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P A R T 7
Drugs acting on the reproductive system
Contraindications and cautions
These drugs are contraindicated in the presence of any
anatomical obstruction or condition that might pre-
dispose to priapism. They cannot be used with penile
implants, and they are not indicated for use in women.
However, sildenafil is used in women for the treatment
of pulmonary arterial hypertension.
Caution should be used in people with bleeding
disorders. The PDE5 inhibitors should also be used cau-
tiously in people with coronary artery disease, active
peptic ulcer, retinitis pigmentosa, optic neuropathy,
hypotension or severe hypertension, congenital pro-
longed QT interval or severe hepatic or renal disorders
because of the risk of exacerbating these diseases.
Adverse effects
Adverse effects associated with alprostadil are local
effects such as pain at the injection site, infection,
priapism, fibrosis and rash. The PDE5 inhibitors
are associated with more systemic effects, including
headache, flushing (related to relaxation of vascular
smooth muscle), dyspepsia, urinary tract infection, diar-
rhoea, dizziness, possible optic neuropathy, possible
eighth cranial nerve toxicity, loss of hearing and rash.
Clinically important drug–drug interactions
The PDE5 inhibitors cannot be taken in combination
with any organic nitrates or alpha-adrenergic blockers;
TABLE 41.3
DRUGS IN FOCUS Drugs used to treat penile erectile dysfunction
Drug name
Dosage/route
Usual indications
alprostadil (Caverject)
2.5 mcg injected intracavernously, titrate the
dose to one that will allow a satisfactory
erection that is maintained no longer than
1 hour; mean dose after 6 months is reported
to be 20.7 mcg
Treatment of penile erectile dysfunction
sildenafil (Viagra,
Revatio)
Viagra: 25–100 mg PO taken 1 hour before
sexual stimulation
Revatio: 20 mg PO t.d.s., at least 4–6 hours
apart
Treatment of penile erectile dysfunction
Treatment of pulmonary arterial
hypertension in men and women
tadalafil (Cialis)
10 mg PO taken before sexual activity; range
5–20 mg PO; limit use to once a day;
2.5–5 mg/day PO for very sexually active
males
Treatment of penile erectile dysfunction
vardenafil (Levitra)
5–10 mg PO taken 1 hour before sexual
stimulation; range 5–20 mg; limit use to once
a day
Treatment of penile erectile dysfunction
Safe medication administration
People who are using PDE5 inhibitors need to be advised to
avoid drinking grapefruit juice while using the drug. Grapefruit
juice can cause a decrease in the metabolism of the PDE5
inhibitor, leading to increased serum levels and a risk of
toxicity. They should also be advised to avoid taking the drug
with or just after a high-fat meal. The presence of fat in the GI
tract will delay the absorption and onset of action of the drug,
which could cause problems for individuals who are timing
onset of action with their sexual activity.
These drugs can have serious cardiovascular effects.
Deaths have been reported in people combining use of such
drugs with other cardiovascular medications. People need to
be aware of the potential risks in taking the drugs alongside
other medications.
Prototype summary: Sildenafil
Indications:
Treatment of erectile dysfunction in
the presence of sexual stimulation; treatment of
pulmonary arterial hypertension.
Actions:
Inhibits PDE5 receptors, leading to a release
of nitrous oxide, which activates cGMP to cause
a prolonged smooth muscle relaxation, allowing
the flow of blood into the corpus cavernosum and
facilitating erection.
Pharmacokinetics:
Route Onset
Peak
Duration
PO 15–30 mins 30–120 mins 4 hours
T
1/2
:
4 hours, with hepatic metabolism and excretion
in the faeces and urine.
Adverse effects:
Headache, abnormal vision, flushing,
dyspepsia, urinary tract infection, rash.
