Sildenafil

Sildenafil is a drug that has a peripheral effect (it is a substance with a selective inhibitory effect on cGMP, a specific component of PDE-5).

This medication is used to stimulate erection in persons with erectile dysfunction, and in addition, it is prescribed for the treatment of pulmonary hypertension, because the principle of its therapeutic effect is based on the ability to vasodilatation. [1]

Indications Sildenafil

It is used in men with erectile dysfunction - in situations where the erection that appears in a man is insufficient for full-fledged sexual contact (or is absent altogether in the presence of sexual stimulation).

In addition, the medication is used to treat hypertension in the lungs .

Release form

The release of the medication is sold in tablets - 1 or 4 pieces each inside a cell package; 1 package inside a bundle.

Pharmacodynamics

Sildenafil helps to relax the smooth muscles in the corpus cavernosum, as well as dilate the arteries of the penis, which increases intracorporeal pressure. An increase in blood volumes inside the cavernous spaces leads to compression of the venous bed, followed by impaired venous blood outflow. As a result, there is no outflow of blood from the cavernous tissue of the penis, which allows you to achieve an erection under the influence of a sexual stimulus.

The drug does not have a direct relaxing effect on the corpus cavernosum; it increases the volume of produced NO and enhances the relaxing activity in relation to the cavernous spaces. During a sexual reaction, sildenafil causes the release of the element NO and the suppression of PDE-5, which leads to an increase in cGMP indicators, relaxation of smooth muscles, as well as an increase in the intensity of blood filling in the cavernous space of the penis. [2]

Because PDE-5 is present not only inside the corpus cavernosum of the penis, but also inside the pulmonary vessels, it was found during testing that sildenafil is very effective as a substance that slows down the activity of PDE-5 in the case of pulmonary hypertension (the resulting narrowing of the lumen of the pulmonary vessels). The expansion of the blood vessels located inside the tissues of the lungs, as in the case of therapy for problems with erection, occurs in connection with the activity of NO.

During clinical trials, it was revealed that Sildenafil has a much more pronounced effect on PDE-5 compared to other PDE isoenzymes.

Pharmacokinetics

Sildenafil has high absorption rates after oral administration. The bioavailability level averages 40% (in the range of 25-63%). Blood values of Cmax when consumed on an empty stomach of 0.1 g of the substance are equal to 18 ng / ml and are noted after 0.5-2 hours.

But at the same time, it should be taken into account that the consumption of fatty foods negatively affects the absorption of the drug - the Tmax indicator is prolonged by 1 hour, and the Cmax values decrease by 29%.

The Vd level of the drug is 105 liters, and the rate of intraplasmic protein synthesis is 96%.

The drug participates in metabolic processes with the help of microsomal intrahepatic isoenzymes, in which N-desmethylmetabolite, which has medicinal activity, is formed (its activity is equal to 50% of the effect of sildenafil), which also undergoes biotransformation.

The term of the half-life of a component in the terminal stage is 3-5 hours. The substance is mainly excreted in feces in the form of metabolic elements (80%); about 13% more is excreted during renal secretion (with urine).

It is also required to take into account that in the elderly, due to age-related changes that affect the rate of development of physiological reactions, the drug clearance rate and its blood values are significantly reduced (by 40%).

Severe disorders in the work of the kidneys lead to a significant decrease in the level of drug clearance and an increase in AUC and Cmax values, respectively, by 100%, as well as 88% relative to the values in individuals without a history of renal impairment.

Hepatic cirrhosis also causes a decrease in the clearance of sildenafil and an increase in Cmax with an AUC of approximately 47% and 84%.

Dosing and administration

Use for erectile dysfunction.

Consume 50 mg of the substance orally, 60 minutes before the planned sexual intercourse.

The above dosage can be changed both downward and upward (up to 25 or 100 mg), taking into account the patient's personal response and the severity of the disease, and at the same time taking into account the intensity of the response to treatment. The size of the maximum daily portion is 0.1 g. It is forbidden to use more than 1 time per day.

Elderly persons with kidney / liver disease can use no more than 25 mg of Sildenafil.

Therapy for pulmonary hypertension.

Ingestion of 20 mg of the substance 3 times a day at regular intervals (6-8 hours), without reference to food intake. A maximum of 60 mg of drugs can be used per day.

• Application for children

The medication should not be used in pediatrics (under the age of 18).

Use Sildenafil during pregnancy

Sildenafil is not used to treat women.

Contraindications

It is contraindicated to use in case of severe personal intolerance to sildenafil, and in addition, in treatment with nitrates or NO donors.

In addition, the medicine is not used for such disorders:

• very high blood pressure (more than 170/110 mm Hg) or excessively reduced (less than 90/50 mm Hg);
• ischemic stroke or myocardial infarction suffered during the previous six months;
• arrhythmia, which is severe;
• HF or angina pectoris.

Side effects Sildenafil

The main side signs:

• lesions of the central nervous system: dizziness, areflexia, headaches, sleep disorders, a feeling of heat with a flush of blood to the face, tremors, pain of a neurological nature, and in addition to fainting, asthenia, depression, paresthesia and hypesthesia;
• disorders of the sensory organs: disorders of visual activity, including conjunctivitis, color blindness, cataracts, loss of clarity of visual objects, photophobia, hemorrhages in the eyeball area, mydriasis, pain affecting the eyeballs, and xerophthalmia. In addition, severe hearing impairment may develop, sometimes reaching its complete loss, or ear ringing or pain;
• disorders affecting the activity of ODA: increased muscle tone, myalgia, muscle weakness, pain affecting the joints, arthralgia, rupture in the tendon area, arthrosis or arthritis, as well as synovitis or tendosynovitis;
• problems with hematopoietic function and CVS: an increase in heart rate, a decrease or increase in blood pressure values, ischemia affecting the myocardium, orthostatic collapse, heart failure and angina pectoris, and in addition, having a functional or structural nature of the disease affecting the heart muscle, cardiac arrest and deviation from normal ECG readings. There is also a decrease in the blood level of leukocytes or erythrocytes, as well as a disorder of intracerebral blood flow associated with increased formation of blood clots;
• disturbances in the work of the urogenital system: nocturia, enuresis, swelling of the genitals, polyuria, infection of the urethra, cystitis, weak orgasm or its absence, as well as breast hypertrophy and ejaculatory disorders;
• disorders of the gastrointestinal tract: dyspepsia, inflammation in the esophagus and problems with swallowing, thinning of feces, gastralgia, nausea, stomatitis, glossitis or gingivitis, and in addition, bleeding in the rectal region, hyposalivation, gastroenteritis, gastritis or colitis and deviation from normal indications for biochemical liver analysis;
• problems with respiratory activity: dyspnea, problems with breathing through the nose, potentiation of cough, bronchial hypersecretion, laryngitis with pharyngitis, runny nose, bronchitis and sinusitis, and besides this symptoms of asthma;
• metabolic disorders: gout, hypernatremia, intense thirst, an increase in blood volumes of uric acid, as well as diabetes, which has a labile nature (accompanied by hypo- and hyperglycemia);
• dermatological lesions: itching, urticaria, ulcers, common herpes and various dermatitis;
• others: back pain, flu-like syndrome, rash, signs of vasodilation, various pathologies of infectious origin, pain in the abdomen or sternum and prostate dysfunction, as well as fever, shock, hyperhidrosis, peripheral edema, allergies, photosensitivity and priapism (rarely ).

Overdose

Clinical tests show that with intoxication with sildenafil, an increase in the intensity of side signs may occur.

With their development, it is necessary to receive medical help with further symptomatic measures. It is also necessary to take into account that dialysis will be ineffective - because sildenafil is rapidly synthesized with intraplasmic protein.

Interactions with other drugs

The use together with cimetidine or erythromycin causes a decrease in drug clearance rates and an increase in its plasma values.

Administration in combination with saquinavir, indinavir or ritonavir causes an increase in plasma Cmax values, as well as the AUC of the drug.

Combination with itraconazole or ketoconazole increases the plasma level of drugs.

Taking with simvastatin leads to the development of a low likelihood of rhabdomyolysis.

The combination with nitrates enhances their antihypertensive activity.

Application in combination with sodium nitroprusside leads to potentiation of the antiaggregatory effect of this component.

Storage conditions

Sildenafil must be kept out of the reach of small children, in a dry and dark place. In this case, the temperature indicators should be no more than 30 ° C.

Shelf life

Sildenafil can be used for a 5-year term from the date of marketing of the therapeutic substance.

Analogs

The analogues of the medication are Maxigra, Taxier, Viagra, Revazio with Viasan, and in addition to Dynamico, Olmax Strong with Silafil and Vigrande with Tornetis. Also on the list are Vizarsin, Sildenafil citrate and Erexesil.

Reviews

Sildenafil receives good reviews from patients - the drug demonstrates a quick and effective effect, eliminating the problem with erectile dysfunction.