Several medications can interfere with the chemical processing of PDE5i medications by the liver. These can include ketoconazole (an antifungal medication known by the brand name Nizoral), erythromycin (an antibiotic), and cimetidine (also known as Tagamet, for reducing stomach acid). A lower dose of PDE5i medications should be used if one is taking any of these medications.

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 PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally.[22]:20–21 Additionally, a cream combining alprostadil with the permeation enhancer DDAIP has been approved in Canada as a first line treatment for erectile dysfunction.[25] Penile injections, on the other hand, can involve one of the following medications: papaverine, phentolamine, and prostaglandin E1, also known as alprostadil.[22]:25
The liver is the largest gland and organ in the body. There are a variety of liver diseases caused by liver inflammation, scarring of the liver, infection of the liver, gallstones, cancer, toxins, genetic diseases, and blood flow problems. Symptoms of liver disease generally do not occur until the liver disease is advanced. Some symptoms of liver disease include jaundice, nausea and vomiting, easy bruising, bleeding excessively, fatigue, weakness, weight loss, shortness of breath, leg swelling, impotence, and confusion. Treatment of diseases of the liver depends on the cause.
"The good news is, our study also found that a large proportion of men were naturally overcoming erectile dysfunction issues. The remission rate of those with erectile dysfunction was 29%, which is very high. This shows that many of these factors affecting men are modifiable, offering them an opportunity to do something about their condition," Professor Wittert says.
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.

Vascular damage may result from radiation therapy to the pelvis and prostate in the treatment of prostate cancer. [36] Both the blood vessels and the nerves to the penis may be affected. Radiation damage to the crura of the penis, which are highly susceptible to radiation damage, can induce ED. Data indicate that 50% of men undergoing radiation therapy lose erectile function within 5 years after completing therapy; fortunately, some respond to one of the PDE5 inhibitors.
The common PDE5 inhibitor drugs approved in the United States are sildenafil (Viagra), vardenafil (Levitra and Staxyn, the generic form), tadalafil (Cialis), or avanafil (Stendra). All of the currently approved PDE5 inhibitors work in the same way. They differ in the number of available doses, how quickly they work and last in your system, the dosing, and to some extent in the side effects. However, they generally share the same indications and contraindications. Currently, tadalafil is the only medication that patients can take on a daily basis and is approved for the treatment of both ED and BPH (benign enlargement of the prostate).
L-arginine, an amino acid that is naturally present in the body and helps make nitric oxide, supports a successful erection. Nitric oxide is responsible for making the blood vessels relax, which helps sustain an erection for men. A 1999 study, observed the effects of six weeks of high-dose (5 grams/day) orally administered nitric oxide (NO) donor L-arginine on men with organic ED. Thirty-one percent of those who took 5 grams/day of L-arginine experienced significant improvements in sexual function. Burns told Medical Daily, “l-arginine and deer antler velvet” have been the most popular go-to natural treatments for men.
Several medications can interfere with the chemical processing of PDE5i medications by the liver. These can include ketoconazole (an antifungal medication known by the brand name Nizoral), erythromycin (an antibiotic), and cimetidine (also known as Tagamet, for reducing stomach acid). A lower dose of PDE5i medications should be used if one is taking any of these medications.
Cavallini, G., Modenini, F., Vitali, G., & Koverech, A. (2005, November). Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy. Urology, 66(5), 1080-5. Retrieved from http://www.sciencedirect.com/science/article/pii/S0090429505006515
Impotence, also called erectile dysfunction, in general, the inability of a man to achieve or maintain penile erection and hence the inability to participate fully in sexual intercourse. In its broadest sense the term impotence refers to the inability to become sexually aroused; in this sense it can apply to women as well as to men. In common practice, however, the term has traditionally been used to describe only male sexual dysfunctions. Professional sex therapists, while they identify two distinct dysfunctions as forms of impotence, prefer not to use the term impotence per se. Thus, because of its pejorative connotation in lay usage and because of confusion about its definition, the word impotence has been eliminated from the technical vocabulary in favour of the term “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.

The most common treatment for erectile dysfunction is drugs known as phosphodiesterase-5 (PDE-5) inhibitors. These include tadalafil (Cialis), vardenafil (Levitra), and sildenafil citrate (Viagra). These are effective for about 75% of men with erectile dysfunction. They are tablets that are taken around an hour before sex, and last between 4 and 36 hours. Sexual stimulation is required before an erection will occur. The PDE-5 inhibitors cause dilation of blood vessels in the penis to allow erection to occur, and help it to stay rigid. Men using nitrate medication (e.g. GTN spray or sublingual tablets for angina) should not use PDE-5 inhibitors.

The art of acupuncture has become the new treatment for everything from back pain, depression, and even ED. Impotence could be more of a state of mind, and acupuncture may help. Through this alternative therapy, fine needles are placed in various parts of the body to relieve pain or stress. Although there are many mixed studies for acupuncture and ED, many tend to confirm positive results. A 1999 study found acupuncture improved the quality of erection and even restored sexual activity in 39 percent of participants.
In most healthy men, some of the drug will remain in the body for more than two days after a single dose of tadalafil. Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, doctors have to lower the dose and frequency of tadalafil in the following examples:
MalaCards based summary : Impotence, also known as erectile dysfunction, is related to vasculogenic impotence and hyperprolactinemia, and has symptoms including angina pectoris, pelvic pain and tremor. An important gene associated with Impotence is NOS1 (Nitric Oxide Synthase 1), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Platelet homeostasis. The drugs Methyltestosterone and Testosterone have been mentioned in the context of this disorder. Affiliated tissues include prostate, spinal cord and endothelial, and related phenotypes are normal and reproductive system
This procedure is usually performed before and after injection of a smooth-muscle-relaxing medication into the penis, which normally should significantly increase the diameter of the penile arteries. The procedure itself is painless. Duplex ultrasonography is most useful in evaluating possible penile arterial disorders, but in those individuals considering surgery for problems with the arteries to the penis, a more invasive study, angiogram, is needed to identify the location of the damaged artery.

Poor sleep patterns can be a contributing factor for erectile dysfunction, Mucher says. One review published in the journal Brain Research emphasized the intricate relationship between the level of sex hormones like testosterone, sexual function, and sleep, noting that testosterone levels increase with improved sleep, and lower levels are associated with sexual dysfunction. Hormone secretion is controlled by the body’s internal clock, and sleep patterns likely help the body determine when to release certain hormones. 
Before taking any medication for erectile dysfunction, including over-the-counter supplements and herbal remedies, get your doctor's OK. Medications for erectile dysfunction do not work in all men and might be less effective in certain conditions, such as after prostate surgery or if you have diabetes. Some medications might also be dangerous if you:
ED exists in approximately 75% of men with SB and is dependent upon the level of the neurologic lesion (54). The level of the neurologic lesions usually corresponds to sensation and penile sensation indicates pudendal nerve signaling. With absent sacral reflexes ED is variable. Furthermore, Diamond et al. reported that 64% of men with lesions below T10 obtained erections versus 14% with a lesion above T10 (55). It has also been suggested that ED may be underreported due to lack of sexual education even in men without associated cognitive impairment (56).
The downside to these prostheses includes the standard risks of surgery, the very low risk of infection — less than 2 percent in most patients, slightly higher in diabetics — and a slight drop in penis length versus a natural erection or other ED treatments. Also, unlike with other methods, any hope for a natural erection is abolished once a pump is implanted. The cost for surgical options varies, and insurance coverage is typically good.
Additionally, the physiologic processes involving erections begin at the genetic level. Certain genes become activated at critical times to produce proteins vital to sustaining this pathway. Some researchers have focused on identifying particular genes that place men at risk for ED. At present, these studies are limited to animal models, and little success has been reported to date. [4] Nevertheless, this research has given rise to many new treatment targets and a better understanding of the entire process.
Moemen et al. compared the effectiveness and satisfaction associated with use of several ED therapies including sildenafil alone, intracavernosal injections (ICI) followed by sildenafil after ICI discontinuation and vacuum erections devices (VED) followed by sildenafil therapy after VED discontinuation (60). Seventy percent of men receiving vasoactive medications preferred sildenafil to ICI, even though rigidity was superior in the ICI group. All men using VEDs were dissatisfied with that form of therapy.
Poor sleep patterns can be a contributing factor for erectile dysfunction, Mucher says. One review published in the journal Brain Research emphasized the intricate relationship between the level of sex hormones like testosterone, sexual function, and sleep, noting that testosterone levels increase with improved sleep, and lower levels are associated with sexual dysfunction. Hormone secretion is controlled by the body’s internal clock, and sleep patterns likely help the body determine when to release certain hormones. 
Ultimately, PDE5i have had a significant impact on the treatment of ED in men with SCI. The ease of use and tolerability of the medication has also led to improved satisfaction and quality of life that had been previously affected by SD. Head to head trials evaluating specific PDE5i within the SCI population are required to further elucidate drug preference. PDE5i should be considered first line therapy, however men with high thoracic and cervical lesions should be warned about an increased chance of dizziness with sildenafil and possibly other PDE5i use.
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It is important for clinicians prescribing these drugs to make the patient aware of the action of the drugs especially the fact that they do not result in an immediate erection, and that they do not cause an erection without sexual stimulation. There is frequently a great expectation when men begin using these drugs and it is wise to temper their enthusiasm and explain they do not work immediately, and may not work every time, but also let the patient know that if these drugs do not work, there are other options.

Six herbs for treating erectile dysfunction Erectile dysfunction can be an embarrassing condition that can leave men unable to achieve an erection or a full orgasm. This MNT Knowledge Center article talks about six different herbal supplements that could help people with erectile dysfunction, including ginkgo biloba, horny goat weed, and red ginseng. Read now
Vacuum devices: Specially designed vacuum devices to produce erections have been used successfully for many years. They are safe and relatively inexpensive. They work by creating a vacuum around the penis that draws blood into the penis, engorging it, and expanding it. There are three components to the device, a plastic cylinder in which the penis is placed, a battery or hand operated pump that draws air out of the cylinder creating the vacuum, and an elastic band (constriction device) that is placed around the base of the penis, to maintain the erection after the cylinder is removed and during intercourse by preventing blood from flowing out of the penis back into the body.
Prior to starting with treatment of erectile dysfunction, it is important to make sure that it is safe from a medical standpoint to participate in sexual activity. Sexual activity is physical exertion, and in some men with significant heart disease, this increase in physical exertion can increase the risk of a heart attack. Thus, it is very important to discuss your cardiovascular risks with your doctor prior to trying any medication or treatment for erectile dysfunction.
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.
The physical side effects of chemotherapy are usually temporary and resolve within one to two weeks after stopping the chemotherapy. However, chemotherapy agents, such as Ciplatin or Vincristine, may interfere with the nerves that control erection leading to possible impotence. Make sure you discuss potential side effects of cancer chemotherapy with your doctor or healthcare provider.
Experiencing ED can also be a reason to try not penetrative sex.  Try planning a sex session with your partner hat isn't focused on your erection at all.  Things like kissing, licking, sucking, foreplay and teasing all are super stimulating and don't focus on penetration.  Feel free to bring each other to orgasm using these ideas and see if you are able to relax and enjoy the experience.  Many men feel like failures when their erections become unreliable.  Having a few successful sexual sessions that lead to orgasm without penetration can put the fun back into having sex.  Many couples find success using this technique and begin to reengage sexually instead of avoiding being sexual for fear of failure.
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.
Your Ro physician may recommend trying the medication under different circumstances. Using the medication the first time can be anxiety provoking so they may suggest using it alone until you are familiar with its effect or side effects. If you’ve been prescribed ED medication on the Ro platform, please contact a physician if you have any questions. You are not alone. Use every tool you can and asking questions when you need answers is one of them.
In a prospective study from the Prostate Cancer Prevention Trial database, Thompson et al reported that men presenting with ED had a significantly higher chance of developing a cardiovascular event over a 7-year follow-up period. [55] The hazard ratio was 1.45, which is in the range of risk associated with current smoking or a family history of MI.

There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil. Patients with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis and lead to permanent impotence. Therefore, if your erection lasts four hours, you should seek emergency medical care.
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.
PDE5i for ED in patients with MS can be considered as reasonably effective and safe. Fowler et al. performed a randomized, multicenter, double-blind, flexible dose trial with open label extensions comparing sildenafil to placebo (75). A nearly 4-fold increase in effective erections was noted in the treatment arm, 96% vs. 24%. Sexual satisfaction and overall satisfaction were also improved in the treatment group based on IIEF scores, and quality of life assessments. Lombardi et al. evaluated tadalafil use in men with MS (71). Seventy eight percent of the men responded with improved erections, better quality of life with regards to sexual function, partner relationship and family life. Just less than half the men who responded to the tadalafil did so at the lower dosage of 10 mg. Subjects in either studies did not have any significant adverse side effects beyond flushing, and headache with PDE5i use.
Having erection trouble from time to time isn't necessarily a cause for concern. If erectile dysfunction is an ongoing issue, however, it can cause stress, affect your self-confidence and contribute to relationship problems. Problems getting or keeping an erection can also be a sign of an underlying health condition that needs treatment and a risk factor for heart disease.
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