Effex Sildenafil, 100 mg, film-coated tablets, 15 pcs., Evalar buy in Moscow at a low price

Effex Sildenafil, 15 pcs., 100 mg, film-coated tablets

To diagnose erectile dysfunction, determine its possible causes and select adequate treatment, it is necessary to obtain a complete medical history and conduct a thorough physical examination. Erectile dysfunction treatments should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie's disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia) (see section C caution").

During post-marketing studies, cases of prolonged erection and priapism have been reported. If an erection persists for more than 4 hours, you should immediately seek medical help. If treatment for priapism is not carried out immediately, it can lead to damage to the tissue of the penis and irreversible loss of potency.

Medicines intended to treat erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.

Sexual activity poses a certain risk in the presence of heart disease, so before starting any therapy for erectile dysfunction, the doctor should refer the patient for an examination of the condition of the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina, stroke or myocardial infarction in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg) or hypotension (BP < 90/50 mm Hg. Art.) (see section Contraindications"). Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of cardiovascular mortality (0.3 per 100 people per year) in patients treated with sildenafil compared with patients treated with sildenafil. those receiving placebo.

Cardiovascular complications

During post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as serious cardiovascular events (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) have been reported. ), which had a temporary association with the use of sildenafil. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events occurred shortly after sexual activity, and some of them occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and these or other factors.

Hypotension

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not a clinically significant phenomenon and does not lead to any consequences in most patients. However, before prescribing sildenafil, the physician should carefully assess the risk of possible undesirable manifestations of the vasodilating effect in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system.

Since the combined use of sildenafil and α-blockers can lead to symptomatic hypotension in some sensitive patients, sildenafil should be administered with caution to patients taking α-blockers (see section "Interaction with other drugs"). To minimize the risk of postural hypotension in patients taking α-blockers, sildenafil should be started only after hemodynamic stability has been achieved in these patients. You should also consider the advisability of reducing the initial dose of sildenafil (see section "Dosage and Administration"). The physician should inform patients about what actions to take if symptoms of postural hypotension occur.

Visual impairment

In rare cases, non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and cause of vision loss or reduction, has been reported during post-marketing use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors, including decreased papilledema/disc ratio (“congestive disc”), age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. An observational study assessed whether recent use of the PDE5 inhibitor class of drugs was associated with acute onset of NPINSID. Results indicate an approximately 2-fold increase in the risk of NPINSID within 5 half-lives of PDE5 inhibitor use. According to the published literature, the annual incidence of NPINSID is 2.5 – 11.8 cases per 100,000 men aged ≥ 50 years in the general population. In case of sudden loss of vision, patients should be advised to stop sildenafil therapy and consult a doctor immediately. Individuals who have already had a case of NPIND have an increased risk of recurrent NPIND. Therefore, the physician should discuss this risk with such patients, as well as discuss with them the potential for adverse effects from PDE5 inhibitors. PDE5 inhibitors, including sildenafil, should be used with caution in such patients and only in situations where the expected benefit outweighs the risk.

A small number of patients with hereditary retinitis pigmentosa have genetically determined dysfunction of retinal phosphodiesterases. There is no information on the safety of sildenafil in patients with retinitis pigmentosa, so the drug should be used with caution (see section "With caution").

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden deterioration or loss of hearing associated with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden deterioration or loss of hearing. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden hearing loss or deterioration has not been established. If there is a sudden deterioration in hearing or hearing loss while taking sildenafil, you should consult your doctor immediately.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donor, on human platelets in vitro. There are no data on the safety of sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, so sildenafil should be used with caution in these patients (see section "With caution"). The incidence of epistaxis in patients with pulmonary hypertension associated with diffuse connective tissue diseases was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3.0%, placebo 2.4%) . Patients receiving sildenafil in combination with a vitamin K antagonist had a higher incidence of epistaxis (8.8%) than patients not receiving a vitamin K antagonist (1.7%).

Use in conjunction with other means of treating erectile dysfunction

The safety and effectiveness of sildenafil in combination with other PDE5 inhibitors or other drugs for the treatment of pulmonary hypertension containing sildenafil (for example, Revazio®) or other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see section "Contraindications").

Impact on the ability to drive vehicles and machinery

Since when taking sildenafil, it is possible to develop dizziness, decrease in blood pressure, develop chromatopsia, blurred vision, etc. side effects, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. You should also be careful about the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

EFFEX® Sildenafil (EFFAX® Sildenafil)

To diagnose erectile dysfunction, determine its possible causes and select adequate treatment, it is necessary to obtain a complete medical history and conduct a thorough physical examination.

Erectile dysfunction treatments should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie's disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia) (see section C caution").

Medicines intended to treat erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.

Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of cardiovascular mortality (0.3 per 100 people per year) in patients treated with sildenafil compared with patients treated with sildenafil. those receiving placebo.

Cardiovascular complications

Hypotension

Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system.

Visual impairment

In case of sudden loss of vision, patients should be advised to stop sildenafil therapy and consult a doctor immediately. Individuals who have already had a case of NPIND have an increased risk of recurrent NPIND. Therefore, the physician should discuss this risk with such patients, as well as discuss with them the potential for adverse effects from PDE5 inhibitors. PDE5 inhibitors, including sildenafil, should be used with caution in such patients and only in situations where the expected benefit outweighs the risk.

A small number of patients with hereditary retinitis pigmentosa have genetically determined dysfunction of retinal phosphodyseterases. There is no information on the safety of sildenafil in patients with retinitis pigmentosa, so the drug should be used with caution (see section "With caution").

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden deterioration or loss of hearing associated with the use of all PDE5 inhibitors, including sildenafil, the majority of these patients had risk factors for sudden deterioration or loss of hearing. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden hearing loss or deterioration has not been established. If there is a sudden deterioration in hearing or hearing loss while taking sildenafil, you should consult your doctor immediately.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donor, on human platelets in vitro

. There are no data on the safety of sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, so sildenafil should be used with caution in these patients (see section "With caution").

The incidence of epistaxis in patients with pulmonary hypertension associated with diffuse connective tissue diseases was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3.0%, placebo 2.4%) . Patients receiving sildenafil in combination with a vitamin K antagonist had a higher incidence of epistaxis (8.8%) than patients not receiving a vitamin K antagonist (1.7%).

Use in conjunction with other treatments for erectile dysfunction

The safety and effectiveness of sildenafil in combination with other PDE5 inhibitors or other drugs for the treatment of pulmonary hypertension containing sildenafil (for example, Revatio®) or other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see section "Contraindications").

Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction

Sildenafil - the first PDE-5 inhibitor

PDE5 inhibitors are highly effective and safe oral medications for the treatment of ED and are recommended as first-line therapy [1].
The number of patients taking these drugs continues to increase in parallel with the increasing prevalence of ED. In 1998, the drug sildenafil was approved for clinical use. This moment became not just the starting point for the existence of another drug on the pharmacological market. It turned out to be the beginning of a new era in the field of sexual medicine, marked by a real breakthrough in the fundamental and clinical spheres, as well as in public perception of sexual pathology.

Sildenafil became the first effective and safe oral drug for the treatment of ED. The history of the discovery of sildenafil was preceded by the accumulation of knowledge about the role of nitric oxide in ensuring the normal functional state of the cardiovascular system, which was initiated by RR Furchgott and JV Zawadski [2]. However, today's use of the drug as an ED therapy is an example of how a chance observation can have a huge impact on the course of scientific progress. During clinical trials of the antianginal properties of sildenafil, researchers noted that although taking the drug is not accompanied by a significant clinical improvement in angina, in many patients it leads to the development of a kind of “side effect”, which consists in improving erectile function. This observation led to further study of the possibility of using this substance in the treatment of ED.

The discovery of sildenafil, a selective PDE5 inhibitor, led to numerous fundamental studies showing that this type of enzyme dominates in cavernous tissue, which ensures the selectivity of the drug. It should be noted that these studies also made it possible to clarify the mechanisms of action of other drugs that have been used in clinical practice for a long time, in particular papaverine and prostaglandin E1 [3], and significantly expand knowledge about the mechanism of erection and its disorders leading to ED.

The emergence of sildenafil also had a great impact on clinical research in the field of sexual medicine. In recent years, terminology has been clarified and new definitions of various forms of sexual disorders have been developed. Clinical trials of sildenafil have stimulated the creation of new diaries and questionnaires to assess the state of male sexual function. Analysis of demographic indicators of participants in large-scale clinical trials has revealed risk factors for ED, which, in turn, has contributed to the understanding of its pathogenesis.

The appearance of sildenafil had a huge public outcry. A large number of patients with ED, who had not previously consulted a doctor, received hope for the restoration of sexual function, and to date, millions of men around the world have returned to normal sexual life thanks to taking this drug.

The dose of the drug is selected by titration, starting from 50 mg, followed by a dose change (either decreasing to 25 mg or increasing to 100 mg) depending on the effect and tolerability. Sildenafil is taken 1 time per day, 1 hour before intended sexual intercourse. The effect of the drug begins 40-60 minutes after administration and lasts for 3-5 hours [3]. It is important to note that taking the drug by itself does not lead to an erection and sexual stimulation is necessary for its effect to begin.

Sildenafil is contraindicated in patients taking nitrates, patients with hypotension, severe hepatic impairment (the drug is metabolized by hepatic cytochrome P450 3A4) and pigmentary retinopathy [20].

The clinical effectiveness of sildenafil has been assessed in numerous studies conducted around the world. S.S. Carson et al. combined data obtained from 11 double-blind, placebo-controlled studies, including a total of almost 3 thousand patients with ED. After 12 weeks after starting to take the drug, an improvement in erection was noted by 76% of men receiving sildenafil and 22% of those receiving placebo, while the percentage of successful attempts at sexual intercourse was 66 and 26% in groups 1 and 2, respectively. The effectiveness of various doses of sildenafil was 65% for 25 mg, 74% for 50 mg, 82% for 100 mg. The high effectiveness of sildenafil was noted in different age groups. Thus, among patients younger and older than 65 years, the effectiveness of sildenafil was 77.6 and 69.2%, respectively. A significantly higher effectiveness of sildenafil compared to that of placebo also occurred in patients with ED of varying severity and different etiologies [4].

The use of sildenafil in special categories of patients with ED

As is known, arterial hypertension (AH) is one of the risk factors for ED. Although sildenafil has some antihypertensive effects, the drug is safe in patients with hypertension, both those receiving and not receiving antihypertensive drugs [5, 6]. The effectiveness of sildenafil in patients with ED and hypertension is high. Among patients with hypertension of various origins, taking placebo and sildenafil was accompanied by an improvement in erection in 18 and 70% of patients, respectively. Among men taking 2 or more antihypertensive drugs, these figures were 17.6 and 71% [6].

Another well-known risk factor for ED is smoking. The effectiveness of sildenafil among smokers was not inferior to that among non-smokers (80 and 74%, respectively) [4].

Many epidemiological studies have shown that depression is the second most common cause of ED after cardiovascular risk factors. In addition, the presence of ED aggravates depressive symptoms. Treatment with sildenafil was not only highly effective in patients with depression in terms of improving erectile function, but was also accompanied by a decrease in the severity of depressive symptoms [7].

Various neurological diseases, as mentioned above, can also cause the development of ED. According to studies, the effectiveness of sildenafil among patients with parkinsonism, multiple sclerosis and spinal cord injuries exceeds 80%, which corresponds to data obtained in the general population of patients with ED [8].

Special groups of patients with ED that is difficult to treat are patients with diabetes mellitus (DM) and patients who have undergone radical prostatectomy (RP).

In patients with diabetes, the effectiveness of sildenafil depends on the severity of the underlying disease and the presence of its complications. Thus, in the study by S.S. Carson et al. among patients with diabetes without complications, 8% of patients receiving placebo and 69% of those receiving sildenafil noted improved erection. In the presence of 1 complication, these figures were 12 and 43%, and in the presence of 2 complications, 10 and 43%, respectively. In all groups, the effectiveness of sildenafil was significantly higher than that of placebo [4].

The effectiveness of ED treatment after RP is determined by a number of factors. According to R. Raina et al., treatment with sildenafil was effective in 71.7% of patients after bilateral nerve-sparing RP, in 50% after unilateral nerve-sparing RP, and only in 15% of patients with ED after non-nerve-sparing surgery [9].

In addition, a feature of the course of ED in such patients is the possibility of progressive improvement of erection for up to 4 years after surgery, and therefore the ineffectiveness of a particular treatment method can be finally judged only several years after surgery. This is confirmed by data from a survey of 316 patients with ED after RP, which in 95% of cases was of a bilateral nerve-sparing nature. The effectiveness of sildenafil was 26% during the first 6 months, 36% in the period from 6 to 12 months, 50% from 12 to 18 months, 60% from 18 to 24 months. after surgery [10].

Analysis of the effectiveness and tolerability of sildenafil

Despite the high effectiveness of sildenafil, there remains a certain number of patients in whom taking this drug does not lead to an improvement in erection. In many cases, this is due to improper medication administration [11]. Patients, especially at the beginning of treatment, should be advised to take sildenafil on an empty stomach at least 30 minutes before the start of sexual activity [21]. It is also important to explain to patients that the effect of the drug develops only against the background of adequate sexual arousal and largely depends on it. In many cases, treatment should be started with 100 mg, which will allow for maximum response early in treatment and give patients confidence in its success [21-23]. In addition, studies have shown that in some patients the maximum effect of sildenafil is achieved by 6-8 doses, and therefore in many patients the final assessment of the effectiveness of the drug should be carried out after several attempts at its use [24, 37, 38].

Noteworthy is the work of A. Eisenhardt et al., who found that the clinical effectiveness of sildenafil depends on genetic factors. When analyzing the relationship between the GNB3 C825T gene polymorphism and ACE I/D, it was found that in the group of carriers of the GNB3 825C allele, sildenafil was effective in only 50% of men, while among those with the TT genotype this figure exceeded 90%. Similar results were obtained regarding the ACE I/D polymorphism: among carriers of the ACE D allele, the effectiveness of sildenafil did not exceed 50%, while in men with genotype II it was 75% [12].

The long-term effectiveness of sildenafil was also studied by Montorsi et al., who surveyed 2618 patients taking the drug for 3 years. Overall, 96% of these patients were satisfied with the treatment, and only 1.6% discontinued it due to low effectiveness [25]. The remaining 2.4% of patients stopped taking the drug for other reasons. Laboratory studies have not confirmed the existence of a tachyphylaxis effect when taking sildenafil [13].

An important characteristic of any pharmacological drug is its side effects. The most common side effects when taking sildenafil include headache (7%), facial flushing (7%), dizziness (2%), dyspepsia (1.8%), nasal congestion (1.4%) and visual disturbances. , usually in the form of blue coloring of objects (1.2%) [26].

It should also be noted that the frequency of side effects decreases as the drug is taken. Thus, in the study by S.S. Carson, the frequency of all side effects, except for visual impairment and dyspeptic disorders, decreased during the period of taking the drug. Headaches at the beginning of the study were noted by 7% of patients with ED, and after 16 weeks. - less than 1%, the frequency of dizziness also decreased from 7% to less than 1%, and nasal congestion - from 1.4% to less than 0.5% [14]. An important circumstance is also that 2/3 of patients during this study increased the dose of sildenafil. Thus, with long-term use, the frequency of most side effects of sildenafil does not exceed that of placebo.

There is growing interest in the possibility of using sildenafil for various diseases in addition to ED. In a study by K. Sairam et al. The effect of sildenafil on the severity of urinary disorders in patients with ED was assessed. After 1 and 3 months. after the start of treatment, there was a significant decrease in the severity of symptoms of lower urinary tract dysfunction, which was accompanied by an improvement in erectile function [15].

Taking sildenafil leads to an improvement in the condition of patients with primary and secondary pulmonary hypertension [27, 28]. Another possible direction for future research with sildenafil is the use of this drug in the treatment of endothelial dysfunction [29-31].

Safety of sexual activity in patients with cardiovascular diseases

Sexual intercourse in most cases is accompanied by physical activity. This makes some people, primarily men suffering from cardiovascular diseases and their partners, worry about the possibility of developing various complications due to sexual activity, which can lead to limitation or complete abandonment of it. These fears are reinforced by stories of famous people whose deaths allegedly occurred during sexual intercourse. At the same time, research data show that the risk of cardiovascular complications in patients suffering from cardiac pathology during and immediately after sexual activity, although it exists, is relatively low. For example, the risk of developing myocardial infarction in a healthy 50-year-old man within 1 year is 1%. As a result of sexual activity, this risk increases to 1.01% in a healthy man and to 1.1% in a man with a confirmed diagnosis of coronary heart disease (CHD) [16]. According to these data, the absolute risk of developing cardiovascular complications for a healthy man is 1 chance in 1 million. This figure increases to 2 chances in 1 million within 2 hours after intercourse for a healthy man and to 20 chances in 1 million for a man. suffering from coronary artery disease [33].

During sexual intercourse, on average, a man’s maximum heart rate reaches 120-130 beats/min, while systolic blood pressure rises to 150-180 mm Hg. Art. [34]. These indicators take place within only 3-5 minutes with an average duration of sexual intercourse from 5 to 15 minutes. The level of stress on the heart is usually expressed in metabolic equivalents (METs). One MET corresponds to an energy requirement expressed in resting oxygen consumption, which is 3.5 ml oxygen/1 kg body weight per minute. In most cases, during sexual activity with a usual partner, the load is 2-3 METs (with a maximum value of 5-6 METs), depending on the intensity and position. This corresponds to walking 1.5 km in 20 minutes or climbing 20 steps in 10 seconds. All of the above indicates that sexual activity in familiar conditions and with a familiar partner does not pose a greater danger for both a healthy man and a patient with coronary artery disease than various forms of everyday physical activity.

In order to standardize the assessment of cardiac risk in men with coronary artery disease who resume sexual activity, several recommendations have been created, the most widely known of which are the Princeton recommendations [16]. In accordance with these recommendations, all patients are divided into 3 risk groups depending on the number of risk factors for coronary artery disease they have and/or the severity of cardiovascular pathology. Most patients are at low risk and do not require additional cardiac examination before resuming sexual activity, which does not pose a risk to them. Patients from the average risk group require additional cardiac examination, after which they are classified as low or high risk. Patients at high risk have severe cardiovascular pathology, accompanied by severe heart failure. These patients require specialized treatment, after which the question of the degree of danger of sexual activity for them is again considered [16].

Changes in cavernous electrical activity and hemodynamics of the penis during treatment with sildenafil

To assess the effect of sildenafil on cavernous electrical activity and hemodynamics of the penis, we conducted our own study [17, 35, 36]. 291 patients with ED of various etiologies aged 21-73 years (average 59.1±14.7 years) after examination, which included a questionnaire to assess male sexual health (International Index of Erectile Function (IIEF)), pharmacodopplerography (FDG) and electromyography (EMG) of the penis were divided into groups comparable in age, severity, suspected etiology and pathogenesis of ED [17]. The sildenafil group included 81 patients who took 25-100 mg of sildenafil 1 hour before sexual intercourse for 6 months. The control examination, carried out monthly, included a survey of IIEF, FDG and EMG of the penis.

The IIEF “erectile function” indicator during treatment with sildenafil increased by 61.7% (p

Thus, according to the results of FDG, sildenafil affects both arterial and venous blood flow in the penis, which makes it primarily indicated for vasculogenic ED. EMG showed an improvement in cavernous electrical activity during treatment with sildenafil, apparently due to improved hemodynamics of the penis and oxygenation of cavernous tissue. In addition, according to the results of the IIEF survey, sildenafil provides a rapid, lasting rehabilitation effect.

New sildenafil drugs

The pharmaceutical market is represented not only by the original drug sildenafil, but also by so-called generics, one of which is the drug Dynamico.

Patient preferences when choosing drugs are influenced by many factors, including effectiveness, quality of erections, durability of improvement, speed of onset and duration of action of the drug, as well as the range of side effects [18]. Efficacy and safety are the most important factors determining patient preferences. The research results show that the clinical effectiveness of Dynamico is comparable to that of the original drug. In addition, the incidence of side effects (headache, skin flushing) was even lower than that of other sildenafil drugs [17]. This is very important for those patients who experienced adverse events during therapy. The drug Dynamico provides high-quality erection with a minimum of side effects and does not cause addiction or dependence [17, 19].

The appearance on the market of new effective and safe drugs that can improve the quality of life of patients with ED makes the therapeutic arsenal of a urologist-andrologist more diverse and allows an increase in the number of patients satisfied with such treatment.

Conclusion

The clinical effectiveness of sildenafil has been assessed in a large number of studies conducted in many countries around the world. Taking the drug leads to an improvement in erectile function in patients of different ages, regardless of the etiology, severity and duration of ED. The effectiveness of the drug is long-term. Sildenafil affects both arterial and venous blood flow in the penis, so the drug is also indicated for vasculogenic ED. When treated with sildenafil, an improvement in cavernous electrical activity is observed, which justifies its use in neurogenic ED. According to the results of the IIEF survey, sildenafil provides a rapid and lasting therapeutic effect. The effectiveness and safety of sildenafil are assessed as good. With both short-term and long-term use, sildenafil does not cause dependence or addiction.

Erectile dysfunction (ED) is characterized by a persistent inability to achieve or maintain an erection sufficient for successful sexual intercourse. This erectile dysfunction is widespread and according to KK Chew et al. by 2025, it is estimated to affect 322 million men worldwide [1].

Data from the latest separate study on the prevalence of ED in 6 regions of the Russian Federation were obtained in 2012 based on an analysis of survey data from 1225 respondents. When analyzing the IIEF-5 questionnaire, it was revealed that only 10.1% of surveyed men had no signs of ED, while a mild degree of ED was noted in 71.3%, a moderate degree in 6.6% and a severe degree in 12 % of respondents. Thus, out of 1225 men surveyed, symptoms of ED were present in 1101 (89.9%) respondents [2].

For many decades, treatment of ED was carried out by specialists who did not have sufficient knowledge of the pathophysiology and mechanisms of erection. Thus, in 1668, intracavernosal injections of salt solutions were first performed, then numerous options for oral therapy with various tinctures (for example, from animal testicles) were used; in the 19th century, subcutaneous injections of ejaculate were proposed; in 1936, the first penile implantation was performed [3 ].

Currently, in the treatment of ED, the polyetiological nature of the disease is taken into account, but the first line of therapy, despite the variety of causes of ED, are phosphodiesterase type 5 inhibitors (PDE-5 inhibitors). The noninvasive nature of PDE5 inhibitor therapy has increased the availability of treatment compared to other treatment modalities, which include intracavernous injections of vasoactive drugs, vacuum devices, penile prostheses, and surgical vascular reconstructions [3].

The history of the use of PDE-5 inhibitors began in March 1998, when the drug sildenafil was approved for use by the Food and Drug Administration (FDA) in the United States of America. With the appearance on the market of this first effective tablet drug for the treatment of ED, sildenafil rightfully became the flagship and gold standard of first-line treatment for ED. Vardenafil and tadalafil, which were introduced somewhat later, are also known as selective PDE5 inhibitors. Thus, sildenafil is the most studied drug among PDE-5 inhibitors in terms of safety and effectiveness.

Sildenafil citrate provides an increase in the concentration of cyclic guasine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum of the penis, which, in turn, leads to an increase in the level of nitric oxide (NO) in these cells and, as a result, to the relaxation of these cells and increased blood flow in the penis. When the NO-cGMP chain is activated, which is observed during sexual arousal, inhibition of PDE5 leads to an increase in cGMP in the corpus cavernosum. The pharmacological effect is achieved only in the presence of sexual stimulation [4].

USE OF SILDENAFIL IN PATIENTS WITH CARDIOVASCULAR DISEASES

In the American Massachusetts Male Aging Study, the incidence of ED in men aged 40-70 years was 52%. In the German study Cologne Male Survey, when analyzing the population, the incidence of ED was 10% in men aged 40-49 years, 16% in men aged 50-59 years, 34% in men aged 60-69 years and more than 50% in men aged from 70 to 80 years [5-7]. Thus, the main group of patients with erectile dysfunction are men over 50 years old; at this age, the incidence of cardiovascular diseases, including myocardial infarction and stroke, increases. Sexual dysfunction in men with cardiovascular disease is common. Many patients stop sexual activity due to fear that physical efforts during sexual activity will be complicated by recurrent myocardial infarction. However, there are a number of studies proving the safety and effectiveness of sildenafil citrate in a group of patients with ED and cardiovascular diseases [8-9].

In a phase II/III, double-blind, open-label study conducted by the FDA, more than 3,700 patients received sildenafil for ED and nearly 2,000 received placebo. Approximately 25% of patients had hypertension and were taking antihypertensive drugs, and 17% had diabetes. In these studies, the incidence of major cardiovascular events was similar in the sildenafil and placebo groups. 28 patients who suffered myocardial infarction during the study were registered. The incidence of myocardial infarction was 1.7% in the sildenafil group and 1.4% in the placebo group. There were no differences in the incidence of cardiovascular disease between the two groups, and no deaths were related to treatment. Histomorphological studies did not find any traces of PDE-5 inhibitors in the area of necrosis and tissue of the ventricles of the heart, but traces of PDE-5 inhibitors were found in the atria [10].

In studies by M. Guazzi et al. It was found that sildenafil improves the condition of the endothelium. The authors noted flow-dependent dilatation of the brachial artery in patients with heart failure and type 2 diabetes mellitus [11].

In patients with heart failure due to ischemic or non-ischemic heart disease without pulmonary disease, a single dose of 50 mg of sildenafil caused a significant increase in cardiac index and a decrease in pulmonary vascular resistance both at rest and during exercise. In patients with coronary artery diseases, a positive effect of sildenafil on skin microcirculation has been established [12].

The vasodilator effect of sildenafil affects both arteries and veins, so the most common side effects are headache and facial flushing. Sildenafil causes a slight decrease in systolic and diastolic blood pressure, but clinically significant hypotension is rare, while co-administration of sildenafil and nitrates causes a more significant drop in blood pressure. For this reason, sildenafil is contraindicated for use in patients within 24 hours after taking short-acting nitrates. Meanwhile, about 5.5 million men require constant intake of nitrates, which leaves the question of further research on the joint use of these substances open [9].

USE OF SILDENAFIL IN PATIENTS WITH DIABETES MELLITUS

In the practice of a therapist, a pressing issue is the use of sildenafil for diabetes mellitus, since in patients suffering from type 1 and type 2 diabetes mellitus, erectile dysfunction occurs three times more often than in the general patient population. Moreover, erectile dysfunction can be considered as an early marker of diabetes mellitus. Thus, 12% of men suffering from erectile dysfunction were diagnosed with diabetes mellitus for the first time during examination. An additional 50% are expected to develop ED within 5–10 years of diagnosis [13]. The mechanism of ED in men with diabetes mellitus is predominantly caused by organic factors: vasculogenic and neurological. Goldstein et al. A study of sildenafil citrate 50 mg in patients with diabetes reported a 52% improvement in erectile function compared with placebo [14]. Similar data were obtained by MS Rendell et al. They noted an improvement in erectile function in 56% of patients taking sildenafil at a dosage of 100 mg versus 10% in the placebo group. Thus, sildenafil is effective and well tolerated in the treatment of organic ED in men with diabetes mellitus [15].

USE OF SILDENAFIL IN PSYCHOTHERAPY PRACTICE

Erectile dysfunction is a polyetiological disease and in some cases can be caused by various psychogenic factors that require specialized therapy. ED can both cause depression and be its consequence.

It has been noted that with monotherapy with antidepressants, antidepressant-induced ED occurs in 37% of cases, manifested by decreased libido, difficult ejaculation and anorgasmia. In a 12-week randomized, double-blind, placebo-controlled study in 20 urology clinics, the effect of sildenafil on erectile dysfunction in men with mild to moderate depressive disorders was assessed. Not only has sildenafil been shown to be an effective drug for the treatment of erectile dysfunction, but it has also been associated with a marked reduction in depressive symptoms and an improvement in quality of life: 60 (90.9%) of 66 men taking sildenafil reported that the treatment improved their erections and 59 (89.4%) %) noted an improvement in the ability to perform sexual intercourse, compared with 8 (11.4%) and 9 (12.9%) of 70 men receiving placebo, respectively [16-17].

A meta-analysis of 9 randomized studies was conducted involving 398 men with ED of mixed etiology who received various treatments: 141 patients used psychotherapy only, 109 only sildenafil, 68 patients used psychotherapy in combination with sildenafil, 20 people used vacuum devices and 59 people included to the control group. The best rates of successful treatment were obtained for a group of patients in which psychotherapeutic treatment was combined with sildenafil [18].

Another study assessed the effect of sildenafil on couple mental health using the Self-Esteem And Relationship (SEAR) questionnaire. According to the results of the survey, after a year of taking the drug, indicators such as general well-being, self-control, and satisfaction in relationships increased significantly. The authors recommend taking the drug to improve the overall mental health of not only the man, but also the couple as a whole [19].

SELECTED ISSUES OF THE APPLICATION OF SILDENAFIL IN VARIOUS UROLOGICAL DISEASES

Currently, the world has extensive experience in the use of sildanafil for various urological diseases complicated by ED.

Lower urinary tract dysfunction and ED

There are several clinical studies demonstrating the effectiveness of PDE5 inhibitors in the treatment of lower urinary tract dysfunction (LUTS). JP Mulhall et al. studied the effect of sildenafil on LUTS in men referred for sexual dysfunction. After the administration of sildenafil, 60% improved their IPSS questionnaire scores. The mean decrease in IPSS scores per week was 2 ± 0.6. The authors concluded that sildenafil helps improve urination in men with mild to moderate forms of LUTS and ED [20].

Many studies have been devoted to studying the role of PDE-5 inhibitors in combination with α-blockers in improving sexual function. SAKaplan et al. reported the results of their experimental work demonstrating the safety and effectiveness of combination treatment with the blocker alfuzosin and sildenafil compared with monotherapy groups in the treatment of LUTS and ED. After 12 weeks of therapy, patients in all groups showed an improvement in IPSS, Qmax and IIEF scores, but the best results were obtained in the combination therapy group. The researchers concluded that treatment with sildenafil in combination with an adrenergic blocker was safe and effective in the treatment of both LUTS and ED [21]. In another randomized, double-blind, placebo-controlled study performed by K. McVary et al. similar results were noted. In this 12-week study, 366 men over 45 years of age with IIEF-5 scores less than 25 and IPSS scores greater than 12 received sildenafil 50 and 100 mg or placebo. The results showed a reduction in mean IPSS score of 6.32 points in the sildenafil group compared to 1.93 in the placebo group. On the IIEF-5 scale, an improvement in the mean score was found by 9.17 compared to 1.86 points when taking placebo (p < 0.0001) [22].

Thus, the use of sildenafil, either alone or in combination with alpha-blockers, has demonstrated efficacy and safety in the treatment of LUTS caused by benign prostatic hyperplasia (BPH) and erectile dysfunction.

Prostate Cancer and ED

Treatment of erectile dysfunction with sildenafil in patients undergoing radiation therapy for prostate cancer (PCa) was initially shown to be effective in uncontrolled studies and later confirmed in a controlled study. 50 patients with ED after radiation therapy for localized prostate cancer took 50 mg of sildenafil. At the same time, a significant improvement in erection was noted by 66-74% of patients [23, 24].

The most significant prognostic factors for the restoration of erectile function after radical prostatectomy are bilateral preservation of the neurovascular bundles and the absence of erectile disorders before surgical treatment. According to M. Tutolo et al. The effectiveness of sildenafil for the treatment of ED in 170 men after radical nerve-sparing prostatectomy was 80% [25]. In a randomized, double-blind, placebo-controlled study, H. Padma-Nathan et al. report that early administration of a PDE5 inhibitor increases the recovery of spontaneous erections, with the effectiveness of sildenafil increasing over time, with better results observed 12–24 months after surgery [26].

Pelvic trauma and ED

Injuries to the pelvis and perineum can cause erectile dysfunction. PJ Harwood et al. noted that as a result of pelvic fracture and urethral injury, 30% and 42% of patients, respectively, had erectile dysfunction [25]. OZ Shenfield et al. reported that after urethroplasty, the administration of sildenafil at a dosage of 100 mg significantly reduced the manifestation of ED in 47% of patients. It has been noted that the drug is most effective for injuries of the genitourinary organs with preserved innervation and blood supply [27-28].

Fertility and ED

Equally important is the assessment of the effect of sildenafil on male fertility. After sildenafil entered the pharmaceutical market, many scientific works were devoted to studying the effect of the drug on the characteristics of sperm in vitro. Research by A.O. Kulikova et al., conducted at the Federal State Budgetary Institution "Research Institute of Urology" of the Ministry of Health of Russia in 2013, showed that in vitro conditions revealed a sharp increase in total sperm motility (A + B) when exposed to sildenafil at a concentration of 25 ng/ml (p < 0.001 ) and a tendency towards inhibition of general mobility (A+B) at drug concentrations above 250 ng/ml (p=0.09). This may indicate the presence of a stimulating effect on spermatogenesis and sperm maturation at a low dose of the drug. According to the data obtained, the author recommends avoiding maximum therapeutic dosages of sildenafil in patients planning pregnancy [29].

Currently, in addition to the original drug sildenafil, a generic Erexezil, produced in Hungary, has appeared on the Russian market. The results of the studies show that the effectiveness and safety of the drug Erexesil is comparable to that of the original drug [30]. Studies have noted a significant positive effect of Erexesil on erectile function. There was an improvement in the quality of life of patients taking this drug [31]. Available release forms of 50 mg and 100 mg No. 1 and No. 4 allow effective dosing of the drug, which ensures an individual approach to the treatment of each patient.

LITERATURE

Chew KK, Earle CM, Stuckey BGA, Jamrozik K, Keogh EJ. Erectile dysfunction in general medicine practice: prevalence and clinical correlates. // Int J Impot Res. 2000. Vol. 12. P. 41–45.
Pushkar D.Yu., Kamalov A.A., Al-Shukri S.H., Erkovich A.A., Kogan M.I., Pavlov V.N., Zhuravlev V.N., Bernikov A.N. Analysis of the results of an epidemiological study of the prevalence of erectile dysfunction in the Russian Federation // Urology. 2012. N 6. P. 5–9.
Jonas U. The history of erectile dysfunction management. // Int J Impot Res. 2001. Vol. 3. P. 3-7.
Boswell-Smith V, Spina D, Page CP. Phosphodiesterase inhibitors. //Br J Pharmacol. 2006. Vol. 147. P. 252–257.
Stolk EA, Busschbach JJ. Are patients and the general public likeminded about the effect of erectile dysfunction on quality of life? // Urology. 2003. Vol. 61, N 4. P. 810-815.
Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. // J Urol. 1994. Vol. 151, N 1. P. 54-61.
Braun M, Wassmer G, Klotz T, Reifenrath B, Mathers M, Engelmann U. Epidemiology of erectile dysfunction: results of the “Cologne Male Survey”. // Int J Impot Res. 2000. Vol. 12, N 6. P. 305-311.
Cakir O. The frequencies and characteristics of men receiving medical intervention for erectile dysfunction: Analysis of 6.2 million patients. // 28th Annual EAU congress, 15-19 March, 2013. Milan. Italy, abst. N 126.
American Heart Association. 1998 Heart and Stroke Statistical Update. Dallas, Tx: American Heart Association; 1997.
Zusman RM. Cardiovascular data on sildenafil citrate. // Am J Cardiol. 1999. Vol. 83(1). P. 44.
Guazzi M, Tumminello G, Di Marco F, Guazzi MD. Influences of Sildenafil on lung function and hemodynamics in patients with chronic heart failure. //Clin Pharmacol Ther. 2004. Vol. 76. P. 371–8.
Lewis GD, Lachmann J, Camuso J, Lepore JJ, Shin J, Martinovic ME, Systrom DM, Bloch KD, Semigran MJ. Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure. // Circulation. 2007. Vol. 115. P. 59-66.
Shabsigh R, Perelman M, Lue TF, Broderick GA, Lockhardt D. Men's health issues: prevalence and correlates of erectile dysfunction. //Jurol. 2005. Vol. 174. P. 662–667.
Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA. Oral sildenafil in the treatment of erectile dysfunction. //N Engl J Med. 1998. Vol. 338. P.1397-1404.
Rendell MS, Rajfer J, Wicker PA, Smith MD. Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. // JAMA. 1999. Vol. 281, N 5. P. 421-426.
Seidman SN, Roose SP, Menza MA, Shabsigh R, Rosen RC. Treatment of erectile dysfunction in men with depressive symptoms: results of a placebo-controlled trial with sildenafil citrate. //Am J Psychiatry. 2001. Vol. 158. P. 1623–1630.
Zajecka J, Mitchell S, Fawcett J. Treatment-emergent changes in sexual function with selective serotonin reuptake inhibitors as measured with the Rush Sexual Inventory. //Psychopharmacol Bull. 1997.Vol. 33. P. 755-760.
Melnik T, Soares B, Nasello AG. Psychosocial interventions for erectile dysfunction. //Cochrane Database of Systematic Reviews. 2007. Vol 3.
O'Leary MP, Althof SE, Cappelleri JC, Crowley A, Sherman N, Duttagupta S. Selfesteem, confidence and relationship satisfaction of men with erectile dysfunction treated with sildenafil citrate: a multicentre, randomized, parallel group, double-blind, placebo controlled study in the United States. // J Urol. 2006. Vol. 175. P. 1058–1062.
Mulhall JP, Guhring P, Parker M, Hopps C. Assessment of the impact of sildenafil citrate on lower urinary tract symptoms in men with erectile dysfunction. //J Sex Med. 2006. Vol. 3, N 4. P. 662-667.
Kaplan SA, Gonzalez RR, Ogiste J, et al. Combination of an alpha-blocker, alfuzosin SR, and a PDE-5 inhibitor, sildenafil citrate, is superior to monotherapy in treating lower urinary tract symptoms (LUTS) and sexual dysfunction. //Jurol. 2006. Vol.175, Suppl. 4 P. 528. Abstract 1638
McVary K, Camps J, Henry G, Camps JL, Jr, Young JM, Tseng LJ, van den Ende G. Sildenafil improves erectile function and urinary symptoms in men with erectile dysfunction and concomitant lower urinary tract symptoms. // J Urol. 2006. Vol. 175, Suppl. 4. P. 527–528. Abstract 1637
Zelefsky MJ, Mckee AB, Lee H, Leibel SA. Efficacy of oral sildenafil in patients with erectile dysfunction after radiotherapy for carcinoma of the prostate. //Urology. 1999. Vol. 53. P. 775–778.
Merrick GS, Butler WM, Lief JH, Stipetich RL, Abel LJ, Dorsey AT. Efficacy of sildenafil citrate in prostate brachytherapy patients with erectile dysfunction. //Urology. 1999. Vol. 53. P. 1112–1116.
Tutolo M, Briganti A, Suardi N, Gallina A, Abdollah F, Capitanio U, Bianchi M, Passoni N, Nini A, Fossati N, Rigatti P, Montorsi F. Optimizing postoperative sexual function after radical prostatectomy. // Ther Adv Urol. 2012. Vol. 4, N 6. P. 347-365.
Padma-Nathan H, McCullough AR, Levine LA, Lipshultz LI, Siegel R, Montorsi F, Giuliano F, Brock G; Study Group. Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve sparing radical prostatectomy. // Int J Impot Res. 2008. Vol. 20, N 5. P. 479-86.
Harwood PJ, Grotz M, Eardley I, Giannoudis PV. Erectile dysfunction after fracture of the pelvis. // J Bone Joint Surg Br. 2005. Vol. 87, N 3. P. 281-90.
Shenfield OZ, Gofrit OD, Gdor Y, Landau I, Katz R, Pode D. The role of sildenafil in the treatment of erectile dysfunction with pelvic fracture urethral disruption. // J Urol. 2004. Vol. 172. P. 2350–2352
Kulikov A.O. The influence of phosphodiesterase type 5 inhibitors on spermatogenesis: Diss. Ph.D. honey. Sci. Moscow. 2013. 178 p.
Randomized, open label, 2-way crossover, bioequivalence study of sildenafil 100 mg tablet and Viagra (reference) following a 100 mg dose in healthy subjects under fasting conditions. // Final integrated clinical and statistical report. Version Date: 2007-02-26.
Instructions for medical use of the drug Erexesil. // URL: https://www.egis.ru/images/science/bioequivalencestudy_2007.pdf

Attached file	Size
1.19 MB

‹ The role of distance education in increasing the level of knowledge of primary care specialists Up Modern views on the problem of erectile dysfunction in patients after surgical correction of cardiovascular diseases (literature review) ›