Sildenafil Citrate

This product is an oral medication for erectile dysfunction (ED). It is the citrate of sildenafil, a selective inhibitor of type 5 phosphodiesterase (PDE5) specific to cyclic guanosine phosphate (cGMP). Mechanism of action: The physiological mechanism of penile erection involves the release of nitric oxide (NO) in the penile sponge during sexual stimulation. NO activation of guanosine cyclase leads to increased levels of cyclic guanosine phosphate (cGMP), which relaxes smooth muscle and fills blood in sponges.

Effect of sildenafil on penile erection response: Sildenafil is a highly selective phosphatidiesterase 5 (PDE5) inhibitor, which is highly expressed in the cavernosa of the penis and low in other tissues, including platelets, vascular and visceral smooth muscle, and skeletal muscle. Sildenafil leads to relaxation of the smooth muscle of the cavernose by selectively inhibiting PDE5, enhancing the nitric oxide (NO) -CGMP pathway, and elevating the level of cGMP, leading to a natural erectile response to sexual stimulation in erectile dysfunction patients. Erectile response generally increases with sildenafil dose and plasma concentration. Experiments showed that the effect lasted up to 4 hours, but the reaction was weaker than 2 hours. Sildenafil response to myocardium: PDE5 does not exist in normal or pathological cardiac conduction tissues, myocardium cells, endothelial cells, and lymphatic tissues, so sildenafil (PDE5 inhibitor) has no positive inotropic effect and cannot directly affect myocardial systolic function.

Effect of sildenafil on cardiac parameters: a single dose of sildenafil 100mg in normal male volunteers showed no clinically significant ecg changes. Eight patients with stable ischemic heart disease received sildenafil 40mg intravenously in 4 doses monitored by a swan-ganz catheter. Systolic and diastolic blood pressure at rest decreased by 7% and 10%, respectively, from baseline. Resting right atrium, pulmonary artery pressure, pulmonary wedge pressure and cardiac output decreased by 28%, 28%, 20% and 7%, respectively. Although this intravenous dose was two to five times higher than the average peak plasma concentration of 100mg for a single oral dose of sildenafil in healthy male volunteers, these hemodynamic responses persisted during exercise.

Sildenafil response to blood pressure: in healthy men, a single dose of sildenafil 100mg resulted in a decrease in supine bp (with a mean maximum of 8.4/5.5mmHg), most significant at 1 to 2 hours after administration, with no difference from placebo at 8 hours after administration. Sildenafil 25mg, 50mg, and 100mg had similar effects on blood pressure and appeared to be independent of dose and blood concentration. Patients who also took nitrates had a greater reduction in blood pressure. Hypotension (90/50 MMHG) and nitrates or nitrate-providing drugs are strict contraindications for sildenafil use. The maximum use of sildenafil for bp occurred approximately 1 h after administration, which was consistent with the drug plasma peak. Thus, sexual activity may induce cardiac events at peak plasma concentrations of sildenafil. Although the hypotensive response to sildenafil is mild and transient (typically bp returns to baseline within 4 hours), the interaction between sildenafil and nitrates can produce a significant and longer duration of bp reduction. Sildenafil has a short half-life and can be eluted within 24 hours (about 6 half-lives). The American College of Cardiology and the American Heart Association have indicated that sildenafil should not be used in the last 24 hours if a nitrate has been used.

Effects of sildenafil on vision: Studies have shown no effect on visual acuity, retinal electrogram, intraocular pressure, or visual nipple size when taken at twice the maximum recommended dose.Transient blue/green color discrimination anomalies may be present. Whether used alone or in combination with aspirin, it has no effect on the duration of bleeding. In vitro, the product enhanced the antiplatelet aggregation of sodium nitroprusside (NO donor) in humans. The combination of heparin and sildenafil has an additive effect on prolongation of bleeding time in rabbits under anesthesia, but no similar human studies have been conducted. A single dose of sildenafil 100mg in healthy volunteers did not affect sperm motility and morphology.

 The basic information

Chemical formula: C28H38N6O11S

Molecular weight: 666.70

CAS no. : 171599-83-0

EINECS no. : 200-659-6

The physical and chemical properties

Melting point: 187-189 ℃

Boiling point: 672.4 ℃

Flash: 360.5 ℃

Density: 1.445 g/cm3

Refractive index: 1.683