The analysis of the use of potentially inappropriate medications in elderly in the Slovak Republic.

Background The prevalence of potentially inappropriate medications (PIM) using explicit criteria has been well documented in European countries, however, there is a lack of evidence in the Slovak Republic. There are no specific guidelines and there is a lack of geriatricians in Slovakia. Higher use of PIM leads to greater healthcare services use as well as increases healthcare costs. Objective The aim of this study was to perform an evaluation of the availability and the actual use of PIM by geriatric patients in the nursing homes in Slovakia. Setting Together 459 residents ≥ 65 years living in nursing homes in the Slovak Republic were included for analysis of their drug therapy. Methods Retrospective analysis of medical records of patients' therapy for evaluation of PIM use. Identification of PIM was based on the Renom-Guiteras EU7 PIM list published in 2015. Main outcome measure Potentially inappropriate medications use. The presence of polypharmacy in patients. Results Inappropriate drug use according to EU7 PIM list was identified in 90.60% (416) patients. The mean number of PIM was 2.34 ± 0.07 PIM/patient/day. Polypharmacy (use of ≥ 5 drugs by patient daily) was found in 83% of all patients. The mean number of prescribed drugs was 8.32 ± 0.17 drugs/patient/day. Out of all 282 PIM listed in EU7 PIM list, there are 150 (53.19%) available on the Slovak market and 86 (30.50%) were used in patients. Patients using at least one PIM took two times more drugs compared to patients without PIM (8.77 ± 0.17 vs. 3.98 ± 0.39 drugs/patient/day, p < 0.001). The most common PIM were PPI (36% of patients), piracetam (17.2%) and alprazolam (16.80%). Conclusions The risk of PIM was almost 9.5 times higher if polypharmacy was present in geriatric patients (OR 9.51, 95% CI, 4.86 - 18.61, p < 0.001). There was a strong, positive correlation (ρ = 0.65) between the number of drugs and the number of PIM (p < 0.01). There was neither association between age/gender of patient and polypharmacy; nor age/gender of patient and presence of PIM. The lack of geriatricians and national guidelines for inappropriate prescribing results in alarmingly high use of PIM in the Slovak Republic.

The Effects of Pycnogenol® as Add-on Drug to Metformin Therapy in Diabetic Rats.

The progression of diabetes mellitus leads in time to the development of serious cardiovascular complications. Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio-protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add-on drug to metformin therapy in streptozotocin (STZ)-induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin-dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy. Copyright © 2016 John Wiley & Sons, Ltd.

Pycnogenol® and its fractions influence the function of isolated heart in rats with experimental diabetes mellitus.

The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractions (buthanolic, water, ethyl acetate) on heart function in rats with experimental diabetes mellitus (DM) and compare their effects to the diabetic group. Their antioxidant activity "in vitro" was also determined. DM rats (streptozotocin over 3 consecutive days at a dose of 25 mg/kg of body weight) had increased systolic blood pressure, thicker left ventriculi wall (LV) and weaker myocardial contraction, prolonged QT interval in comparison to controls rats. In comparison to the diabetic group, PYC (20 mg/kg b.w./day) suppressed the influence of DM on the LV, improved contraction, increased coronary flow and displayed negative effect on electrical activity of hearts. The most effective of PYC's fractions was the water fraction. It improved biometric parameters and hemodynamic function of the DM hearts, enhanced shortening the QT interval, reduced the amount of dysrhythmias of the DM hearts and had the strongest antioxidant activity. In conclusion, DM damaged isolated rat heart function. Only the water fraction improved the function of the diabetic heart. The different results of three fractions and PYC on myocardial function may be caused by a various lipo- and hydro-philic action of the PYC components.

Glucose and blood pressure lowering effects of Pycnogenol® are inefficient to prevent prolongation of QT interval in experimental diabetic cardiomyopathy.

Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark - Pycnogenol(®) (PYC) with hypoglycaemic and antioxidant properties in 8-9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50 mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p<0.05) and significantly increased mean arterial blood pressure (by 19%; p<0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p<0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p<0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p<0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy.

Pycnogenol improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats.

We studied whether Pycnogenol (PYC) may attenuate the development of experimental streptozotocin-induced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)-producing molecules (gp91(phox)-containing NADPH oxidase and NO-signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91(phox) (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha-tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS-producing enzymes and cytoskeletal components.