Vacuum Constriction Device: A New Paradigm for Treatment of ED in Australia

In 1996, the American Urological Association began to recommend the vacuum constriction device (VCD) as an alternative to the treatment of erectile dysfunction (ED). Since then, millions of Americans have benefitted from the device. It remains well-accepted and popular among patients due to its efficacy, noninvasiveness, ease of administration, and affordability. Nearly all patients, including those with hematological disorders, experience some degree of erection with the device. The process of applying negative pressure to passively fill the corpus cavernosum via arterial and venous sources remains the basis of mechanism since its conception in 1874. With the advent of oral pharmacotherapy for the treatment of ED, for example Viagra in Australia  , its usage and availability have decreased tremendously. However, its application is being expanded into new realms. Penile rehabilitation following prostatectomy is a perfect example. Despite increasing success of surgical and medical therapy for ED, the demand for a noninvasive, effective, safe, drug-free, and cost-effective treatment persists. This chapter presents the development of VCD, its mechanism of action, indications, safety profile, efficacy, and future directions.

Introduction

In 1996, the American Urological Association began to recommend the vacuum constriction device (VCD) as an alternative to the treatment of erectile dysfunction, also ED can be treated with generic Viagra in Australia (ED). Since then, millions of Americans have benefitted from the device. It remains well-accepted and popular among patients due to its efficacy, noninvasiveness, ease of administration, and affordability. Nearly all patients, including those with hematological disorders, experience some degree of erection with the device. The process of applying negative pressure to passively fill the corpus cavernosum via arterial and venous sources remains the basis of mechanism since its conception in 1874. With the advent of oral pharmacotherapy for the treatment of ED, its usage and availability have decreased tremendously. However, its application is being expanded into new realms. Penile rehabilitation following prostatectomy is a perfect example. Despite increasing the success of surgical and medical therapy for ED, the demand for a noninvasive, effective, safe, drug-free, and cost effective treatment persists. This chapter presents the development of VCD, its mechanism of action, indications, safety profile, efficacy, and future directions.

Self-Injection, Transurethral Therapy in Erectile Dysfunction Part 2

PGE1 (Alprostadil)

Alprostadil acts via multiple pathways to cause cavernosal vascular smooth muscle relaxation and thus erection. The best characterized of these pathways is via increase in cAMP, which results in increased activity of cAMP dependent kinases, thus decreased cytoplasmic Ca2+, and relaxation of smooth muscle. Other less well character-ized pathways including cAMP mediated increases in cGMP and the indirect blockade of adrenergic and angiotensin II signaling by PGE1, are also likely to play a role.

Prostaglandin E1 is now the preferred inject-able agent and only transurethral erectile agent. Trade names for the injectable form are Caverject™ (Pfizer Inc.) and Edex/Viridal™ (Schwarz Pharma). Generic injectable alprostadil is also available and typically is more cost effective, but does not include sophisticated delivery systems as described below. MUSE ™(Medicated Urethral System for Erection, Vivus Inc.) is currently the only transurethral erectile agent approved by the FDA. Typical doses are 10–20 mg for injectable alprostadil and 250–1,000 mg for MUSE™ alprostadil.

Response rates to alprostadil alone are high. In his 1996 metaanalysis, Porst reported a 70% rate of erection sufficient for intercourse with alprostadil injection alone in greater than 10,000 patients. This included 4,500 patients from his own series and more than 5,000 from a literature review. A later publication by Porst reported on 162 patients using alprostadil ICI, 58 of which were followed for 4 years for a total of 16,886 injections. Success rates were greater than 90% in each year of the study.

Perhaps more important than generalized efficacy is efficacy in PDE5I non-responders. Shabsigh et al. reported on 67 patients with no response to PDE5Is. Of these, 59 (88%) reported achieving erections suitable for intercourse using ICI.

Nagai et al. reported a similar study which tested the efficacy of intracavernous alprostadil on 64 patients who failed PDE5I therapy. Ninety-one percent of these patients achieved erections suitable for intercourse with ICI alprostadil therapy.

Interestingly, the converse is also sometimes true and approximately a third of patients who do not respond to intracavernous therapy respond to PDE5Is. McMahon et al. challenged 93 men who previously failed ICI with ED with oral sildenafil, 50 mg, escalating to 100 mg if the low dose was unsuccessful and found that 34% achieved erections suitable for intercourse. Thirty of these 32 required the 100 mg dose of sildenafil.

Administration

Caverject™ comes in two forms, a vial containing powdered alprostadil and a prefilled dialable syringe (Caverject™ Impulse). The first type comes in doses of 5 mg, 10 mg, and 20 mg and requires premixing with a diluent, which is either bacteriostatic water or simply sterile water. The penis is grasped by the glans and stretched against one thigh. The site is cleaned with an alcohol swab and the solution is injected into the corpus cavernosum. Care is taken to avoid the neurovascular structures on the dorsum of the penis and the corpus spongiosum on the ventral side of the penis. Pressure should be applied to the injection site for 5 min to prevent hematoma formation. The patient is instructed to alternate sites.

Caverject™ Impulse is available in two strengths 10 mg and 20 mg. Administration is similar except that both the diluent and the drug are present in the same syringe, and mixing is accomplished by turning the plunger rod. The patient’s dose is then dialed in on the syringe and the drug is injected in the same fashion as the original drug.

Edex™ is a system somewhat similar to Caverject™ Impulse. It consists of a reusable injection device with single use and dual chambered medication cartridges.

The cartridge is inserted into the injection device and the plunger is depressed to add the diluent to the medication. The medication is then swirled into the diluent and injected into the penis as per the above directions for Caverject™.

Generic alprostadil is available in powdered vials which require mixing with diluent and are administered as per the directions for Caverject™. Premixed generic alprostadil can also be obtained from specialized pharmacies. Recommended needle size is ½ in., 27–30 gauge.

Side Effects

Penile pain is the most significant side effect of alprostadil. In his 1996 literature review, Porst describes the experience of 2,745 patients over ten publications. He notes that the rate of penile pain with ICI alprostadil is 7.2%. Higher rates of pain are noted by the European Alprostadil Study Group. They noted that 44% of their 848 patients experienced penile pain, but this was described as mild in over half of those patients and only 3% discontinued because of pain. Smaller studies note intermedi-ate outcomes. Priapism and fibrosis occurred at low rates of 0.36% and 0.8%. The European Alprostadil Study Group notes 0.9% and 4% rates for those same phenomena.

Self-Injection, Transurethral Therapy in Erectile Dysfunction Part 1

Abstract Currently there are three main agents for intracavernosal injection (ICI) therapy and one agent for intraurethral therapy approved by the FDA for the treatment of erectile dysfunction (ED). These effective agents were the focus of intense interest in the mid1990s, but were quickly relegated to second line therapy after the appearance of sildenafil. Indeed, while sildenafil prescriptions nearly doubled to 14 million from 1998 to 2001, prescriptions for alprostadil injections dropped by one third to 159,000 and MUSE™ prescriptions fell by two thirds to 132,000. It must be noted, however, that the phosphodiesterase-5 inhibitors (PDE5Is) are ineffective in about 22–35% of. Furthermore, of the men treated with oral agents, a significant proportion will ultimately fail (even after PDE5I dose escalation) secondary to progression of their disease. Additionally, there are a significant number of men with contraindications to PDE5Is. The result is a large number of men who are unable to utilize oral treatments for erectile dysfunction. Fortunately, second line therapies in the form of vacuum erection devices (discussed in detail in a separate chapter), ICI and MUSE™ are highly effective treatments that may be used when PDE5Is are contraindicated.

Introduction and Viagra sildenafil Australia

Currently there are three main agents for intracavernosal injection (ICI) therapy and one agent for intraurethral therapy approved by the FDA for the treatment of erectile dysfunction (ED). These effective agents were the focus of intense interest in the mid1990s, but were quickly relegated to second line therapy after the appearance of sildenafil. Indeed, while sildenafil prescriptions nearly doubled to 14 million from 1998 to 2001, prescriptions for alprostadil injections dropped by one third to 159,000 and MUSE™ prescriptions fell by two thirds to 132,000. It must be noted, however, that the phosphodiesterase-5 inhibitors (PDE5Is) are ineffective in about 22–35% of men. Furthermore, of the men treated with oral agents, a significant proportion will ultimately fail (even after PDE5I dose escalation) secondary to progression of their disease. Additionally, there are a significant number of men with contraindications to PDE5Is. The result is a large number of men who are unable to utilize oral treatments for erectile dysfunction. Fortunately, second line therapies in the form of vacuum erection devices (discussed in detail in a separate chapter), ICI and MUSE™ are highly effective treatments that may be used when PDE5Is are contraindicated. Interestingly, there is also a significant subset of men who prefer intracavernous injection to PDE5I therapy, even when both are effective. Hatzichristou et al. tested the efficacy of sildenafil in 155 men who were using intracavernous injections and obtaining successful results. Seventy-five percent  of those men achieved erections sufficient for intercourse. Of those 116 men in whom both treatments were successful, 33% (38 men) chose to continue intracavernous injection therapy instead of switching to oral medications. In short, despite being overshadowed by the mass marketing and convenience of administration of PDE5Is, knowledge and utilization of ICI and MUSE™ remain critical in the approach to treatment of erectile dysfunction.