Alprostadil should not be used in men with urethral stricture (scarring and narrowing of the tube that urine and the ejaculate pass through), balanitis (inflammation/infection of the glans [tip] of the penis, severe hypospadias (a condition where the opening of the urethra is not at the tip of the penis, rather on the underside of the penis), penile curvature (abnormal bend to the penis), and urethritis (inflammation/infection of the urethra).
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.

When sexually stimulated there is a release of a chemical, nitric oxide (NO) in the blood vessels of the corpus cavernosum. The NO stimulates the production of a compound called cGMP, which causes relaxation of the smooth muscle in the blood vessels supplying the corpus cavernosum. PDE 5 is an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP by PDE5, these medications allow cGMP to build up in the penis. cGMP causes muscles in the corpora cavernosa of the penis to relax. When the muscle is relaxed, more blood can flow into the penis and fill the spaces in the penis. As the penis fills with blood, the veins in the penis are compressed, and this results a hard erection. When the effect on PDE5 decreases, the cGMP levels go down and the muscle in the penis contracts, causing less blood to flow into the penis and allowing the veins to open up and drain blood out of the penis.
ED usually has a multifactorial etiology. Organic, physiologic, endocrine, and psychogenic factors are involved in the ability to obtain and maintain erections. In general, ED is divided into 2 broad categories, organic and psychogenic. Although most ED was once attributed to psychological factors, pure psychogenic ED is in fact uncommon; however, many men with organic etiologies may also have an associated psychogenic component.
In some cases, ED can be a warning sign of more serious disease. One study suggests ED is a strong predictor of heart attack, stroke, and death from cardiovascular disease. The researchers say all men diagnosed with ED should be evaluated for cardiovascular disease. This does not mean every man with ED will develop heart disease, or that every man with heart disease has ED, but patients should be aware of the link.
Patients with both ED and cardiovascular disease who receive treatment with an oral PDE5 inhibitor require education regarding what to do if anginal episodes develop while the drug is in their system. Such education includes stressing the importance of alerting emergency care providers to the presence of the drug so that nitrate treatment is avoided.

One must be very careful using both PDE5 inhibitors and medications commonly used to treat an enlarged prostate, alpha-blockers (for example, tamsulosin [Flomax], terazosin [Hytrin]). It is recommended that one be on a stable dose of the alpha-blocker prior to starting a PDE5 inhibitor and that one start on a low dose of the PDE5 inhibitor and increase as tolerated and needed to treat the erectile dysfunction. Similarly, if you are on a PDE5 inhibitor and your doctor recommends that you start an alpha-blocker for your prostate, you should start at a low dose and increase as tolerated and needed to treat your prostate symptoms.
The association between low testosterone and ED is not entirely clear. Although these 2 processes certainly overlap in some instances, they are distinct entities. Some 2-21% of men have both hypogonadism and ED; however, it is unclear to what degree treating the former will improve erectile function. [17] About 35-40% of men with low testosterone see an improvement in their erections with testosterone replacement; however, almost 65% of these men see no improvement. [15]
One must be very careful using both PDE5 inhibitors and medications commonly used to treat an enlarged prostate, alpha-blockers (for example, tamsulosin [Flomax], terazosin [Hytrin]). It is recommended that one be on a stable dose of the alpha-blocker prior to starting a PDE5 inhibitor and that one start on a low dose of the PDE5 inhibitor and increase as tolerated and needed to treat the erectile dysfunction. Similarly, if you are on a PDE5 inhibitor and your doctor recommends that you start an alpha-blocker for your prostate, you should start at a low dose and increase as tolerated and needed to treat your prostate symptoms.
The first step in treating the patient with ED is to take a thorough sexual, medical, and psychosocial history. Questionnaires are available to assist clinicians in obtaining important patient data. (See Presentation.) Successful treatment of sexual dysfunction has been demonstrated to improve sexual intimacy and satisfaction, improve sexual aspects of quality of life, improve overall quality of life, and relieve symptoms of depression. (See Treatment.)
Much of the emphasis on erectile pathophysiology has been placed on penile smooth muscle function and cavernosal hemodynamics. The neuroanatomy and neurophysiology of erection can be characterized but its full extent is poorly understood. Neurologic disease does not always reproducibly affect erections in a uniform manner compared to other types of sexual dysfunction (SD). This offers many obstacles to understanding the role the nervous systems plays in SD and consequently obscures what treatment options readily optimize erections specific to the neurologic insult.
Is your erectile dysfunction due to psychological (stress, relationship problems, etc.) or physical factors? Your doctor may ask if you note erections at night or in the early morning. Men have involuntary erections in the early morning and during REM sleep (a stage in the sleep cycle with rapid eye movements). Men with psychogenic erectile dysfunction (erectile dysfunction due to psychological factors such as stress and anxiety rather than physical factors) usually maintain these involuntary erections. Men with physical causes of erectile dysfunction (for example, atherosclerosis, smoking, and diabetes) usually do not have these involuntary erections. Men with psychogenic erectile dysfunction may relate the onset of problems to a "stressor," such as failed relationship. Your doctor may suggest a test to determine if you have erections during sleep, which may suggest that there may be a psychological cause of the erectile dysfunction.
PDE 5 inhibitors are broken down primarily by enzyme, cytochrome P450enzyme CYP3A4. Medications that decrease or increase the activity of CYP3A4 may affect levels and effectiveness of PDE 5 inhibitors. Such drugs include medications for the treatment of HIV (protease inhibitors) and the antifungal medications ketoconazole and itraconazole. Thus caution is recommended.
Their treatment plan will include a great deal of information about ED. It is important you take the time to read it all. You will be better prepared to manage your condition as a partner—and not just a patient. Also, erectile dysfunction is often a symptom of a more serious underlying condition—like heart disease, diabetes, high blood pressure, or even depression. That’s why we want you to learn as much as you can. Nothing would be a sign of our success more so then if you could resolve the condition that causes your ED instead of needing to use the medications your doctor prescribes. We strongly recommend optional laboratory tests. You do not need to get them to receive treatment but it can be one of the best things you can do for your health in the long run.

Patients with both ED and cardiovascular disease who receive treatment with an oral PDE5 inhibitor require education regarding what to do if anginal episodes develop while the drug is in their system. Such education includes stressing the importance of alerting emergency care providers to the presence of the drug so that nitrate treatment is avoided.
The physical examination can reveal clues for physical causes of erectile dysfunction. A doctor will perform an assessment of BMI and waist circumference to evaluate for abdominal obesity. A genital examination is part of the evaluation of erectile dysfunction. The examination will focus on the penis and testes. The doctor will ask you about penile curvature and will examine the penis to see if there are any plaques (hard areas) palpable. The doctor will examine the testes to make sure they are in the proper location in the scrotum and are normal in size. Small testicles, lack of facial hair, and enlarged breasts (gynecomastia) can point to hormonal problems such as hypogonadism with low testosterone levels. A health care provider may check pulses in your groin and feet to determine if there is a suggestion of hardening of the arteries that could also affect the arteries to the penis.
In the Massachusetts Male Aging Study (MMAS) among a community-based survey of men aged 40-70 years, 52% of the men reported some degree of erectile difficulty. Complete ED, defined as the total inability to obtain or maintain suitable erections during sexual stimulation, as well as the absence of nocturnal erections (normal erections [four to six/night], which occur during sleep), occurred in 10% of the men in the study. Lesser degrees of mild and moderate ED occurred in 17% and 25% of participants.
Sildenafil has been previously suggested as a treatment option for ED in men with epilepsy (77,78). However, Matos et al. warned that PDE5i are potentially pro-convulsant and should be used with great caution in men with epilepsy (79). Animal studies in rat and mice overwhelmingly suggest PDE5i can reduce seizure threshold. In human trials, seizures were rare but reported. PDE5i exerted their proconvulsive effect by lower seizure threshold possibly by worsening sleep or obstructive sleep apnea, causing cardiovascular changes, or leading to EEG changes specifically with tadalafil use.
Because impotence can be due to health problems that can affect the whole body, and because it can interfere with one’s quality of life, it is important to talk with your doctor if you have trouble attaining or maintaining an erection. With increasing discussion of impotence in the media, coupled with advances in treatment, men are now much more comfortable talking with their doctors about impotence. It is currently estimated that between 15 and 30 million men in the United States are affected by impotence (Source: NIDDK).
The first line and by far the most common treatment today is with the prescription drug sildenafil citrate, sold under the brand name Viagra. An estimated 20 million prescriptions for the pill have been filled since it was approved by the FDA in March 1998. It is also the most effective treatment with a success rate of more than 60%. The drug boosts levels of a substance called cyclic GMP, which is responsible for widening the blood vessels of the penis. In clinical studies, Viagra produced headaches in 16% of men who took it, and other side effects included flushing, indigestion, and stuffy nose.
ED occurs in up to 70% of men with MS, and MS is one of the most prevalent neurological disorders that affect the younger adult population worldwide (33-35). The mean time for SD and ED to develop is about 9 years and is rarely a presenting symptom of MS (36). Men with MS and ED may continue to have nocturnal erections, and psychogenic erections; however, this does not mean they have psychogenic ED but could be an indicator that MS involves the spinal cord (37).
Depression and anxiety: Psychological factors may be responsible for erectile dysfunction. These factors include stress, anxiety, guilt, depression, widower syndrome, low self-esteem, posttraumatic stress disorder, and fear of sexual failure (performance anxiety). It is also worth noting that many medications used for treatment of depression and other psychiatric disorders may cause erectile dysfunction or ejaculatory problems.
High cholesterol and triglyceride levels increase the risk of cardiovascular disease. Getting your cholesterol and triglyceride levels in an optimal range will help protect your heart and blood vessels. Cholesterol management may include lifestyle interventions (diet and exercise) as well as medications to get your total cholesterol, LDL, HDL, and triglycerides in an optimal range.
The most common inflatable prosthesis is the three-piece penile prosthesis. It is composed of a pair of cylinders that are surgically placed into the corpora cavernosa, a reservoir containing sterile fluid that is placed in the abdomen and a pump that is placed in the scrotum. Tubing connects the cylinders, reservoir, and the cylinders. By pressing the pump several times, fluid is transferred from the reservoir into the cylinders. As the cylinders fill with fluid, they increase in width and this causes the erection. When one is finished with sexual activity, pressing the release valve on the pump allows the fluid to drain out of the cylinders back into the reservoir. Given the mechanical nature of the three-piece prosthesis, it has a greater risk of mechanical malfunction; however, modifications have been made such as lock out valves to prevent the prosthesis from automatically inflating as well as improving the tubing to prevent tubing leaks.

When stimulated by the nerves, the spongy tissue arranges itself in such a way that more blood can be stored in the penis. The veins running through the outer sheath of the penis then compress which stops the blood from leaving the penis. As the blood is stopped from flowing out, the penis fills with blood and stretches within the outer casing, giving an erection.

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