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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
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monotherapy alone over 24 months.
20
In 2010, Jalyn
a single-capsule combination of dutasteride 0.5 mg
and tamsulosin 0.4 mg was approved for use in
the United States in men with sBPH based on two
year study results from the CombAT trial, Table 3.
Combination therapy should be considered in all men
with symptoms as a result of BPE and BOO.
Erectile dysfunction
Pathophysiology
Erectile dysfunction (ED) is defined as the inability
to achieve or maintain an erection sufficient for
satisfactory sexual performance.
21
Approximately
50% of men over the age of 40 are affected by ED.
22
The etiology of ED covers the spectrum of medical
pathology including neurogenic, cardiovascular,
hormonal/endocrine, psychiatric, and pharmacologic
induced. Treatment options are varied and should be
tailored to patient specific requirements.
The pathophysiology to produce penile erection for
sexual intercourse relies on a cascade of neurovascular
events. Starting with appropriate sexual stimulation,
parasympathetic nerve fibers cause endothelial cells
to release nitric oxide (NO) which enter corporal
smooth muscle inciting the conversion of cyclic
guanine triphosphate (cGPT) to cyclic guanosine
monophosphate (cGMP). This step stimulates penile
corporal smoothmuscle relaxation and increased blood
flow producing penile rigidity necessary for erection
and sexual function. Detumescence occurswhen cGMP
is hydrolyzed by the isoenzyme phosphodiesterase-
type 5 (PDE-5).
23
Circulating androgens can also play
a key role on libido and regulation of cGMP, PDE-5,
and NO synthase expression.
24
Pharmacology
Medical oral therapy for ED
The phosphodiesterase-5 inhibitors (PDE-5i) sildenafil
[Viagra], vardenafil [Levitra], and tadalafil [Cialis]
are common oral treatment options for ED, Table 4.
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They function by inhibiting the degradation of cGMP
by PDE-5 amplifying the effect of NO and preventing
detumesence. All PDE-5i are comparable in efficacy
but differ in their pharmacokinetics and side effect
profiles. These differences are attributed to their
interactions with the different PDE isoenzymes. Eleven
different isoenzymes of PDE have been identified in
human tissues. For instance, the PDE-6 isoenzyme is
concentrated in the eye. Sildenafil has a high affinity
for PDE-6 leading to a “blue haze” effect that is rarely
seen with the other agents in this class. Vardenafil has
been found to prolong the QT interval while tadalafil
can be associated with muscle pain in 9% of patients.
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All three PDE-5i can lead to facial flushing, headache,
and rhinitis. These medications should be taken 20-60
minutes prior to the onset of sexual activity allowing
time to reach maximum plasma concentration. In
2008, the FDA approved tadalafil as a once daily
dosing regimen to prevent the inconvenience of
“on demand” dosing.
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TABLE 4.
Oral phosphodiesterase-5 (PDE-5) inhibitors for erectile dysfunction (ED)
Name
Dose
Time to maximum
Serum Affected
Side effects/Notes ++
(Brand)
plasma concentration half life by food
Sildenafil
25 mg-100 mg
60 minutes
4 hrs
Yes;
Visual disturbances
(Viagra)
30-60 minutes
delays onset (“blue haze”)
before sexual activity,
Max 1x day
Vardenafil
5 mg-20 mg
60 minutes
4 hrs
Yes;
Increases QT interval;
(Levitra)
25-60 minutes
delays onset avoid use with other
before sexual activity
medications which
Max 1x day
have similar side effect
Tadalafil
10 mg-20 mg
120 minutes
17.5 hrs No
Myalgia, back pain
(Cialis)
30 min before
sexual activity
Max 1x day
Daily dosing:
2.5 mg-5 mg daily
++ Class side effects include: headache, flushing, rhinitis, dyspepsia
LIU ET AL.