Penile erection is a vascular event that requires an intact endothelium to occur. A dysfunctional endothelium is an early marker for the development of atherosclerotic changes and can also contribute to the occurrence of acute cardiovascular events. The pathogenesis of both endothelial and erectile dysfunction (ED) is intimately linked through decreased expression and activation of endothelial nitric oxide (NO) synthase, and the subsequent blunted physiological actions of NO naturally occurring with aging. It is now well-understood that ED is a symptom of underlying disease rather than a disease itself; for this reason in the near future both general practitioners, internal medicine practitioners and many specialists will have to interplay with sexual medicine. Aging in the man is also associated with several changes in arterial structure and function, part of them related to the decline of circulating levels of steroids, that is, testosterone and estradiol. These changes may be responsible, in part, for the lack of efficacy of ED treatments. The recent discovery that chronic administration of phosphodiesterase type 5 inhibitors may improve erectile and endothelial responsiveness of men previously non-responsive to on-demand regimes, and the knowledge that testosterone is one of the main modulators of the expression of penile phosphodiesterase type 5 isoenzyme, opens a new scenario in the treatment of men with ED and co-morbidities. The aim of this review is to discuss the pathophysiology of endothelial dysfunction and its relationship with ED in the aging male, and to suggest possible strategies to improve arterial function with regard to sexual dysfunctions.

All PDE5-i are equally effective and safe for the treatment of ED. On-demand use of any PDE5-i is also safe for patients with comorbid conditions. Tadalafil seems to be the preferred drug by patients and physicians, probably due to its peculiar pharmacological profile that makes sexual intercourse more spontaneous for the patients. Preliminary data suggest that the use of vardenafil may also be beneficial in cases of ED associated with premature ejaculation. Daily treatment is another option in men with ED and documented vascular or prostate disease. In geriatric or in difficult-to-treat populations, the evaluation of testosterone plasma levels will help to predict the efficacy of any PDE5-i. Remarkably, when such drugs are withdrawn for any reason, ED most often continues to occur because of the presence of an underlying disease.

No abstract

BackgroundCiticoline is able to potentiate neuroplasticity and is a natural precursor of phospholipid synthesis, or rather serves as a choline source in the metabolic pathways for biosynthesis of acetylcholine. Several studies have shown that it can have beneficial effects both in degenerative and in vascular cognitive decline. The aim of the present study was to review the pharmacokinetics and pharmacodynamics of this drug and its role in cognitive impairment according to the present medical literature.MethodsA MEDLINE® search was made using the following key words: citicoline, pharmacokinetics, pharmacodynamics, elderly, cognitive impairment, vascular dementia, and Alzheimer’s disease. Recent studies on the possible role of citicoline in increasing sirtuin 1 (SIRT1) expression were assessed. Some personal studies were also considered, such as the VITA study and the IDEALE study.ResultsAdministered by both oral and intravenous routes, citicoline is converted into two major circulating metabolites, cytidine and choline. It is metabolized in the gut wall and liver. Pharmacokinetic studies suggested that it is well absorbed and highly bioavailable with oral dosing. A number of studies have clearly shown the possible role of citicoline in cognitive impairment of diverse etiology. It can also modulate the activity/expression of some protein kinases involved in neuronal death and increases SIRT1 expression in the central nervous system. The VITA study and the IDEALE study suggested that both parenteral and oral citicoline are effective and safe. Other studies have clearly demonstrated citicoline’s effects on several cognitive domains. Conversely, some studies did not point out any evidence of efficacy of this drug.ConclusionCiticoline appears to be a promising agent to improve cognitive impairment, especially of vascular origin. In fact, so far it appears as a drug with the ability to promote “safe” neuroprotection, capable of enhancing endogenous protective. Large clinical trials are needed to confirm its benefits.

Erectile dysfunction (ED) is one of the most common chronic diseases affecting men and its prevalence increases with aging. It is also the most frequently diagnosed sexual dysfunction in the older male population. A number of different diseases potentially worsening sexual function may occur in elderly people, together with polypharmacy. Related causes of ED are variable and can include arterial, neurogenic, hormonal, cavernosal, iatrogenic, and psychogenic causes. The aim of the present review was to examine the main aspects of erectile dysfunction going through epidemiology and pathophysiology and revise most of ED in elderly disabled men and in those affected with psychiatric disorders. Lastly we tried to focus on the main aspects of nonpharmacological and pharmacological treatments of ED and the recreational use in the elderly. Phosphodiesterase-5 inhibitors (PDE5-I) are commonly used for on-demand or chronic treatment of ED. It is widely known that PDE5-I have lower response rates in older men than in younger patients, but they have the advantages of ease of use and excellent safety profile, also in the elderly. The old and new PDE5-I as well as the alternative treatments for ED are extensively discussed.