Viagra (Sildenafil)
Sildenafil (Viagra) was developed more than 10 years ago as an antihypertensive and antianginal drug. It proved ineffective in these applications but was shown to affect the smooth muscles of the penis.
Pharmacology.
Sildenafil is a selective inhibitor of cGMP-specific PD-5 and therefore inhibits the degradation of cGMP. PD-5, the predominant type in the corpus cavernosum, also is present in other tissues (e.g., lungs, platelets, and eye). The selective inhibition of this enzyme facilitates the release of nitric oxide and smooth muscle relaxation of the corpus cavernosa. Sildenafil enhances erection by augmenting nitric oxide–mediated relaxation pathways. It has been suggested that sildenafil’s mechanism of action is due to cross-talk between cGMP- and cAMPdependent transduction pathways within the cavernous muscles.
Pharmacokinetics.
Sildenafil is readily absorbed after oral administration and reaches peak plasma levels after about an hour. It undergoes hepatic metabolism and has a terminal half-life of about 4 hours.
Dosage.
An initial dose of 50 mg is taken about an hour prior to sexual activity to induce penile erection. Orally administered sildenafil is an effective and well-tolerated treatment for men with ED, including those with diabetes mellitus. It has also been used for so-called salvage therapy in men who do not respond to intracorporeal injections of other agents.
Adverse Effects.
Headache is a common side effect, as are flushing and rhinitis. More serious side effects include definite or suspected myocardial infarctions and cardiac arrest.
