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    • Cardiovascular Side Effects: Theory or Clinically Relevant?

      Soon after the approval of sildenafil for treatment of ED, several reports of adverse events temporarily related to use of sildenafil raised concerns regarding the safety of PDE-5 inhibitors, particularly in patients with cardiovascular disease. However, detailed statistical analyses, considering that the patient population using these agents is characterized by a high prevalence of cardiovascular risk factors, did not confirm an increased cardiovascular risk of sildenafil use. Neither prospective clinical trials nor retrospective analyses revealed an increased risk for sildenafil alone or for vardenafil or tadalafil. Some theoretical concepts were initially suggested to explain the cardiac events in men taking PDE-5 inhibitors. Direct effects of PDE-5 inhibitors in altering myocardial contractility, altered response of the heart to adrenergic stimulation by...

    • Effects in the Cardiovascular System (part 2)

      There is another class of agents requiring special attention: α-blockers (e.g., doxazosin, terazosin, or tamsulosin) used as antihypertensive agents or in the treatment of benign prostate hyperplasia because of potential enhancement of blood pressure-lowering effects. For vardenafil, tadalfil, and sildenafil, the label precaution is used for a combination with α-blockers—especially with higher doses. No more than 25 mg of sildenafil should be taken within a 4-h window with an α-blocking agent. In summary, the three available inhibitors of PDE-5 are well-tolerated by most of the cardiovascular patients, and blood pressure-lowering effects are mild. Generally, a base-line blood pressure of more than 90/60 mmHg should be a prerequisite for PDE-5 inhib-itors (or any vasodilator) to be applied. Various antihypertensive agents can...

    • Effects in the Cardiovascular System

      Because smooth muscle cells of both the arterial and venous system contain significant amounts of PDE-5, blood pressure-lowering effects of the three agents are especially important. In a study by Zusman et al. oral administration of sildenafil resulted in a non-dose-dependent reduction of arterial systolic and diastolic blood pressure of 7 to 10 mmHg. These mild blood pressure-lowering effects were similar in patients with hypertension; small reductions in blood pressure were also observed with vardenafil and tadalafil. Most importantly, combination with a broad spectrum of antihypertensive agents was well-tolerated, as investigated in several studies in normotensive and hypertensive patients. However, there are two important exemptions: Nitrates or any drug serving as a nitric oxide donor must not be combined with...

    • Sildenafil, Vardenafil, Tadalafil: Basic Mechanism of Action

      For the physician interested in cardiovascular issues, PDE-5 inhibitors, now broadly used for the treatment of ED, are a highly interesting class of agents. Sildenafil, the first available agent for treatment of ED, was initially developed to find a novel anti-anginal concept. Although its anti-anginal potency was not promising in the first clinical studies, the “side effect” of enhancing penile erections soon became the main target of further clinical research. In several tissues, smooth muscle cells relax in response to nitric oxide (NO), which stimulates the enzyme guanylate cyclase, resulting in increased intracellular concentra-tions of cyclic guanosine monophosphate (cGMP). PDE-5, the major target of the PDE-5 inhibitors sildenafil, vardenafil, and tadalafil, catalyzes the breakdown of cGMP. There-fore, in tissues containing...

    • ED: First Warning Sign of Silent Cardiovascular Disease?

      A detailed medical history, including sexual and psychosocial history and an updated list of the medications, should be obtained from any patient seeking help for ED. As mentioned earlier, because of the close association between cardiovascular risk factors and ED, searching for potential cardiovascular disorders in these patients appears worth-while. In some cases, ED may be a warning sign of silent cardiac disease before symp-toms of heart disease are present. Among patients with type 2 diabetes mellitus, ED was identified as a highly efficient predictor of silent coronary artery disease apart from traditional risk factors such as smoking, micro-albuminuria, and lipid abnormalities. Furthermore, a strong association between endothelial dysfunction of peripheral arteries (measured as vasodilation of the brachial artery) and...

    • Erectile Dysfunction – Conclusion

      ED is highly prevalent among men, regardless of geography or ethnicity. Its prevalence and incidence are associated with aging, cardiovascular disease, diabetes, hyperlipid-emia, lifestyle issues (such as smoking, alcohol abuse, obesity, and sedentary lifestyle), depression, pelvic surgery, neurological disorders, trauma, symptoms of benign prosta-tic hyperplasia, side effects from medication, and psychological and interpersonal factors. The severity of ED is also a prognostic marker of important medical diseases. ED has a significant negative impact on the quality of life of patients and their partners. Treatment-seeking behavior is influenced negatively by certain barriers, including the belief that ED is a normal part of aging, denial, and embarrassment.

    • Treatment – Erectile Dysfunction

      In the Cross-National Survey on Male Health Issues, the aim was to describe the motivators and barriers influencing treatment-seeking behavior in men with ED. Screening included 32,644 men. Follow-up questionnaires were completed by 2831 men who suffered from ED. Men were recruited in waiting rooms in general practice offices. Treatment-seeking among men who suffered from ED was highest among Spanish men (48%) and lowest for German and Italian men (27 and 28%, respectively). Rate of cur-rent ED medication use among men suffering from ED was quite low across all countries, ranging from only 8% in France and Italy to 14% in the United States. The top three barriers to seeking ED treatment were the belief that ED was a normal...

    • Treatment – Seeking Behavior

      In a study using questionnaires sent to 108 patients, 100 (93%) responded. Researchers looked at hospital records and data from the survey. Only 32% continued self-injection treatment, about half of those (56%) discontinued within the first year, and patients who stopped therapy were significantly older and had poor initial impressions of therapy. Similarly to other studies, the authors concluded that dropout had little to do with side effects or etiology. In a study of 195 men comparing treatment compliance and treat-ment choice with marital satisfaction using the Maudsley Marital Questionnaire, no dif-ferences were found between the four groups tested: patients on intracavernosal injection treatment, patients who dropped out during the trial-dose phase, patients on other treat-ment, and patients who renounced...

    • Erectile Dysfunction – Economical

      An attempt was made to estimate the economical impact of ED in the United Kingdom. In this study (conducted from 1997 to 1998) on the cost of ED in the National Health Service (NHS), it was estimated that £53 million was spent to manage 113,600 patients with ED. The main cost driver was outpatient visits, which accounted for 65% of the cost. Drugs accounted for 25% and genito-urinary consultations, and pros-theses accounted for only 4% of the cost. It was estimated that the NHS managed 35% of the population with ED. Assuming that this was representative, the total population of individuals in the United Kingdom was estimated to be approximately 325,600. It has been further estimated that these men incur...

    • Impact of Erectile Dysfunction

      ED is highly prevalent, the incidence is strongly age-related, and it is progressive and undertreated. The word population is rapidly aging. In 2000, 13% of the world’s population was older than 65 yr, and it is estimated that by 2020, this population will increase to 20%. The projections made in 1998—namely, that a fourfold increase in the ED industry would occur by 2002, from about $0.9 to $5 billion—have been proven. The impact of a condition with such escalating proportions seems obvious. The economical impact of a medical condition or disease is not limited by the cost of diag-nosis and treatment, but it includes the impact on the patient and society in various ways, such as loss of time at...

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