Sildenafil (PDE5 Inhibitor): General Description
Sildenafil is a potent phosphodiesterase 5 inhibitor and under certain conditions increases cGMP effects by this nucleotide degradation inhibition. The drug acts only in terms of sexual stimulation and restores natural response to sexual stimulation.
The First PDE5 inhibitor changed erectile dysfunction pharmacotherapy. The possibility of oral administration, effectiveness, and safety has led to the increase in a number of patients who began to seek for erectile dysfunction treatment. Before sildenafil development, only about 2% of patients suffering from erectile dysfunction were willing to talk about their problem. After sildenafil introduction, the number of such patients has increased to 18%.
Sildenafil is rapidly absorbed and starts to act within 1 hour, elimination half-life is 4-6 hours. However, due to relatively high concentrations in plasma achieved in therapeutic dose range (25, 50 and 100 mg), functional and pharmacodynamic periods are much longer. Some patients had erection persisting for 36 hours after receiving a single dose.
Sildenafil is effective for erectile dysfunction treatment caused by a wide range of reasons. Erection occurs in 65-70% of patients (percentage of diabetic patients is slightly lower). Erection degree at the intracavernosal administration is higher, but oral administration convenience determines its popularity among patients.
Side Effects and Contraindications
Common side effects of Sildenafil are related to the cardiovascular system:
- nasal breathing disorders;
All of them are probably a consequence of PDE5 inhibition, i. e. the main drug action mechanism. Dysphagia and dyspepsia, observed at high dosages, may also be connected to PDE5 inhibition, in this case, of a lower esophageal sphincter. In some cases, patients themselves are trying to eliminate a headache and dyspepsia with NSAIDs and H2-receptors antagonists respectively.
5% of patients observed reversible vision disorders in form of color perception change (blue aura) caused by thePDE5 inhibitor. This happens because of low selectivity which sildenafil shows compared to PDE6, involved in retinal color perception transmission.
By increasing NO concentration, sildenafil also enhances nitroglycerine, isosorbide and other products based on organic nitrates, effect. Due to pronounced vasodilation, mediated by NO, it can lead to significant hypotension development. For this reason, this agent is absolutely contraindicated for patients taking such drugs.
The substance is eliminated mainly in the liver by means of CYP3A4. Dosage should be reduced for elderly patients and patients with nephatony and hepatism. When receiving CYP3A4 inhibitors such as cimetidine, ketoconazole, and erythromycin, you must decrease sildenafil dosage. There is data that sildenafil has an impact on vasoactive agents effects, such as amlodipine and ACE inhibitors. Cardiovascular risk problem bothers patients taking sildenafil, which may also adversely affect this drug administration.
Recently, vardenafil PDE5 inhibitor was introduced in clinical practice for erectile dysfunction treatment, which presumably has more rapid action onset than sildenafil. Tadalafil is a long-acting drug with elimination half-life 17,5 hours, which is more convenient for patients.