© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
21
Apractical primary care approach to lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH-LUTS)
in patients with a history of non-arteritic anterior
ischemic optic neuropathy (NAION).
33
Cardiac status
must be assessed for patient risk before taking these
medications.
43
Similar to the alpha-blockers, the PDE5i
have no impact on prostate growth.
Treatment: alpha-blocker or PDE5i with an
antimuscarinic or beta 3 agonist
Addition of an antimuscarinics or beta 3 agonist with an
alpha-blocker or PDE5i is appropriate if the patient has
symptoms of both irritation and obstruction as well as bother.
LUTS can be a mixture of obstructive (outlet) and
irritative (bladder) symptoms. Treatment of the
bladder outlet with an alpha-blocker or PDE5i may
resolve symptomology enough so that the patient
is satisfied. However, in a subset of patients who
have an improvement in urinary hesitancy, flow and
emptying – the symptoms of urgency, daytime and
nighttime urinary frequency, with or without urgency
incontinence may persist and be bothersome enough
for further therapy. In this case the option of using a
medication for these overactive bladder symptoms
has been shown to provide significant symptomatic
relief. Currently there are two classes of medications
available for overactive bladder: antimuscarinics and
beta 3 agonists, Table 5.
The European Association of Urology (EAU)
guidelines state that muscarinic receptor antagonists
might be considered in men with moderate to severe
LUTS who have been adequately treated for their
obstruction and whose residual complaints are
predominantly bladder storage symptoms.
44
The
combination therapy of an alpha-blocker togetherwith a
muscarinic receptor antagonist aims to antagonize both
alpha1-adrenoceptors andmuscarinic cholinoreceptors
in the lower urinary tract, thereby using the efficacy of
both drug classes to achieve synergistic effects.
45,46
The
availablemedications include darifenacin, fesoterodine,
oxybutynin, propiverine, solifenacin, tolterodine and
trospium chloride. The most common side effects
include dry mouth, constipation, micturition difficulty,
nasopharyngitis anddizziness.
33
Nodifferences in terms
of pharmacokinetic or pharmacodynamic properties of
the combined use of both drugs have been described
compared to the use of the single drugs.
44
In multiple studies, when alpha-blockers were
used with antimuscarinics the combination of
drugs was, in general, more efficacious in reducing
voiding frequency, nocturia, or IPSS compared to
alpha-blockers or placebo alone. Furthermore, the
combination treatment significantly reduced urgency
urinary incontinence episodes as well as urgency and
significantly increased quality-of-life.
45-47
Adverse
events of both drug classes appear during combination
treatment of alpha-blockers and muscarinic receptor
antagonists. Measuring of PVR urine is recommended
during combination treatment to assess increase or
urinary retention although the incidence of increased
PVR and retention was rare.
44
There is currently only one beta 3 agonist available
(mirabegron). This medication is newly available and,
of present, has not been studied in combination with
an alpha-blocker. The indications for use include urge
urinary incontinence, urgency and urinary frequency.
The main adverse reactions include hypertension,
nasopharyngitis, urinary tract infections and headache.
Caution should be used in patients with clinically
significant bladder outlet obstruction.
33
PDE5i are also newly indicated and, currently, there
are no published studies for use with antimuscarinics
or beta 3 agonists.
Treatment: alpha-blocker or PDE5i with a
5-alpha reductase inhibitor (5-ARI)
The addition of a 5-ARI with either an alpha-blocker or a PDE5i
is appropriate for the symptomatic patient with BPH-LUTS
who has identified bother and has a PSAof 1.5ng/mLor greater.
As mentioned before, identification of sexual dysfunctionmay
assist in the choice of the alpha-blocker or PDE5i.
Patients with a large prostate may find that treating
the dynamic component of BPH-LUTS with only an
alpha-blocker or PDE5i is not sufficient. Neither of
those medications will halt the growth of the prostate
and this enlargement may result in worsening
symptoms as well as the risk of acute urinary retention
and possibly the need for surgical intervention. The
goal of therapy then becomes treating the progression
by reducing the static component of this enlarged
gland. As mentioned earlier, Crawford identified
five risk factors for disease progression which include
PSA, prostate size, age, urinary flow and PVR.
28
In the
office of the PCP, PSA is one of practical importance
as was explained earlier.
Understanding how the prostate grows is essential
in understanding the role of the 5-ARI. Prostate growth
is stimulated by dihydrotestosterone (DHT) with is
converted from testosterone by the 5-alpha reductase
enzyme. Decreases inDHT have been shown to induce
prostatic epithelial apoptosis and atrophy which in
turn leads to approximately 18%-28% reduction in
prostate size and approximately a 50% reduction in
PSA levels after 6-12 months.
48-50
