Sildenafil is a selective inhibitor of cyclic guanosine phosphate (cGMP) -specific phosphodiesterase type 5 (PDE5) and is an oral treatment for ED. The physiological mechanism of normal penile erection involves the release of nitric oxide (NO) during sexual stimulation. Nitric oxide activates the guanylate cyclase in the smooth muscle cells of the penile cavernose, leading to an increase in cGMP levels, which causes the smooth muscle in the sponge to relax, the cavernous sinus to dilate, and blood to flow into the penis to achieve erection. Erectile dysfunction is mainly due to the smooth muscle relaxation disorder in the cavernosa of the penis. Sildenafil has no direct relaxation effect on isolated human sponges, but can enhance the effect of nitric oxide by inhibiting the decomposition of cGMP by PDE5 in sponges. When sexual stimulation causes local nitric oxide release, sildenafil inhibits PDE5, which can increase the level of cGMP in the sponge body, relax the smooth muscle of the cavernosum, and blood flows into the cavernosum. Studies have shown that erectile response increases with increasing dose and plasma concentration, and the efficacy lasts for 4h (but is weaker than 2h). In vitro experiments showed that sildenafil had high selectivity for PDE5, which was more than 80 times that of PDE1, 700 times that of PDE2 and PDE4, and 4000 times that of PDE3. Since PDE3 is related to the control of myocardial contractility, there is no PDE5 in the myocardium, so sildenafil has no positive inotropic effect and does not directly affect myocardial contractility. However, sildenafil can cause systemic circulation vasodilation, and high dose (100mg) oral administration can lead to a decrease in supine blood pressure [average maximum reduction of 1.12/0.73kPa (8.4/5.5mmHg)], and the most significant decrease in blood pressure 1 ~ 2 hours after taking sildenafil. Therefore, sexual activity may induce cardiac events at peak blood concentration. Sildenafil is only 10 times more selective for PDE5 than PDE6, an enzyme present in the retina, so sildenafil may cause abnormal color vision at high doses or at high blood concentrations. In addition to human spongy smooth muscle, low concentrations of PDE5 were also found in platelets, blood vessels, visceral smooth muscle and skeletal muscle. Sildenafil may enhance its antiplatelet aggregation (in vitro), platelet thrombosis (in vivo), and peripheral vasodilation (in vivo) by inhibiting PDE5 in these tissues. 
Sildenafil is absorbed quickly after oral administration, takes effect in 10 to 40 minutes, and its absolute bioavailability is about 40%. The peak plasma concentration (Cmax) was reached 30 ~ 120min after fasting oral administration, and 90 ~ 180min after postprandial oral administration. The blood concentration and cmax were 2ng/ml and 440ng/ml respectively 24h after oral administration of 100mg in healthy volunteers. Increased area under curve (AUC) in patients with abnormal liver function, severe renal insufficiency or over 65 years of age. About 96% of sildenafil and its main circulating metabolite (n-demethylated) bind to plasma protein, and the protein binding rate is independent of the total drug concentration. The tissue was well distributed and the distribution volume (Vd) was 105L. Sildenafil is primarily cleared by the liver microsomal enzyme cytochrome P450 3A4 (CYP 3A4, the primary pathway) and cytochrome P450 2C9 (CYP 2C9, a secondary pathway). Its main metabolite (n-demethylated) has a PDE selectivity similar to that of sildenafil, and its plasma concentration is about 40% of that of sildenafil, so about 20% of sildenafil's pharmacological effects are due to its metabolites. The elimination half-life of sildenafil and its metabolites is about 4h, 80% of the dose is excreted mainly in the form of metabolites through feces and 13% through kidney. Sildenafil was detected in semen of healthy volunteers at less than 0.001% of the dose administered 90 minutes after administration. 
Used to treat penile erectile dysfunction (ED). 
1. People allergic to sildenafil.
2. Nitroglycerin, sodium nitroprusside or other organic nitrates are being used. 
1. For most patients, the recommended dose is 50mg, taken as needed approximately one hour before sexual activity, followed by sexual stimulation. However, it can be taken at any time within 0.5 ~ 4h before sexual activity. Based on the efficacy and tolerance, the daily dose can be adjusted between 25 ~ 100mg, and the medication should not be taken more than once a day. (1) dose for renal insufficiency the recommended initial dose for severe renal insufficiency (AUC and cmax almost double when creatinine clearance is less than or equal to 30ml/min) is 25mg. (2) dose for liver insufficiency the recommended starting dose for patients with liver impairment (e.g., cirrhosis, with an increase in AUC and cmax of 84% and 47%, respectively) is 25mg.
The recommended starting dose for people over 65 years of age is 25mg.
3. Dose for other diseases (1) 25mg is the appropriate initial dose for those taking potent cytochrome P4503A4 inhibitor and erythromycin simultaneously. (2) a maximum dose of sildenafil of 25mg per 48h is recommended for patients taking HIV protease inhibitors such as ritonavir.