Both erectile dysfunction and heart disease have been linked with impaired activity of nitric oxide, the body’s most powerful vasodilator. An endogenous (produced by the body) compound called asymmetric dimethylarginine is an L-arginine analog, which interferes with the production of nitric oxide and may increase the risk for erectile dysfunction and heart disease.
Despite all the options and alternatives, sometimes there’s no suitable alternative to a prescription that contributes to ED. You might have an adverse reaction to an particular medication or an alternative is unavailable in your state, health insurance plan, or your budget. There are good reasons you were prescribed your original medication in the first place.
Treatment of ED which was previously confined to invasive procedures, cavernosal injections or to rather ineffective oral medications was revolutionized in 1999 with the introduction of the orally administered PDE5 inhibitor sildenafil. Phosphodiesterase type 5 inhibitors are the first-line therapy for ED of organic aetiology unless there is a specific contraindication to their use. This class of agents is widely used because of its effectiveness and safety.38 Interactions with cardiovascular drugs have been minimal with the exception of nitrates and other nitric oxide (NO) donors (such as nicorandil), where co-administration may result in severe vasodilation and hypotension. However, nitrates are often overused in clinical practice; therefore, the option of their discontinuation should be considered. A strong body of clinical data shows that all three agents (sildenafil, tadalafil, and vardenafil) do not increase the risk of non-fatal myocardial infarction, stroke, or cardiovascular deaths. These drugs do not exacerbate ischaemia or worsen exercise tolerance in patients with known CAD who achieve levels of exercise comparable or greater than that achieved during sexual intercourse.38,39 Phosphodiesterase type 5 is expressed throughout the human body, including the pulmonary and systemic vasculature and hypertrophied myocardium. While currently their only additional indication, beyond ED, is idiopathic pulmonary hypertension (for sildenafil and tadalafil), they show potential to be of benefit in several other conditions, such as CAD and systolic heart failure.39 Mechanisms of benefit of PDE5 inhibitors include pulmonary and systemic vasodilation, increased myocardial contractility, reduced large artery stiffness and wave reflections, improved endothelial function, and reduced apoptosis, fibrosis and hypertrophy through mechanisms involving NO, cyclic guanosine monophosphate, protein kinase G and Rho kinase.39 A very important issue is whether treatment of ED per se (and not of its risk factors and comorbidities) will have an impact on cardiovascular risk. While this applies to all therapeutic modalities of ED, it is particularly pertinent for PDE5 inhibitors, since they represent the mainstay of ED therapy. Data are limited to date. Gazzaruso et al.21 showed a trend of PDE5 inhibitors to reduce cardiovascular morbidity and mortality in diabetic patients with silent CAD and ED, while Frantzen et al.40 showed that 2 years after the introduction of sildenafil, the relative risk of the incidence of CVD among men with ED compared with healthy men significantly decreased from 1.7 to 1.1.

Abstract | Full Text | Full Text PDF | PubMed | Scopus (66) | Google ScholarSee all References However, α-blockers are a well-known cause of retrograde ejaculation secondary to a reversible relaxation of bladder neck smooth muscle.50x50Meinhardt, W, Kropman, RF, Vermeij, P, Nijeholt, AA, and Zwartendijk, J. The influence of medication on erectile function. Int J Impot Res. 1997; 9: 17–26
Abstract | Full Text | Full Text PDF | PubMed | Scopus (58) | Google ScholarSee all References Theoretically, the risk of a cardiac event during sexual activity should be increased. Sexual activity is associated with an elevated heart rate, blood pressure level, and myocardial oxygen demand, and this increase in hemodynamic stress may result in myocardial ischemia.79x79Kimmel, SE. Sex and myocardial infarction: an epidemiologic perspective. Am J Cardiol. 2000; 86: 10F–13F
Combination therapy has proven effective for some men who don’t respond adequately to oral medicines. The idea is to use two drugs with different mechanisms of action for better results. Commonly, sildenafil is used in combination with pellets of alprostadil (synthetic prostaglandin E1) that are inserted into the urethra (the tube in the penis that carries urine from the bladder to the outside of the body). Alprostadil also increases the blood supply to the penis, but by different means.
Abstract | Full Text PDF | PubMed | Scopus (1528) | Google ScholarSee all References After sexual intercourse, this risk increases approximately 2-fold, to 2 chances per million per hour, but only for the 2 hours after intercourse. For low-risk patients with no history of cardiovascular disease and an annual myocardial infarction risk of 1% per year, the risk increases to 1.01% with weekly sexual activity.8x8Muller, JE, Mittleman, A, Maclure, M, Sherwood, JB, Tofler, GH, and Determinants of Myocardial Infarction Onset Study Investigators. Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular physical exertion. JAMA. 1996; 275: 1405–1409
The body’s source for nitric oxide production is the amino acid L-arginine, which is naturally found in many foods. The average American ingests about 3,000–5,000 mg of L-arginine per day, as it is an amino acid naturally contained in many foods. Meats of all varieties, nuts, and dairy products are rich in L-arginine, so the body is accustomed to intake levels of several thousand milligrams every day.
Abstract | Full Text PDF | PubMed | Scopus (16) | Google ScholarSee all References These medications cause intracavernosal pressure changes in animal models, and human studies have noted deleterious effects on erectile function, decreased libido, and ejaculatory problems.42x42Weiss, RJ. Effects of antihypertensive agents on sexual function. Am Fam Physician. 1991; 44: 2075–2082

PubMed | Google ScholarSee all References This prolonged excretion half-life produces enhanced erections up to 36 hours after oral dosing, thereby potentially allowing for more spontaneous engagement of intercourse. The efficacy of tadalafil in the treatment of ED has been proved in randomized double-blind, placebo-controlled trials.78x78Porst, H, Padma-Nathan, H, Giuliano, F, Anglin, G, Varanese, L, and Rosen, R. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology. 2003; 62: 121–125


A deficiency of L-arginine, however, does not generally disrupt nitric oxide synthesis because L-arginine availability is not the rate-limiting step in this process. In fact, research over the past five years has identified an endogenous (occurs in the body naturally) inhibitor called “asymmetric dimethylarginine” or ADMA, an amino acid which blocks the production of nitric oxide. By acting as an L-arginine mimic, this damaging look-alike effectively elbows out L-arginine and pushes it off to the side in the biochemical pathway leading to the synthesis of nitric oxide. ADMA is relatively elevated in patients with hypertension, high levels of cholesterol, triglycerides, homocysteine and low-density lipoprotein (LDL), and low levels of high-density lipoprotein (HDL), as well as with aging itself. This inhibitor of nitric oxide synthesis may very well be the common factor shared by all of these abnormal conditions. Increased levels of this detrimental inhibitor (ADMA) block nitric oxide production, leading to endothelial dysfunction.
In the vessels that supply the heart, healthy arteries enlarge in diameter up to 50% during exercise when sufficient nitric oxide is present. Because of its brief half-life, a continual supply of nitric oxide is required for optimal effect. If the supply of nitric oxide is inadequate, endothelial dysfunction—a core factor in heart disease—is made worse. Endothelial dysfunction can trigger the growth of coronary plaque.8

Crossref | PubMed | Scopus (42) | Google ScholarSee all References Apomorphine does not appear to have any notable cardiovascular adverse effects and has been used successfully in Europe. However, apomorphine use has been associated with other unpleasant adverse effects such as nausea and emesis, and the drug has not been approved by the US Food and Drug Administration (FDA) for use in the United States.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Sildenafil has a 4000-fold increased selectivity for PDE-5 over PDE-3, has negligible effects on heart rate, and has only a modest effect on blood pressure level in healthy persons, with an average systolic pressure decrease of 10 mm Hg with a single dose of 100 mg.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C

Crossref | PubMed | Google ScholarSee all References In study patients taking these medications compared with controls, significant decreases in total cholesterol and low-density lipoprotein cholesterol levels were found, as well as significant increases in length of maximal tumescence per nocturnal penile tumescence testing at 2 weeks. Hypoglycemia secondary to the use of insulin or hypoglycemic agents may result in ED or orgasmic dysfunction.4x4Feldman, HA, Goldstein, I, Hatzichristou, DG, Krane, RJ, and McKinlay, JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994; 151: 54–61


Penile prosthesis is a viable option for men who cannot use sildenafil and who find the injections or vacuum erection therapy distasteful. A non-adjustable semi-rigid prosthesis is easy to insert and has no postoperative mechanical problems. The inflatable prosthesis has a pump that is put in the testicular sac for on-demand inflation and deflation. Future versions will have a remote control device similar to a garage-door opener.
Experts feel that treating erectile dysfunction on your own, without consulting a doctor, is unsafe. "If you have ED, the first thing you need is a diagnosis," says impotence expert Steven Lamm, MD, a New York City internist and the author of The Hardness Factor (Harper Collins) and other books on male sexual health. He says men with severe erectile dysfunction probably need one of the prescription ED drugs, which include Levitra (vardenafil) and Cialis (tadalafil) as well as Viagra. But, he says, mild ED -- including the feeling that "you're not as hard as you could be" -- often responds to natural remedies.
• Medications: About 25 percent of ED cases are caused by drugs. Many medications, including common medicines prescribed for diabetes and its complications, can cause ED. The most common offenders are blood pressure drugs, antihistamines, antidepressants, tranquilizers, appetite suppressants, and cimetidine (an ulcer drug). In addition, over-the-counter medications, including certain eye drops and nose drops, have been associated with ED. That does not mean you should stop taking these medications! Rather, you should discuss them with your doctor to determine whether a different dosage, an alternate medicine, or additional treatments will resolve the ED.
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