The term impotence has usually been employed to indicate the inability of the
male to attain and maintain erection of the penis sufficient to permit
satisfactory sexual intercourse. The preferred term is now erectile dysfunction
(ED). ED is a common problem, especially among older men. In the U.S. alone,
approximately 10 million men suffer from ED. According to the National Center
for Health Statistics (1989), ED results in nearly a half-million outpatient
visits. While erectile function may not be the most important indicator of
sexual satisfaction, ED may contribute to mental stress that effects
interactions with family and associates.
A comprehensive review of the pharmacology of various agents used in the
treatment of ED reveals a continuing emergence of knowledge about their
mechanism(s) of action and their clinical efficacy. Both systemic and
locally-active agents are available. Their site(s) of action may be peripheral
or central acting. Sometimes, a combination of agents is effective, but often
this is determined by the etiology of the ED. Significant insight has been
gained in the last decade with respect to the pharmacologic action of drugs used
in the treatment of ED.
Pharmacologic Options:
Viagra is available as an oral tablet ranging from 25 to 100 Mg. A
starting dose of 50 Mg taken about one hour prior to sexual intercourse has been
recommended. Viagra has been reported as a safe and efficacious treatment for
ED, however, it is ineffective in approximately 27 to 35% of the population and
has been associated with a variety of adverse effects including headache,
flushing, dyspepsia, and adverse interaction with nitrates and inhibitors of
cytochrome P450 enzymes. Viagra should not be taken in conjunction with nitrate
therapy.
While testosterone can enhance male sexual function, testosterone
therapy for the treatment of ED should be discouraged unless the etiology is
clearly related to low testosterone levels. Testosterone therapy in men with
normal levels may enhance sexual behavior, but is without significant effects
upon erectile function. Transdermal patches (e.g., Testoderm, Androderm)
and topical testosterone gel (e.g., Androgel) are commercially available.
Improvements following testosterone (transdermal) may require several months of
therapy. Transdermal delivery systems may provide better consistency in serum
testosterone than injections, but are perhaps more expensive. There is always
the chance of the patches falling off while showering or skin irritations, which
require removal of the patches.
Alprostadil binds with PGE receptors, and the resultant relaxation
response in the smooth muscle is mediated by cAMP. Little is known about the
pharmacokinetics of PGE1 but it is believed that as much as 80% may be
metabolized in one pass through the lungs. In all probability, this rapid
degradation by the lungs accounts for its lack of any significant cardiovascular
system side-effects when administered intracavernosally. It can also be
metabolized in the penis. Alprostadil has also been used in combination with
other agents, such as papaverine, and the combination was superior to only
alprostadil. Alprostadil is available as a transurethral system (Muse), a
topical cream with penetration enhancers, or intracavernosal injection. One
study showed that the injection is more efficacious. It is effective therapy
with tolerable side-effects.
Apomorphine, along with sildenafil, is one of the few orally active
pharmacological agents used in the treatment ED. Several studies have
demonstrated that apomorphine stimulates erection in humans. In particular,
apomorphine can induce penile erection in normal men, in men that are impotent,
and in alcoholics. Apomorphine has been used to treat ED In patients with
co-existing benign prostatic hyperplasia (BPH), with coronary artery disease,
and with hypertension. When formulated into a controlled release sublingual
tablet, it becomes a very effective orally active drug. Durable erections
without side-effects can be attained at a dose range of 3 to 4 mg.
Papaverine is particularly known as a smooth muscle relaxant and
vasodilator. Its principle pharmacological action is as a non-specific
vasdilator of the arterioles and capillaries. Papaverine dosages may range from
15 to 60 Mg. Major side-effects include priapism and corporeal fibrosis.
Intra-corporeal scarring may be related to the low pH which is necessary in
order to solubilize the drug. These side-effects are greatly reduced when
papaverine is used in very low dosages combined with phentolamine and
alprostadil.
Phentolamine may provoke a reflex, increasing sympathetic outflow and
release of norepinephrine. When phentolamine is used for the treatment of ED, it
is often used in combination with other agents (e.g. papaverine) to enhance its
efficacy. The combination of phentolamine and papaverine for the treatment of ED
has been studied extensively. This combination can be efficacious and may induce
erections sufficient for sexual intercourse in over 90% of cases. Phentolamine
has been used orally and intracavernosally. It has also been shown to be
effective buccally.
Forskolin As reported in the Journal of Urology, 1997 Nov;158(5):1752-8;
discussion 1758-9, the drug called forskolin, has demonstrated safety and
efficacy in patients with vasculogenic impotence resistant to standard 3-agent (phentolamine/papaverine/prostaglandin
E1) pharmacotherapy. Forskolin acts synergistically with prostaglandin E1 to
produce improvement in rigidity and/or erection duration with no adverse events.
If you would like more information in forskolin, please call and ask for Neil,
Scott or Tuan.
