Vardenafil and tadalafil belong to the same group of chemical compounds as sildenafil, namely phos-phodiesterase type 5 (PDE-5) inhibitors. Some men cannot benefit from sildenafil or the two newer PDE-5 inhibitors because they have low levels of nitric oxide. British investigators reported in late 2002 that three different types of compounds are being studied as possible medications for men with low levels of nitric oxide. They are Rho-kinase inhibitors, soluble guanylate cyclase activators, and nitric oxide-releasing PDE-5 inhibitors.

Treatments include psychotherapy, adopting a healthy lifestyle, oral phosphodiesterase type V (PDE5) inhibitors (Viagra, Levitra, Cialis, Stendra, and Staxyn), intraurethral prostaglandin E1 (MUSE), intracavernosal injections (prostaglandin E1 [Caverject, Edex], Bimix and Trimix), vacuum devices, penile prosthesis and vascular surgery, and (in some cases) changes in medications when appropriate.
The primary nerve fibers to the penis are from the dorsal nerve of the penis, a branch of the pudendal nerve. The cavernosal nerves are a part of the autonomic nervous system and incorporate both sympathetic and parasympathetic fibers. They travel posterolaterally along the prostate and enter the corpora cavernosa and corpus spongiosum to regulate blood flow during erection and detumescence. The dorsal somatic nerves are also branches of the pudendal nerves. They are primarily responsible for penile sensation. [10]
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. 
In prescribing sildenafil, a doctor considers the age, general health status, and other medication(s) the patient is taking. The usual starting dose for most men is 50 mg, however, the doctor may increase or decrease the dose depending on side effects and effectiveness. The maximum recommended dose is 100 mg every 24 hours. However, many men will need 100 mg of sildenafil for optimal effectiveness, and some doctors are recommending 100 mg as the starting dose.
Somatomotor penile innervation originates in Onuf’s nucleus in the S2-4 spinal segments. These nerves travel to the ischiocavernosus and bulbocavernosus muscles when activated lead to contraction necessary for the rigid-erection phase. Several animal studies show that stimulation of the somatomotor pathways may also be under sympathetic control, and adrenergic stimulation may lead to contraction of these muscles during ejaculation (13,14). Somatomotor spinal reflexes may also be initiated by genital stimulation. For instance, the well-known bulbocavernosus reflex is evidence this reflex exists; however the clinical significance of its absence in the neurological assessment of ED has not been substantiated (15).

MSA is a neurodegenerative disease of undetermined etiology, where ED is an early prominent sign occurring in 40% of men at the time of diagnosis (46,47). ED occurs in the majority of patients and the exact cause of it is unknown (48). Like PD, MSA likely affects the dopaminergic pathways within the brain essential for arousal (49). Orthostatic hypotension (OH) as a causal factor has been refuted by evidence that sildenafil can overcome reduced filling pressures, and the ED usually precedes the development of OH (46,49,50). Similar to other neurologic disorders that lead to ED, other disease related factors such as psychosocial stress, the burden of chronic illness, changed appearance, fatigue, decreased fine motor movement of fingers, immobility and diminished self-esteem due to loss of independence may contribute as well (51).
The most common inflatable prosthesis is the three-piece penile prosthesis. It is composed of paired cylinders, which doctors surgically insert inside the penis. Patients can expand the cylinders using pressurized fluid (see figure 3). Tubes connect the cylinders to a fluid reservoir and pump, which doctors also surgically implant. The reservoir is usually in the pelvis. A doctor places the pump in the scrotum. By pressing on the pump, sterile fluid transfers from the reservoir into the cylinders in the penis. An erection is produced primarily by expansion of the width of the penis, however, one model can increase in length a small amount also. Lock-out valves in the tubing prevent the fluid from leaving the cylinder until a release valve is pressed. By pressing the relief valve and gently squeezing the penis, the fluid within the cylinders transfers back into the reservoir.

Following a detailed discussion about the history of erectile dysfunction and its risk factors, your doctor will examine the testicles and penis to help determine the cause of erectile dysfunction. Your doctor will check reflexes and pulses in the area to see if problems with blood vessels or nerves are contributing to the erectile dysfunction. If necessary, your doctor will order tests to help diagnose erectile dysfunction.
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The phrase “use it before you lose it” can be applied when it comes to helping men with ED regain normal erectile function. Pelvic exercises, more commonly known as kegel exercises, are used to promote urinary continence and sexual health. They help to strengthen the bulbocavernosus muscle, which does three things: allows the penis to engorge with blood during erection, it pumps during ejaculation, and it helps empty the urethra after urination, according to Healthline.

Induction of erection occurs after stimulation of the cavernous and pelvic nerve plexus. Conversely, stimulation of the sympathetic trunk leads to detumescence. The reflex erectile response requires that the sacral reflex arc remain intact. Tactile and sensory signals are received by the somatic sensory pathways and integrate with parasympathetic nuclei within the sacral spinal cord (S2-4) leading to induction of erection via cholinergic signaling. These reflexogenic erections remain intact with upper motor neuron injuries. Psychogenic erections do not require that the sacral reflex arc remain intact. In a cat models, spinal cord removal below L4/L5 led to absence of a reflexogenic erection but stimulation of the medial preoptic area (MPOA) or placement near a female cat in heat led to erection (5,6). Psychogenic erections occur via induction of central pathways traveling from the brain through the sympathetic chain. Non-penile sensory pathways induced by sight, sound, touch and smell travel through the MPOA to the erection centers within the cord T11-L2, and S2-S4 to induce erections (7). When a sacral lower motor neuron injury is present in men, below T12 these types of erections are more likely to occur (8). Spinal cord lesions above T9 are not associated with psychogenic erections (9). Rigidity of erections is less with psychogenic erections because the thoracolumbar sympathetic outflow may contain a decreased concentration of neurons compared to the parasympathetic outflow from the sacral spinal cord.
The causes of erectile dysfunction include aging, high blood pressure, diabetes mellitus, cigarette smoking, atherosclerosis (hardening of the arteries), depression, nerve or spinal cord damage, medication side effects, alcoholism or other substance (drug) abuse, pelvic surgery including radical prostatectomy, pelvic radiation, penile/perineal/pelvic trauma such as pelvic fracture, Peyronie's disease (a disorder that causes curvature of the penis and sometimes painful erections), and low testosterone levels.
Since sexual arousal is a complex process involving hormones, emotions, nerves, muscles, blood vessels and the brain, a malfunction in any of these can lead to ED. Stress, exhaustion and psychological issues can also contribute, and anxiety over maintaining an erection can actually make it harder to attain. In short, any condition that inhibits blood flow to the penis can lead to ED.
There's no one cure that works for every case of erectile dysfunction, but there are many options that can successfully treat the condition. If ED is caused by an underlying medical condition, sometimes treating that condition will get rid of the symptoms of erectile dysfunction. This may include psychological counseling for problems like stress or relationship issues. Other times, a variety of medications - either taken by mouth or injected or inserted into the penis - can successfully treat erectile dysfunction. Surgical procedures may get rid of symptoms permanently, while constrictive devices and penis pumps can be temporary solutions. Talk to your doctor to find a treatment method that's most effective for you.
Another tip is to make sure you communicate with your partner what you like during the process of sex.  Many men are not communicative about what really turns them on.  If you are not aroused by what is going on, then you might experience ED.  Make sure you tell your partner what turns you on.  Communicating about intimacy should also lead to feeling more connected with your partner aiding in relaxing when you are sexual together.
A variety of lifestyle choices can affect the ability to achieve and maintain an erection, so preventing ED is possible in some cases. Men are encouraged to manage chronic health problems with their doctors and to exercise regularly. They also should avoid smoking and excess alcohol and get help for anxiety or depression, according to the Mayo Clinic.
Inflatable prostheses are complex mechanical devices that imitate the natural process of erection. Parts are inserted surgically into the penis and scrotum, and activated by squeezing. When erection is no longer desired, a valve on the pump is pressed, and the penis becomes flaccid. Self-contained single-unit prostheses are similar to the inflatable types, but more compact. The entire device is implanted into the penis. When erection is desired, the unit is activated by either squeezing or bending, depending on which of the two types of self-contained prostheses is used.

What you need to know about delayed ejaculation Delayed ejaculation is a sexual disorder that can be distressing for a man and his partner and may disrupt a relationship. There are many reasons why delayed ejaculation occurs, including tissue damage, age, drugs, and the side effects of medication. They may be physiological or psychological. Find out how to get help. Read now

Oral therapies via the PDE5i sildenafil, vardenafil, and tadalafil have been proven to be generally safe and effective in select NED populations. The majority of the treatment effectiveness data has been generated in the SCI population. Data regarding the use of PDE5i outside of the SCI population is lacking (58). Furthermore, the ED that exists in the population with neurologic disorders is often multifactorial and may be caused by psychogenic, psychosocial, hormonal, medication-related and disability-related factors. A careful evaluation of each patient must be performed to isolate these factors prior to initiating vasoactive therapy.
Sexual functioning involves a complex interaction among biologic, sociocultural, and psychological factors, and the complexity of this interaction makes it difficult to ascertain the clinical etiology of sexual dysfunction. Before any diagnosis of sexual dysfunction is made, problems that are explained by a nonsexual mental disorder or other stressors must first be addressed. Thus, in addition to the criteria for erectile disorder, the following must be considered:
The information shared on our websites is information developed solely from internal experts on the subject matter, including medical advisory boards, who have developed guidelines for our patient content. This material does not constitute medical advice. It is intended for informational purposes only. No one associated with the National Kidney Foundation will answer medical questions via e-mail. Please consult a physician for specific treatment recommendations.
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.
Because the burning side effect is triggered by alprostadil, the formulations with the least alprostadil — tri-mix and certain versions of bi-mix — could work for men who experience burning with the single-drug formula. But some men might choose alprostadil alone because the multi-drug cocktails can cost more and must be dispensed by a compounding pharmacy — one that is authorized to mix medications on site — which could mean the added hassle of a long drive to pick up the drug.
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).
Occasional successful sexual function and early morning erections do not preclude the possibility of endocrine dysfunction. Since abnormally low levels of testosterone frequently are the primary cause of impotence, it is recommended that determination of the blood level of testosterone be an integral part of the total evaluation of the impotent patient.
Erectile dysfunction is the inability to develop or maintain an erection that is rigid enough to allow penetration of the vagina, and therefore functional sexual intercourse. Generally, the term erectile dysfunction is applied if this occurs frequently (75% of the time) over a significant period if time (several weeks to months). If this is the case, the term impotence may also be used.
Depending on the cause, erectile dysfunction (ED) may be curable, but the condition is almost always treatable for most men. The first step is to visit your doctor, because several health conditions -- and the medications that treat them -- can cause ED. For example, cardiovascular (heart and blood vessel) disease causes arteries to narrow, which decreases blood flow to the penis and can cause trouble getting or maintaining an erection.

The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction. [12]
Metabolism (breakdown) of vardenafil can be slowed by aging, liver disease, and concurrent use of certain medications (such as erythromycin [an antibiotic], ketoconazole [Nizoral, a medication for fungal/yeast infections], and protease inhibitors [medications used to treat AIDS]). Slowed breakdown allows vardenafil to accumulate in the body and potentially increase the risk for side effects. Therefore, in men over 65 years of age with liver disease, or who are also taking medication(s) that can slow the breakdown of vardenafil, the doctor will initiate vardenafil at low doses to avoid its accumulation. For example,
Tests such as the bulbocavernosus reflex test are used to determine if there is sufficient nerve sensation in the penis. The physician squeezes the glans (head) of the penis, which immediately causes the anus to contract if nerve function is normal. A physician measures the latency between squeeze and contraction by observing the anal sphincter or by feeling it with a gloved finger inserted past the anus.
Alprostadil may also be administered into the urethral opening of the penis. In MUSE (medical urethral system for erection), the man inserts a thin tube the width of a vermicelli noodle into his urethral opening and presses down on a plunger to deliver a tiny pellet containing alprostadil into his penis. The drug takes about 10 minutes to work and the erection lasts about an hour. The main side effect is a sensation of pain and burning in the urethra, which can last about five to 15 minutes.
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.

Treatment depends on the underlying cause. In general, exercise, particularly of the aerobic type, is effective for preventing ED during midlife. Exercise as a treatment is under investigation.[22]:6, 18–19 For tobacco smokers, cessation often results in a significant improvement.[23] Oral pharmacotherapy and vacuum erection devices are first-line treatments,[22]:20, 24 followed by injections of drugs into the penis, as well as penile implants.[22]:25–26 Vascular reconstructive surgeries are beneficial in certain groups.[24]
Currently, placement of a penile prosthesis is the most common surgical procedure performed for erectile dysfunction. Penile prosthesis placement is typically reserved for men who have tried and failed (either from efficacy or tolerability) or have contraindications to other forms of therapy including PDE5 inhibitors, intraurethral alprostadil, and injection therapy.
Erectile dysfunction can cause strain on a couple. Many times, men will avoid sexual situations due to the emotional pain associated with ED, causing their partner to feel rejected or inadequate. It is important to communicate openly with your partner. Some couples consider seeking treatment for ED together, while other men prefer to seek treatment without their partner's knowledge. A lack of communication is the primary barrier for seeking treatment and can prolong the suffering. The loss of erectile capacity can have a profound effect on a man. The good news is that ED can usually be treated safely and effectively.
This category of treatments includes external vacuum therapies: devices that go around the penis and produce erections by increasing the flow of blood in, while constricting the flow out. Such devices imitate a natural erection, and do not interfere with orgasm. External vacuum therapy mechanisms are approximately 95 percent successful in causing and sustaining an erection. All are portable, and costs range between $200-$500, covered under most insurance plans and Medicare Part B.
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
Testosterone replacement therapy may improve energy, mood, and bone density, increase muscle mass and weight, and heighten sexual interest in older men who may have deficient levels of testosterone. Testosterone supplementation is not recommended for men who have normal testosterone levels for their age group due to the risk of prostate enlargement and other side effects. Testosterone replacement therapy is available as a cream or gel, topical solution, skin patch, injectable form and pellet form placed under the skin.

Aging, liver and kidney problems, and concurrent use of certain medications (such as erythromycin [an antibiotic] and protease inhibitors for HIV) slows the metabolism (breakdown) of sildenafil. Slowed breakdown allows sildenafil to accumulate in the body and potentially may increase the risk of side effects. Therefore, in men over 65 years of age, in men with significant kidney and liver disease, and in men who also are taking medications called protease inhibitors, the doctor will initiate sildenafil at a lower dose (25 mg) to avoid accumulation of sildenafil in the body. A protease inhibitor ritonavir (Norvir) is especially potent in increasing the accumulation of sildenafil, thus men who are taking Norvir should not take sildenafil doses higher than 25 mg and at a frequency of no greater than once in 48 hours. Other medications that may affect the level of sildenafil include erythromycin and ketoconazole.

The prostaglandin E1 is contained in a small suppository located at the tip of an applicator. You should urinate first as this lubricates the urethra and makes it easier to insert the applicator into the tip of the urethra (urethral meatus, the opening at the tip of the penis that urine passes through). A patient can release the suppository into urethra by gently wiggling the applicator and pressing the button at the end. Rubbing the penis allows the suppository to dissolve, and the prostaglandin is absorbed through the tissue of the urethra into the penis. It takes 15 to 30 minutes for this occur. Once into the penis, the prostaglandin causes increased blood flow into the penis. The prostaglandin can be present in the ejaculate, and thus doctors recommend that men use a condom when having intercourse with a pregnant partner. Men may need to use a condom if vaginal irritation occurs in female partner.
If you have unstable heart disease of any kind, heart failure or unstable, what we call angina, contraindication to using the medications. All right? So if you’re in an unstable medical state, these medications are not a good idea. Now, there are relative issues. If you may be taking a blood pressure medicine or a medicine for your prostate which dilates your blood vessel a little bit– you know, the typical ones are what we call the alpha blockers– you may have an additive effect from the medication. But for the most part, the medicines are incredibly safe.
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