treatment of the signs and symptoms of BPH. Alfuzosin is an alpha-1 blocker of adrenoreceptors in the prostate. Blockade of adrenoreceptors may cause smooth muscles in the bladder neck and prostate to relax, resulting in improvement in urine flow rate and reduction in symptoms of BPH.
Indoramin
This agent is not available in the United States. Indoramin improves urine flow rates by blocking alpha-1 adrenoreceptors in the bladder neck and prostate, thus relaxing smooth muscle in those sites. Indoramin also reduces the frequency of micturition.
The advantage of indoramin over nonselective alpha-adrenergic blockers includes lower incidence of adverse effects. Because of availability of longer-acting, once-daily selective agents, clinical utility of this agent for BPH has been reduced.
Terazosin (Hytrin)
Terazosin is a quinazoline compound that counteracts alpha1-induced adrenergic contractions of bladder neck, facilitating urinary flow in the presence of BPH. It is indicated for the treatment of symptomatic BPH and hypertension. Its effect on voiding symptoms and flow rates is dose-dependent. It improves irritative and obstructive voiding symptoms. Improvement in flow rate is objective. A Hytrin starter pack is available for easy dosing progression to 5 mg.
Doxazosin (Cardura, Cardura XL)
Doxazosin is indicated for the treatment of urinary outflow obstruction and irritative symptoms associated with BPH and hypertension. It inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure. It is a long-acting alpha1-blocking agent with a profile similar to that of terazosin. Doxazosin improves irritative and obstructive voiding symptoms.
Tamsulosin (Flomax)
Tamsulosin is indicated for the treatment of the signs and symptoms of BPH. It is an alpha-adrenergic blocker specifically targeted to alpha-1 receptors. Tamsulosin has the advantage of producing relatively less orthostatic hypotension; it requires no gradual up-titration from the initial dosage. It inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure. It improves irritative and obstructive voiding symptoms.
Silodosin (Rapaflo)
Silodosin is indicated for the treatment of the signs and symptoms of BPH. Silodosin selectively antagonizes postsynaptic alpha1-adrenergic receptors in the prostate, bladder base, prostatic capsule, and prostatic urethra. This action induces smooth muscle relaxation and improves urine flow.
5-Alpha-Reductase Inhibitors
Class Summary
These agents are used to treat symptomatic BPH in men with an enlarged prostate. They inhibit the conversion of testosterone to DHT, causing DHT levels to drop, which, in turn, may decrease prostate size. [54, 55]
Finasteride (Proscar)
Finasteride is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. When combined with doxazosin, it can also reduce the risk of symptomatic progression of BPH. Finasteride inhibits conversion of testosterone to DHT, causing serum DHT levels to decrease. It is beneficial in men with prostates larger than 40 g and can improve symptoms and reduce prostatic size by 20-30%. Reduction in prostate size is sustained for 5 years following treatment. Finasteride improves urinary flow rate by 2 mL/s.
Dutasteride (Avodart)
Dutasteride is indicated for the treatment of BPH as monotherapy or in combination with tamsulosin. Dutasteride improves symptoms, reduces urinary retention, and may decrease the need for BPH-related surgery. It inhibits 5alpha-reductase isoenzymes types I and II. This agent suppresses conversion of testosterone to DHT by more than 95%, causing serum DHT levels to decrease.
Phosphodiesterase-5 Enzyme Inhibitors
Class Summary
These agents mediate smooth muscle relaxation in the lower urinary tract, thus improving the symptoms of BPH.
Tadalafil (Cialis)
PDE5 selective inhibitor. Inhibition of PDE5 increases cGMP activity, which increases vasodilatory effects of nitric oxide. Sexual stimulation is necessary to activate response. Tadalafil has been approved by the FDA for the treatment of BPH signs and symptoms.
PDE5 inhibition has been shown to induce smooth muscle relaxation in the lower urinary tract. It has also been approved for the treatment of simultaneous BPH and ED.
Increased sensitivity for erections may last 36 h with intermittent dosing. Low-dose daily dosing may be recommended for more frequent sexual activity (ie, twice weekly); men can attempt sexual activity at anytime between daily doses.
Combination Products
Class Summary
Various combination products are emerging on the market to improve patient compliance and symptoms.
Dutasteride and tamsulosin (Jalyn)
The combination of dutasteride, a 5-alpha-reductase inhibitor, and tamsulosin, an alpha-adrenergic antagonist is indicated for benign prostatic hypertrophy in men with an enlarged prostate. Each cap contains dutasteride 0.5 mg and tamsulosin 0.4 mg.
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Benign prostatic hyperplasia. Normal prostate anatomy is shown. The prostate is located at the apex of the bladder and surrounds the proximal urethra.
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Benign prostatic hyperplasia (BPH) diagnosis and treatment algorithm.
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Benign prostatic hyperplasia. Basic management of lower urinary tract symptoms (LUTS) in men.
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