Magazine Compares Viagra & Levitra
for Men who Fail Viagra?
4th Quarter, 2003--- Two new ED drugs, vardenafil
(Levitra, Bayer) and tadalafil
(Cialis, Lilly/ICOS), have completed extensive clinical testing,
and both drugs have gained FDA's approval. Both are inhibitors of type
5 phosphodiesterase (PDE-5), thus sharing the same basic mechanism of
Pfizer), which was approved in March, 1998. All three are taken
orally prior to planned sexual activity, acting to increase blood flow
in the penis in response to sexual stimulation. However, there are important
differences between the three, differences that could influence safety,
specificity, duration of action, and ultimately, public acceptance within
this class of drug.
Giles Brindley and Drug Therapy for ED
Modern drug therapy for ED was advanced enormously in 1983 when British
physiologist Giles Brindley, Ph.D. dropped his trousers and demonstrated
to a shocked AUA audience his phentolamine-induced erection. The drug
Brindley injected into his penis was a non-specific vasodilator, an
alpha-blocking agent, and the mechanism
of action was clearly corporal smooth muscle relaxation.
The effect that Brindley discovered, established the fundamentals for
the later development of specific,
safe, orally-effective drug therapies, ie, PDE-5 inhibitors.
Inhibition and Smooth Muscle Relaxation
Phosphodiesterase (PDE) is an enzyme that causes breakdown of cyclic
GMP, which is the direct intracellular mediator in the nitric oxide
(nonadrenergic, noncholinergic) pathway. Discovery
of this pathway led to a Nobel Prize in 1998 for the scientists responsible.
The nitric oxide system causes relaxation of smooth muscle in blood
vessel walls, ie, vasodilation, in various organ systems.
direct intracellular mediator of the nitric oxide pathway is cGMP. PDE
catalyzes the degradation of cGMP. This pathway is active in numerous
organ systems, and as of this writing, a number of different PDEs are
known. The various PDEs differ in their physiologic roles and tissue
distribution. Type 5 PDE is concentrated in the penile smooth
muscle of the corpus cavernosum, where its normal function is
to inhibit erection by degradation of cGMP, the mediator of erection.
Viagra and the new drugs Cialis and Levitra all inhibit PDE-5,
which is an inhibitor for corporal smooth muscle relaxation, resulting
in increased blood flow in the penis in response to sexual stimulation.
Comparison of Viagra, Cialis, & Levitra
No head-to-head trial comparing the 3 PDE inhibitors has been performed.
However, some differences between the 3 are basic: a table has been
created to illustrate the major differences. An obvious proviso is that
extensive data are available on Viagra (more than 20 million men treated,
more than 1100 peer-reviewed articles as of Feb. ’03), but only
limited data on Cialis and Levitra. Drs. Gresser and Gleiter from the
U. Tubingen in Germany have compared the three drugs via literature
review (Eur. J. Med. Res. 7:435, 2002)
In brief, efficacy is approximately 70% with all 3 drugs. The side effect
profile is similar among the 3 drugs, except that blue discoloration
of vision (overlap with PDE-6 in the retina) is seen only with Viagra
(<0.5%) and muscle aches only with Cialis (~5%). Otherwise, vasodilatory
side effects (headaches, nasal congestion, flushing) are common with
all, but are mild, and only rarely cause men to drop out of clinical
trials (2-3% quit rate). All 3 will carry a contra-indication in men
using organic nitrates. Otherwise, the long half-life of Cialis (17.5
hours) is noteworthy, earning this drug the nickname ‘weekender,’
as a single dose taken on Friday would still be exerting an effect Sunday
(or even Monday).
Alternative PDE-5 inhibitors Cialis and Levitra will soon be in competition
with Viagra, and the launch of these new drugs is certain to bring many
men with ED into doctors’ offices. Aside from the long half-life
of Cialis, and the excellent track record of Viagra, the differences
between the 3 drugs are not great. All appear to be effective and safe,
provided concomitant nitrates are avoided,. A potential for serious
hypotension exists should an organic nitrate be used along with any
of these three PDE-5 inhibitors.