Transcript Sildenafil citrate

CVD and Sexual
Dysfunction
Melvin Cheitlin MD
Jonathan Abrams MD
Nancy Houston-Miller RN
Nitric oxide release in sexual
stimulation
CNS erotic
stimulation
Neural
transmission
Penile
endothelial
cells
NITRIC OXIDE
Role of cyclic-GMP in penile
erection
smooth muscle
relaxation
vessel dilatation
nitric oxide
Blood filling
lacunae in corpus
cavernosum
pushing against
tunica albuginea
cyclic-GMP
obstruction of
venous outflow
Sildenafil inhibits the enzyme
PDE-5
Sildenafil citrate
Nitric oxide
X
phosphodiesterase-5
Cyclic GMP
X
Sildenafil side effects
Sildenafil citrate
specific for phosphodiesterase-5 (PDE-5)
in penis
selectivity for PDE-6 in retina
(responsible for visual side effects)
drop in systolic pressure 8-10 mm Hg
drop in diastolic pressure 5-6 mm Hg
erection tenable only when accompanied
by stimulation of nitric oxide
(ie, erotic stimulation)
Sildenafil and vasodilatation
Sildenafil citrate
normally SLOW vasodilation
no increase in HR
no sympathetic response
no increase in cardiac output
no increase in contractility
BUT
interacts with organic nitrates to produce
significant hypotension
Sildenafil, original studies
No differences in MI or death were seen
between those on placebo versus sildenafil
in studies of > 3700 people.
The following subjects were excluded:
- patients with stroke or MI within 6 months
- patients with unstable angina, CHF
- patients with uncontrolled diabetes or
BP > 150/110 or < 90/50
-patients with severe renal or hepatic
disease
Sildenafil, original studies
Less than 25% of patients in these
studies were over 65 years.
Patients with hypertension in the original
safety trials were typically on simple
regimens to control their blood pressure.
The effect of sildenafil on patients with
hypertension and who are on multiple
medications is not known.
Physical burden of sexual
activity
General energy expenditure in sexual
activity is 3-7 metabolic equivalents
(METS), comparable to mild to moderate
physical activity.
This expenditure depends on baseline status
and differences in fitness levels.
Use stress testing to risk stratify certain
patient populations (eg, recent MI,
hospitalization for unstable angina, CHF,
multiple drugs for HTN…).
Risk for acute MI during
sexual activity
There exists a 2-fold increase in risk for MI
within 2-3 hours following sexual activity.
The baseline risk of having an MI during
sex is very low, less than 1% in terms of all
infarctions.
The risk factors for coronary artery disease
and erectile dysfunction are comparable.
When in doubt, stress test prior to
resumption of sex or de novo sex in
sedentary men at risk.
The use of both nitrates and
sildenafil results in hypotension
Nitrates
Sildenafil citrate
+
-
Nitric oxide
phosphodiesterase-5
Cyclic GMP
HYPOTENSION
The concomitant use of
sildenafil and nitrates is
contraindicated.
All men presenting with acute coronary
syndromes must be asked if they’ve
used Viagra within the preceding 24
hours.
All patients given Viagra must be
repeatedly told not to take nitrates.
Discussing sexual history with
patients
As late as 1996, less than 1/3 of patients
received sexual counseling at the time of MI,
while up to 85% of patients appear willing to
talk to their physician about sex.
When health-care professionals neglect to
discuss their patients’ sexual history, patients
experience:
- conflicts in relationships
- diminished quality of life
- decreased frequency of sexual activity
Key points in counseling a
patient on sexual activity
Provide information on the risks of
sexual activity.
In clinically low-risk individuals, risk of
AMI is 1% per year.
By including sex at a frequency of once
per week, then the risk of AMI is 1.01%
per year.
In high risk patients having sex once per
week, the risk of AMI is 1.2% per year.
Key points in counseling a
patient on sexual activity
Provide information on when to
resume sexual activity.
Generally, in first 2-6 weeks after AMI it
is safe to resume sexual activity.
Up to 80% of patients NOT provided this
information are fearful in the first 6
months while resuming activity.
Key points in counseling a
patient on sexual activity
Transition to full sexual participation
may involve masturbation so that
patients feel more comfortable
resuming sexual intercourse.
Patients should be aware of their
environment, avoiding sexual activity
in association with heavy meals,
alcohol, temperature changes and
fatigue.
Key points in counseling a
patient on sexual activity
Physicians and patients should be
aware of energy costs ( 2.5-3 METS).
This workload is not significantly
different with regard to position during
sex.
The sex act is not a steady-state
workload, unlike treadmill testing.
Patients should be cautioned about
warning signals such as chest
discomfort and shortness of breath.
Key points in counseling a
patient on sexual activity
Physicians should be aware of
medications that may be of use in
treating sexual dysfunction.
Sildenafil is contraindicated in patients
taking long acting nitrates.
Other side effects include impaired color
discrimination, headache, flushing and
rhinitis.
Concomitant use of certain medications
is associated with increased plasma
levels of sildenafil.
Sexual counseling in women
with cardiovascular disease
Women have greater difficulty with
psychosocial adjustment, higher levels of
anxiety, depression and sleep disturbances
after MI and the development of coronary
artery disease. Up to 1/3 of women may
not resume sexual function at all.
A need for counseling exists irrespective of
marital status.
Many more studies are needed.
CVD and sexual dysfunction
“One of the biggest issues with physicians is
the long list of things they have to discuss
with patients. Unless we begin to cue them
in some way, to bring this subject up, it’s
another one that gets lost along the way.
The issue of erectile dysfunction… has to be
brought to the forefront.”
Nancy Houston-Miller
Associate Director
Stanford Cardiac Rehabilitation Program
Stanford University School of Medicine
Stanford, CA