Clinical Update

Benign prostatic hypertrophy (BPH) is the most common benign neoplasm among men; it increases in prevalence with age. With the enlargement of the prostate, additional pressure on the urethra results in obstruction of urinary flow. By age 70, half of all men exhibit some level of prostatic enlargement, with the proportion increasing to about 90% by age 85. In its extreme forms, BPH can lead to urinary retention, renal insufficiency, urinary tract infections, hematuria, and kidney stones.

As a result of BPH, transurethral resection of the prostate has been a prominent surgical procedure. For symptoms of moderate-tosevere BPH that become bothersome, however, nonsurgical treatments range from natural remedies, such as saw palmetto (Serenoa repens), to sympathetic alpha-1 receptor blockers, such as terazosin and doxazosin.

Pharmacology

Contractions of the smooth muscle of the prostate are associated with nearly half of the urinary outflow obstruction associated with BPH. This contraction is mediated by reversible alpha-1 receptor activity. Blocking these specific receptors provides some relief of symptoms.

Selective alpha-1 receptor blocking agents also lower blood pressure by reducing the contractility of cardiovascular musculature. In the past, alpha-1 blocking agents were recommended among first-line treatments of hypertension. Their use for this indication, however, has dropped considerably due to an increased incidence of associated congestive heart failure. As a treatment for hypertension, alpha-1 blocking agents are used primarily as secondary and adjunct treatment.

Certain alpha-1 blocking agents, such as terazosin and doxazosin, also can slightly reduce total serum cholesterol, triglycerides, and low-density lipoproteins. The net reduction for this effect is between 2% and 4%.

Administration and Dosing: Terazosin

When used to treat the symptoms of BPH, the initial dose of terazosin is 1 mg at bedtime. Dosing is increased gradually to 2, 5, and 10 mg daily to achieve the desired response. It generally takes 4 to 6 weeks to observe full benefits in most patients, but some patients may require doses as high as 20 mg daily. Food has little effect on the absorption of terazosin. If treatment is interrupted for several days, therapy should resume using the same initial upward titration.

Administration and Dosing: Doxazosin

Doxazosin dosing also begins with a 1-mg bedtime dose, with upward titration to 2, 4, and 8 mg as necessary. Dosing increases should be made at intervals of at least 1 to 2 weeks. Although daily doses of 16 mg have been used, exceeding an 8-mg daily dose is not recommended. Blood pressure should be routinely checked during initial treatment and with adjustments in dosing.

Side Effects and Drug Interactions

The adverse effects tend to be mild during treatment with terazosin for BPH. Because alpha-1 receptor blocking can be effective in reducing blood pressure, men may experience dizziness, postural hypotension, headache, and sleepiness. These effects have caused 9% of patients to stop terazosin treatment during clinical trials. The gradual titration of the dose helps minimize the postural effects, and nighttime dosing tends to accommodate the associated somnolence of terazosin. Supportive measures during episodes of syncope generally are adequate.

Doxazosin has similar dose-related effects that usually occur within 2 to 6 hours following administration. This is a further encouragement to taking the drug at bedtime. About 10% of patients taking doxazosin experience headache, and 3% experience sleepiness. Sweating, xerostomia, and facial edema also have been reported.

Outlook

After age 50, as many as 1 in 3 men may experience symptoms consistent with BPH. By 2010, with the number of men over 50 expected to double in the United States, this "target demographic" for both hypertension and BPH will increase the attractiveness of using alpha- 1 blocking drugs such as terazosin and doxazosin for simultaneous treatment of both conditions. Terazosin is available in 1, 2-, 5-, and 10-mg strengths from Geneva Laboratories and Sandoz. Doxazosin is available in doses ranging from 1 mg to 8 mg from several sources, including Apotex Corp, Ethex, Mylan Pharmaceuticals Inc, and Purepac Pharmaceuticals.

Mr. Middleton is an instructor of pharmacology at Kellogg Community College in Battle Creek, Mich.