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 people with erectile dysfunction, and is also prescribed for the treatment of pulmonary hypertension, because the principle of its therapeutic effect is based on the ability to dilate blood vessels. [ 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 sexual intercourse (or is absent altogether in the presence of sexual stimulation).

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

Release form

The drug is released in tablets - 1 or 4 pieces inside a cell package; 1 package inside a pack.

Pharmacodynamics

Sildenafil helps to relax the smooth muscles in the cavernous bodies and dilate the arteries of the penis, which increases intracorporeal pressure. Increased blood volumes inside the cavernous spaces lead to compression of the venous bed with subsequent disruption of venous blood outflow. As a result, there is no outflow of blood from the cavernous tissue of the penis, which allows an erection to be achieved under the influence of a sexual stimulus.

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

Because PDE5 is present not only inside the corpus cavernosum of the penis but also inside the pulmonary vessels, testing has shown that sildenafil is very effective as a substance that inhibits the activity of PDE5 in cases of pulmonary hypertension (the ongoing narrowing of the lumen of the pulmonary vessels). The expansion of the blood vessels located inside the lung tissue, as in the case of therapy for erectile dysfunction, occurs due to the activity of NO.

During clinical trials, it was found 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 average bioavailability level is 40% (in the range of 25-63%). Blood Cmax values when taking 0.1 g of the substance on an empty stomach are 18 ng / ml and are noted after 0.5-2 hours.

However, it is important to take into account that the consumption of fatty foods has a negative effect on the absorption of the drug - the Tmax indicator is prolonged by 1 hour, and the Cmax values are reduced by 29%.

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

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

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

It is also necessary to take into account that in elderly individuals, 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 renal impairment results in a significant reduction in drug clearance and an increase in AUC and Cmax values by 100% and 88%, respectively, relative to values in individuals without a history of renal impairment.

Hepatic cirrhosis also causes a decrease in sildenafil clearance and an increase in Cmax and AUC values by approximately 47% and 84%.

Dosing and administration

Use for erectile dysfunction.

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

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

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

Therapy for pulmonary hypertension.

Oral use of 20 mg of the substance 3 times a day at equal time intervals (6-8 hours), without reference to food intake. A maximum of 60 mg of the drug can be used per day.

• Application for children

The medication cannot be used in pediatrics (under 18 years of age).

Use Sildenafil during pregnancy

Sildenafil is not used for treatment in women.

Contraindications

Contraindicated for use in case of severe personal intolerance to sildenafil, as well as during treatment with nitrates or NO donors.

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

• very high blood pressure (more than 170/110 mmHg) or excessively low (less than 90/50 mmHg);
• ischemic stroke or myocardial infarction suffered in the previous six months;
• arrhythmia of severe severity;
• HF or angina.

Side effects Sildenafil

Main side effects:

• CNS dysfunction: dizziness, areflexia, headaches, sleep disorders, feeling of heat with a rush of blood to the face, tremor, pain of a neurological nature, and in addition fainting, asthenia, depression, paresthesia and hypoesthesia;
• sensory disorders: visual disorders, including conjunctivitis, color blindness, cataracts, blurred vision, photophobia, hemorrhages in the eyeball, mydriasis, pain affecting the eyeballs, and xerophthalmia. In addition, severe hearing loss may develop, sometimes leading to complete hearing loss, or ear ringing or pain;
• disorders affecting the functioning of the musculoskeletal system: increased muscle tone, myalgia, muscle weakness, pain affecting the joints, arthralgia, rupture in the area of tendons, arthrosis or arthritis, as well as synovitis or tenosynovitis;
• problems with hematopoietic function and cardiovascular system: increased heart rate, decreased or increased blood pressure, ischemia affecting the myocardium, orthostatic collapse, heart failure and angina, as well as functional or structural diseases affecting the heart muscle, cardiac arrest and deviation from normal ECG readings. A decrease in the blood level of leukocytes or erythrocytes is also noted, as well as a disorder of intracerebral blood flow associated with increased thrombus formation;
• disorders of the urogenital system: nocturia, enuresis, genital swelling, polyuria, urinary tract infections, cystitis, weak orgasm or its absence, as well as hypertrophy of the mammary glands and ejaculatory disorders;
• gastrointestinal disorders: dyspepsia, inflammation in the esophagus and problems with swallowing, loose stools, gastralgia, nausea, stomatitis, glossitis or gingivitis, as well as bleeding in the rectal area, hyposalivation, gastroenteritis, gastritis or colitis and deviations from normal values in biochemical analysis of the liver;
• problems with respiratory activity: dyspnea, problems with breathing through the nose, cough potentiation, bronchial hypersecretion, laryngitis with pharyngitis, runny nose, bronchitis and sinusitis, as well as symptoms of bronchial asthma;
• metabolic disorders: gout, hypernatremia, intense thirst, increased blood uric acid levels, as well as diabetes of 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, allergy, photosensitivity and priapism (rarely).

Overdose

Clinical trials show that sildenafil intoxication may result in increased intensity of adverse effects.

If they develop, it is necessary to obtain medical assistance with further symptomatic measures. It is also necessary to take into account that dialysis will be ineffective - because sildenafil is quickly synthesized with intraplasmic protein.

Interactions with other drugs

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 AUC of the drug.

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

Taking it together with simvastatin leads to a low risk of rhabdomyolysis.

Combination with nitrates enhances their antihypertensive activity.

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

Storage conditions

Sildenafil should be stored in a dry, dark place, out of the reach of small children. The temperature should not exceed 30°C.

Shelf life

Sildenafil can be used for a period of 5 years from the date of sale of the therapeutic substance.

Analogues

Analogues of the drug are Maxigra, Taxier, Viagra, Revatio with Viasan, and in addition to this, Dinamico, Olmax Strong with Silafil and Vigrande with Tornetis. Also on the list are Vizarsin, Sildenafil Citrate and Erexezil.

Reviews

Sildenafil receives good reviews from patients – the drug demonstrates a fast and effective effect, eliminating the problem of erectile dysfunction.