Mechanism of Action
- Parasympathetic stimulation results in release of nitric oxide, which stimulates guanylate cyclase to convert GTP to cyclic GMP
- cGMP causes smooth muscle relaxation, allowing blood to fill the corpora cavernosa, resulting in erection
- Phosphodiesterase type 5 (PDE5) breaks down GMP; sildenafil inhibits PDE5

Pharmacokinetics
- Rapidly absorbed on oral administration
- Peak levels in 1 hour
- Food slows absorption, but does not affect the AUC
- Well distributed in the body
- Metabolised in the liver; CYP3A4 is major route, CYP2C9 is minor route

Assessment
- Assessed based on responses to questionaire, including International Index of Erectile Function (IIEF) questions
- Evaluated in ED with no organic cause or causes such as spinal cord injury and diabetes
- Assessed for effects on erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction
- Compared with placebo

Clinical Efficacy
- Superior to placebo for ED of various aetiologies, i.e., organic, psychogenic, mixed
- Increased frequency, firmness and maintenance of erections, frequency of attempted and successful sexual intercourse

Indication
Treatment of Erectile Dysfunction (ED)

Dosage
50 mg approximately 1 hour before sexual activity. Maximum 100 mg. May be decreased to 25 mg, based on effectiveness and tolerability. Maximum recommended dosing frequency is once daily.

Contraindications
- Patients using nitrates
- Hypersensitivity

Cardiac Risk
Cardiac adverse events e.g., myocardial infarction, reported following use of sildenafil, were not a direct effect of the drug; however caution is advocated in patients at cardiovascular risk.

Drug Interactions
- Interacts with other drugs metabolised by cytochrome P450, e.g., cimetidine, erythromycin, saquinavir, ketoconazole (all increase sildenafil plasma conc. and/or AUC)
- Rifampicin may decrease sildenafil levels
- No effect of tolbutamide, warfarin, serotinin uptake inhibitors, tricyclic antidepressants, thiazide diurectics, ACE inhibitors, calcium channel blockers.

Adverse Effects
- Headache, flushing and dyspepsia are the commonest adverse effects
- Cardiovascular adverse events were not found to be directly related to sildenafil