© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
13
Benign prostatic hyperplasia (BPH) management in the primary care setting
which allows a less constricted urinary flow. The alpha
blockers have a quick onset of action, within 3 to 5 days.
Once the medication is stopped, symptoms usually
return to pre-treatment, baseline levels. There are five
main alpha-blockers: two second-generation drugs—
terazosin (Hytrin) and doxazosin (Cardura)
8
—
and
three third-generation drugs—tamsulosin (Flomax),
alfuzosin (Xatral),
9
and silodosin (Rapaflo). Both
terazosin and doxazosin require dose titration because
of their anti-hypertensive properties. Tamsulosin,
alfuzosin, and silodosin usually do not require dose
titration and have fewer cardiovascular side effects.
10
All five agents are generally equally effective
11
and their
side effects include light-headedness from orthostatic
hypotension (5%-10%of patients), dizziness (5%-10%),
weakness (5%), headache (5%), asthenia (5%-10%),
nasal congestion (5%), and retrograde ejaculation
(3%-10%).
7
Although alpha blockers improve urine
flow quickly, they do not reduce prostate size, and as
a result they do not reduce the risk of future urinary
retention or the need for BPH-related surgery.
12
In
patients with severe allergies to sulpha, an allergic
reaction to tamsulosin has been reported, and therefore
this drug should be avoided in such patients.
Intraoperative floppy iris syndrome was observed
during cataract surgery in some patients who currently
or previously were taking alpha blockers. Therefore, if
cataract surgery is a possibility, consideration should
be given to avoiding alpha blockers until after the
surgery. The ophthalmologist should be informed if
the patient has been on alpha blockers for as long as 6
to 9 months prior to any cataract intervention.
Silodosin (Rapaflo) is a super selective alpha
blocker that has recently become available in Canada.
This drug blocks alpha-1a receptors and, to a much
lesser degree, alpha-1b and alpha-1d receptors.
This heightened selectivity may result in fewer
cardiovascular side effects, which aremainly regulated
by alpha-1b receptors.
13
A number of studies have
confirmed the safety of silodosin, especially in terms
of cardiovascular safety. There are negligible effects
on heart rate or ECG, including PR segment and QRS
complex.
14
Side effects include upper respiratory
tract infection (2%-19% of patients), diarrhea (2%-7%),
dizziness (3%-5%), and orthostatic hypotension (3%).
Alterations in ejaculatory function range from 5% to
28%,
with a median of 20% of patients experiencing
retrograde ejaculation. However, only about 2% of
patients discontinued silodosin therapy based on
ejaculatory dysfunction alone.
15
A major study comparing silodosin versus
tamsulosin was published in Europe
16
and involved
1228
patients randomized to tamsulosin versus
silodosin versus placebo for 12 weeks. This study
found no significant differences between tamsulosin
and silodosin in terms of IPSS for storage or voiding
symptoms, which suggests that both drugs are
equally efficacious in the treatment of BPH. Two
other studies
17,18
have suggested that silodosin may
be more effective than tamsulosin, but in both these
studies suboptimal dosing of tamsulosin (0.2mg daily)
was used as the comparator. Ejaculatory dysfunction
was higher in the silodosin group (14.2%) versus the
tamsulosin group (2.1%). Interestingly, patients with
ejaculatory dysfunction had the highest efficacy with
silodosin, suggesting that the presence of ejaculatory
dysfunction can be used as a surrogate for efficacy.
19
Cardiovascular side effects were comparable for both
groups, and although silodosin demonstrated a more
favorable cardiovascular profile than tamsulosin, this
difference was not statistically significant. Recent
studies have suggested that silodosin may have a
quicker onset of action than tamsulosin.
19
Silodosin has recently been examined in men with
chronic prostatitis/chronic pelvic pain syndrome.
20
In this study, equal numbers of 151 patients were
randomized to silodosin 4 mg, silodosin 8 mg, and
placebo. Compared to placebo, the 4 mg dose of
silodosin was associated with a significant reduction in
chronic prostatitis symptoms andan improvedqualityof
life. Therewas no additional benefit fromthe 8mg dose.
5-
alpha reductase inhibitors
The 5-ARIs, Table 2, inhibit the conversion of
testosterone to DHT, the main mediator of BPH
progression. This causes the prostate to decrease in
size and slow the progress of prostate growth.
21,22
The
onset of action with 5-ARIs is slower than with alpha
blockers, and usually takes 4 to 6 months. The two
main 5-ARIs are finasteride (Proscar)
23
and dutasteride
(
Avodart).
24
Finasteride inhibits the type 2, 5-alpha
reductase isoenzyme, whereas dutasteride inhibits
both type 1 and type 2 isoenzymes. With this dual
blockade, dutasteride lowers DHT production in the
prostate by over 90%, whereas finasteride lowers DHT
by 70%.
1
As a result, dutasteride may have a faster
onset of action than finasteride. The 5-ARI side effects
include erectile dysfunction (ED, in 5%-8%of patients),
ejaculatory dysfunction (1%-5%), decreased libido
(5%),
and, rarely, gynecomastia (1%). By shrinking
the prostate, the 5-ARIs have been shown to improve
BPH-related symptoms and to reduce the risk of future
urinary retention and BPH–related surgery.
21
Alpha blockers do not affect PSAand have no effect
on prostate cancer risk. However, the 5-ARIs lower
PSAby 50% after 6 months on therapy.
25
For example,
