Viera Kristová

Adverse drug reactions related to hospital admission in Slovak elderly patients

The aims of the present study were: to evaluate the prevalence of adverse drug reactions (ADRs) leading to hospitalization in elderly patients; to analyze the drugs which have been identified as having causal relationship with ADRs and to identify risk factors which predispose the patient to such ADRs. The study has been performed in 600 patients aged> or =65 years, hospitalized in a general hospital between 1 December 2003 and 31 March 2005. The ADRs recorded in patients documentation as one of the reasons for hospital admission were evaluated. ADRs leading to hospital admission were recorded in 47 (7.8%) patients. ADRs in 43 patients represented A-type ADRs which are preventable. The most frequent ADRs were cardiovascular disorders. According to the results of multivariate analysis ischemic heart disease (odds ratio (OR)=4.50; 95% confidence interval (CI)=1.36-14.88), depression (OR, 2.49; 95% CI, 1.08-5.77) and heart failure (OR, 2.08; 95% CI, 1.13-3.81) were the most important patient-related characteristics predicting ADRs leading to hospitalization. The majority of ADRs in elderly patients could be avoided. Regular re-evaluation of the medication as well as taking into account the specific features of elderly patients represent the most important tools for ADR prevention.

Protection of the vascular endothelium in experimental situations.

Protection of the vascular endothelium in experimental situations One of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 found in vitro were partly confirmed in vivo. Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effect in vivo.

Analysis of non-steroidal anti-inflammatory drug use in hospitalized patients and perception of their risk

ABSTRACT Non-steroidal anti-inflammatory drugs (NSAIDs) belong to the most widely prescribed and used pharmacological agents worldwide. Data gathered in the last decade show increased incidence of thrombotic events during NSAID administration. Analysis of NSAID usage and assessment of risk for development of cardiovascular adverse effects is needed for improving patient safety. For limiting the impact of adverse effects on the health of patients, NSAID users should be informed about the possible adverse effects and their symptoms to ensure early detection and treatment discontinuation. In the presented study, we retrospectively analyzed the administration of NSAIDs in a group of patients (n=428) in need of analgesic treatment hospitalized at a department of internal medicine. Factors increasing the risk for cardiovascular adverse effects were also investigated. A separate questionnaire study was conducted to gather information concerning the knowledge of hospitalized NSAID users (n=251) about adverse effects of the medication used. For purpose of comparison, we conducted a similar study in a group of 234 random respondents from a shopping center. Data were evaluated using descriptive statistics, Student´s t-test and chi-squared test. Our results suggest that the majority of patients treated with NSAIDs have factors indicating increased risk of development of adverse effects, most commonly arterial hypertension (58.2% of patients). The results of our questionnaire study show limited knowledge of NSAID users about the risk of the therapy. Nearly half of the respondents were unaware of any adverse effects. We consider as alarming that only a limited number of respondents were informed by their physician or pharmacist about the possible risks of treatment. In conclusion, we found that hospitalized NSAID users often have a history of diseases predisposing to the development of cardiovascular adverse effects of NSAIDs. Despite this, their knowledge about the risk of treatment is insufficient.

Long-term Treatment with Hesperidin Improves Endothelium-dependent Vasodilation in Femoral Artery of Spontaneously Hypertensive Rats: The Involvement of NO-synthase and Kv Channels.

Hesperidin is the most common flavonoid found in citrus fruits and is expected to exert vasodilation action relevant to its health benefits. The present study aimed to explore the effect of hesperidin on the vascular responses in normotensive and hypertensive rats and the involvement of NO‐synthase and Kv channels. The 15‐week‐old Wistar and spontaneously hypertensive rats (SHR) were randomized to orally receive either hesperidin (50 mg/kg/day) or a corresponding volume of the water for 4 weeks. Vascular responses of isolated femoral arteries were studied with myograph in control conditions and during inhibition of NO‐synthase with l‐NNA and Kv channels with 4‐AP. Hesperidin had no effect on blood pressure. Endothelium‐dependent vasodilation in Wistar and SHR was significantly improved by the treatment with hesperidin. The contraction responses after l‐NNA were increased in all groups of rats to similar extent, but relaxatory responses were significantly attenuated only in SHR. The inhibition of Kv channels significantly reduced endothelium‐dependent vasodilatory responses in only in SHR administered with hesperidin. The results of our experiment indicate that hesperidin might improve the endothelium‐dependent vasodilation during hypertension, possibly through the enhancement of Kv channels function. Copyright

Trends in vascular pharmacology research in the Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Bratislava

Trends in vascular pharmacology research in the Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Bratislava Research in the Department of Pharmacology started to focus intensively on fetal circulation in the 60s. Results of experiments contributed to clarification of the conversion of fetal circulation type to the adult type: the mechanism of the ductus arteriosus closure, examination of fetal and neonatal pulmonary vessel responses. In the early 80s, increased attention was dedicated to fetal vascular endothelium, later on to vascular reactivity in relation to the endothelium in adult animals. We developed original models of vascular endothelial damage using the perfusion method (repeated vasoconstrictive stimuli, deendothelization by air bubbles). We developed a new technique for in vitro endothelial loss quantification on Millipore filters. Under in vitro conditions, the protective effects of sulodexide and pentoxifylline on vascular endothelium were evaluated. In recent years were studied protective effects of selected substances in vivo in models of endothelial damage (e.g. stress, toxic tissue damage, diabetes mellitus, hypertension). The role of potassium channels in the hypertension model was studied in cooperation with the Czech Academy of Sciences. Assessment of vascular reactivity in the diabetic model was significantly improved by computer. In addition to experimental work, the department is solving problems of clinical pharmacology - especially drug risk evaluation (non-steroidal anti-inflammatory drugs). Recently, we have dealt with pharmacoepidemiological studies in geriatric patients and with cardiovascular risk of NSAIDs in relation to pharmacotherapy. The results of these studies may be an impulse for targeted problem solving in our experiments.