Benign prostatic hypertrophy (BPH) isthe most common benign neoplasmamong men; it increases in prevalence withage. With the enlargement of the prostate,additional pressure on the urethra results inobstruction of urinary flow. By age 70, half ofall men exhibit some level of prostaticenlargement, with the proportion increasingto 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 resectionof the prostate has been a prominent surgicalprocedure. For symptoms of moderate-tosevereBPH that become bothersome, however,nonsurgical treatments range from naturalremedies, such as saw palmetto(Serenoa repens), to sympathetic alpha-1receptor blockers, such as terazosin and doxazosin.
Contractions of the smooth muscle of theprostate are associated with nearly half of theurinary outflow obstruction associated withBPH. This contraction is mediated byreversible alpha-1 receptor activity. Blockingthese specific receptors provides some reliefof symptoms.
Selective alpha-1 receptor blocking agentsalso lower blood pressure by reducing the contractilityof cardiovascular musculature. In thepast, alpha-1 blocking agents were recommendedamong first-line treatments of hypertension.Their use for this indication, however,has dropped considerably due to an increasedincidence of associated congestive heart failure.As a treatment for hypertension, alpha-1 blockingagents are used primarily as secondary andadjunct treatment.
Certain alpha-1 blocking agents, such as terazosinand doxazosin, also can slightly reduce totalserum cholesterol, triglycerides, and low-densitylipoproteins. The net reduction for this effect isbetween 2% and 4%.
Administration and Dosing: Terazosin
When used to treat the symptoms of BPH, theinitial dose of terazosin is 1 mg at bedtime.Dosing is increased gradually to 2, 5, and 10 mgdaily to achieve the desired response. It generallytakes 4 to 6 weeks to observe full benefitsin most patients, but some patients may requiredoses as high as 20 mg daily. Food has littleeffect on the absorption of terazosin. If treatment is interrupted for several days, therapyshould resume using the same initialupward titration.
Administration and Dosing:Doxazosin
Doxazosin dosing also begins with a1-mg bedtime dose, with upward titrationto 2, 4, and 8 mg as necessary.Dosing increases should be made atintervals of at least 1 to 2 weeks.Although daily doses of 16 mg havebeen used, exceeding an 8-mg dailydose is not recommended. Blood pressureshould be routinely checked duringinitial treatment and with adjustmentsin dosing.
Side Effects and Drug Interactions
The adverse effects tend to be mildduring treatment with terazosin forBPH. Because alpha-1 receptor blockingcan be effective in reducing bloodpressure, men may experience dizziness,postural hypotension, headache,and sleepiness. These effects havecaused 9% of patients to stop terazosintreatment during clinical trials.The gradual titration of the dose helpsminimize the postural effects, andnighttime dosing tends to accommodatethe associated somnolence ofterazosin. Supportive measures duringepisodes of syncope generally are adequate.
Doxazosin has similar dose-relatedeffects that usually occur within 2 to 6hours following administration. This isa further encouragement to taking thedrug at bedtime. About 10% of patientstaking doxazosin experienceheadache, and 3% experience sleepiness.Sweating, xerostomia, and facialedema also have been reported.
After age 50, as many as 1 in 3 menmay experience symptoms consistentwith BPH. By 2010, with the number ofmen over 50 expected to double in theUnited States, this "target demographic" for both hypertension and BPH willincrease the attractiveness of using alpha-1 blocking drugs such as terazosin anddoxazosin for simultaneous treatment ofboth conditions. Terazosin is available in 1,2-, 5-, and 10-mg strengths from GenevaLaboratories and Sandoz. Doxazosin isavailable in doses ranging from 1 mg to 8mg from several sources, includingApotex Corp, Ethex, Mylan PharmaceuticalsInc, and Purepac Pharmaceuticals.
Mr. Middleton is an instructor of pharmacologyat Kellogg CommunityCollege in Battle Creek, Mich.