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:
There are, as you listen to all of the advertisements, if your erection lasts for more than four hours, there are very, very unusual cases where that can happen. There are very rare cases of visual problems. There are even rarer cases of hearing problems. But with every medication, there always a potential downside. But the absolute contraindication is an unstable medical condition, an unstable cardiovascular condition, being on nitrates.

Factors that mediate contraction in the penis include noradrenaline, endothelin-1, neuropeptide Y, prostanoids, angiotensin II, and others not yet identified. Factors that mediate relaxation include acetylcholine, nitric oxide (NO), vasoactive intestinal polypeptide, pituitary adenylyl cyclase–activating peptide, calcitonin gene–related peptide, adrenomedullin, adenosine triphosphate, and adenosine prostanoids.
A meta-analysis of 36 744 men with ED in 12 prospective cohort studies found that the presence of ED significantly increased the risk of CVD, CAD, stroke and all-cause mortality, and the presence of ED was an independent risk factor for CVD. Ponholzer et al found that men with moderate to severe ED had a 65% increased relative risk for developing symptomatic CAD compared with men who did not have ED.26

There are treatments available to help you to get and maintain an erection. In addition, making healthy changes to your lifestyle could help with impotence. Switching to a healthier balanced diet, taking more exercise and cutting down on or giving up alcohol and cigarettes could help you to see an improvement in sexual function. If you think that the problem may be related to stress or anxiety, counselling can also help.
Sexual stimulation causes the release of neurotransmitters from cavernosal nerve endings and relaxation factors from endothelial cells lining the sinusoids. NOS produces NO from L-arginine, and this, in turn, produces other muscle-relaxing chemicals, such as cGMP and cyclic adenosine monophosphate (cAMP), which work via calcium channel and protein kinase mechanisms (see the image below). This results in the relaxation of smooth muscle in the arteries and arterioles that supply the erectile tissue, producing a dramatic increase in penile blood flow.
It is important that all erectile dysfunction is reported to your doctor, as sometimes it can be an indicator of something physically wrong with you that has to be treated. Also, your doctor is in the best position to find the reason for your erectile dysfunction. Routine questions and tests will provide a guide to the cause and allow your doctor to decide what kind of treatment you might need to deal with it. This may involve referral to a specialist. Detailed information can be found at the website of the Impotence Association – www.sda.uk.net
For example, many men with diabetes mellitus may develop erectile dysfunction during their young and middle adult years. Physicians, diabetes educators, and patients and their families are sometimes unaware of this potential complication. Whatever the causal factors, discomfort of patients and health care providers in discussing sexual issues becomes a barrier to pursuing treatment.
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
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
If you have been having ED for more than two months, you should see a doctor to find the cause. To detect the cause of ED, your doctor will take a history of when you started to have problems with erections and sex drive, illnesses or injuries that could cause ED, and any recent physical or emotional changes in your life. You also will need to review all the medications you take. The evaluation most often includes a physical exam.

The penis contains three cylinders, the two corpora cavernosa, which are on the top of the penis (see figure 1 below). These two cylinders are involved in erections. The third cylinder contains the urethra, the tube that the urine and ejaculate passes through, runs along the underside of the penis. The corpus spongiosum surrounds the urethra. Spongy tissue that has muscles, fibrous tissues, veins, and arteries within it makes up the corpora cavernosa. The inside of the corpora cavernosa is like a sponge, with potential spaces that can fill with blood and distend (known as sinusoids). A layer of tissue that is like Saran Wrap, called the tunica albuginea, surrounds the corpora. Veins located just under the tunica albuginea drain blood out of the penis.
Qaseem, A., Snow, V., Denberg, T. D., Casey, D. E., Forciea, M. A., Owens, D. K., & Shekelle, P. (2009). Hormonal testing and pharmacologic treatment of erectile dysfunction: A clinical practice guideline from the American College of Physicians. Annals of internal medicine, 151(9), 639-649. Retrieved from http://annals.org/aim/article/745155/hormonal-testing-pharmacologic-treatment-erectile-dysfunction-clinical-practice-guideline-from
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