Phosphodiesterase type 5 inhibitors: the day after.
OBJECTIVE
Review the literature on phosphodiesterase type 5 inhibitors (PDE5-Is), addressing critical issues in their current and future use, assessing unanswered questions, and identifying research needs.


METHODS
A MEDLINE search was conducted on PDE5-Is, with emphasis on clinical trials and experience, for interpretation and analysis of their present and future role.


RESULTS
Although approximately 40 million patients with erectile dysfunction have been treated successfully worldwide with the three available PDE5-Is, inappropriate instructions, lack of follow-up, and lack of patient-centered care models are the main reasons for "non-response," leading to drop-out rates of >50%. Patients with severe neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5-Is. Preservation of corporal smooth muscle with chronic administration of PDE5-Is has been reported and substantial evidence indicates that these drugs have beneficial effects on endothelium and cardiovascular function; sildenafil has been approved for the treatment of idiopathic pulmonary hypertension. Improvement of lower urinary tract symptoms in men with benign prostatic hyperplasia after PDE5-I administration has been also suggested.


CONCLUSIONS
The data indicate the necessity for (1) exploration of the pharmacologic characteristics of the three PDE5-Is; (2) research on their pharmacologic differences because some actions seems to be drug-specific; (3) development of alternative management strategies, such as chronic, low, everyday doses of PDE5-Is, if the monthly cost is affordable; and (4) clinical trials on use of PDE5-Is to treat other chronic conditions. The door for innovative therapeutic approaches will open, specifically for cross-risk factor treatment with PDE5-Is or their use in combination treatments or new multimodal pills that take advantage of drugs that exert pleiotropic vascular actions.
Hatzimouratidis
Konstantinos
K
2nd Department of Urology, Papageorgiou General Hospital and Center for Sexual and Reproductive Health, Aristotle University of Thessaloniki, Greece.
Hatzichristou
Dimitrios
D
D000818:Animals; D002243:Carbolines / Q000009:adverse effects / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D011687:Purines / Q000009:adverse effects / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use; D000068581:Tadalafil; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride
D002243:Carbolines; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D000068677:Sildenafil Citrate