C H A P T E R 4 1
Drugs affecting the male reproductive system
635
tadalafil (
Cialis
) and vardenafil (
Levitra
). Box 41.3
contains more information about
Viagra.
Therapeutic actions and indications
When injected directly into the cavernosum, alprosta-
dil acts locally to relax the vascular smooth muscle and
allow filling of the corpus cavernosum, causing penile
erection. The PDE5 inhibitors sildenafil, tadalafil and
vardenafil are selective inhibitors of cyclic guanosine
monophosphate (cGMP). The PDE5 inhibitors are taken
orally and act to increase nitrous oxide levels in the
corpus cavernosum. Nitrous oxide activates the enzyme
cGMP, which causes smooth muscle relaxation, allowing
the flow of blood into the corpus cavernosum. They
prevent the breakdown of cGMP by phosphodiesterase,
leading to increased cGMP levels and prolonged smooth
muscle relaxation, thus promoting the flow of blood into
the corpus cavernosum, resulting in penile erection.
The prostaglandin alprostadil and the PDE5 inhib-
itors are indicated for the treatment of penile erectile
dysfunction. The PDE5 inhibitors have the advantage
of being oral drugs that can be timed in coordination
with sexual activity, based on the drug’s onset. Silde-
nafil (
Revatio
) is also approved for the treatment of
pulmonary arterial hypertension. By relaxing smooth
muscle, the pulmonary artery relaxes and there is less
resistance and pressure in the pulmonary bed. Tadalafil
is also approved for daily use in men who are very active
sexually. A person might select this drug if the timing
of sexual stimulation is not known and may be several
hours away. See Table 41.3 for usual indications for all
four of these drugs.
Pharmacokinetics
After injection, alprostadil is metabolised to inactive
compounds in the lungs and excreted in the urine. The
PDE5 inhibitors are well absorbed from the GI tract,
undergo metabolism in the liver and are excreted in the
faeces. The differences among the three PDE5 inhibitors
lie in their onset and duration of action. Sildenafil has
a median onset of 27 minutes and duration of 4 hours.
People are encouraged to take the drug 1 hour before
anticipated sexual stimulation. Vardenafil has a mean
onset of action of 26 minutes and duration of 4 hours; it
is also intended to be taken 1 hour before sexual stimu
lation. Tadalafil has an onset of action of 45 minutes
and duration of 36 hours.
None of these drugs is indicated for use in women,
so no adequate studies have been done during pregnancy
and breastfeeding. Because the effects on pregnancy are
not known, if alprostadil is being used, condoms should
be used during intercourse with a pregnant woman.
Viagra—wonder drug?
The release of the drug Sildenafil (Viagra) to treat penile
erectile dysfunction caused a tremendous stir in society.
This was the first oral drug developed to treat a disorder
that was common in ageing men but was seldom
mentioned or discussed. Viagra, which facilitates penile
erection approximately 1 hour after it is taken, returned
sexual function to many of these men.
For many months after its release, the drug was
the centre of controversy, news coverage and debate.
Stand-up comedians, television situation comedies and
Internet joke networks were buzzing with the latest Viagra
jokes. Insurance companies debated covering the cost of
this drug. Was it like cosmetic surgery, and not a necessary
treatment, or was it a necessary aid to human physiology?
Most insurance companies ended up covering the cost of
Viagra.
Women’s rights groups voiced concern that no
drug was approved and covered to help facilitate a
woman’s sexual response. Viagra is in trial stages for
the treatment of sexual dysfunction in women; early
reports seem to indicate that it is not effective. However,
Viagra has proven to be very effective at increasing
sexual functioning for many men. Its success has led to
the development of two new drugs in the same class
of phosphodiesterase type 5 (PDE5) inhibitors, tadalafil
(Cialis) and vardenafil (Levitra).
The use of these drugs is not without risks. Deaths
have occurred when these drugs were combined with
nitrates (e.g. glyceryl trinitrate) or alpha-adrenergic
blockers. Headache, flushing, stomach upset and urinary
tract infections often occur.There have been reports of
sudden loss of vision and hearing.These drugs can be
used only once daily, and they do not work without sexual
stimulation. Absorption is delayed if they are taken with a
high-fat meal, and people need to plan accordingly. People
also should be reminded that they need to use protection
against sexually transmitted infections.
When Viagra was the hot, new drug, there was
tremendous demand for it from the public.This demand
put healthcare providers in the position of ensuring that
the drug was right for the person’s actual needs.The cause
of penile erectile dysfunction should be determined, if
at all possible. If this is a problem that the person has
never before discussed with the healthcare provider, there
could be an underlying medical condition that should be
addressed.The adverse effects, timing of administration
and drug combinations to avoid should be discussed with
the person before the drug is prescribed.
With pharmaceutical companies now advertising in
magazines, on television and over the Internet, healthcare
providers are often asked for specific prescription
drugs based on media advertising.This relatively new
phenomenon in healthcare presents new challenges to the
healthcare provider to ensure quality teaching to help the
person understand the actual uses, effects and rationales
for a specific drug therapy.
The evidence
BOX 41.3
