Penegra 50 mg online

Apomorphine

can

However, studies have shows a lower efficacy for apomorphine compared to oral sildenafil (81,82).

Apomorphine has a set role in the management of PD for non-motor symptoms, and has been reported to cause spontaneous erections and possible hypersexuality in PD men (83,84).

Its role in the management of ED has been postulated for men with PD but should be considered as an alternative to sildenafil.

Intracavernosal injections (ICI) Intracavenosal therapy involves injection of a vasoactive agent into the corpora cavernosa to effect smooth muscle relaxation and tumescence.

In 1983, Brindley injected the corpora of several SCI men with phentolamine (85). Two out of the three men had a sufficient erection produced. Since then multiple reports on the efficacy of intracavernosal therapy have been published using, phentolamine, papaverine, prostaglandin, vasoactive intestinal peptide (VIP), and these medications in combination (86-90). These medications have been found to be extremely effective for neurogenic ED due to their ability act locally and essentially bypassing neuronal pathways.

Local therapies are usually considered second-line after PDE5i fail to elicit a desired response which can occur in about 25–30% of men with ED, in general (91).

Furthermore, the locally delivered medications can be quite dangerous if not used appropriately as priapism and significant pain with injections can occur. These specific occurrences have been suggested as a reason for high discontinuation rates with intracavernosal therapy (92).

Papaverine is an opium alkaloid that acts as a non-specific PDEi that increases intracellular cAMP and cGMP leading corporal smooth muscle relaxation (93).

Intracavernosal papaverine injection was the first clinically effective pharmacological therapy for ED and led to a full erection in at least half of the patient in early studies (94,95). Alprostadil is a potent vasodilator and smooth muscle relaxant identical to the naturally occurring PGE1.

PGE1 binds with specific receptors on smooth muscle cells and activates intracellular adenylate cyclase to produce cAMP, which in turn induces tissue relaxation through a second messenger system (96).

PGE1 is the only FDA approved form of intracavernosal therapy and is available commercailly as EDEX, or Caverject.

Its efficacy was demonstrated in several clinical trials where the rate of responders ranged from 40% to 80% (97,98). The

most

Common associated adverse effects were facial flushing and headache. VIP in combination with phentolamine is currently being used in the UK and Europe and is seeking regulatory approval for use in the United States.

Phentolamine blocks post synaptic adrenergic ?1 receptors preventing smooth

muscle

Consequently, this may be a reason phentolamine is not prescribed as monotherapy, and frequently is combined with papaverine, alprostadil or VIP.

Multiple combinations of intracavernosal therapy exist and the effectiveness of them varies based on patient characteristics and varying dosing strength ( Table 1 ). Combination therapy have been extremely effective in the SCI population, and have several advantages including a reduction in cost per dose and side effects base on the lowered dose of each component (101,102).

Effectiveness of combination therapy in the spinal cord population is well established, but no specific dose recommendations can be made based on the data (103-106). The use of combination therapy on other forms of neurogenic ED have not been well studied, but there use can be trialed as second-line therapy, or for populations were the side effects of PDE5i may preclude use such as in MSA due to hypotension. Alprostadil may be delivered via the urethra in the form of a pellet (MUSE) (107). This form of therapy has been trialed in SCI men with intermediate success (108).

Bodner trialed MUSE dose escalation in SCI men and found 1,000 ?g to be the most effective dose.

Several men had hypotension when a constriction ring was not used in conjunction with the MUSE therapy. Vacuum erection devices (VED) VED involved placing the penis in a clear plastic tube where negative pressure created by the vacuum pump leads to penile engorgement and tumescence. Usually a constriction ring can be placed on the base of penis following penile engorgement. Some men complain of bruising, a “cold” penis penegra 50 mg online and pain associated with the constriction ring; however, in some men with NED sensation may not be intact mitigating the side effects of VEDs.

VEDs have reported effectiveness up to 90% in certain ED populations and it remains a non-invasive means to achieve and erection.

(109) compared VEDs with papaverine injections in 18 males with SCI. The injections and pumps were equally effective in inducing erections and no adverse effects from the treatments were reported.

Treatment arms were crossed over, subsequently seven men chose the VED and seven men chose the papavarine highlighting equal efficacy in this population. In another treatment arm topical minoxidil was applied without any effective erections achieved by the study subjects.

VEDs in general penegra 50 mg online have great success in the neurogenic population.

Limitations that may affect use are limited manual dexterity, cost due to non-insurance coverage, lack of spontaneity, artificiality of erection, obesity/buried penis, and anticoagulant use.

Prior to the introduction of PDE5i in 1998, intracavernosal vasoactive medications and penile implant surgery were the mainstays of treatment.

Penile implant surgery involves placement of inflatable or malleable rods within the corpora cavernosa to provide rigidity for intercourse.

Choice of which implant to place usually depends upon manual dexterity and function of the patient, patient anatomy, physician preference and surgical approach.

performed penile implant surgery in 245 men with neurolgic impairment caused by spinal cord injury, CNS neoplasm, CNS infection, MS and SB (110). Mean follow-up time of 7.2 years was achieved in 195 patients, 50 patients were excluded for lost to follow-up or death from nonurological causes.

Interestingly, 135 patients underwent penile implantation to assist with management of urinary incontinence and improve ability for condom/intermittent catheterization. Ninety-two patients patient underwent implantation for ED.

Eighty two percent of patients were satisfied with implantation for ED, and 67% of partners were satisfied.

Complications included infection (5%), perforation (0–18%), and technical dysfunction (7–33%).

Perforation rates were high with the malleable device when it was placed through a subcoronal incision.

After adopting an infrapubic approach the perforation rates dropped substantially.

Since the advent of PDE5i, many other selective and non-selective peripheral acting compounds have been developed or are in development. Avanafil has shown promising results in treating ED in post-prostatectomy patients with suspected cavernous nerve injury (111). Other PDE5i marked in Asia such as udenafil, and mirodenafil also effective at treating ED may minimize side effects due to shorter half-lives (112-114). Soluable guanylate-cyclase inhibitors and potassium channel activators are compounds that have induced erections in animal models but remain experimental requiring further investigation (115-117).

Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties.

Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization (118).

It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine (32,119).

Melanocortin receptor agonists were found to induce erections serendipitously.