If PDE5 drugs don't work or cannot be used because of potential side effects, your doctor can recommend other therapies. The drug alprostadil (Caverject, Edex, Muse) allows blood to flow more freely in the penis, leading to an erection. The drug can be injected with a tiny needle into your penis. Or, a small pellet (suppository) can be inserted into the opening of the penis. Suppositories and injections are effective in the majority of men.

Erectile dysfunction is defined as the persistent inability to achieve or maintain penile erection sufficient for satisfactory sexual performance. The Massachusetts Male Aging Study surveyed 1,709 men aged 40–70 years between 1987 and 1989 and found there was a total prevalence of erectile dysfunction of 52 percent. It was estimated that, in 1995, over 152 million men worldwide experienced ED. For 2025, the prevalence of ED is predicted to be approximately 322 million worldwide.

If PDE-5 inhibitors are not suitable or don’t work, other therapies include injections into the base of the penis, which cause flow of blood into the penis and a fairly immediate erection that lasts around an hour. The drugs injected are alprostadil (Caverject and Erectile dysfunctionex) and Invicorp (VIP and phentolamine). Alprostadil may also be inserted as a gel into the opening of the penis. This is not suitable if your partner is pregnant.
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.
In patients who either fail to respond to first or second-line therapy, or are not interested in the conservative therapies, penile prosthesis implantation is available. Malleable and rigid implants were available for many years, but in 1973 the world of penile prosthetics took a giant leap forward with the advent of the inflatable penile implant. Most implants done nowadays are of the inflatable variety. Adverse events including malfunction and infection are rare, and patient satisfaction is very high.45
In addition, when research has shown a nutrient such as zinc or niacin to improve sexual function, it's usually in people who are deficient in it. So, before you stock up on over-the-counter nutritional supplements for ED, speak with your doctor. He can test you for deficiencies and steer you toward the most effective and safest way to treat your erectile dysfunction. 
Ultrasound with Doppler imaging (ultrasound plus evaluation of blood flow in the arteries and veins) can provide additional information about blood flow of the penis and may help in the evaluation of patients prior to surgical intervention. This study is typically performed after the injection of a chemical that causes the arteries to open up, a vasodilator (prostaglandin E1), into the corpora cavernosa in order to cause dilation of blood vessels and promote blood flow into the penis. The rate of blood flow into the penis can be measured along with an evaluation of problems with compression of the veins.
Besides PDE5 inhibitors and among second-line therapies are VCDs which are clear plastic chambers placed over the penis, tightened against the lower abdomen with a mechanism to create a vacuum inside the chamber. This directs blood into the penis. If an adequate erection occurs inside the chamber, the patient slips a small constriction band off the end of the VCD and onto the base of the penis. An erection beyond 30 min is not recommended. These devices can be a bit cumbersome, but are very safe.40
Some men should not take PDE5 inhibitors. They can cause hypotension (abnormally low blood pressure that can lead to fainting and even shock) when given to patients who are taking nitrates (medications taken for heart disease). Therefore, patients taking nitrates daily should not take any of the PDE5 inhibitors. Nitrates relieve angina (chest pain due to insufficient blood supply to the heart muscle because of narrowing of the coronary arteries); these include nitroglycerine tablets, patches, ointments, sprays, and pastes, as well as isosorbide dinitrate and isosorbide mononitrate. Other nitrates such as amyl nitrate and butyl nitrate also are in some recreational drugs called "poppers."
Psychological Causes of ED – Between 10% and 20% of ED cases have a psychological cause. Because arousal starts in the brain, psychological issues can be a significant contributing factor to erectile dysfunction. Mental health conditions like depression or anxiety can negatively impact your libido, making it more difficult for you to become aroused.
NO is produced by the enzyme NO synthase (NOS). [13] NOS plays many roles, ranging from homeostasis to immune system regulation. To date, 3 subtypes have been identified: nNOS, iNOS, and eNOS, which are produced by the genes NOS1, NOS2, and NOS3, respectively. This nomenclature is derived from the sources of the original isolates: neuronal tissue (nNOS), immunoactivated macrophage cell lines (iNOS), and vascular endothelium (eNOS). The subtypes are not, however, limited to the tissues from which they were first isolated.
A cold slice of watermelon can do more than just satisfy thirst and hunger during the warm summer months; it can help with bedroom satisfaction. Citrulline, the amino acid found in high concentrations of watermelon, is found to improve blood flow to the penis. A 2011 study revealed men who suffered from mild to moderate ED and took L-citrulline supplementation showed an improvement with their erectile function and were very satisfied. Natural watermelon juice, or “nature’s Viagra,” can also be easier on the stomach, since taking pills like Viagra can cause nausea and diarrhea.

Other treatment options such as penile self-injection therapy, external vacuum pumps and the medicated urethral system for erection are in rare occasions an effective long-term treatment. Only a very small percentage of men will continue with these treatments as evidenced by a very high drop out rate and a very low refill rate. These treatments require extensive planning which interferes with spontaneity. This may be the reason why the refill rate is so low and the drop out of treatment so high.  

Alprostadil (also known as prostaglandin E1 [PGE1]) is the prominent known smooth-muscle dilator of the corpus cavernosum. Its mechanism of action is believed to be the promotion of intracellular accumulation of cyclic adenosine monophosphate, thereby causing decreased intracellular accumulation of calcium and resulting smooth muscle relaxation. Alprostadil can be delivered to the erectile tissue either via an intraurethral suppository that is massaged and then absorbed across the corpus spongiosum of the urethra to the corpora cavernosa, or directly injected into the corpora cavernosa. When administered urethrally, doses are substantially higher than when directly injected (typical dosing is 500 mcg to 1 mg intraurethral compared with 2.5 mcg to 20 mcg intracavernosal).

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.

The pathogenesis of organic ED is related to dysfunction of the endothelium. Endothelial cells can become injured through a variety of mechanisms, most of which cause oxidative stress on the tissues. Many of these causes of oxidative stress are related to lifestyle issues which lead to hypertension, diabetes and dyslipidaemia (figure 1). Endothelial cell dysfunction results in reduction of endothelium-dependent vasorelaxation as well as increased adhesion of leukocytes to the endothelium. Endothelial cell injury then leads to a variety of sequelae, including ED, other types of vasoconstriction, atherosclerosis and thrombus formation.18
Approximately 95% of penile implant surgeries are successful in producing erections that enable men to have sexual intercourse. Moreover, patient satisfaction questionnaires show that up to 90% of men who have undergone penile implants say they would choose the surgery again, and overall satisfaction ratings are higher than those reported by men using oral medication or penile injection therapy.
As is true in so many medical conditions, lifestyle modifications, considered first-line therapy, can have a salutary effect in ED management, and men should be encouraged to make the necessary changes to the benefit of their sexual function and to their overall health as well. Despite the benefits of behaviour modification, men presenting with ED want the physician to help with measures that can have an immediate impact.
Vacuum pumps are effective in most men. Successful erections are achieved in up to 90% of men using the vacuum device, however only about 69% men continue to use the device for two years or longer. The most common cause of failure is improper use of or unfamiliarity with the device. Other drawbacks to the use of vacuum devices include the need to assemble the equipment and the difficulty in transporting it. Many men also lose interest in the device because of
The vascular processes that produce an erection are controlled by the nervous system and certain prescription medications may have the side effect of interfering with necessary nerve signals. Among the possible culprits are a variety of stimulants, sedatives, diuretics, antihistamines, and drugs to treat high blood pressure, cancer, or depression. But never stop a medication unless your doctor tells you to. In addition, alcohol, tobacco, and illegal drugs, such as marijuana, may contribute to the dysfunction.
Approximately 95% of penile implant surgeries are successful in producing erections that enable men to have sexual intercourse. Moreover, patient satisfaction questionnaires show that up to 90% of men who have undergone penile implants say they would choose the surgery again, and overall satisfaction ratings are higher than those reported by men using oral medication or penile injection therapy.
In this study, ED proceeded CVD in almost 70% of cases. Similarly, many men with ED have been found to have pre-existing CVD. A study by Vlachopoulos et al evaluated the incidence of asymptomatic CVD in 50 men with ED.22 These authors found that 19% of men with ED had asymptomatic CVD. Similarly, Mulhall and colleagues found that 20% of men presenting with ED and vascular insufficiency on penile duplex had asymptomatic CVD.23

VIP is a neurotransmitter with regulatory actions on blood flow, secretion and muscle tone with intracorporal adenylate cyclase activation and smooth muscle relaxation. VIP has been shown to elevate cAMP intracellular concentrations without affecting cGMP levels. However, when VIP is given alone it may not induce erection and requires combination with phentolamine or papaverine for it to be effective (88). 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.

The inability to achieve or sustain a sufficiently firm penile erection (tumescence) to allow normal vaginal sexual intercourse. The great majority of cases are not caused by organic disease and most men experience occasional periods of impotence. It is often related to anxiety about performance and is usually readily corrected by simple counselling methods which prescribe sensual massage but forbid coitus. Organic impotence may be caused by DIABETES, MULTIPLE SCLEROSIS, spinal cord disorders and heart disease. Many cases can be helped by the drug SILDENAFIL (Viagra).
A vacuum erection device helps draw blood into the penis by applying negative pressure. This type of device is sometimes referred to as penis pump and may be used just prior to sexual intercourse. Several types of FDA approved vacuum therapy devices are available under prescription. When pharmacological methods fail, a purpose-designed external vacuum pump can be used to attain erection, with a separate compression ring fitted to the base of the penis to maintain it. These pumps should be distinguished from other penis pumps (supplied without compression rings) which, rather than being used for temporary treatment of impotence, are claimed to increase penis length if used frequently, or vibrate as an aid to masturbation. More drastically, inflatable or rigid penile implants may be fitted surgically.

There are myriad factors, both mental and physical, that may contribute to your erectile dysfunction symptoms. Some of the most common impotence causes include diabetes, hypertension, prostate problems, low testosterone and obesity, which can not only put a damper on your sexual enjoyment, but play a key role in your total male vitality, too. (Even medications that are often prescribed to control some of the aforementioned issues can be behind some of the frustrating symptoms of ED.) There are factors like depression, stress and anxiety that can leave you longing for your glory days, and the coping mechanisms like alcohol and tobacco that can make a roll in the sheets less satisfying for you and your partner. We’ll listen to you with a compassionate ear and thoughtfully consider what may be contributing to your ED symptoms, then draw up your perfect, personalized treatment.
"Medications that create blood flow to the penis can't help when an erection is blocked by the fear or anxiety of the fight-or-flight response,” says Feloney. “This type of erectile dysfunction probably has a lot to do with evolution — men didn't need an erection when a dinosaur was chasing them." The best way to treat erectile dysfunction caused by performance anxiety, depression, a poor relationship, or stress may be with a combination of ED drug treatment and sex therapy, individual therapy, or couples therapy from sexual health professionals.
A larger national study, the National Health and Social Life Survey, looked at sexual function in men and women.4 This study surveyed 1,410 men aged 18 to 59 and also documented an increase in ED with age. Additionally, the study found a decrease in sexual desire with increasing age. Men in the oldest cohort (50 to 59) were more than 3 times as likely to experience erection problems and to report low sexual desire compared with men 18 to 29. Experience of sexual dysfunction was more likely among men in poor physical and emotional health. The study also concluded that sexual dysfunction is an important public health concern and that emotional issues are likely to contribute to the experience sexual dysfunction.
Then you have to be able to make the right diagnosis. What is the basis for their erectile dysfunction? Is it psychogenic? Is it some sort of neurological or blood vessel or hormonal issue? So you have to make a diagnosis. You have to be able to make an assessment. And then only after those things are done, then you start to think about medications.
In rare cases, the drug Viagra ® can cause blue-green shading to vision that lasts for a short time. In rare cases, the drug Cialis® can cause or increase back pain or aching muscles in the back. In most cases, the side effects are linked to PDE5 inhibitor effects on other tissues in the body, meaning they are working to increase blood flow to your penis and at the same time impacting other vascular tissues in your body. These are not ‘allergic reactions'.
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