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Update on Short-Acting vs. Long-Acting PDE5i + Life-Style Changes vs. PDE5i

Seth D. Cohen

The medical management of erectile dysfunction(ED) has evolved greatly over the past 20 years. Prior to the early 80’s we were able to offer patients one of two definitive surgical therapies for the management of their erectile dysfunction: implantation of penile prosthesis and penile revascularization. The first approved phosphodiesterase inhibitors (PDE5i) for the treatment of ED was sildenafil citrate (1998). Currently, there are four FDA approved oral medications indicated for the treatment of ED (sildenafil, vardenafil, tadalafil and avanafil), all of which predominantly inhibit PDE5.

Despite their similar modes of action, PDE5i differ in their biochemical properties, pharmacokinetic profiles, and clinical performance. Most distinctive is their half-life, with sildenafil, vardenafil and avanafil having half-lives of approximately 4-5 hours, compared with tadalafil, with a half-life of 17.5 hours. The median time to maximum concentration (t max) is 30 minutes for avanafil, 1 hour for sildenafil and vardenafil, and 2 hours for tadalafil.

The abundance of choices poses the question, "which PDE-5 inhibitor?" relevant for clinicians, patients and their partners. A significant percentage of men initiating treatment will ultimately switch between inhibitors or discontinue therapy (poor compliance). Properly counseling patients and their partners as to the appropriate treatment choice is paramount to optimizing compliance. It is widely accepted that there are no significant differences in the safety and efficacy of the 4 PDE5i, although avanafil has shown great promise in reducing the typical side effects.

Lifestyle modifications should be certainly considered an integral part of the treatment regimen for ED, both independently and in conjunction with other management options. The risk of developing ED is closely associated with the presence of co-morbidities such as diabetes, cardiovascular disease, and metabolic syndrome. Prevention or appropriate treatment of these disease states, can positively impact sexual health.