Sildenafil Citrate in Managment of Erectile Dysfunction

Erectile dysfunction belongs to hormonal-metabolic and psychosomatic disorders in modern men, and has a pronounced tendency to progress with increasing age of the male. What is also an indispensable attribute of an aging person. The modern person is growing old faster on average 10-15 years than his parents and grandparents in his time. Over the past 20 years, the clinical portrait of patients has changed dramatically. After all, most men, even at a young age today, have excessive body weight or obesity.

erectile dysfunction

ED as a polyethological symptom with multifactorial pathogenesis

Accelerated aging of the population significantly increases the risk of developing ED in modern men. This is not an independent disease. Today ED is regarded as a clinical symptom of cardiovascular diseases. They are the main problem of men's health in the 21st century. According to the generally accepted modern point of view, ED is a polyetiological organic progressive chronic disease of the cavernous bodies of the penis with a multifactorial neurovasculature-hormonal pathogenesis, which is based on endothelial dysfunction. That is why the presence of such a symptom in a man is an early marker of cardiovascular diseases, diabetes and other serious diseases, and its detection should be accompanied by mandatory tests for each patient. Studies in Finland (TAMUS) have shown a risk of developing ED for 5 years after the detection of diabetes, cardiovascular disease, cerebrovascular disease. Therefore, today there is no doubt that the problem of ED is not an isolated urological problem, and should be considered in conjunction with the patient's overall somatic state. The report published in 2003 shows the results of a standardized questionnaire survey of about 600 men between the ages of 40 and 70 in 4 countries. The frequency of ED in Italy was 17%, in Brazil - 15%, in Japan - 34% and in Malaysia - 22%. 27,839 men aged 20 to 75 years participated in the Men's Attitudesto Life Events and Sexuality (MALES) study, the prevalence of ED in Europe, South and North America was shown. In the questionnaire, ED was detected on average in 16% of cases. It should be noted that ED has a different frequency of occurrence in different countries, for example 10% in Spain and 22% in the USA.

Statistical data on the prevalence of ED in Russia were absent until 2012, and the statistics of the incidence of the USA and Europe, does not always correspond to the Russian reality. Most urologists diagnose ED only in case of complaints from the patient, without revealing it actively. However, in 2012, 1225 respondents were questioned about the prevalence of ED in urologically healthy men aged 20 to 75 years. Analysis of the questionnaire of the International Index of Erectile Function (ICEF) -5 revealed that 10.1% of the men surveyed had no signs of ED, a mild degree of ED was noted in 71.3%, an average degree of 6.6% and a severe degree of 12% of respondents. Thus, symptoms of ED were present in 1101 respondents (89.9%) of 1,225 men interviewed. It is worth noting the excessive body weight in a large number of men (48%), And we know that overweight is a risk factor for ED development.

ED: paradigms of diagnosis and pharmacotherapy

With age, the frequency of somatic complication increases, which adversely affects the erectile function of men. If a man in old age has good health, then, as a rule, he preserves sexual, erectile functions. A good erection is the absence of endothelial dysfunction, neuronal dysfunction and an adequate level of androgens against a background of qualitative psychoemotional status. Thus, today we are talking about "wise aging", and the goal of pathogenetic medicine of the XXI century. Is a man ageless, i. a man without age, who, despite the years, remains active and in demand. Today, mankind can not boast of its achievements in the field of increasing the duration of the quality life of an aging man. But if you start to make efforts to preserve health, including sexual, then, obviously, you can count on success. At least, this reliably relates to ED, which today is a well-known earliest marker of any endothelial dysfunction, including cardiac and cerebral dysfunction. Therefore, if we learn early to identify, or even better - early to begin prophylaxis of ED, then it is safe to say that our men will be protected from strokes and heart attacks, which means they will age properly, which will increase the duration of their quality life. Unfortunately, not all clinicians share this view of ED.

Inhibitors of phosphodiesterase type 5 (PDE-5) are the universally recognized "gold standard" for the pharmacotherapy of the first line of ED. This fact gives rise to a negative consequence: all patients with ED are the same and take the same drugs - PDE-5 inhibitors. This approach leads to the development of resistance to PDE-5 inhibitors. In other words, these drugs become ineffective in a particular patient either immediately or after a period of clinical effectiveness.

The dominant strategy of ED therapy is to identify its etiology and treat the underlying cause of erectile dysfunction, and not only to improve erectile function. However, practice shows that the treatment of ED (at best only at the initial stage) is to prescribe to all patients only one group of drugs - PDE-5 inhibitors. Of course, no one questions the pathogenetic efficacy of this group of drugs for any endothelial dysfunction, including ED. But if the task is to eliminate the causes of endothelial dysfunction in patients, then the question of optimizing the clinical use of PDE-5 inhibitors in the treatment of patients with ED becomes very urgent. After all, monotherapy with such drugs today is more and more often not effective enough, because they eliminate only one factor of erectile dysfunction. Moreover, the clinical efficacy and possible side effects of various PDE5 inhibitors depend on individual characteristics of the individual. Therefore, a man must test each of the drugs and choose the best option for himself. In general, the treatment of ED will be more effective and maximally pathogenetic if we learn to detect at least 4 mechanisms of ED (endothelium condition, androgenic status, neurothelia, psychological status).

As is known, sildenafil is a potent selective inhibitor of cGMP-specific PDE-5. The physiological process of erection is triggered during sexual stimulation. The essence of this process is to relax the smooth muscle tissue of the cavernous body and increase the flow of blood. At the initial stage, the release of nitric oxide (NO) in the cavernous body. Further, the level of cyclic guanosine monophosphate (cGMP) increases. The amount of this element is responsible for the degree of relaxation and, as a consequence, the intensity of the blood flow. In the process of decay of this substance, the cavernous body passes into a state of tonus, and the erection is weakened. The vast majority of cases of erectile dysfunction is associated with the process of too intensive decay of cGMP. Sildenafil reduces the intensity of this process by inhibiting PDE-5, which is responsible for the degradation of cGMP. That is sildenafil does not have a direct effect on the cavernous body and will be effective only under the condition of sexual stimulation and the desire to commit sexual intercourse.

The pharmacokinetics and clinical effectiveness of sildenafil have been well studied and proven in numerous clinical studies conducted since 1998 - the year of the appearance of sildenafil in the arsenal of effective and pathogenetic drugs for the treatment of ED.