Erectile dysfunction (ED) is a highly prevalent medical condition. Nearly one in 10 men between the ages of 40 and 70 report dissatisfaction with some aspect of their sexual function.
In the past 15 years there has been much more scientific interest in ED, and this has resulted in the development of sildenafil (Viagra), the first efficacious and safe oral treatment.
Although the number of patients seeking treatment for ED has increased dramatically over the past three years, the sales of sildenafil have not been as projected because:
- Patients are reluctant to discuss sexual issues, and physicians do not feel comfortable opening the discussion.
- Elderly men lose their interest in sex, and with advancing age normal erections are not necessarily essential for a sexually active life.(1)
- Coverage of sildenafil by health insurance plans is a contentious issue.(2)
Drugs currently used for erectile dysfunction
Discoveries of the regulatory mechanisms of penile erection have led to the development of centrally and locally acting central nervous system drugs.
Phosphodiesterase type V (PDE5) inhibitors
Research into ED has focused primarily on the physiological mechanisms of penile erection as the end result of corpus cavernosum smooth muscle relaxation. The sympathetic nervous system, through stimulation of alpha- adrenoceptors, is the prime determinant of cavernosal smooth muscle contraction and detumescence.
Release of nitric oxide following sexual stimulation from nonadrenergic noncholinergic nerves and vascular endothelium activates guanyl cyclase and induces intracellular cyclic guanosine monophosphate (cGMP) synthesis. In turn, cGMP lowers intracellular concentrations, inhibits contractility of the penile smooth muscle and induces an erectile response.
PDE5 is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Sildenafil citrate is a potent reversible and selective PDE5 inhibitor.
Sildenafil citrate
Postmarketing data obtained since the introduction of sildenafil as the first oral agent for ED in males indicate that the efficacy and safety of sildenafil citrate are consistent with the data obtained in clinical trials.(3)
The introduction of medications for ED has enabled impotent men who also have heart disease to engage in sexual activity and has highlighted the need for more detailed information about cardiovascular physiology during coitus. The American College of Cardiology (ACC) and the American Heart Association (AHA) have therefore provided practice guidelines for sildenafil use in men who have ED and are at cardiovascular risk.(4)
Optimal therapeutics and prevention of adverse drug effects begin with complete information. It is therefore vital that information in the package insert is complete and relevant as far as possible to both physicians and patients.(5)
Apomorphine SL
Apomorphine SL was developed by TAP Pharmaceuticals. Two doses, 2 and 3mg, have been recently approved in Europe and become available in EU countries.
Intracavernosal and intraurethral alprostadil
Almost one third (30%) of men with ED do not respond to oral drugs, and another 15% have contraindications to currently available therapy. A subset of patients therefore prefer injection therapy due to its predictable short time to onset of erection and reliable rigidity compared with oral drugs.(6)
Drugs in development
The efficacy and safety of several next-generation (more selective) PDE5 inhibitors for use in the treatment of ED (eg, IC351 and vardenafil) are under evaluation in phase III clinical trials. Other areas being investigated include Rho-kinase antagonism and gene therapy.
[[HPE03_table1_17]]
Authors
Anastasia Argyriou PhD
Pharmacist
Hippocrates General Hospital of Thessaloniki
Greece
Dimitrios Hatzichristou MD PhD
Assistant Professor of Urology/ Andrology
Aristotle University of Thessaloniki
Greece
President
European Society for Sexual and Impotence Research (ESSIR)
References
- Avis NE. Sexual function and ageing in men and women: community and population-based studies. J Gend Specif Med 2000;3:37-41.
- Smith KJ, Roberts MS. The cost-effectiveness of sildenafil. Ann Intern Med 2000;132:994-5.
- Eid JF. Sildenafil citrate: current clinical experience. Int J Impot Res2000;12 Suppl 4:S62-6.
- Cheitlin MD, Hutter AM Jr, Brindis RG, et al. Use of sildenafil in patients with cardiovascular disease. Technology and Practice Executive Committee. ACC/AHA expert consensus document. Circulation 1999;99:168-77.
- Cohen JS. Is the sildenafil product information adequate to facilitate informed therapeutic decisions? Ann Pharmacother 2001;35:337-42.
- Porst H. Current perspectives on intracavernosal pharmacotherapy for erectile dysfunction. Int J Impot Res 2000;12 Suppl 4:S91-100.
