A wide variety
of drugs have been used for the treatment of erectile dysfunction. Major
advances have been made in the understanding of the mechanism of drug actions
and of penile erection, and presently,
there seems to be a rational basis for the therapeutic classification of
currently used drugs. Such a useful classification was suggested by (Heaton et
al.,1997), in which ED treatment were divided into five major classes by
their mode of action:
1)
Central
initiators
Drugs that have
been associated with central initiation include apomorphine (Heaton et al,
1995), other dopamine agonists, serotonin agonists, oxytocinergic agonists, and
melanocyte-stimulating
hormone analogues (Wessells et al.,1997). They will
specifically treat failures of erectile initiation and should also reinforce
the peripheral neural signal to enhance adequate vasodilation.
Apomorphine (Uprima®), a dopaminergic
agonist, Apomorphine is a potent emetic that acts on central dopaminergic
(D1/D2) receptors. the side effect, notably nausea. Bremelanotide is a melanocortin analog that
acts centrally and Common side effects include flushing and nausea. ( DeBusk and
Drory 2000, and DeBusk et al., 2004
).
2)
Peripheral
initiators:
The drugs in the
class of peripheral initiators cause vasodilation through their actions in
vascular tissue. These vasoactive agents act directly on vascular smooth muscle
cells or indirectly, leading to the release of vasoactive agents from vascular
endothelial cells e.g. nitric oxide (Rajfer et al., 1992) and
prostacyclin (Furchgott and Zawadzki, 1980; Palmer et al, 1987). most
common forms of peripheral initiator treatment PGE1(Padma-Nathan, 1990),3-morpholinosydnonimine
(SIN- 1) (Stief et al., 1992), vasoactive intestinal polypeptide (VIP)
(Gerstenberg, 1992), calcitonin gene related peptide (CGRP) (Stief et al,
1991) and K-channel openers (Stief et al, 1991).
Oral
therapy PDE 5 inhibitors
(sildenafil, tadalafil, vardenafil) were found to help achieve and
maintain erections by (1) enhancing the effects of the neurotransmitter nitric
oxide (NO), and (2) maintaining higher levels of the enzyme cGMP, the two key
players in penile erection. They do that by selectively inhibiting cGMP –
specific phosphodiestrase type 5 (PDE5), leading to elevated cGMP levels. This,
in turn, increases blood flow to the genitals and leads to stronger erections
and intensified sensation. Side effect include: Include facial flushing,
headaches, and indigestion, dyspepsia nasal congestion, visual disturbance,
colour sensitivity (Brock et al., 2002), (Goldstein et al., 1998, Langtry and
Markham, 1999 and Hellstrom et al., 2002).
3)
Central
conditioners:
Testosterone is
the best example of a drug that may act as a CNS conditioner (Morales et al,
1994). Drugs in this class enable or enhance erectile function centrally and may
overlap with drugs that affect libido and orgasm.
4)
Peripheral
conditioners
These agents
increase the activity of peripheral systems that support or cause erections and
are currently being developed aggressively. There are various pharmacological strategies
that can be used to increase the effect of a normal proerectile system: a
proerectile pathway can be enhanced (decreasing neurotransmitter or messenger
inactivation, increasing sensitivity, etc.), or a balancing or erectolytic
pathway can be attenuated. Phosphodiesterase inhibitors (Virag et al.,
1996) slow the degradation of the active cyclic nucleotide, causing activity to
be prolonged.
Sympatholytic
agents reduce general vasoconstrictive alpha- adrenergic activity (Porst et
al., 1996). Peripheral conditioners slow activity where there is an initiated
erection. They are difficult to standardize from the point of view of
assessment because the total response will depend on both the stimulus and the
agent. The stimulus is difficult to standardize, and study design is critically
important.
Other oral drugs used include, Oral phentolamine (Vasomax®)
has been reported to improve erection. Side effects of the medication include
headache, facial flushing, and nasal congestion.
5)
Others:
Some of the
treatment available for erectile dysfunction include the use of
1) Drugs such as sildenafil citrate (Viagra®), vardenafil citrate
(Levitra®), tadalafil citrate (Cialis®).
2) Hormone replacement therapy
3) Penile implants for the treatment of erectile dysfunction and (Brock et
al., 2002).
i) Withdrawal of Offending Medications
Drugs used as Antihypertensive, cardiovascular
disease, anxiety, depression or psychosis are implicated in causing erectile
dysfunction. Antihypertensive patients placed on drugs, such as thiazide
diuretics and beta blockers, who present with a complain of erectile
dysfunction perhaps can be switched to alternative drugs, such as
angiotensin-converting enzyme inhibitors or calcium channel blockers (e.g.,
diltiazem, nifedipine, amlodipine), which may cause less of a problem (American
Association of Clinical Endocrinologists —2003).
ii) Vacuum
Constriction Device
Vacuum constriction device (VCD), trans-urethral
suppositories alprostadil (MUSE®) and
intra-cavernous injection (ICI) (Caverject®, Edex®, or Mixtures) therapy including papaverine, phentolamine,
VIP (vasoactive intestinal polypeptide), and ketanserin. The erection is
attained via vacuum suctioning of blood that is trapped in the penis with a
constriction device. Its side effects include petechiae, numbness and a trapped
ejaculate (Montague et al., 1996).
iv) Vascular
Surgery
Penile prosthesis
surgery was described in the early 1930s. The superficially placed rigid
prosthesis made from synthetic material soon followed. It was not until the
early seventies that satisfactory results were seen with the introduction of
modern prosthetic devices which fit into the corpora cavernosa and provided
both good functional as well as cosmetic results (Pharmacy
Benefits Management-Medical Advisory Panel, 1999).
Penile arterial bypass
surgery was first reported in the early seventies as a treatment for erectile
dysfunction with many variations in technique existing in the literature.
Finally, venous leak surgery was re-introduced in the early eighties to treat
corporal veno-occlusive dysfunction. To this day, prosthesis surgery is
considered the standard surgical treatment of erectile dysfunction except in a
judiciously selected group of patients, which can be offered curative vascular
surgical repair, Young patients with congenital or traumatically acquired ED
may be candidates for curative surgical therapy (arterial bypass or venous
surgery). Patients with generalized penile disease should be offered prosthesis
surgery. Indications for prosthesis surgery include: patients with a poor
response to non-surgical therapies (Pharmacy Benefits Management-Medical
Advisory Panel,
1999).
V) Natural and herbal products
Yohimbine is an alpha 2-adrenergic receptor antagonist produced from the bark of the yohimbe tree. Its Frequent side effects include palpitation, fine tremor, elevation of blood pressure, and anxiety (Carey and Johnson, 1996).
· Maca
maca (Lepidium meyenii) has aphrodisiac and fertility-enhancing properties. Maca is also used for increasing energy, stamina, and athletic performance. Maca has effects on impotence as well. improvement in sexual desire (Gonzales et al., 2002), increase in seminal volume, sperm counts, motile sperm numbers, and sperm motility (Gonzales et al., 2001). This herb has shown definitive effects on male sexual function, as a libido-enhancing agent, and as an enhancer of spermatozoa related fertility functions. Just as importantly, its beneficial effects do not appear to be mediated via hormonal manipulation.
maca (Lepidium meyenii) has aphrodisiac and fertility-enhancing properties. Maca is also used for increasing energy, stamina, and athletic performance. Maca has effects on impotence as well. improvement in sexual desire (Gonzales et al., 2002), increase in seminal volume, sperm counts, motile sperm numbers, and sperm motility (Gonzales et al., 2001). This herb has shown definitive effects on male sexual function, as a libido-enhancing agent, and as an enhancer of spermatozoa related fertility functions. Just as importantly, its beneficial effects do not appear to be mediated via hormonal manipulation.
· Ginseng
Ginseng (Panax ginseng) is well-known for its energy enhancing effects; it appears to have some impact on sexual function as well. A group of patients treated with an extract of ginseng had increased numbers of sperm and improved motility. Ginseng increase in total and free testosterone, dihydrotestosterone, LH, and FSH, while prolactin was decreased. The active constituents in ginseng (ginsenosides) are known to have effects on the hypothalamic-pituitary-adrenal axis (Salvalti et al., 1996). Ginseng enhances libido and sexual performance, these effects of ginseng may not be due to changes in hormone secretion, but to direct effects of ginseng, or its ginsenoside components, on the central nervous system and gonadal tissues. Indeed, there is good evidence that ginsenosides can facilitate penile erection by directly inducing the vasodilatation and relaxation of penile corpus cavernosum. Moreover, the effects of ginseng on the corpus cavernosum appear to be mediated by the release and/or modification of release of nitric oxide from endothelial cells and perivascular nerves. Ginseng has also been found to affect the central nervous system, significantly altering the activity of hypothalamic catecholamines involved in sexual behavior and hormone secretion. Recent findings that ginseng treatment decreased prolactin secretion also suggest a direct nitric oxide-mediated effect of ginseng on the pituitary. Additional studies lend growing support for the use of ginseng in the treatment of sexual dysfunction and provide increasing evidence for a role of nitric oxide in the mechanism of ginsenoside action (Duke and James, 1985).
Ginseng (Panax ginseng) is well-known for its energy enhancing effects; it appears to have some impact on sexual function as well. A group of patients treated with an extract of ginseng had increased numbers of sperm and improved motility. Ginseng increase in total and free testosterone, dihydrotestosterone, LH, and FSH, while prolactin was decreased. The active constituents in ginseng (ginsenosides) are known to have effects on the hypothalamic-pituitary-adrenal axis (Salvalti et al., 1996). Ginseng enhances libido and sexual performance, these effects of ginseng may not be due to changes in hormone secretion, but to direct effects of ginseng, or its ginsenoside components, on the central nervous system and gonadal tissues. Indeed, there is good evidence that ginsenosides can facilitate penile erection by directly inducing the vasodilatation and relaxation of penile corpus cavernosum. Moreover, the effects of ginseng on the corpus cavernosum appear to be mediated by the release and/or modification of release of nitric oxide from endothelial cells and perivascular nerves. Ginseng has also been found to affect the central nervous system, significantly altering the activity of hypothalamic catecholamines involved in sexual behavior and hormone secretion. Recent findings that ginseng treatment decreased prolactin secretion also suggest a direct nitric oxide-mediated effect of ginseng on the pituitary. Additional studies lend growing support for the use of ginseng in the treatment of sexual dysfunction and provide increasing evidence for a role of nitric oxide in the mechanism of ginsenoside action (Duke and James, 1985).
· Pygeum
Pygeum (Pygeum africanum) seems to have an effect on male fertility as a result of this herb’s effects on prostatic secretions. An important part of the ejaculate, these secretions are designed to assist spermatic survival outside of the body. Sperm motility is affected by the pH of prostatic fluid and some studies have demonstrated a beneficial effect of pygeum on prostatic fluid pH.(Clavert et al.,1986) (Lucchetta et al.,1984). In addition to this effect, pygeum has been shown to be useful for treating prostatitis and sexual disturbance, improve urinary parameters and sexual activity (Carnini,1999) .
· Others
Zinc, selenium, glutathione, vitamin E and vitamin C, have also been reported to have beneficial antioxidant effect (Agarwal, 2002).
Pygeum (Pygeum africanum) seems to have an effect on male fertility as a result of this herb’s effects on prostatic secretions. An important part of the ejaculate, these secretions are designed to assist spermatic survival outside of the body. Sperm motility is affected by the pH of prostatic fluid and some studies have demonstrated a beneficial effect of pygeum on prostatic fluid pH.(Clavert et al.,1986) (Lucchetta et al.,1984). In addition to this effect, pygeum has been shown to be useful for treating prostatitis and sexual disturbance, improve urinary parameters and sexual activity (Carnini,1999) .
· Others
Zinc, selenium, glutathione, vitamin E and vitamin C, have also been reported to have beneficial antioxidant effect (Agarwal, 2002).