© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
rationale for their use is based on the fact that the NO-
cGMP pathway is the primary mechanism by which
relaxation of the corporal smooth muscle as well as
the muscle of the penile vessels occurs.
110
Of the four
available PDEi today, both sildenafil and vardenafil
have comparable pharmacokinetics i.e. peak levels in
the blood occur about 1 hour after oral ingestion and
the serum half life is about 6 to 8 hours. Both agents
require an empty stomach for optimum reabsorption.
Avanafil, the first oral PDE5i to be approved by the
FDA in the past 10 years may have an earlier onset of
action then the previous three agents and absorption
is reported to be not be affected by food. On the other
hand, tadalafil reaches a peak level in the blood stream
about 2 to 3 hours after ingestion while its half-life is
more extended to about 17 to 18 hours. The absorption
of this agent from the gut is not negatively impacted
by food.
The PDE5i all have common side effects usually
referable to vasomotor function. These include
headache, flushing, lightheadedness, etc. Sildenafil
is associated at times with visual changes e.g.
seeing blue tint while tadalafil has been associated
with back discomfort and muscle aches. All of the
aforementioned side effects are dose dependent and
reversible. Extremely rare but troubling side effects
include non-arteritic ischemic optical neuropathy
(NAION) and hearing loss both of which do not seem
to be dose related
The success rates for the PDEi in rigorous scientific
studies range from 60%-80% in most populations and
early expectations of similar success among the general
population were similarly high. Unfortunately, in real
life a certain percentage of menwith EDdo not seem to
be achieving their desired or expected goal with these
agents. The discontinuation rate for PDE5i use among
men diagnosed as having ED by their physicians
appears to be high even among those who initially
responded to the medication, reaching up to 57% in a
3 year follow up.
111,112
Discussions about appropriate expectations are
key to optimize PDE5i therapy outcomes. Myths
and misunderstandings about sexual activity can
directly cause sexual difficulties as well as generate
anxiety, guilt and worry that negatively impact on
sexual response and erectile ability. Helping men to
have realistic expectations and to understand healthy
function, and honest, constructive communication
with their partners and a focus on less genital touch,
can encouragemore satisfactory sexual interaction and
a healthier sexual life in a non-pharmacologic means.
Men need to be told that although the medication
is likely to have a positive and significant effect
on erectile function in men with ED, the degree of
effect can vary based on a variety of physiologic and
psychosocial factors. The PDE5i biochemical effect
does not provide 100% success in all men, and appears
to be significantly decreased in men with diabetes or
who have had a radical prostatectomy.
113,114
A step-wise approach meant to deal with oral
treatment ED failures includes reevaluation and
adjustment of therapy with 1) hypogonadism
treatment if present, 2) dose titration, and 3) patient
instruction on optimal use of medication. If the man is
still not satisfied, this algorithm suggests considering
alternative oral or local therapy with additional
education and counseling followed by referral to a
specialist if needed.
115
Our goal as clinicians for men with ED is to 1) help
improve sexual function and regain self-esteem,
2) improve theman’s senseofwell-being, and3) improve
relationships.
116
We know that improving physiologic
erectile function in men with ED is an important part,
but only one part of the desired outcome. Many other
issues can influence the likelihood of achieving the
desired outcomes including 1) the man’s psychosocial
milieu, 2) the presence of other sexual issues or
risk factors for physical sexual dysfunction, 3) the
availability and receptivity of a partner, and 4) partner
interaction. A trusting physician-patient partnership
enhances the likelihood of a successful therapeutic
outcome. Optimism is an essential management tool
for PCPs to use in responding to sexual issues.
Follow up for treatment of ED
Follow up is an essential part of management of
erectile dysfunction. Patients should be seen at 4-6
weeks after initiation of treatment to evaluate progress.
Comparison to baseline can be done by verbal
exchange or by using the standardized questionnaire
measuring erectile function (SHIM). Reviewing the
success or lack of success of treatment, any adverse
effects, and considering dose or treatment alterations
is more likely to achieve the patient’s goal. Further
education and/or basic sex counseling can be provided
to the patient with or without his partner.
When to refer
Consultation with subspecialists may be appropriate
at varying intervals when managing a man with ED.
The major factor is the PCP’s comfort in discussing
and managing treatment options. The obligation of
the PCP is to recognize ED and make the patient feel
comfortable about seeking help. Initial work up and
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