Introduction: Pharmacokinetic properties of β1 selective adrenergic blocking agents pre-determine their clinical use in individual patients dependent on age, genetic polymorphisms, comorbidities, concomitant therapies, and kidney or liver dysfunction. Areas covered: This paper reviews multiple searches of studies considering the pharmacokinetics of β1 selective blockers published in scientific journals from 1966 to June 2014. The pharmacokinetic parameters of these drugs in healthy populations, as well as changes of their values in the settings of advanced age, liver or renal failure, other comorbidities and enzyme or transporter polymorphisms are reviewed. Expert opinion: There is significant imbalance in the number and quality of studies on the pharmacokinetics of β1 selective blockers. Some members of the drug class, such as celiprolol and betaxolol were clearly under-investigated. Additionally, many questions about the extent and cause of pharmacokinetic variability of even the most widely studied β1 blockers, such metoprolol and bisoprolol, remain unanswered. In order to acquire complete and detailed knowledge of all factors that could influence pharmacokinetics of β1 selective blockers, population pharmacokinetic approaches linked with studies of genetic polymorphisms should be increasingly used in the future. This strategy provides methodological rigor and an ability to test effects of numerous factors at the same time.

Lekari opste medicine se cesto susrecu sa hitnim stanjima u svojoj praksi. Da bi se lekar brzo snasao u takvoj situaciji i primenio odgovarajucu terapiju pravovremeno, neophodno je da pri sebi ima pripremljenu odabranu kolekciju lekova koji mogu resiti sva ili gotovo sva hitna stanja. U lekarskoj torbi bi trebalo da se nađu sledeci lekovi: paracetamol (za blage do umerene bolove i povisenu temperaturu), morfin (za jake bolove), nalokson (za lecenje trovanja heroinom), ceftriakson (za meningokokni meningitis), salbutamol (za prekid napada bronhijalne astme), hidrokortizon (za prekid napada bronhijalne astme), glukagon (za tesku hipoglikemiju), glukoza (za blagu do umerenu hipoglikemiju), diazepam (za prekid febrilnih konvulzija ili epileptickog statusa), adrenalin (za anafilaksu i zastoj srca), atropin (za simptomatsku bradikardiju), hlorpiramin (za akutne alergijske reakcije), aspirin (za akutni infarkt miokarda), nitroglicerin (za akutni koronarni sindrom), metoklopramid (za mucninu i povracanje), haloperidol (za delirijum), metilergometrin (za krvarenje posle porođaja ili pobacaja), furosemid (za akutni edem pluca) i flumazenil (za trovanje benzodiazepinima). Za svaki od navedenih lekova lekar treba dobro da poznaje preporucene doze, indikacije, kontraindikacije i najvažnija upozorenja. Svi navedeni lekovi su dostupni na domacem tržistu ili putem specijalnog uvoza, tako da lekar opste prakse može da popuni svoju torbu svim potrebnim lekovima i efikasno i bezbedno zbrine svako od hitnih stanja.

ABSTRACT Introduction: Many factors concomitantly influence the quality of life of patients with schizophrenia in a long-stay psychiatric facility. Th e appropriate selection of antipsychotics and the intensity of their adverse effects exert a significant influence on the quality of life of these patients. Th e aim of this study was to identify the influence of antipsychotic-related factors on the quality of life of patients with schizophrenia. Methods: Th e study included 102 beneficiaries at the Institute for Accommodation of Adults “Male Pčelice” in Kragujevac. Th e patients were interviewed on in one day using the questionnaire issued by the World Health Organization. The specified data were obtained from the health files of the beneficiaries. We performed a comparison between patients receiving only atypical antipsychotics, typical antipsychotics or a combination thereof. Results: Th e patients who were receiving only atypical antipsychotics demonstrated better physical health quality of life scores in comparison to those who received combined antipsychotics (77.14 vs. 68.57; U = 332.0; p = 0.02). A statistically significant difference in the mental health quality of life domain was observed between groups of patients receiving various antipsychotic treatments (31.96 vs. 55.27 vs. 49.46; c2 = 7.02; p = 0.03). Conclusion: Patients in a long-stay psychiatric facility who received atypical antipsychotics demonstrated a better quality of life in comparison to those who received typical antipsychotics, possibly due to the superior safety profile of atypical antipsychotics and a greater feeling of individual contentment. SAŽETAK Uvod: Na kvalitet života osoba koje boluju od shizofrenije utiče mnogo faktora istovremeno. Kod pacijenata u institucionalnom smeštaju adekvatan izbor antipsihotika i intezitet neželjenih dejstva lekova ima veliki uticaj na kvalitet života ovih pacijenata. Cilj ove studije je bio da se utvrdi uticaj faktora vezanih za antipsihotike na kvalitet života pacijenata koji boluju od shizofrenije. Metode: Istraživanjem je obuhvaćeno ukupno 102 korisnika Zavoda za smeštaj odraslih lica „Male Pčelice” Kragujevac. Korisnici su ispitani u samo jednom izabranom danu korišćenjem upitnika Svetske zdravstvene organizacije. Određeni podaci su prikupljeni iz zdravstvenih kartona korisnika. Poređene su grupe korisnika koji koriste samo apitičan ili tipičan antipsihotik ili kombinaciju ove dve grupe antipsihotika. Rezultati: Korisnici koji koriste samo atipičan antipsihotik imaju bolji skor fi zičkog zdravlja od korisnika koji koriste kombinaciju antipsihotika (77,14 vs. 68,57; U = 332,0; p = 0,02). Postoji statistički značajna razlika u skoru domena psihičkog zdravlja u zavisnosti od grupe antipsihotika koji je korisniku propisan (31,96 vs. 55,27 vs. 49,46; c2 = 7,02; p = 0,03). Zaključak: Korisnici ustanove za dugotrajan smeštaj psihijatrijskih bolesnika koji primaju apitične antipsihotike imaju bolji kvalitet života u odnosu na pacijente koji primaju tipične antipsihotike, verovatno zbog manje izraženih neželjenih dejstava atipičnih antipsihotika i boljeg osećaja subjektivnog zadovoljstva.

Abstract In 2013, the regulatory authorities of the European Union and the US issued, almost simultaneously, new editions of the industry guidelines for the requirements of drug testing during their development for drug–drug and drug–food interactions. That being said, there are significant differences in the requirements set by both guidelines, and the aim of this article is to point out those differences. In this review, the author carefully and comprehensively compared the publicly available guidelines via the official Food and Drug Administation’s (FDA) and European Medicine Agency’s (EMA) websites, highlighting the differences between the two sets. Unlike the guidelines provided by the FDA, the EMA guidelines lack set requirements for testing interactions with therapeutic proteins as well as with the usage of pharmacodynamics end-points. It also does not set standards for the use of the ‘no interaction’ declaration in the summary of product characteristics. On the other hand, the FDA currently lacks guidance for testing drug–food interactions, the use of the Relative Induction Score correlation method, and proving existence of reversible inhibition and mechanism-based inactivation. It is important to note that, while there are differences in the requirements for the FDA’s and the EMA’s drug interaction guidelines, they are not substantial and are mostly relating to the scope of requirements and precision of the standards set.

Hawthorn has been present for a long time in traditional medicine as antihypertensive, hypolipidemic, anti-inflammatory, gastroprotective, antimicrobial agent. Hawthorn can be used for the cure of stress, nervousness but there is no published paper about actions of Crataegus nigra Wald. et Kit. fruits. The present study was carried out to test free-radical-scavenging and anxiolytic activity of C. nigra fruits. DPPH (alpha,alpha-diphenyl-beta-picrylhydrazyl) assay was used to measure antioxidant activity. BHT, BHA, PG, quercetin and rutin were used as standards. The total amount of phenolic compounds, procyanidins, and flavonoids in the extracts, was determined spectrophotometrically. Results were expressed as equivalents of gallic acid, cyanidin chloride and quercetin equivalents, respectively. LC-MS/MS was used for identification and quantification of phenolic composition. The anxiety effect, expressed as the difference in time spent in the open and closed arms, was measured and compared between groups. Phenolic compound content of Crataegus nigra fruits was 72.7 mg/g. Yield of total flavonoid aglycones was 0.115 mg/g. Procyanidins were 5.6 mg/g. DPPH radical-scavenging capacity of the extracts showed linear concentration dependency, IC50 value were 27.33 microg/mL. Anxiolytic effect was observed. Species Crataegus nigra fruits hydroalcoholic extract showed antioxidant and anxiolytic activity.

BACKGROUND/AIM Recent studies have shown that biological treatments for rheumatoid arthritis can change the course of rheumatoid arthritis and improve functional ability of patients with rheumatoid arthritis. In spite of this fact, use of biological therapy is still limited by high prices of these medicines, especially in countries in socioeconomic transition. The aim of our study was to compare cost-effectiveness of a combination of tocilizumab and methotrexate with methotrexate alone for rheumatoid arthritis in Serbia, a country in socioeconomic transition. METHODS For the purpose of our study we designed a Markov model using data on therapy efficacy from the available literature, and data on the costs of health states calculated from records of actual patients treated in the Clinical Center Kragujevac, Serbia. The duration of one cycle in our model was set at one month, and the time horizon was 480 months (40 years). The study was done from the social perspective, and all the costs and outcomes were discounted for 3% per year. RESULTS Treating rheumatoid arthritis with disease-modifying antirheumatic drugs (DMARDs) alone was more cost-effective in comparison with a combination of biologic treatment with tocilizumab and DMARDs. The total costs for treating a patient with DMARDs for one year were on average 261,945.42 RSD, or 2,497.70 Euro and the total costs for treatment with tocilizimab plus DMARDs were on average 1,959,217.44 RSD, or 18,659.20 Euro. However, these results are susceptible to changes in costs and treatment effects of tocilizumab in patients with more severe forms of rheumatoid arthritis. CONCLUSION Our results show that the use of tocilizumab for rheumatoid arthrits in economic environment of Serbia is not cost-effective. Use of tocilizumab for treating rheumatoid arthritis can become affordable, if costs of its use become lower. In order to start using expensive biologic medicines in patients in transitional countries, special strategy and pricing policy of international pharmaceutical companies are necessary, which would include calculation of prices of biologic medicines on the basis of local pharmacoeconomic studies.

ObjectivesThe objective of this study was to estimate the prevalence of potential drug-drug interactions (DDIs) among outpatients of city region Novi Sad, Serbia, and to investigate predictors of potential DDIs.MethodsCross-sectional prescription database study was conducted. In the analysis were randomly included 10% outpatients with polypharmacy (n=4467), who visited Health Center over 1-month period (November 1–30, 2011). All drug combinations with potential for clinical significant DDIs were identified, according to Drug Interaction Facts by David S Tatro. A logistic regression analysis was conducted to examine patient and drug therapy characteristics as predictors of potential DDIs.ResultsThe prevalence of clinical significant potential DDIs was 33.31%. Odds of exposure were the highest among those aged 65 years or older (odds ratio (OR)=5.204; 95% confidence interval (CI) 2.694–10.052, p<0.001), those with ≥ 4 diagnosed diseases (OR=4.451; 95% CI 3.349–5.914, p<0.001), and those who used ≥ 5 drugs (OR= 5.735; 95% CI 4.876–6.747, p<0.001). Chronic diseases as well as their therapy also presented predictors of DDIs.ConclusionApproximately one-third of outpatients living in Novi Sad were exposed to potential DDIs. Based on the present results could be defined recommendations for the management potential clinical significant DDIs.

[Purpose] The extent of functional independence ultimately achieved by an individual patient will be influenced by a variety of medical and non-medical factors. [Subjects and Methods] this study included 419 patients with spinal cord lesions treated in the Clinic for Rehabilitation “Dr M. Zotovic”, Belgrade, Serbia, from January 2000 to December 2009. The patients were divided in two groups according to achievement of increase in Functional Independence Measure (FIM) score of more than 13 at discharge compared to admission. A variety of clinical variables were followed in both groups. [Results] one hundred twenty-one patients (28.9%) showed improvements in FIM score of ≤13, while 298 (71.1%) patients showed an increases in FIM score of >13 at discharge compared to admission. Better functional recovery was observed in patients with non-traumatic spinal cord lesions, lower neurological levels of the lesion (OR = 6.07), and in patients treated surgically, but the level of the spinal cord lesion was the most influential factor affecting outcome. [Conclusion] the patients with spinal cord lesions should not only be grouped by traumatic and non-traumatic lesions only, but also sub-categorized, according to the etiology, level of injury and treatment method.

The aim of this study was to evaluate and compare the antimicrobial activity of four essential oils that belong to Lamiaceae family (sage, oregano, thyme) and eucalyptus oil. Gas chromatography coupled with mass spectrometry (GC-MS) revealed that the highest percent of essential oils 98.93% include three classes of compounds - monoterpene hydrocarbons, aromatic hydrocarbons and oxidized monoterpenes. The main components are oxidized monoterpenes: carvacrol (59.03%); thymol (36.12%), eucalyptol (20.66%), hydrocarbon monoterpenes: limonene (30.96%) and α-pinene (12.21%) and aromatic monoterpene, p-cymene (22.25%) All essential oils showed great potential of antimicrobial activity against several bacteria and yeast C. albicans, using the agar diffusion method with wells. Minimum inhibitory concentration (MIC) for the essential oils has been determined by the broth dilution method and valued in the range from 1 to 5 μL/m, depending on the essential oil and bacteria tested, and up to 100 μL/ml for C. albicans. The essential oils of Lamiaceae family exhibited a strong antibacterial activity for tested microorganisms, while the essential oils of thyme were especially recognized.

Development of an available drug delivery system is of great interest considering the therapeutic effects of formulations with violate essential oils, especially assuming the fact that using essential oils as antimicrobial agents is a rather expanded in antimicrobial therapy nowadays. In this paper, the chitosan microparticles with encapsulated thyme essential oil were prepared in the emulsion by cross-linking method. The effect of thyme oil and glutaraldehyde initial concentrations on particle size, morphology, and particle size distribution was investigated. In addition, the influence of these parameters on the encapsulation of thyme oil in chitosan microparticles, concerning thyme oil loadings and encapsulation efficiency was also tested. The particles showed a spherical shape with an average diameter of 4.71±1.42 to 13.65±4.34 μm, depending on the concentration of the essential oil and glutaraldehyde that were used. The diameter of microparticles appeared to increase with increasing the thyme essential oil concentration, and decreased with the increase of glutaraldehyde concentration. It was shown that the concentration of glutaraldehyde did not affect the degree of encapsulation, but the increase in the initial concentration of thyme oil increased the degree of encapsulation of this essential oil in chitosan microparticles. All particles containing thyme essential oil, as well as essential oil of thyme itself showed significant antimicrobial activity against Staphylococcus aureus ATCC 25923, Esherichia coli ATCC 25922, Candida albicans ATCC 24433 and Enterococcus faecalis ATCC 25929. This study showed a great potential of the use of thyme essential oil as an antimicrobial agent, especially when encapsulated in a drug delivery system with controlled release of the active antimicrobial component.

Studies on the effects of microwaves on the growth of microbial cultures were searched for in biomedical journals indexed in MEDLINE from 1966 to 2012. The published studies showed that microwaves produce significant effects on the growth of microbial cultures, which vary from the killing of microorganisms to enhancement of their growth. The nature and extent of the effect depend on the frequency of microwaves and the total energy absorbed by the microorganisms. Low energy, low frequency microwaves enhance the growth of microorganisms, whereas high energy, high frequency microwaves destroy the microorganisms. However, neither the effects of a wide spectrum of frequencies nor the effects of a wide range of absorbed energies have been investigated.

BACKGROUND/AIM Severe dental anxiety (SDA) is the most severe form of dental anxiety, thus the aim of this study was to determine the factors associated with SDA in students of health-related disciplines. METHODS In this case-control study the cases were students with severe dental anxiety. The study was conducted at the Faculty of Medical Sciences, University of Kragujevac, Serbia. The participants were undergraduate students attending lectures during spring semester 2010/2011 (n = 1,812). A random sample of 800 students was assessed for the association between various risk factors and the severe dental anxiety. The main outcome measures were the data on demographics, dental anxiety, habits concerning oral hygiene, nutrition, general anxiety and (co)morbidity which were collected from the study participants by semi-structured questionnaire. RESULTS Less frequent visits to the dentist (OR adjusted = 7.02 [2.65; 18.60]) and visiting the dentist only when there is a dental problem (OR adjusted = 8.08 [1.28; 50.93]) were associated with severe dental anxiety. The same was true for improper oral hygiene (OR adjusted = 4.25 [1.16; 15.60]). Factors as changing toothbrush more frequently (OR adjusted = 0.33 [0.14; 0.76]) and having chronic disease (OR adjusted = 0.01 [0.00; 0.09]) were inversely associated with severe dental anxiety. The level of education of students was not associated with severe dental anxiety. CONCLUSION Inappropriate oral hygiene, less frequent changes of a toothbrush and less frequent visits to the dentist are important risk factors for severe dental anxiety.

Potentilla species have been used in traditional medicine in the treatment of different ailment, disease or malady. Potentilla reptans (P. reptans) has been scarcely studied. The aim of this study was to test antioxidant and anti-inflammatory activity of P. reptans aerial part and rhizome. DPPH assay was used to measure antioxidant activity of aqueous plant extracts. Anti-inflammatory effect was evaluated by experimental animal model of phenol-in-acetone induced mice ear edema. DPPH radical-scavenging activity of both tested extracts was concentration dependent with IC50 values 12.11 μg/mL (aerial part) and 2.57 μg/mL (rhizome). Maximum anti-inflammatory effect (61.37%) was observed after administration of 10 mg/ear of the rhizome extract and it was 89.24% of effect induced by dexamethasone as a standard. In conclusion, P. reptans rhizome aqueous extract possesses anti-inflammatory effect and higher antioxidant activity than aerial part.

OBJECTIVE: Comparison of COPD financial burden and underlying factors, between Eastern upper middle income and a Western European high income, healthcare settings. METHODS: The patient sample was 433 in Belgium and 322 in Serbia, age ≥ 40, with spirometry and clinically confirmed COPD diagnosis. Belgian trial followed patients prospectively during 2006, using structured survey of clinicians in charge. Serbian trial conducted in 2008, retrieved data from clinical invoice database. Time horizon was one year and perspective of third party payers was taken into account for both studies. Clinical outcomes of interest were disease exacerbation, hospital admission and death. Economic inputs referred to COPD-attributable medical services consumption value during observed period of time. RESULTS: Average annual cost was 1,812.84 € for the Serbian patients and 1,738.13 €/year for the Belgian patients (not including the value of laboratory diagnostics or imaging techniques). Severity grade and duration of hospital admissions significantly directly correlated with overall cost in both populations. Pattern of diagnostic procedures requested and ATC classes of drug consumed to treat COPD remains similar and comparable in both countries. GDP per capita ratio in respective years (10.4: 37.4), exhibits the paradox of patient being much less affordable to treat in a less developed society. CONCLUSIONS: Burden of COPD in Europe is huge and, due to contemporary life style expected to grow further. We compared cost of illness structures between two societies with different macroeconomic past in healthcare financing and management. According to our findings, direct medical costs were driven by exacerbations and hospital admissions. Significantly cheaper human labor caused higher relative relevance of drug acquisition expenses in the East and higher portion of hospital admission costs in the West. More in-depth research of indirect COPD attributable costs (e.g. lost productivity, absenteeism, premature death etc) will be needed in future. It implies serious health policy necessities to provide accessibility of care.