Mechanism of action:

• Sildenafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for the degradation of cGMP in the corpus cavernosum. Sildenafil has no direct resting effect on the isolated human corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in a smooth muscle relaxant and blood flow to the corpus cavernosum. Sildenafil has no effect in the absence of sexual stimulation at the recommended dose.
• Dapoxetine is a potent selective serotonin reuptake inhibitor (SSRI) with IC50 at 1.12 nm, while its major human metabolites, desmethyldapoxetine (IC50 <1.0 nM) and didesmethyldapoxetine (IC50 = 2.0 nM) are equivalent or low-potency (POPE). (IC50 = 282 nM)).
• Human ejaculation is primarily mediated by the sympathetic nervous system. The ejaculation pathway arises from a spinal reflex center, mediated by the stem of the brain, which is initially affected by multiple nuclei in the brain (medial prophylactic and paraventricular nuclei).
• The mechanism of action of dapoxinate in premature ejaculation is thought to be associated with the inhibition of neuronal burst of serotonin and subsequent potentiation of neurotransmitters at pre- and postsynaptic receptors.

Pharmacokinetics:

• In absolute bioavailability studies, plasma concentrations of sildenafil were determined using high-performance liquid chromatography (HPLC) and atmospheric pressure chemical ionization mass spectroscopy. The calibration range of the assay was 0.1–2.0 ng ml- 1. The range of quantization for sildenafil was 0.3 ng ml 1 1 and the variance of interassay ranged from% 35 to 8.6%. Total plasma concentrations of sildenafil and its main active metabolite, UK-103,320, were determined using automated sequential trace enrichment of dialysates and HPLC as described by Cooper et al., in a food-effect and dose-proportionality study. The calibration range of the assay was 0.1–2.0 ng ml 1. Quantification was 1 ng mL of 1 for both sildenafil and UK-103,320. The overall centrifuge (CV) is 5.1%, 3.2% and 3.0% sildenafil and 3.4%, 3.1% and 2.9% UK, 103,320 concentrations for 3.00, 125 and 200 ng ml – 1, respectively. The assay inaccuracy (bias) in all concentrations ranged from and2.3% to 3.5% for sildenafil and from 4.8% to 4.8% for UK-103,320.

Pharmacodynamics:

• In vitro studies have shown that sildenafil is selective for phosphodiesterase-5 (PDE5) 11,12,13,14,15,16,8,9. Its effect is more potent on PDE5 than other known phosphodiesterase 11, 12,13,14,15,15,16,8,9. Notably, PDE6 has more than 10-fold selectivity that is involved in the phototransfection pathway in the retina 11,12,13,14,15,16,8,9. PDE1 has 80-fold selectivity, and PDE is 700-fold over 2, 3, 4, 7, 8, 9, 10 and 11,12,13,14,15,16,8,9. And finally, sildenafil has more than 4,000-fold selectivity for PDE3 to PDE5, a CMP-specific phosphodiesterase isoform involved in the control of card-contractivity 11,12,13,14,15,16,8,9. Sildenafil causes a mild and transient decrease in systemic blood pressure, which, in the vast majority of cases, does not translate into a clinical effect 11,12,13,14,15,16,8,9. After a chronic dose of 80 mg, the decrease in systolic and diastolic blood pressure three times a day for patients with hypertension with a mean change from baseline was 9.4 mmHg and 9.1 mmHg, respectively, 11,12,13,14,15,16,8, 9. After a chronic dose of 80 mg, a decrease in blood pressure was observed in patients with pulmonary arterial hypertension three times a day (a decrease in systolic and diastolic pressure of 2 mmHg) 11,12,13,14,15,16,8,9 . At the recommended dose of 20 mg three times a day, no reduction in systolic or diastolic pressure was observed 11,12,13,14,15,16,8,9.

Precautions:

• Before taking sildenafil, tell your doctor or pharmacist if you are allergic to it; Or if you have any other allergies. This product may contain inactive ingredients, which may cause allergies or other problems. Talk to your pharmacist for more details.
• Before using this medicine, tell your doctor or pharmacist your medical history, especially: Heart problems (such as heart attack or life-threatening irregular heartbeat in the past 6 months, chest pain / angina, heart failure), stroke in the last 6 months, kidney disease, liver disease, high or Low blood pressure, severe body water loss (dehydration), penis conditions (Such as angulation, fibrosis / scarring, peyronie’s disease), history of painful / prolonged erection (priapism), conditions that may increase the risk of priapism(eg sickle cell anemia, leukemia, multiple myeloma), eye conditions Problems (eg retinitis) pigmentosa, sudden loss of vision, NAION).

Side effects:

• Dizziness, headache, flushing or stomach upset may occur. Changes in vision, such as increased sensitivity to light, blurred vision, or difficulty distinguishing blue and green may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist immediately.
• To reduce the risk of dizziness and lighthouse, rise slowly when getting up from a sitting or lying position.
• Remember that your doctor has prescribed this medicine because he or she has decided that the benefit to you outweighs the risk of side effects. Many people using this medicine do not have serious side effects.
• Sexual activity can put extra pressure on your heart, especially if you have heart problems. If you have a heart problem and experience any of these serious side effects while having sex, stop immediately and seek medical help: severe dizziness, fainting, chest / jaw / arm pain, nausea.

Dosage:

• Viagra is usually taken only when 30 minutes to 1 hour before sexual activity. You can take it 4 hours before sexual activity. Do not take Viagra more than once per day.
• Shake the oral suspension (liquid) before measuring the dose. Use the provided dosage syringe, or use a pharmaceutical dose-measuring device (not kitchen spoons).

Over dosage:

If you take too much: There may be dangerous levels of medicine in your body. Symptoms of an overdose of this medicine may include: Low blood pressure, fainting.

Warning:

• Do not take sildenafil if you are using nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, and some recreational drugs such as “poppers” including nitrate medication for chest pain or heart problems. Taking sildenafil with a nitrate medication can cause a sudden and severe decrease in blood pressure. Some medicines may cause undesired or dangerous effects when used with sildenafil. Tell your doctor about all your current medications, especially Riociguat (Adempus). Do not take sildenafil with riociguat.

Duration of action:

• Sildenafil usually takes 30 to 60 minutes to work for erectile dysfunction. You can take it up to 4 hours before having sex. Taking sildenafil alone will not cause erections. For this you need to work.

Drug- drug interactions:

• Sildenafil may cause a severe drop in your blood pressure when used with nitrates. A severe drop in blood pressure can lead to dizziness, fainting, and rarely a heart attack or stroke. Do not use sildenafil with any of the following: something used to treat recreational drugs called “poppers” containing chest pain / angina (nitrates such as nitroglycerin, isosorbide), amyl nitrate, amyl nitrite or butyl nitrite.
• If you are taking an alpha blocker drug (such as doxazosin, tamulosin) to treat an enlarged prostate / BPH or high blood pressure, your blood pressure may be very low leading to dizziness or fainting. Your doctor may begin treatment with low doses of sildenafil to reduce your risk of low blood pressure.

Adverse effects:

The components of the drug may cause some adverse effects.

Diarrhea;

Nausea;

Dizziness;

Head ache;

Incorrect color perception;

Temporary color blindness;

Sneeze;

Indigestion;

Cardiopulmus

Pregnancy:

If you are taking sildenafil for the treatment of erectile dysfunction, then you should know that it does not cure erectile dysfunction or increases sexual desire. Sildenafil does not prevent the spread of pregnancy or sexually transmitted diseases such as human immunodeficiency virus (HIV).

Fertility:

Sildenafil had no statistically significant effect on sperm motility, count, or density; Percentage of abnormal sperm forms; or percentage of living sperm. It also did not affect the ejaculation volume or viscosity. All measures were within normal limits.

Containdication:

The drug is not recommended in the following cases:

high blood pressure;

Hypotension;

Leukemia;

Ischemic heart disease;

Heart failure;

Diseases of the cardiovascular system;

Choroid retinitis.

Storage:

Store at room temperature away from light and moisture. Do not store in the bathroom.

Breastfeeding:

Limited data indicate that sildenafil and its active metabolites in sildenafil are poorly excreted in breastmilk. The amount swallowed by the baby is small and it is unlikely to cause any adverse effects in breastfed infants.