Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor used in patients that suffer from erectile dysfunction. The typical prescription for erectile dysfunction is the brand name Viagra. It targets the corpus cavernosum of the male genitalia to inhibit PDE-5, increasing blood flow, leading to an erection [2]. Viagra comes in 25 mg, 50 mg, and 100 mg tablets. The recommended dosage is one pill approximately one hour before sexual intercourse, although it may be taken anywhere from 30 minutes to 4 hours before sexual intercourse [2]. Viagra should not be taken more than once daily with 100 mg being the max dosage [2]. Viagra is available intravenously but is normally only prescribed in pill form. Dose adjustments should be made with…show more content… Nitric oxide binds to and activates guanylate cyclase, the enzyme responsible for producing cyclic guanosine monophosphate (cGMP). The enhanced effects of nitric oxide are due to the inability of the PDE-5 inhibitors to degrade cGMP which produces the smooth muscle relaxation in the corpus cavernosum allowing for an influx of blood leading to an erection. Sildenafil has no effect on patients without sexual stimulation because it only inhibits the PDE-5. The erection is primarily caused by the release of nitric oxide during sexual stimulation, and the enhanced downstream effects occur due to the PDE-5 inhibition. The corpus cavernosum is not the only location of PDE-5 receptors. Other tissues that have these receptors are some smooth and skeletal muscle, platelets, the brain, heart, liver and kidneys as well as the pancreas, prostate, testis, and bladder. Sildenafil will bind to the PDE-5 receptors within all of these tissues which ultimately leads to other downstream effects that are noted as side…show more content… It is almost completely absorbed reaching peak plasma concentrations within 30 – 120 minutes when taken on an empty stomach and has a half-life of 4 hours [1][2]. Absorption time is delayed by approximately 1 hour when taken with a meal high in fats [2]. Sildenafil hits peak plasma concentration at 531 ng/mL [5]. Sildenafil is approximately 96% bound to albumin and has a volume of distribution of 105 L at steady state. The relatively high volume of distribution relates good distribution into the tissues [2][5]. Sildenafil is highly metabolized during its first pass through the liver by cytochrome P450 3A4 and 2C9, but primarily through CYP3A4 [2]. Sildenafil is metabolized into UK-103,320 by N-demethylation which is then further metabolized into UK-150,564. Both metabolites have similar structure and binding affinities as sildenafil [2][5][6]. Sildenafil is excreted mainly in feces and some in urine with no unchanged drug present indicating that hepatic clearance is the primary clearance mechanism via biotransformation with a rate of clearance of 41 L/hr [5][6].
Geriatric patients and those with mild to moderate hepatic impairments showed a decreased rate of clearance with significantly higher values for AUC and Cmax [2]. Patients with mild renal impairments did not show any difference in clearance, but those with severe renal impairment showed decreased
