Making medication communication visible in community pharmacies-pharmacists' experience using a question prompt list in the patient meeting.

BACKGROUND: Even though patient engagement in the pharmacy encounter is low, few studies focus on activating patients. A Question Prompt List (QPL) has been used successfully in other parts of healthcare to encourage patients to raise their questions and concerns. For a QPL to be useful in a pharmacy setting, it first must be considered valuable and be accepted by pharmacists. OBJECTIVE: To investigate the experience of community pharmacists using a QPL in counseling patients about prescribed medications. METHODS: An explorative, qualitative study was conducted in 2020. A QPL, for use in pharmacy counseling, was developed based on previous literature. Semi-structured interviews were held with pharmacists. A thematic analysis approach was conducted, and the analytical framework Technology Acceptance Model (TAM) was used. RESULTS: Data were collected in 7 Swedish community pharmacies in interviews with 29 purposefully selected pharmacists. Three themes were identified: Perceived usefulness: the impact of the QPL on patient activation in the encounter, Perceived ease of use of the QPL in pharmacies, and Increasing the perceived usefulness and ease of use of the QPL. The pharmacists perceived patients as more active in the meeting when using the QPL. The list focused the conversation on medications, which the pharmacists appreciated from a professional point of view. They described the QPL as a useful tool that could easily be integrated into the dispensing process and required little training; however, challenges described were, for example, time constraints and stress. CONCLUSIONS: Pharmacists reported that using a QPL improved patient participation in the encounter. Encouraging counseling on medications was seen as beneficial from a professional point of view. In the early adoption phase, the QPL was easy to implement and did not increase the pharmacists' workload. A QPL appears to be a promising tool for pharmacists to improve the quality of the consultation experience.

Accuracy and reproducibility of two scales in causality assessment of unexpected hepatotoxicity.

WHAT IS KNOWN AND OBJECTIVE: There is almost no published information about reliability of scales for causality assessment in hepatotoxicity at pharmacovigilance centres. The aim of this study was to compare two commonly used scales in cases of unexpected hepatotoxicity, in evaluating their accuracy and reproducibility at pharmacovigilance centres (in signal detection). METHODS: Two scales [Council for International Organizations of Medical Sciences or Rousel Uclaf Causality Assessment Method (CIOMS/RUCAM) and NARANJO] were compared in 19 cases of unexpected hepatotoxicity reported during 2004-2009. Data of the cases (with initial clinical assessments) were collected by a network of medical specialists using a structured reporting form. Later, two independent observers assessed each case using both scales. The accuracy and reproducibility of the scales were analysed by Kappa weighted (Kw) test. RESULTS: Both scales (CIOMS/RUCAM vs. NARANJO) showed moderate agreement with the initial clinical assessments (accuracy) for observer A (Kw: 0·56 vs. 0·60) and substantial agreement for observer B (Kw: 0·72 vs. 0·70), with high agreement between observers (Kw: 0·84 vs. 0·67). Both observers (A vs. B) found low agreement between scales (Kw: 0·21 vs. 0·50), with lower scores for the CIOMS/RUCAM scale in 11 and nine cases, respectively. For an early perception of unexpected serious reactions, the scale is more useful if it is not asked for 'previous knowledge' and if it gives higher causality score. WHAT IS NEW AND CONCLUSION: The CIOMS/RUCAM scale showed similar accuracy, but better reproducibility (agreement between observers) than the NARANJO scale, and therefore is recommended for use at pharmacovigilance centres. Fine-tuning of the CIOMS/RUCAM method could contribute to better detection of unexpected hepatotoxicity.

Evaluation of the anti-inflammatory and cytotoxic activities of naphthazarine derivatives from Onosma leptantha.

The root extracts of Onosma leptanhtha were evaluated for their anti-iflammatory and cytotoxic activities. The cyclohexane extract, which appeared as the most active in both assays, has been further subjected to bioassay-directed fractionation to afford the naphthazarine derivatives: beta,beta-dimethylacrylshikonin (1), isovalerylshikonin (2) and acetylshikonin (3). The evaluation of the anti-inflammatory activity was performed on carrageenan-induced rat paw edema test. All the tested compounds proved to be active, while compound 3 showed the best anti-inflammatory effect. In addition, the cytotoxic activity of the extracts and isolated compounds, was also assayed against L1210 murine lymphoblastic leukemia cell line, and human fibrosarcoma HT-1080 cells. Compound 1 exhibited remarkable cytotoxic activity (390 nM for L1210 cells), which is superior to that of shikonin, which was used as control.

Fullerenes in biomedicine.

Studies on the biological properties of fullerene C(60) and its derivatives started a decade ago as curiosity-driven studies and are now flourishing as an area of transdisciplinary research. This paper summarizes the results of studies on the biological activity and applications of selected functionalized fullerenes that were published in the last few years. Apart from literature data, we present most of our results of in vitro and in vivo studies with fullerenol C(60)(OH)(24) anti-oxidative and free radical scavenger activities in chemical and biological systems; cytotoxicity against human tumor cell lines; protective effects against various cytotoxic drugs and irradiation; effects on cell cycle and apoptosis, and in vivo radioprotective and cardioprotective effects. The fullerene family of carbon molecules has been a central focus in the emerging fields of nanotechnology and nanomedicine. Fullerenes take an important place in the development of nanobiotechnology and nanomedicine-related products.

Diuretic activity of Maydis stigma extract in rats.

Maydis stigma (corn silk) is a herbal drug reputed for the treatment of urinary ailments in various traditional medicine systems. To determine its influence on urinary volume and the excretion of sodium, potassium and chloride, 5% and 10% decoctions were administered daily to adult male Wistar rats for eight days. The concentration of electrolytes and urea in plasma, the influence of treatment on urinary pH value as well as creatinine clearance were also investigated. Daily oral administration of 5% decoction at the dose of 10 ml/kg led to a significant and acute diuresis in rats, reaching the peak value in the first 24 h of treatment. Over a similar period, application of 10% decoction did not affect urinary excretion of water, but significantly increased the pH value of excreted urine. A significant decrease in sodium and chloride plasma levels was observed in both treated groups. The creatinine clearance was markedly increased after the treatment with both extracts. Our findings indicate that the diuretic effect of 5% aqueous Maydis stigma extract is in accordance with the increase in glomerular filtration rate and inhibition of sodium and chloride tubular reabsorption, caused a by still unidentified intrinsic factor, but not the salt-loading effect.

The efficacy of selenium, WR-2721, and their combination in the prevention of adriamycin-induced cardiotoxicity in rats.

It is known that the antineoplastic drug adriamycin (ADR) can cause cardiotoxic effects. Some data imply that pretreatment with selenium (Se) and the radio- and chemoprotector, amifostine (WR-2721), may confer a protective effect. The aim of this study was to evaluate the efficacy of single doses of Se and WR-2721, alone or in combination, in the prevention of acute ADR-induced cardiotoxicity in male Wistar rats. Se, in the form of sodium selenite (1.6 mg/kg i.p.), and WR-2721 (300 mg/kg i.p.) were given 24 hours and 20 minutes, respectively, before ADR (6 mg/kg i.v.). The cardiotoxicity of ADR was recorded 48 hours after its administration because earlier studies revealed that structural damage of the myocardium occurs within this period. Evaluation of these toxic effects, as well as of the cardioprotective efficacy of the administered drugs, was performed using (1) ECG-records before and during the infusion of the proarrhythmogenic compound, aconitine (8 microg/kg/min i.v.) and (2) the serum activity of creatine kinase (CK), aspartate aminotransferase-(AST), lactate dehydrogenase (LDH), and its isoenzyme alpha-hydroxybutyrate dehydrogenase (alpha-HBDH). The results showed that the arrhythmogenic dose of aconitine was significantly reduced in ADR-treated rats (57.22 vs. 99.65 microg/kg in control; p < 0.05) and that this proarrhythmogenic compound caused a significant increase in heart rate in such animals compared to controls. Pretreatment with Se, WR-2721, and their combination partly reversed the arrhythmogenic dose of aconitine to control (72.09, 82.1, and 88.99 microg/kg, respectively). Se failed to prevent an aconitine-induced increase in heart rate, whereas WR-2721 and their combination successfully counteracted this effect. In addition, ADR produced a significant increase in the serum activity of all monitored enzymes. Pretreatment with Se failed to prevent this increase, whereas pretreatment with WR-2721 did. The best result was obtained with their combination. We conclude that the radio- and chemoprotector, WR-2721, particularly in combination with Se, may provide a significant protective effect against acute ADR-induced cardiotoxicity in rats.

Cold restraint-induced gastric lesions in individual- and group-stressed rats.

The aim of the present study was to 1) determine the intensity of cold restraint-induced gastric lesions and core body temperature in single- and group-stressed rats, and establish a correlation between them; and 2) determine the influence of visual contact among animals during cold restraint on development of gastric stress ulcer. Therefore, adult male Wistar rats were put into individual or group restraint boxes (composed of two, three, six or nine single boxes) with or without possibility of visual contact and then exposed 2 hr to the cold (4 degrees C). Core body temperature was measured just before and after cold restraint using a digital rectal thermometer. The results showed that: 1) single stressed animals expressed significantly higher ulcer index than those stressed in group of three, six and nine rats; 2) there was no significant difference in degree of hypothermia among rats exposed to various group paradigms; and 3) there was no significant difference in ulcer index among animals stressed in conditions with or without visual contact. An absence of significant difference in ulcer index between single and paired stressed rats implies that three is the lowest number of animals per group at which an influence of group size on behavioral and adaptive mechanisms in rats exposed to cold restraint becomes manifest.

Open field behavior in nucleus basalis magnocellularis-lesioned rats treated with physostigmine and verapamil.

The present study was done to investigate and compare the effect of acetylcholinesterase inhibitor, physostigmine (0.030, 0.045, 0.060 and 0.075 mg/kg sc) and Ca-antagonist, verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg sc) on open field behavior in male Wistar rats with bilateral electrolytic lesions of nucleus basalis magnocellularis (NBM). NBM-lesions produced a significant increase and decrease of ambulation and number of inner squares entered, and defecation, respectively, with no influence on grooming in rats exposed to novel environment. Physostigmine and verapamil in all tested doses, given 30 min before the test did not affect the open field behavior in control animals. In contrast to that, physostigmine (0.045, 0.060 and 0.075 mg/kg) and verapamil (2.5 and 5.0 mg/kg) significantly reduced ambulation and number of inner squares entered in NBM-lesioned rats. Also, physostigmine in a dose of 0.060 mg/kg significantly decreased defecation and in doses of 0.060 and 0.075 mg/kg the grooming, as well. On the other hand, verapamil only in a dose of 2.5 mg/kg significantly increased defecation. It could be concluded that lesions of NBM in rats induced disturbances in the open field behavior, which might be successfully ameliorate by physostigmine and verapamil treatment.

Effect of physostigmine and verapamil on active avoidance in an experimental model of Alzheimer's disease.

The present study was performed to investigate and compare the effect of acetylcholinesterase inhibitor, physostigmine (0.045, 0.060 and 0.075 mg/kg sc, 30 min before the tests) and Ca-antagonist, verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg sc, 30 min before the tests), on two-way active avoidance (AA) learning (acquisition and performance) in nucleus basalis magnocellularis (NBM)-lesioned rats. Bilateral electrolytic lesions of NBM induced significant decrease of acquisition and performance of AA responses in rats. Physostigmine (0.060 mg/kg) significantly improved only acquisition of AA, while verapamil (2.5 and 5.0 mg/kg) significantly improved both type of AA behavior in NBM-lesioned rats. These results suggest that altered calcium homeostasis might play significant role in pathogenesis of experimental induced Alzheimer's disease (AD) and that administration of calcium antagonist such as verapamil might successfully ameliorate disturbances of learning and memory appeared after lesions of NBM.

Neuroprotective effect of chronic verapamil treatment on cognitive and noncognitive deficits in an experimental Alzheimer's disease in rats.

It is well known that disturbance of calcium homeostasis has a significant role in the development of neurodegenerative disorders, such as Alzheimer's disease (AD). Our recent data suggest that acute treatment with the calcium antagonist verapamil can improve some behavioral deficits in an experimental model of AD. Therefore, the present study was done to establish the effect of chronically administered verapamil on cognitive and noncognitive behavior of rats with bilateral electrolitical lesions of nucleus basalis manocellularis (NBM)--an animal model of AD. The NBM lesions produce a deficit in performance of diverse behavior tests: active avoidance (AA), low level of fear (the open field test) as well as aggressive (the test of foot-shock induced aggression) and depressive (the learned helplessness test) behavior. Verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg i.p.) or saline solution (1 ml/kg i.p.) were injected 24 hr after the lesion of NBM and then repeatedly administered during the next 8 days (twice a day). Performance of the two-way active avoidance test, the open field test, the foot shock-induced aggression test and the learned helplessness test were done on day 4 after the last verapamil or saline treatment (day 13 after the lesion). Verapamil in doses of 2.5 and 5.0 mg/kg significantly ameliorated the deficit in the performance of AA, the open field behavior, and the depression, but not the aggressive behavior. The obtained beneficial effect of chronic administered verapamil suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a reasonable way to prevent the behavioral deficits in an experimental model of AD.

Behavioral and adaptive status in an experimental model of Alzheimer's disease in rats.

Ten days after bilateral electrolytic lesions of nucleus basalis magnocellularis (NBM) we tested behavioral (spontaneous motor activity, acquisition and performance of two-way active avoidance, fear-response in open field test, foot shock induced aggression, depression-response in learned helplessness test) and adaptive status (body temperature at standard, hot and cold environment as well as cold restraint-induced gastric lesions) in adult male Wistar rats. Compared to intact control and sham-operated rats, the bilateral NBM-lesioned rats showed the significant impairment of learning behavior and reduced fear, aggression and depression as well as altered body temperature at standard and stressed conditions. Namely, it was established that body temperature in NBM-lesioned rats was significantly lower at standard laboratory conditions, but in these rats body temperature significantly was raised after exposing to cold and hot environment. On the other hand, spontaneous motor activity and number and length of cold restraint-induced gastric lesions (erosions and petechiae) in NBM-lesioned rats were similarly to those in both controls. It could be concluded that NBM plays a significant role in cognitive, emotional and adaptive processes in the rats.

[Adverse effects and toxicity of beta blockers]. / Nezeljeni efekti i toksicnost beta blokatora.

The adverse effects and interactions as well as clinical manifestations and treatment of beta blocker overdosage are reviewed. The most common adverse effects of these drugs arise from their pharmacological action and can be predicted and avoided. The serious unexpected adverse effects, like the so-called "practolol syndrome", are rare and do not occur in asso- ciation with currently available beta blockers. Drug interactions with beta blockers are not very common and have only minor clinical significance. Beta blockers have an extremly high benefit/risk ratio. Most patients who take an overdose of beta blockers are successfully treated.