By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville
Dr. Kuritzky is a retained consultant for Boehringer Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals, Janssen, Lilly, Novo Nordisk, Pfizer, and Sanofi.
Daily Use of PDE5 Inhibitors
Source: Shim YS, et al. Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on cognition, depression, somatization and erectile function in patients with erectile dysfunction: A double-blind, placebo-controlled study. Int J Impot Res 2014;26:76-80.
In the united states, most men who use PDE5 inhibitors (i.e., avanafil, sildenafil, tadalafil, vardenafil) for restoration of sexual function use them on a PRN basis. One of the reasons for PRN use is that the short half-life of all currently FDA-approved PDE5 inhibitors, except tadalafil, is too short to provide sustained 24-hour enhancement of cyclic GMP, the chemical messenger responsible for corpora cavernosa vascular dilation. Because of its 18-hour half-life, tadalafil is well suited to low-dose daily administration, but the time to onset of efficacy may be somewhat slower than the other PDE inhibitors.
In Korea, another PDE5 inhibitor — udenafil — is approved for the treatment of erectile dysfunction (ED). Similar to tadalafil, udenafil has a long half-life (11-13 hours), making it suitable for once-daily administration. In contrast to tadalafil, it has a more rapid onset of action (time to maximum plasma concentration = 0.8-1.3 hours) than tadalafil (2 hours). Shim et al performed a 2-month, placebo-controlled trial of once-daily udenafil among men (n = 49) with ED. The outcomes included not only erectile function but also assessments of depression (PHQ-9), somatization (PHQ-15), and cognitive function (Korean MMSE and Seoul Neuropsychological Screening Battery).
As has been shown with other PDE5 inhibitors, there was a substantial improvement in erectile function. In addition, treatment with udenafil improved measurements of cognition, depression, and somatization compared to placebo. Improved erectile function has previously been shown to improve depression and quality of life, but Shim et al suggest that there may also be direct central nervous system, vascular, and nitrergic pathways that could lead to the outcomes improvement they detected.
Refining the List of Things Not to Do for Long-Term Care Residents
Source: Five treatments to avoid in long-term care residents. Ann Long-Term Care: Clin Care Aging 2014;22:18-19.
The american geriatrics society in partnership with the American Board of Internal Medicine Foundation has identified some commonly used treatments that may either lack benefit or even be harmful to long-term care residents (LTCR). The five specific items are: 1) If you are going to treat dementia with cholinesterase inhibitors, perform periodic cognitive assessments to confirm whether they are providing benefit. 2) When you consider screening tests (e.g., mammography, colonoscopy, PSA), consider the likely life expectancy of your patient, as well as the potential consequences of overdiagnosis. 3) Instead of relying on appetite stimulants to enhance waning appetite, consider behavioral and social factors affecting appetite, such as support for eating at mealtime. 4) Don’t prescribe a new medication without confirming other currently prescribed medications to avoid duplication and adverse interactions. 5) When possible, do not use physical restraints in the face of delirium since they have been associated with injury and even death; instead treat the underlying cause(s), promote a physiologic sleep-wake cycle, and consider options to manipulate the environment to enhance orientation.
Remembering to include these five issues in managing LTCR will hopefully improve outcomes and reduce medical misadventure.
Do Clinicians Really Need to Know What microRNAs Are?
Source: Leroith D. microRNAs: What the clinician should know about this new frontier. Diabetes Care 2014;37:1176-1177.
Primary care clinicians are sometimes mistakenly described as not caring about the pathophysiology, but rather, more pragmatically interested in "just tell me what to do." Instead, in my experience, primary care clinicians are very interested in the pertinent pathophysiology: i.e., having insight into the story line that gives clarity about why a particular medication is chosen, why some medications are complementary, and others not, etc.
Recently, microRNAs (miRNA) have been recognized to play an important role in diabetes, cardiovascular disease, and even cancer. Although miRNA literature at this point may seem "alien" to most clinicians, there have been more than 25,000 publications on the topic since their discovery in 2000. miRNA is measurable in plasma, saliva, and urine. Particular subgroups of miRNA have been identified in persons with diabetic retinopathy.
The basic function of miRNA is to regulate the activity of specific target messenger RNA, thereby altering production of individual proteins. A primary action of miRNA appears to be to suppress protein production, such that activation of miRNA results in reduction of specific proteins. A recent study found an association between specific miRNA and glucose perturbations, such that essentially half of abnormal glucose excursions could be explained by abnormalities in miRNA.
At the current time, miRNA is primarily a research tool, but investigators are hopeful that identification of specific miRNA associated with disorders as diverse as obesity, diabetes, and cancer may lead to early identification of pathology, and hopefully even the opportunity for improved disease modification.