Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Antihypertensive Medication Nonadherence and Blood Pressure

Source: Rose AJ, et al. Effects of daily adherence to antihypertensive medication on blood pressure control. J Clin Hypertens 2011;6:416-421.

It comes as no surprise that when patients do not take their blood pressure (BP) medication, a lapse in BP control is anticipated. On the other hand, when a patient presents with an elevated BP and acknowledges omitted doses, it is difficult to be sure whether the observed elevation in BP is solely due to recent omissions, an underlying worsening of BP (requiring an augmentation rather than just simple restoration of treatment), rebound BP elevation, or some combination of these elements. To gain a more concrete insight into the anticipated impact of omitted BP medication in a typical patient population, Rose et al reviewed data from a population (n = 869) enrolled in a trial investigating the effects of physician communication on BP control. A component of the study design was utilization of medication bottles with memory caps that recorded timing and frequency of opening, providing a detailed view of medication administration.

When comparing BP after a 7-day period of poor adherence (< 60% of prescribed medication administered) to a prior period of excellent adherence, BP was 12/7 mmHg higher immediately following the week of poor adherence.

Clinical inertia — failure to intensify treatment despite suboptimal goal attainment — is sometimes innocently propagated by clinician uncertainty about whether uncontrolled BP should simply be attributed to missed doses or needs treatment augmentation. The authors suggest that clinicians consider a maximum BP excursion of 15/8 mmHg as potentially likely due to poor medication adherence, and that when BP elevation is greater than this amount, consider augmentation of antihypertensive treatment rather than simply encouraging better adherence to the existing regimen.

PDE5 Inhibition and Cognitive Function

Source: Shim YS, et al. Effects of repeated dosing with Udenafil (Zydena) on cognition, somatization and erection in patients with erectile dysfunction: A pilot study. Int J Impot Res 2011;23:109-114.

The therapeutic realm of pde5 inhibitors has expanded to include not only erectile dysfunction (ED) but also pulmonary hypertension. Animal studies have identified PDE5 activity in the brain, which can be impacted by currently available PDE5 inhibitors since they readily cross the blood-brain barrier. In the animal CNS, increased cyclic GMP (a pharmacodynamic effect of PDE5 inhibition) is seen in pathways associated with memory; studies have confirmed enhanced cognition in animals with impaired cognition related to diabetes, anticholinergic medications, and hyperammonemia who are treated with PDE5 inhibitors.

Udenafil is a PDE5 inhibitor not available in the United States but already in use in other countries (e.g., Korea, Russia) for treatment of ED. Shim et al undertook a trial of udenafil in men with ED but without known cognitive dysfunction (n = 30). Subjects underwent a battery of tests of cognitive function at baseline and 8 weeks later. Testing metrics included measures of general cognitive function, verbal learning for episodic memory, and frontal executive function.

Several tests of cognitive function showed statistically significant improvement. Cognitive function improvement was greater in men whose sexual function scores improved the most. The authors suggest further exploration of the effects of PDE5 inhibition on cerebral flow to gain greater understanding of the favorable cognitive effects they have demonstrated.

Can Appendicitis be Cured with Antibiotics Alone?

Source: Vons C, et al. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: An open-label, non-inferiority, randomised controlled trial. Lancet 2011; 377:1573-1579.

Sometimes, acute appendicitis (aap) just goes away. We know this because of abdominal explorations that disclose evidence of chronic appendicitis, indicative of one or more prior episodes. Four randomized trials support the relevance of antibiotic treatment for AAP, but definitive conclusions about the appropriate role of antibiotics in AAP treatment have been limited by aspects of previous study design.

Vons et al performed a controlled trial of adult patients with CT-confirmed uncomplicated AAP who were randomized to antibiotics (amoxicillin/clavulanic acid 3-4 g/d) or surgery. Although one group was assigned to surgery alone, the surgical group also actually received a single parenteral 2 g dose of amoxicillin/clavulanic acid at induction of anesthesia; additionally, if complicated appendicitis was discovered at surgery (i.e., the appendicitis had progressed or was misdiagnosed by CT), antibiotics were subsequently administered even in the surgery group.

Peritonitis within 30 days of intervention — the primary endpoint of the trial — occurred more often in the antibiotic group (8% vs 2%), hence the noninferiority of antibiotic treatment was NOT confirmed. If future tools can do a better job of identifying those who truly have uncomplicated appendicitis, antibiotics may prove to be a more valuable first-line treatment.