Modern view on the use of sildenafil citrate

The review examines the epidemiology, etiology and pathogenesis of erectile dysfunction. The clinical effects of the most long-used drug for the treatment of erectile dysfunction, sildenafil, which is also a reference drug in comparative clinical studies of the effectiveness of phosphodiesterase type 5 inhibitors, are characterized. It is noted that taking sildenafil leads to an improvement in the condition of patients of different ages, regardless of the etiology, severity and timing of erectile dysfunction. Data on the safety of the drug sildenafil are provided. The prospects for long-term continuous use of the drug are discussed.

Introduction

Erectile dysfunction (ED) is a pressing problem in urology. This is due not only to the high prevalence of ED in the population, but also to a revision of views on the causes of ED, changes in therapeutic approaches, the study of the relationship between ED and symptoms of the lower urinary tract, the need to correct erectile dysfunction after various urological operations (radical prostatectomy, urethroplasty, transurethral endoscopic surgery) [1–3].

ED is defined as the permanent or temporary inability to achieve and maintain an erection sufficient for successful sexual intercourse. Despite the fact that ED is not life-threatening, the appearance of sexual disorders leads to rapid personal and social maladaptation of the patient. In addition, in some cases, ED may be the first symptom of serious diseases (diabetes mellitus, demyelinating diseases of the spinal cord).

According to classical population studies conducted in the 20th century, the prevalence of ED increases with age. In men over 21 years of age, the incidence of ED is 10%, and among men over 60 years of age this figure triples. In the most socially active category of men (40–70 years old), 50% suffer from ED. Moreover, the frequency of ED is approximately the same among representatives of all races and continents [4].

Description and main characteristics

Sildenafil is a drug used by men to increase potency. Contains the active ingredient of the same name and is available in the form of granules with different dosages of the main component - from 35 to 140.5 mg per 1 piece. The most well-known brand of the drug, which also contains sildenafil, is Viagra.

The product is dispensed from pharmacies only with a prescription. The shelf life is 3 years from the date of production. It must be stored under standard conditions - a dark place, temperature up to 25 degrees.

Composition of the drug

Sildenafil for women is an aphrodisiac. The drug is available in tablet form for oral use. The pills are coated with a special coating to protect the stomach. Pharmacies offer the following types of dosages: twenty-five, fifty and one hundred milligrams.

The main active ingredient is sildenafil citrate. Excipients include lactose monohydrate, microcrystalline cellulose, magnesium stearate, indigo carmine, titanium dioxide, polyvinylpyrrolidone.

Contraindications

The use of Silenafil has a fairly wide range of contraindications:

• hypersensitivity to the active substance or auxiliary components of the drug;
• severe disturbances in liver function;
• low blood pressure (less than 90/50);
• recently suffered pathologies associated with cerebral circulatory disorders;
• recent myocardial infarction;
• phenylkenothuria;
• loss of vision in one eye;
• hereditary retinal dystrophy;
• simultaneous use with Amylnitrite, nitrates and other nitric oxide NO donors;
• simultaneous use with the drug "Ritonavir";
• children under 18 years of age.

There are other contraindications. For example, the drug is not recommended for use by men who should not be sexually active due to severe heart failure.

Hypertensive patients with blood pressure above 170/100 should take this medication with caution, as well as in the presence of:

• severe arrhythmia that threatens life;
• left ventricular obstruction;
• conditions that predispose to prialism;
• ischemic optic neuropathy;
• anatomical deviations of the penis (deformation, Peyronie's disease and others).

Causes of erectile dysfunction

Traditionally, the causes of erectile dysfunction are divided into organic and psychogenic. However, psychogenic factors, as a rule, are secondary in nature, reflecting the response of the patient’s higher nervous activity to a primary violation of sexual function. Thus, in the vast majority of cases, ED is caused by organic disorders of the blood circulation and innervation of the penis, which is confirmed by numerous fundamental studies of the mechanisms of erection and clinical experience in treating patients with ED.

Among the organic causes of erectile dysfunction are hormonal disorders associated with a primary or secondary decrease in testosterone levels due, for example, to trauma, inflammation of the testicles, or increased levels of prolactin in the body, which suppresses testosterone production. ED can also be caused by systemic damage to the vascular bed as part of atherosclerosis, diabetic macroangiopathy and neuropathy, autointoxication as part of renal and liver failure, demyelinating diseases of the central nervous system (multiple sclerosis, Alzheimer's disease), and exposure to medications (antidepressants). In addition, ED can be caused by traumatic disruption of the innervation and blood circulation of the penis as a result of operations on the pelvic organs, radiation and various injuries. A separate group of causes includes ED, which occurs as a result of the loss of the veno-occlusive mechanism in the veins of the penis, which leads to rapid loss of erection.

Based on the above facts, the appearance of erectile dysfunction in socially active men should be a reason to consult a doctor. Unsubstantiated advertising of herbal medicines and dietary supplements in the media has led to patients self-medicating for a long time. They often turn to specialists already having severe vascular and neurogenic disorders, accompanied by severe fibrosis of the corpora cavernosa, which leads to an increase in the frequency of penile arthroplasty.

Side effects

In some cases (often due to an overdose), minor side effects are possible:

• dyspepsia;
• dizziness;
• headache;
• feeling of nasal congestion;
• flushes of blood;
• temporary vision problems;
• noise in ears;
• hypersensitivity reactions.

In rare cases, the following were observed:

• temporary deafness;
• cardiopalmus;
• nosebleeds;
• skin rash;
• nausea;
• myalgia;
• chest pain;
• fast fatiguability;
• an erection that lasts too long.

Features of the drug use

The positive effect of Sildenafil on women is possible only during sexual intimacy, when active stimulation occurs. If taking the drug is accompanied by deterioration in hearing or vision (fogging, color vision disturbances), then it is best to abandon it and find a more suitable drug from your doctor.

Also, Sildenafil tablets are not recommended to be combined with other drugs of the same spectrum of action. There are no special recommendations for the use of the medicine while driving a vehicle. A physician will be needed if the patient has active hypotension.

Sildenafil has a whole list of side effects that will increase if the dosage is exceeded for some reason.

"Sildenafil": instructions for use

The drug is taken orally and washed down with a small volume of water. The standard single dosage is 50 mg one hour before sexual intercourse. If the effect is insufficient, increase the dosage by 2 times (subject to normal tolerance and absence of contraindications). The maximum amount per day is 100 mg, frequency of use is 1 time per day.

For older people, the same dosages are established. In this case, the daily intake rate can be adjusted in the presence of certain diseases:

1. Renal dysfunction – 25 mg.
2. Liver dysfunction – 25 mg.
3. Simultaneous use with other drugs such as Ketoconazole, Cimetidine (except Ritonavir), Erithoromycin - up to 25 mg.

These restrictions are not “hard” ones. If the effect is insufficient, the daily dosage can be gradually increased to 50 mg, then to 100 mg.

When is the drug taken?

Most often, Sildenafil is prescribed to men if drug treatment of potency is required. The drug also has a positive effect on women suffering from insufficient lubrication and vaginal dryness.

Taking the drug is recommended for the following symptoms:

1. Low level of sensations during sexual contact;
2. Lack of sexual desire for psycho-emotional or physiological reasons;
3. Lack of orgasm or too long approach;
4. Sexual coldness in women;
5. High pressure in the pulmonary artery.

special instructions

One-time use is allowed without consulting a doctor, except in cases associated with severe pathologies of the cardiovascular system, kidneys or liver. For long-term use, preliminary consultation with a specialist is recommended.

In extremely rare cases, cardiac instability may occur. In case of overdose, myocardial infarction, including death, cannot be ruled out. Complications can develop during, after, or even without sexual intercourse.

Sildenafil leads to dilation of blood vessels, which leads to a slight, reversible decrease in blood pressure. Therefore, on the eve of the appointment, the doctor should assess the possible risks associated with a decrease in blood pressure.

Mechanisms of occurrence and maintenance of erection

Let us briefly describe the basic mechanisms of the occurrence and maintenance of an erection. Somatic innervation of the penis is carried out from the sacral erection center, which is located at the level of S2–S4. In the latter, impulses come from the cerebral cortex as a result of audiovisual and tactile stimulation. At the endings of the efferent fibers, nitric oxide is released, which is the main mediator of relaxation of the vascular bed of the corpora cavernosa of the penis. The production of nitric oxide in the endothelium of the vessels of the cavernous bodies leads to the expansion of the latter and the occurrence of an erection. Nitric oxide is synthesized from the amino acid L-arginine after exposure to the enzyme NO synthetase. By penetrating the cell membrane and activating the system for the production of cyclic guanosine monophosphate (cGMP), nitric oxide leads to relaxation of the smooth muscle cells of the vessels of the cavernous bodies of the penis both during systole and diastole. To maintain an erection during the time required for sexual intercourse, the inclusion of mechanisms that prevent the outflow of venous blood from the penis is required. This effect is achieved by compression of the venous plexus between the tunica albuginea and the cavernous sinuses. Additional compression is carried out using voluntary contraction of the ischiocavernosus muscles. The enzyme cGMP phosphodiesterase type 5 blocks the intracellular cGMP production system, thus causing detumescence. The sympathetic innervation of the penis is also responsible for the cessation of erection; the sympathetic center is located at the Th4–L2 level, and the effect occurs through the release of norepinephrine and interaction with alpha-adrenergic receptors of cavernous smooth muscle cells. Subsequently, smooth muscle cells contract, which leads to loss of erection.

Drug treatment of erectile dysfunction

Phosphodiesterase type 5 inhibitors affect the relaxation of smooth muscle cells through competitive interaction with phosphodiesterase type 5 and promote the accumulation of cGMP inside cavernous smooth muscle cells, as well as in the cells of the smooth muscle layer of the penile arteries. Today, there are five drugs in the class of phosphodiesterase type 5 inhibitors on the market: sildenafil, vardenafil, tadalafil, udenafil and afanafil. All of them are characterized by a similar mechanism of action and approximately the same safety profile. Currently, according to the recommendations of the European and American Urological Associations, a particular drug is prescribed depending on the patient’s preferences or personal experience, as well as in accordance with the recommendations of the urologist. Accordingly, in order to instruct the patient and determine the optimal dosage regimen for the drug if the patient has concomitant diseases, the physician must know the pharmacokinetic and pharmacodynamic characteristics of the drugs.

Clinical efficacy of sildenafil

Sildenafil is the most studied drug from the entire group of phosphodiesterase type 5 inhibitors. In addition, it is a reference drug for comparative clinical studies of the effectiveness of other phosphodiesterase type 5 inhibitors.

Sildenafil began to be used in the late 1990s, so the experience of its use exceeds 15 years. The history of the discovery of sildenafil is widely known: during clinical trials of the new antianginal drug, scientists noted a side effect, which was the improvement of erectile function. Moreover, unlike other drugs for the treatment of ED on the market at that time, no cases of priapism were observed while taking it.

The emergence of sildenafil prompted a number of clinical studies in this area. The term “impotence” has been replaced by the concept of “erectile dysfunction”, which implies the potential possibility of correcting existing disorders in the sexual sphere. Clinical studies of sildenafil have led to the development of new diaries and questionnaires to assess the state of male sexual function. Analysis of demographic indicators of participants in large-scale clinical trials made it possible to identify risk factors for ED, which in turn contributed to understanding the mechanisms of its development. Evidence has begun to accumulate that most cases of ED have an underlying somatic nature, and psychological problems are often secondary to primary vascular or nerve damage. Patients with erectile dysfunction who had not previously consulted a doctor received hope for improved sexual function, and to date, millions of men around the world have returned to their sexual lives thanks to taking this drug.

The clinical effectiveness of sildenafil citrate has been studied in numerous studies. One of the largest meta-analyses combined data obtained from 11 double-blind, placebo-controlled studies, which included a total of more than 2,500 patients with erectile dysfunction [4]. In the main group, an improvement in erection was noted in 76% of patients versus 22% in the placebo group, which led to a significant difference in the frequency of successful attempts at sexual intercourse - 66 and 26%, respectively. The effectiveness of various dosages of the drug was 65% for 25 mg, 74% for 50 mg and 82% for 100 mg. The high effectiveness of sildenafil was noted in different age groups. In the category of patients under 65 years of age, the effectiveness of the drug was 77.6% versus 69.2% in the older age group. According to research, the drug is effective compared to placebo in patients with erectile dysfunction, regardless of the cause of its development and severity.

Despite the high effectiveness of therapy with phosphodiesterase type 5 inhibitors, there remains a certain cohort of patients in whom taking this drug does not lead to an improvement in erection. Possible causes include improper medication administration [5]. Patients, especially at the beginning of treatment, should be advised to take sildenafil on an empty stomach at least 30 minutes before the planned start of sexual intercourse. Patients should be informed 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 begin with a maximum therapeutic dosage of 100 mg, which will allow for maximum results at the beginning of treatment and instill confidence in the success of therapy. In addition, studies have shown that in some patients the maximum effect of sildenafil is achieved by the sixth to eighth dose, and therefore in many patients the final assessment of the effectiveness of the drug should be made after several attempts to use it.

Sildenafil in the treatment of erectile dysfunction after prostatectomy

Effective selection of therapy for ED after prostatectomy is currently one of the urgent problems of urology, which is due to the increase in the number of operations, the development of nerve-saving surgical techniques, and the introduction of robotics. Numerous studies have examined risk factors for the onset of ED after surgery: type of surgery (non-nerve-sparing, mono- or bilateral nerve-sparing techniques), patient age, preservation of erection before surgery, socio-economic conditions (level of education, patient income), tumor stage, prostate size , urologist experience.

R. Raina et al. showed that sildenafil therapy is effective in 71.7% of patients after bilateral nerve-sparing surgery, in 50% after unilateral nerve-sparing prostatectomy and in 15% of patients after non-nerve-sparing surgery. It has been shown that one of the features of ED after radical prostatectomy is the possibility of progressive improvement of erection several years after surgery, therefore, long-term follow-up is necessary to make a final judgment about the effectiveness of therapy [6].

EK Hong et al. observed 316 patients with ED after radical prostatectomy, which in 95% of cases was bilateral nerve-sparing. The effectiveness of sildenafil was 26% during the first 6 months, 36% from 6 to 12 months, 50% from 12 to 18 months and 60% from 18 to 24 months after surgery [7].

Currently, most authors believe that to prevent the development of ED after radical prostatectomy, long-term use of phosphodiesterase type 5 inhibitors, and in particular sildenafil, in low therapeutic doses is necessary. This therapy is justified by data on the improvement of blood flow in the corpora cavernosa against the background of long-term continuous use of drugs, which serves as prevention of the development of a local scar-sclerotic process. H. Padma-Nathan et al. studied the effectiveness of sildenafil in the prevention of ED after radical prostatectomy [8]. As a result of the study, patients who underwent bilateral nerve-sparing surgery and did not suffer from ED before surgery, starting from the second month of the postoperative period, received sildenafil in doses of 100 and 50 mg or placebo at bedtime for 36 weeks. Eight weeks after stopping treatment, 27% of men receiving sildenafil reported the ability to lead a normal sexual life, compared with only 4% of those receiving placebo [8].

Sildenafil therapy can be an effective method of preventing ED in patients after radical prostatectomy as a result of improving the blood supply to the cavernous tissue, preventing the development of fibrotic changes in it. Long-term use of the drug in small doses for the rehabilitation of patients after transurethral and oncoproctological operations is based on the same principles [8].

Natural pathogen

Sildenafil is an artificial substance created in a laboratory. To obtain it, a special technology was used that cannot be repeated at home.

Many people still prefer natural ones to any chemical substances and try to use in their diet products that are natural pathogens (aphrodisiacs). Aphrodisiacs are products that affect the body in such a way that, with their constant use, a person’s libido increases, sexual function and sensitivity improve.

Natural pathogens are chocolate, honey, olive oil, coffee, mushrooms, bananas, strawberries, seaweed, dates, coconuts, pine nuts, horseradish, onions, garlic, carrots, herbs (dill, parsley, celery), asparagus, eggs, caviar , seafood (shrimp, mussels, oysters, snails), seasonings (saffron, vanilla, anise, ginger, cinnamon, ginseng), aloe, avocado, artichoke.

When is it prohibited to use the drug?

Alcohol does not in any way affect the effects of Sildenafil, which has been proven by medical research. No increase in side effects will occur if the blood contains 0.3 ppm of alcohol (200 grams of white wine).

Before taking the drug, consult a doctor. Self-medication can cause negative consequences, since there are many reasons why using a remedy for treatment is not recommended. There are a number of diseases when the use of Sildenafil is strictly prohibited.

These are the following diseases:

• Aortic stenosis;
• Poor blood supply to the heart muscle;
• Low blood pressure;
• Heart failure;
• Myocardial damage, accompanied by an increase in heart size, heart failure and abnormal heart rhythm;
• Deviation in the development of the retina;
• Minor age;
• High sensitivity to the components of the product, up to the occurrence of an allergic reaction;
• The occurrence of a stroke or heart attack in the last six months;
• Anemia;
• Heart rhythm failure.

Drug price

You can buy Sildenafil for women either at your nearest pharmacy or place an order online. In the latter case, the doctor's prescription will need to be shown to the courier at checkout. Below is the price of the drug in several pharmacies.

What analogues of the drug exist?

Generics of Sildenafil, that is, drugs created on its basis with the same chemical composition and therapeutic properties, can also be called its analogues. In the pharmacy chain you can find:

• Tornetis;
• Dynamic;
• Vizarsin;
• Taxier;
• Allmax strong;
• Caverject;
• Levitra;
• Cialis;
• Tentex forte;
• Rileys.

Dynamico

Taxier

Tentex Forte

Rileys

All of them have the same effect on the body, have a stimulating effect and improve the perception of sex.

How does the medication interact with other drugs?

The simultaneous use of Sildenafil with ketoconazole, erythromycin and cimetidine complicates the process of removing the drug from the body, its amount in the blood increases sharply. When taken together with sodium nitroprusside and other organic nitrates, a sharp decrease in blood pressure occurs, which is contraindicated in people with hypotension.

Sildenafil should not be used together with medications for patients with diabetes.

Generics

As mentioned above, Sildenafil is used to eliminate poor blood circulation in the pelvic organs, to enhance sexual lust and receptivity of erogenous zones.

A familiar drug based on sildenafil is called Viagra. In fact, this is the “pioneer” of all medications to improve the quality of sex. Viagra is still actively sold in the pharmacy chain. At the same time, it is very expensive. Its price is two to four times higher than that of its synonyms.

To be more precise, subsequent drugs created on the basis of sildenafil are generics of Viagra. How do generics differ from a unique drug?

The technology for developing the original product is as follows:

1. Isolation of a chemical substance and analysis of its properties;
2. Conducting laboratory tests to identify the greatest number of beneficial and negative properties and determining the daily dosage;
3. Development of a method and technology for removing the main active substance on a production scale;
4. Purification of the active substance from unnecessary impurities, since their presence can provoke allergies and other third-party effects;
5. Development of a unique name for the drug and its mass release on the pharmaceutical market.

Each genuine drug has a mandatory patent, the period of which is limited. Basically, the certificate is issued for a period of five to ten years. When the patent expires, another pharmaceutical company has the right to use the original composition, but produce it as its own product.