Sildenafil – The mechanism of action

The realization of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, subsequent relaxation of the smooth muscle tissue of the cavernous body and an increase in blood flow. Sildenafil does not have a direct relaxing effect on the isolated human cavernous body, but it enhances the effect of nitric oxide by inhibiting PDE-5, which is responsible for the breakdown of cGMP.

Sildenafil is selective against PDE-5 in vitro, its activity against PDE-5 exceeds the activity against other known PDE isoenzymes: PDE-6 — by 10 times; PDE-1-by more than 80 times; PDE-2, PDE-4, PDE-7–PDE-11 — by more than 700 times. Sildenafil is 4000 times more selective against PDE-5 compared to PDE-3, which is of crucial importance, since PDE-3 is one of the key enzymes for the regulation of myocardial contractility.

A prerequisite for the effectiveness of sildenafil is sexual stimulation.

Sildenafil restores impaired erectile function under conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.

Sildenafil: clinical data

Cardiological studies. The use of sildenafil in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers. The maximum decrease in systolic pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg, and diastolic pressure-5.3 mm Hg. A more pronounced, but also transient effect on blood pressure was observed in patients taking nitrates.

In a study of the hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe coronary artery disease (more than 70% of patients had stenosis of at least one coronary artery), systolic and diastolic pressure at rest decreased by 7 and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not disrupt blood flow in stenosed coronary arteries, and also led to an increase (by about 13%) in adenosine-induced coronary flow in both stenosed and intact coronary arteries. In a double-blind placebo-controlled study, 144 patients with erectile dysfunction and stable angina, taking antianginal drugs (except nitrates), performed physical exercises until the severity of angina symptoms increased. The duration of the exercise was significantly longer (19.9 seconds; 0.9-38.9 seconds) in patients taking sildenafil in a single dose of 100 mg, compared with patients receiving placebo.

In a randomized, double-blind, placebo-controlled study, the effect of changing the dose of sildenafil (up to 100 mg) was studied in men (n=568) with erectile dysfunction and arterial hypertension taking more than two antihypertensive drugs. Sildenafil improved erection in 71% of men compared to 18% in the placebo group. The frequency of adverse effects was comparable to that in other groups of patients, as well as in those taking more than three antihypertensive drugs.

Studies of visual disorders. In some patients, 1 hour after taking sildenafil at a dose of 100 mg, a slight and transient impairment of the ability to distinguish shades of color (blue/green) was detected using the Farnsworth-Mansell 100 test. After 2 hours after taking the drug, these changes were absent. It is believed that the violation of color vision is caused by the inhibition of PDE-6, which is involved in the process of color transmission in the retina of the eye. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, IOP or pupil diameter.

In a placebo-controlled cross-sectional study of patients with proven early-age macular degeneration (n=9), sildenafil in a single dose of 100 mg was well tolerated. There were no clinically significant changes in vision assessed by special visual tests (visual acuity, Amsler grid, color perception, color passage modeling, Humphrey perimeter and photostress).

Effectiveness. The efficacy and safety of sildenafil were evaluated in 21 randomized, double-blind, placebo-controlled trials lasting up to 6 months in 3,000 patients aged 19 to 87 years with erectile dysfunction of various etiologies (organic, psychogenic or mixed). The effectiveness of the drug was evaluated globally using an erection diary, the international index of erectile function (a validated questionnaire on the state of sexual function) and a partner survey.

The effectiveness of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse, has been demonstrated in all studies conducted and confirmed in long-term studies lasting 1 year. In fixed-dose studies, the ratio of patients who reported that the therapy improved their erection was 62% (sildenafil 25 mg dose), 74% (sildenafil 50 mg dose) and 82% (viagra – sildenafil 100 mg dose) compared to 25% in the placebo group. The analysis of the international index of erectile function showed that in addition to improving the erection, treatment with sildenafil also increased the quality of orgasm, allowed achieving satisfaction from sexual intercourse and general satisfaction.

According to the generalized data, among the patients who reported an improvement in erection during treatment with drugs, there were 59% of diabetic patients, 43% of patients who underwent radical prostatectomy and 83% of patients with spinal cord injuries (versus 16, 15 and 12% in the placebo group, respectively).

sildenafil

Pharmacokinetics

The pharmacokinetics of sildenafil in the recommended dose range is linear.

Suction. After oral administration, sildenafil is rapidly absorbed. The absolute bioavailability on average is about 40% (from 25 to 63%). In vitro, sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) suppresses the activity of human PDE-5 by 50%. After a single dose of sildenafil at a dose of 100 mg, the average Cmax of free sildenafil in the blood plasma of men is about 18 ng/ml (38 nM). Cmax when taking sildenafil orally on an empty stomach is achieved on average within 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the absorption rate decreases: Cmax decreases by an average of 29%, and Tmax increases by 60 minutes, but the degree of absorption does not significantly change (AUC decreases by 11%).

Distribution. The Vss of sildenafilum is on average 105 liters. The association of sildenafil and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose of viagra (an average of 188 ng) was detected in semen 90 minutes after taking the drug.

Metabolism. Sildenafil is metabolized mainly in the liver under the action of the isoenzyme CYP3A4 (main pathway) and the isoenzyme CYP2C9 (minor pathway). The main circulating active metabolite formed as a result of N-demethylation of sildenafil undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of sildenafil, and its activity against PDE-5 in vitro is about 50% of the activity of sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of tablets. The N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 hours.

Withdrawal. The total clearance of sildenafil is 41 l / h, and the final T1/2 is 3-5 h. After oral administration, as well as after intravenous administration, sildenafil is excreted as metabolites, mainly by the intestines (about 80% of the oral dose) and to a lesser extent by the kidneys (about 13% of the oral dose).

Special patient groups: Old age. In healthy elderly patients (older than 65 years), the clearance of sildenafil is reduced, and the concentration of free sildenafil in blood plasma is about 40% higher than in young patients (18-45 years). Age does not have a clinically significant effect on the frequency of side effects.

Impaired renal function. With mild (creatinine Cl 50-80 ml/min) and moderate (creatinine Cl 30-49 ml/min) degree of renal insufficiency, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. In severe renal insufficiency (creatinine Cl < 30 ml/min), the clearance of sildenafilum decreases, which leads to an approximately twofold increase in the values of AUC (100%) and Cmax (88%) compared with those of normal renal function in patients of the same age group.

Liver function disorders. In patients with cirrhosis of the liver (classes A and B according to the Child-Pugh classification), the clearance of medication decreases, which leads to an increase in the values of AUC (84%) and Cmax (47%) compared to those with normal liver function in patients of the same age group. The pharmacokinetics of viagra in patients with severe hepatic impairment (Child-Pugh Class C) has not been studied.

Diagnosis of erectile dysfunction today

Diagnosis of erectile dysfunction (ED). ED is a widespread condition that is not life – threatening, but affects the physical and mental health of men. ED has a significant impact on the quality of life of both the man himself and his partner and family members.

According to the World Health Organization (WHO), erectile dysfunction is observed in every tenth man over the age of 21. At the age of 40-50 years, ED is detected in 40% of men, in 50-60 years in 57%. Every third man over the age of 60 is not able to perform sexual intercourse at all.

To date, it is known that an erection is a complex psychoneurovascular reaction that occurs as a result of the close interaction of the endocrine, nervous, and cardiovascular systems. When these systems become discoordinated and men lose the ability to achieve or maintain sufficient erections to satisfy their sexual needs, a condition called ED develops.

ED is a multifactorial, polyethological disease. The occurrence of an adequate erection of the penis can be significantly influenced by three key factors: systemic diseases, poor nutrition and medication. It should be noted that with age, the frequency of somatic burden increases, which negatively affects erectile function, in particular, arterial hypertension, coronary heart disease and diabetes mellitus develop. In this regard, a comprehensive personalized approach to the diagnosis of ED is needed to determine the true cause of the development of ED and determine further treatment tactics.

Today, in addition to lifestyle modification (maintaining sufficient physical activity, quitting smoking) and limiting risk factors (normalizing lipid levels, blood pressure, and blood sugar), there are three lines of ED therapy. The first line includes the use of phosphodiesterase inhibitors of the fifth type, the second – vacuum devices for erection, shock wave therapy, intracavernous injections. Finally, the third-line method is the implantation of penile prostheses (phalloprosthesis). To determine the pathogenetic treatment of ED, its nature should be established. A personalized treatment and diagnostic approach with the use of additional research methods will allow you to get the expected better treatment results in the long term.

Diagnosis of erectile dysfunction

One of the paradigms of modern ED diagnostics currently implies a single algorithm for examining all patients. However, this position leads to ineffective treatment.

It is known that ED is not a disease, but a symptom. For example, to date, there is sufficient evidence that ED can be a potential marker of cardiovascular diseases, since it occurs due to endothelial dysfunction, damage to the coronary arteries and peripheral vessels. Thus, endothelial dysfunction can lead to a violation of the mechanisms of normal blood flow in the pelvis, as well as in the coronary circulation system. At the same time, the pathogenetic causes of endothelial dysfunction may be different.

In this regard, today more than ever, the question of optimizing the existing modern methods of diagnosing ED, aimed at assessing the state of the endothelium, as well as the androgen and psychosexual status of a man, is relevant. The main task of the survey is to form a complete objective picture of the state of health of a man and actively correct the detected deviations. In this case, the treatment of ED will be highly effective, as pathogenetically justified and safe as possible.

Currently, the examination of men suffering from ED includes a number of laboratory and instrumental diagnostic measures. In addition to assessing the history of the disease, sexual disorders, conducting questionnaires (according to the International Index of Erectile Function, the Questionnaire of Age-related symptoms of Androgen Deficiency in men, the Hospital Scale of Anxiety and Depression), laboratory tests (determining the level of glucose, total testosterone, lipid profile, etc.), special research methods deserve special attention. These include assessment of nocturnal penile tumescence and rigidity, pharmacodopplerography of penile vessels, assessment of systemic endothelial function, electrophysiological examination of the penis, and cavernosography.

Assessment of nocturnal penile tumescence and penile rigidity

The greatest difficulties in the study of erectile disorders are caused by the differential diagnosis of psychogenic and organic disorders of erectile function. The preservation of spontaneous erections in the absence of adequate ones is considered an indirect sign of psychogenic disorders. A differential diagnosis between psychogenic and organic forms of ED can be made, including the assessment of nocturnal penile tumescence.

Nocturnal penile tumescence was first described by H. M. Halverson in 1940, who observed infants, and then by P. Ohlmeyer in 1944, who observed healthy men of all ages. In healthy men, during the night in the REM sleep phase, there are three to five episodes of spontaneous erections lasting on average about 10-15 minutes (from 20% of the sleep time during puberty to two to seven minutes in older age).

Monitoring of the development of nocturnal penile tumescence is carried out using the RigiScan computerized system, developed in 1985.The system allows you to qualitatively and quantitatively evaluate nocturnal erections. To date, the study of nocturnal penile tumescence remains an important tool in the diagnosis of ED, since it makes it possible to analyze the effectiveness of adequate therapy aimed at restoring sexual disorders.

Thus, it was shown that the assessment of penile tumescence helps to predict the effect of taking phosphodiesterase inhibitors of the fifth type (viagra, cialis, levitra or their analogues). S. M. Elhanbly demonstrated a positive correlation between rigidity in the head and base of the penis and the effectiveness of sildenafil.

In men who have undergone radical nerve-sparing prostatectomy, the assessment of nocturnal penile tumescence is important for an adequate choice of pharmacotherapy for the purpose of early recovery of sexual function. According to A. Bannowsky, with a well-performed operation, episodes of spontaneous erection are observed as early as the first night after the removal of the urethral catheter. In the absence of nocturnal penile tumescence, it is assumed that the neuronal integrity of the cavernous nerve has been damaged, and then, according to the authors, it is necessary to additionally use intracavernous injections to restore erectile function.

Assessment of nocturnal penile tumescence is also important for young males with spina bifida pathology, since the level of spinal cord damage plays a key role in the rehabilitation of sexual function.

diagnosis of erectile dysfunction

However, in patients with diabetes, the value of this test is reduced, since many of them have concomitant somatic diseases and take medications that affect the reliability of the results.

False-positive results can be observed in neurogenic ED. False negative-in old age of the patient, with his agitation, depressive states, sleep disorders and hypogonadism, as well as taking alcoholic beverages, antiandrogens, antidepressants, barbiturates, benzodiazepines, diuretics, sympatholytics, anticholinergic anticonvulsants, sedatives and narcotic drugs, nicotine.

However, the mechanism of development of spontaneous erections differs from adequate ones, and patients who have excellent nocturnal erections may have signs of ED. In this regard, the normal values according to the results of the study of nocturnal penile tumescence do not exclude organic ED. Therefore, the question of the diagnostic value of this method of investigation remains debatable to this day, and the assessment of nocturnal penile tumescence is mainly used in scientific and clinical studies.

Conclusion

The presented review of works published over the past decade confirms the fact that the main task of diagnosis of erectile dysfunction is to establish its true cause. It is obvious that it is advisable to use research methods with proven effectiveness, since this will ensure an effective approach to treatment. Currently, methods for diagnosis of erectile dysfunction need to be optimized. It is necessary to develop a personalized diagnostic algorithm aimed at assessing the state of the cardiovascular system, endothelium, androgen status, etc. to improve the effectiveness and safety of treatment for men suffering from various forms of ED.

Erectile dysfunction (ED) and cardiovascular diseases

Numerous studies in recent years have proven the relationship between ED and cardiovascular diseases. They are often caused by atherosclerosis, which is preceded by dyslipidemia. Atherosclerosis of the arteries of the penis, manifested by ED, is often the primary symptom of systemic atherosclerosis. Therefore, the detection of atherosclerosis in the vessels of one localization increases the chance of finding it in the vessels of another localization. Thus, like fever in the prodrome of influenza, ED can serve as a reliable predictor of cardiovascular diseases in general and atherosclerosis in particular.

Therefore, when dyslipidemia is detected, in order to improve the state of erectile function, in addition to PDE-5 inhibitors, the patient should be additionally prescribed hypolipidemic drugs, such as statins. Such combination therapy with regular use significantly increases the effectiveness of treatment with PDE-5 inhibitors. So, against the background of constant intake of atorvastatin (Liprimar), sildenafil increases the International index of erectile function by 50% (without it-25%). In addition, combined therapy with PDE-5 inhibitors and antihypertensive drugs prevents the progression of atherosclerosis.

ED and cardiovascular diseases

The most difficult joint decision has to be made by a urologist and a cardiologist in men of the intermediate risk group, which includes patients with moderate stable angina, who have suffered a myocardial infarction within two to six weeks, as well as having extracardial manifestations of atherosclerosis (consequences of a brain stroke, obliterating atherosclerosis of the lower extremities) and left ventricular dysfunction/chronic heart failure of the second functional class (according to the classification proposed by the New York Association of Cardiologists).

On the one hand, the use of PDE-5 inhibitors, the gold standard in the treatment of ED, is generally quite safe. PDE-5 inhibitors (sildenafil citrate – Viagra) were originally developed as vascular drugs that significantly improve microcirculation by enhancing NO-dependent vasodilation. So, against the background of taking sildenafil citrate in patients with chronic stable angina, the time to a possible pain attack increased more than twice, the time to an attack requiring limited physical activity – more than three times, and the time to a decrease in the ST segment by 1 cm on an electrocardiogram – by more than 30%.

The risk of myocardial infarction with this drug was 0.5–0.8% (placebo – 0.9%), brain stroke – 0.3–0.4% (placebo – 0.9%), and the frequency of serious cardiovascular complications-2.3 – 3.9 (placebo–4.9) per 100 patient – years. On the other hand, in order to safely restore sexual activity, an in-depth cardiological examination and further follow-up by a cardiologist is necessary to determine which risk group (low, high) the patient belongs to. These circumstances once again emphasize the need for close professional contact between a urologist and a cardiologist in an individual solution to the problem of restoring sexual activity of a patient with cardiovascular diseases.

Erectile dysfunction in diseases of the internal organs

There are numerous risk factors that create favorable conditions for the development of erectile dysfunction (ED): atherosclerosis, coronary heart disease, arterial hypertension, kidney and liver failure, nervous (neuroses, multiple sclerosis, Alzheimer’s disease, neuropathies of various origins), mental (depression, astheno-depressive and hypochondriac conditions), endocrine (diabetes mellitus, hypo-and hyperthyroidism, androgen deficiency, hyperprolactinemia, obesity, metabolic syndrome) and urological (for example, chronic prostatitis) diseases. The most common conditions for which ED becomes one of the characteristic and persistent manifestations are age-related testosterone deficiency (18.3%), diabetes mellitus (35%), arterial hypertension (31%), dyslipidemia as a precursor of atherosclerosis (21%). In addition, the cause of ED can be the use of medications: antihypertensive agents (thiazide diuretics, beta-blockers), cardiac glycosides, blood sugar-lowering agents, hormones (estrogens, progestins, glucocorticoids, antiandrogens, gonadotropin-releasing hormone agonists), tranquilizers, nonsteroidal anti-inflammatory drugs, H2-receptor blockers, etc.

Today, phosphodiesterase inhibitors of the fifth type (PDE-5), intracavernous injections and endophalloprosthetics can solve the problem of ED in the vast majority of cases. However, the current effective treatment of ED is not a private task aimed at restoring impaired sexual function. Due to the variety of causes, ED should be considered as a symptom complex that is part of the clinical picture of a number of diseases of internal organs and systems (somatic), which directly depends on them in terms of severity and severity.

In this regard, the diagnosis of ED, especially developed against the background of diseases of internal organs, and the appointment of therapy, on the one hand, require the knowledge and participation of such specialists as a general practitioner, therapist, cardiologist, neurologist, nephrologist, and on the other, make it necessary for a urologist, andrologist, and sex therapist to closely study internal medicine – the very somatic diseases that are closely related to ED. In other words, ED, like most men’s health problems, is multidisciplinary. Therefore, men with erectile dysfunction have a chance to undergo a detailed medical examination, and as a result of the complex treatment prescribed in time, to improve not only their sexual life, but also, last but not least, their overall health.

Erectile dysfunction as a manifestation of endothelial dysfunction

There is no doubt that organic ED is based on a violation of the function of the vascular endothelium (endothelial dysfunction), which is aggravated by hypertension, dyslipidemia and diabetes mellitus. These disorders cause oxidative stress with a violation of the balance of pro-and antioxidant systems of the endothelium and the further development of persistent vasoconstriction, leading to the progression of hypertension, atherosclerosis with the development of coronary heart disease, their complications as a result of thrombosis with brain strokes and myocardial infarction, and, significantly, an early predictor in the form of ED. According to one study, 57% of men who underwent coronary artery bypass grafting had already suffered from ED long before the operation, and 64% of men hospitalized for the first acute myocardial infarction noted significant erectile dysfunction.

This is indirectly confirmed by common risk factors for ED and coronary heart disease, which include hypertension, diabetes, dyslipidemia, depression, smoking, inactivity, and obesity. Thus, ED should be considered one of the early symptoms of cardiovascular disease. Sometimes patients with cardiovascular diseases are more concerned about ED than the risk of myocardial infarction on the background of coronary heart disease or brain stroke on the background of arterial hypertension. Causing psychological stress in a man, ED can not only aggravate the course of arterial hypertension and coronary heart disease, but also significantly disrupt the relationship between sexual partners, closing the pathological circle of the pathogenesis of the disease.

Erectile Dysfunction. Androgen-Deficiency

Due to the fact that ED is largely endothelial dysfunction, any drug effects aimed at improving the function of the vascular endothelium are considered favorable. In this regard, it is necessary to mention the well-known drug Impaza, which contains antibodies to human endothelial NO-synthase in ultra-low doses. According to the creators, the drug blocks its own antibodies to endothelial NO-synthase, increasing its activity. In this case, the potentiated antibodies to the endogenous regulator do not suppress its activity, but specifically modify it. In ultra-low doses, they have a specific effect, a safety profile equal to homeopathic drugs, do not cause increased individual sensitivity and, therefore, when administered orally, they can be a component of balanced therapy.

The overall sexual satisfaction of patients taking this drug, according to various studies, reaches 74%. At the same time, in 92.6% of patients with mild and moderate ED, regardless of age and duration of the disease, erectile function improves, in 51.8% – orgasm increases, in 48% – libido increases, in 82% – satisfaction with sexual intercourse increases [9]. The advantages of Impaza include the possibility of using it against the background of constant intake of nitrates, and if necessary, the drug can be combined with PDE-5 inhibitors, which significantly increases the therapeutic effect. For example, the International index of erectile function increases by 11% in monotherapy with Impaza of severe forms of ED, and in combination with Viagra – by 34%.

Erectile dysfunction and hypertension

Arterial hypertension in patients with ED is observed in more than 50% of cases and requires mandatory correction. Recovery of sexual function in hypertension may also have adverse consequences, since during sexual intercourse, systolic blood pressure and heart rate may increase by 50-70%. It has been shown that background antihypertensive therapy not only does not reduce the effectiveness of sildenafil, but also reduces the likelihood of developing undesirable side effects from taking this PDE-5 inhibitor. Thus, the feeling of hot flashes without antihypertensive therapy was observed with a frequency of 15.1%, against the background of taking one antihypertensive drug – 12.6%, two-10.4%, dizziness without therapy-2.8%, and when taking three antihypertensive drugs or more-only 1.7%.

Conclusion

The features of the etiology and pathogenesis of ED in somatic diseases of mature and elderly men determine the need to consider this symptom complex from a multidisciplinary perspective. Urologists need to improve their knowledge of somatic medicine. In addition, a patient with ED needs to consult therapists, cardiologists, and endocrinologists. Only joint efforts can improve the quality of life, as well as the prevention of sexual dysfunction in men of working, active mature and elderly age.

About such things as erectile dysfunction and chronic prostatitis, ED and androgen deficiency, Ed and cardiovascular diseases, we will talk in our next article.

Erectile dysfunction: modern clinical practice

It is noted that in the treatment of patients with erectile dysfunction, drugs that include biologically active substances isolated from long-leaved eureka and epimedium grass are widely used. They are involved in maintaining an erection and restoring sexual function. The use of such drugs leads to a decrease in the manifestations of erectile dysfunction, pathogenetically justified and clinically justified.

The lack of assisted reproductive technologies until the beginning of the last century equated erections with the ability to procreate. However, the current view of erectile dysfunction (ED) has changed, and the erectile component is considered separately as one of the main elements of a man’s quality of life.

The results of a multicenter epidemiological study indicate a high (up to 89.9%) incidence of ED. The prevalence of ED is due to both the coverage of a larger number of the population by narrow specialists, and the introduction of modern survey methods.

Among the specific tests used in the diagnosis of ED (excluding laboratory diagnostics of hypogonadism, diabetes mellitus, hypercholesterolemia, etc.), one can distinguish pharmacological erection induction (when taking phosphodiesterase inhibitors of the fifth type, prostaglandin E1) with the assessment of the vascular component using ultrasound, cavernosometry/cavernosography, monitoring of induced and spontaneous erections (using Neva, Snap-Gauge, RigiScan devices), as well as various combinations of these methods.

erectile dysfunction

Phosphodiesterase inhibitors of the fifth type remain the first-line drugs for ED treatment. However, they have side effects, which limits their use. The World Health Organization emphasizes the importance of using herbal preparations, given their low cost, effectiveness and good tolerability (they rarely cause adverse reactions). These advantages, the possibility of long-term use with minimal medical supervision, as well as centuries of experience in herbal medicine determine the fact that patients prefer non-toxic preparations of plant origin. Next, the article will consider the points of application of biologically active substances isolated from Eureka longleaf and epimedium grass – the most commonly used components of phytopreparations that are prescribed for ED.

Historical analysis of the formation of the basic principles of the diagnosis of erectile dysfunction

The first mention of the need to examine men is found in the so – called Decree of Gratian “Concordia discordantium canonum” (1140) – the first general code of canon law of the Catholic Church. Its operation not only regulated the life of the clergy, but also extended to many aspects of the life of the laity and minorities who do not belong to the Christian community.

In the treatise “Chirurgia Magna” (1363), which is kept in the Vatican Apostolic Library, surgeon G. de Chauliac first described the diagnostic criteria for ED as a necessary component of the divorce process. Following the Lord’s commandment to “be fruitful and multiply” (Genesis 1:28) was reflected in the fact that by the early Middle Ages, the church had become the first center for identifying ED, since the inability to perform sexual intercourse allowed the marriage to be declared invalid. It was stated that ” … even a eunuch can marry, provided that he retains the ability to have an erection.” The church could approve remarriage even for women, but not for an impotent man. The induced erection was monitored visually during a procedure called “Congress”. Sexual partners “lay together for several days” in the presence of “a married matron, accustomed to such things… who should offer (partners)… spices and herbs, rub them with oils…” After observing the erection and attempts at coitus, the matron reported to the clergyman about what she saw. The assessment of vascular reactions was carried out using a “cold water test”, which allows you to assess how much the veins on the scrotum and penis were compressed. The study was conducted in water so cold and for so long that the subject’s penis became “…the same size as that of a two-year-old boy”.

The pharmacological induction of erection was described in sufficient detail by Constantinus Africanus in the treatise “Viaticum in the chapter De Coiti” (“On copulation”). This work lists the active, from the point of view of the medieval worldview, drugs for inducing an erection: the brains of thirty male sparrows, the perinephral fat of a slaughtered goat, and honey. It should be noted that these funds were not aimed at achieving pleasure, but at the possibility of procreation and procreation.

Pope John XXI (1210-1277), in his work “Practica medicinae, quae thesaurus pauperum nuncupatur”, cited 34 recipes for aphrodisiacs and 56 erectile compounds that were used as pharmacological active agents, and “if (with them) it was impossible to perform coitus, then the fault belongs to the man”.

Thus, it was the church that laid down the basic principles of the diagnosis of ED, which were improved over time.

Biochemical justification of the use of herbal medicine in ED

As mentioned earlier, one of the promising areas of ED treatment is long-term safe phytotherapy with complex drugs, which include extracts of Eureka longleaf and epimedium grass. The analysis of available modern literary sources allowed us to determine their points of application and the mechanism of action.

The use of phytopreparations allows the treatment of ED for a long time, avoiding polypragmasia and side effects characteristic of synthesized drugs.

Restoration of potency after transurethral resection

Transurethral resection of the prostate is a minimally invasive and effective operation that is prescribed to patients with benign prostatic hyperplasia. Despite the minimal invasiveness, this method is characterized by some complications, among which there is a violation of potency. This condition is quite a serious problem, especially for young men. Fortunately, the violation of potency can be temporary and with proper, professional treatment disappears after a certain time.

Why is potency disturbed after surgery

According to the results of numerous studies, it was found that up to 40% of patients who underwent transurethral resection of the prostate gland face erectile dysfunction of various degrees of severity. The exact causes of this complication have not yet been established, but scientists have several assumptions. The psychological factor is also not ignored. The experiences of a man before surgery on an important organ for him have a negative effect on the erection. This is also facilitated by the painful sensations after transurethral resection – some men noted that because of the postoperative pain when urinating, they are afraid to enter into an intimate relationship. However, after 3-6 months, when the pain went away, they had a complete recovery of the erection.

What should I do if potency has disappeared after transurethral resection?

First of all, you need to contact a competent specialist. Self-medication, the use of traditional medicine and other methods can significantly worsen the patient’s condition. Before you start to restore potency, you need to be diagnosed and determine the cause of its violation. To do this, you will need to go through several stages:

  1. Interview with a doctor, analyze complaints, collect anamnesis, study the details of the operation.
  2. Laboratory tests. The doctor may prescribe the determination of the level of hormones in the blood, etc.
  3. Instrumental examination. It may include such methods as transrectal ultrasound of the prostate gland, Dopplerography of the vessels of the penis.

Experts emphasize that a decrease in the quality of sexual life is quite common, especially in elderly patients who have undergone any manipulations on the prostate gland. Do not hesitate to visit the doctor and try to solve the problem yourself. This approach can only make the situation worse.

transurethral resection

How to restore an erection after transurethral resection of the prostate gland

Modern medicine can offer several ways to help restore potency. Treatment can be complex, or limited to only one method. The exact plan is always developed individually and may include:

  • LOD-therapy. This method allows you to increase blood circulation in the vessels of the penis, restore the destroyed nerve connections and reflex mechanisms that are involved in the occurrence and maintenance of potency, due to local negative pressure. The treatment is relatively simple, but requires a certain amount of time to achieve the result.
  • Shock-wave therapy. The efficiency of the method is about 70%. The procedure helps restore blood circulation in the cavernous bodies, accelerates tissue regeneration after surgery, and relieves inflammation and pain. Of course, all these processes have a positive effect on potency.
  • Drug therapy. It includes the appointment of special drugs in tablet form, as well as injections into the penis. The latter method is considered the most effective, although not the most pleasant.
  • Related procedures. The recovery process can be affected by the patient’s exercise and lifestyle. In particular, it is recommended to give up smoking and other bad habits, it is necessary to eat properly, to be in the fresh air more often, to lead a mobile lifestyle.

In exceptional cases, when conservative treatment does not bring the desired result, penile prosthetic surgery (phalloprosthesis) may be prescribed. It should be approached very carefully, especially in elderly patients.

Thus, there are various ways to restore potency after transurethral resection of the prostate. Initially, it is important to determine the cause of this problem and find out the individual characteristics of the patient. It is impossible to get such information on your own, so if you develop erectile dysfunction, you should contact a urologist-andrologist. The doctor will conduct an examination, prescribe the necessary diagnosis and select the optimal treatment plan, which will need to be strictly followed. Only if all these conditions are met, you can achieve the maximum chance of recovery.

How to replace Viagra – effective natural substitutes

Replace Viagra with natural aphrodisiacs

Natural aphrodisiacs affect erectile function and increase sexual activity, but they can not be considered a full-fledged substitute for Viagra. Yes, they increase sexual arousal, but they do not affect the state of the enzymes, and also do not suppress the premature release of seminal fluid.

The most effective natural aphrodisiacs are:

  • shellfish;
  • greenery;
  • nuts;
  • honey;
  • coffee;
  • dark chocolate;
  • cayenne pepper.

how to replace viagra

Natural Viagra for Men

You can take organic supplements, the action of which is aimed at restoring the process of blood circulation in the pelvis. These preparations may contain ginseng extract, deer antler (we do not trust this), walnut and other additives.

Such drugs stimulate the work of the reproductive system, improve the overall well-being and the state of the nervous system, restore the production of sperm. Home-made Viagra is called ginseng tincture. To prepare it, you need to put 100 grams of ginseng in a glass dish, pour 500 milligrams of vodka, and insist for a month. Take the product 30 drops once a day for one month.

What drugs can be taken instead of Viagra

There are a lot of such drugs, we will present two of them, this is Cialis Soft – an effective drug that provides a long-term stimulating effect. In the composition of the drug contains Tadalafil. The substance increases the quality of erection and blocks the process of early ejaculation. The effect of the product lasts at least 24 hours. And Levitra, which contains the inhibitor Vardenafil, which, like the main component of Viagra, suppresses premature ejaculation by reducing the production of the enzyme PDE-5. The action of the product lasts eight to ten hours.

We also recommend Dapoxetine – an effective tool for prolonging sexual intercourse. The drug has an inhibitory property, without reducing the sensitivity of the nerve endings. The effect lasts four hours, but dapoxetine is intended only for episodic use. It is effective for serious erectile dysfunction and does not cause any addiction.

The first experience of using viagra

My experience of using viagra: just a clarification: I did not take the original viagra, but its generic with the same name as the active substance – “Sildenafil”.

First: the drug itself does not raise anything (in the sense of viagra does not create an erection). Its action is different – it does not allow you to fall (supports an erection). And one more thing-without sexual actions, he will not show himself in any way. That is, you can swallow viagra, and go to sweep the streets or play playstation – an erection will not arise just like that. But it is worth hugging your beloved, stroking her ass – and immediately get the proper effect. This effect holds perfectly, even if “tired after work”. Adds stamina.

It was interesting to find out – will there be a permanent erection for two hours after the reception? No, when the goal of sex is achieved, everything calms down. However, if you want to repeat the process soon, you do not need to swallow the second tablet – the first and second time will work. By the way, the pill should be taken an hour before the process.

About the side effects. It is written about increased heart rate, increased blood pressure and shifted color perception. I didn’t notice anything like that, although I sometimes suffer from high blood pressure.

And about the regularity. In my 40+ years, if you sleep with your wife a couple of times a month, it’s not bad. So here about excessive dosage and fear of side effects is not worth it. Those who are going to eat it every day by handfuls-not viagra, but a psychologist is needed. Here is a mode of reception and really inspires concern.

experience of using viagra

A few reviews about the first experience of taking viagra

You can read reviews from our clients in the Testimonials section.

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How to take Viagra for the first time?

So, how to take viagra for the first time for those who have never tried it and decided? Viagra is one of the most popular medications for restoring a healthy erection and treating premature ejaculation. The drug has a high-quality and fast action, is suitable for men of all age categories, has a minimal risk of side effects in the absence of contraindications. You can use Viagra every day. The drug is not addictive when taken regularly.

It accumulates in small amounts in the blood, but in the absence of severe liver pathologies, it does not harm health and does not cause complications of existing chronic ailments. Taking Viagra is recommended for men who are not able to achieve a strong erection on their own and hold it for a full-fledged sexual act. Erectile dysfunction is the most common disease, which is expressed by a sluggish and short-lived erection, premature ejaculation of seminal fluid and low sexual energy.

Viagra can be drunk as an auxiliary product in the complex therapy of prostatitis or infertility. The drug is suitable for healthy men who want not only to increase the duration of their intimacy, but also to enhance the sensations received from orgasm. To achieve a temporary effect, it is recommended to take Viagra occasionally.

How to take Viagra for the first time. Dosage.

The drug is available in three standard dosages: 25, 50 and 100 mg. It is not obvious that the higher the dose, the more effective the drug will be. It’s different for everyone. For example, a high dose of “Viagra” in women can lead to the fact that the clitoris will become too sensitive and instead of the pleasure of making love will turn into a monstrous torment. On the other hand, too low a dosage of the drug may not be enough for a full-fledged erection in a man.

Viagra for the first time

There are several approaches to selecting the dosage of the drug. Usually, the drug is prescribed in an average dosage of 50 mg, and then, depending on the effect that has occurred (or has not occurred), the dosage is adjusted or, in the case of a good effect, does not change. Another approach is to start treatment with a minimum dosage, increasing it until a good therapeutic effect occurs.

The maximum daily dose is 100 milligrams. This amount of the component is safe for middle-aged men who do not have chronic kidney or liver pathologies. The effect of the drug persists for four hours.

The selection of the dose should be handled by a doctor who will do it more professionally and with less risk to your health.

Dosage and age

Older men and those who suffer from chronic liver or kidney diseases should reduce the daily dose to 25-50 milligrams (depending on their state of health). With regular use of the product (more than twice a week), you should also reduce the daily dose of the active substance.

With frequent use, it is recommended to use 25 milligrams once every 24 hours. When using medications containing vasodilators, it is necessary to use a minimum dose of Viagra (up to 25 milligrams per day), after receiving medical advice. Before starting treatment of sexual dysfunction with Viagra, a number of contraindications should be excluded.

Viagra for the first time: Features

Take the Viagra tablet 55-60 minutes before the start of sexual intercourse. The drug should be washed down with warm water or other non-alcoholic liquid. You can use Viagra regardless of the meal. During treatment, it is recommended to refuse to take food products whose fat content is higher than 30%. Fatty foods prevent high-quality absorption of drugs into the blood and slow down the action of this product.

Give preference to cereals, fruits and vegetables. Viagra can not be drunk at the same time with medications that contain nitrates, alpha-blockers, nitric oxide donators, inhibitors of other types. These substances reduce the effect of Sildenafil, increasing its concentration in plasma. The break between taking these substances and Viagra should be three weeks. Terms of release and storage of Viagra tablets are indicated on the package. Do not take the product after its expiration date. Before treatment, read the instructions. Make sure that the air temperature in the room does not exceed 25 degrees Celsius.

In addition, do not lose hope for those men who did not help Viagra the first time. The drug can be taken daily without worrying about health. In addition, it is recommended to make several attempts, and the drug will definitely help next time. At the same time, you need to follow the dose set by the doctor.

Try Viagra, interaction with alcohol

Experts believe that the maximum dose of alcohol, in which the risk of side effects is minimal, and the effectiveness is optimal, is 100 g of vodka. In other words, in terms of pure alcohol, about 40 g. This is equivalent to 400-450 ml of table wine, 700 ml of beer, 600 ml of gin and tonic.

Men often wonder whether it is possible to combine drugs that are used to treat impotence (Viagra, Levitra, Cialis) with alcohol.

You need to make a choice either sex or alcohol, if you want to get drunk, then go and get drunk, only when you drink Viagra in full out, there will be no effect. If you want to have sex, then you go to the pharmacy buy Viagra, Cialis or Levitra, then invite your girlfriend to coffee (restaurant, who has what finances) order a glass of wine (no more), drink and go to have sex.

Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil) are selective competitive inhibitors of PDE5. The molecules of these drugs are similar in structure to the cGMP molecule, but their effect is that they block the action of the PDE5 enzyme. From the point of view of pharmacochemistry, even minor differences in the structure of molecules can lead to a pronounced difference in their action. A striking example of the similarity in structure and differences in properties are the molecules of testosterone and estradiol.

Try Viagra and alcohol

To date, there is no convincing evidence that the combined use of “Viagra” and alcoholic beverages (in moderation) can lead to any fatal consequences.

A man weighing 80 kg can drink about 100 g of vodka and take Viagra without consequences.

From the point of view of chemistry, the main component of Viagra (sildenafil) does not interact with alcohol, this is what is called science proven. But life has proven that after an immoderate amount of alcohol in the blood (everyone has it, of course, different), there may be problems with an erection in principle. Some even turn off the entire motor system, and the consciousness that guides them meaningfully, but such, in fact, do not buy Viagra.

You can take Viagra (sildenafil) with alcohol, but you risk turning the holiday into a nightmare. Why? Alcohol increases the load on the heart, increases the number of contractions of the heart muscle, heart work increases. Viagra also has an effect on the heart, increases the number of contractions.

Putting one on top of the other, the heart begins to experience a double load. The pressure increases, there is a headache, heaviness in the head, redness of the face. Those Sami phenomena that are observed with a hangover. However, if there are no problems with high blood pressure, and vice versa, if the pressure is low, then such side effects may not happen, and the viagra taken after alcohol will pass without unnecessary inconvenience and will give a satisfactory result.

Also, alcohol can increase the side effects of Viagra.

Among the various side effects of Viagra are dizziness, headache, upset stomach, redness of the face, muscle pain, diarrhea, which can also be a side effect of alcohol consumption. That is why the use of Viagra increases the chances of unpleasant side effects from these drugs, reducing the chances of normal sex.

Well, getting drunk when taking Viagra is stupid, not only because there will be no effect, but because even if there is an effect, then when you wake up in the morning you will hardly remember, and your headache (hangover) will not make you feel cheerful, so Viagra and alcohol are not only physically incompatible, but also morally.

But it’s stupid to blame the consequences of binge drinking on Viagra: “everything would be fine if I hadn’t already drunk Viagra.” Everything would be fine if you didn’t drink the “extra” half a bottle of vodka. And with an erection, and with well-being, and with memories of the time spent.

Cialis and alcohol

Cialis is recommended to be used orally before the intended sexual activity, regardless of the concomitant intake of food or alcohol. According to the information in the annotation to the drug, Cialis does not interact with alcohol, when they are used together, neither the concentration of ethanol nor the therapeutic dose of Cialis does not change. This is quite understandable: pharmacodynamic studies have shown that the active substance of Cialis practically does not interact with those drugs whose metabolism requires the participation of the cytochrome P450 enzyme system. A small amount of alcohol will not cause any problems, but a significant dose of alcohol can interact with Cialis.

Small doses of alcohol (200 grams of wine or 0.5 liters of beer or 100 grams of vodka) with Cialis will not cause any problems for most men.

Try Viagra, interaction with alcohol

Studies have shown that the effect of Cialis does not depend on alcohol and a hearty dinner, no doubt, for Russian men this will be another argument in favor of the drug. However, it should be noted that alcohol in large doses itself negatively affects the erection and, in addition, alcohol abuse can cause erectile dysfunction.

However, we must not forget that Cialis and alcohol have a systemic effect: Cialis and alcohol dilate the walls of blood vessels, which can lead to a sharp drop in blood pressure, especially in the presence of provoking factors. This is stated in the annotation, but not too “loudly”. Clearly, those who had dizziness and an orthostatic reaction after taking alcohol will have the same reactions when using Cialis (as a result of a vascular response), and with a combination of Cialis and alcohol, these side effects will increase.

Currently, Cialis is the only phosphodiesterase-5 inhibitor, the effect of which persists for more than a day – up to 36 hours.