The biological activity assessment of potential drugs acting on cardiovascular system using Lipinski and Veber Rules

Advanced computational methods (in silico) play major role in the early stages of developing new pharmaceuticals. Precise knowledge on molecular structure gives the possibility of forecasting the drug candidates basic properties. Despite many drugs registered in the arrhythmia treatment, this disease currently is still a big therapeutic problem. Therefore, intensive search for new drugs acting on the cardiovascular system are performed. In the presented work, 77 pyrrolidin-2-one derivatives were analyzed for antiarrhythmic activity. Values of the key parameters proposed by Lipinski and Veber were obtained using computational chemistry methods. It's worth pointing out that the studied group of derivatives shows similar physicochemical properties to the anti-arrhythmic drugs used

Differences of capsaicinoids content in pericarp and paste of soft-flesh Capsicum spp. fruit

ABSTRACT The subject of the research was to compare the content of capsaicinoids in pericarp with their content in whole fruits, mixed and pressed through sieves. The research material was constituted by fruit of three soft-flesh lines of F 6 generation selected from interspecific hybrids of Capsicum frutescens L. × Capsicum annuum L. and one breeding line of C. frutescens L. The analysis of the capsaicinoids content was made using HPLC method. Capsaicin and dihydrocapsaicin content in all examined genotypes was always higher in the paste than in the pericarp. The several-times increase of the content of the discussed compounds was undoubtedly the consequence of the effect of their considerable amounts being released from the Paweł Nowaczyk, Lubosława Nowaczyk, Magdalena Banach, Ineza Król 100 interlocular septa and the placenta. Typically for each of the examined lines, a much higher content of capsaicin than dihydrocapsaicin was observed

Studies on the Activity of Selected Highly Lipophilic Compounds toward hGAT1 Inhibition. Part II

In this paper, we describe the latest results involving molecular modeling and pharmacodynamic studies of the selected highly lipophilic compounds acting by human GABA transporter 1 (hGAT1) inhibition. The chemical interaction of 17 GABA analogues with a model of hGAT1 is described using the molecular docking method. The biological role of GAT1 is related to the regulation of GABA level in the central nervous system and GAT1 inhibition plays an important role in the control of seizure threshold. To confirm that GAT1 can be also a molecular target for drugs used to treat other neurological and psychiatric diseases (e.g., pain and anxiety), in the in vivo part of this study, potential antinociceptive and anxiolytic-like properties of tiagabine, a selective GAT1 inhibitor, are described

Narcolepsy in the light of modern diagnostic, clinical and therapeutic concepts

Narcolepsy is a chronic neurological disease classified as hypersomnia of central origin. Core symptoms of the disease (hypersomnia and cataplexy) are particularly burdensome for patients. The etiology of the disease is not fully understood. There are several theories explaining the essence of the disease. One of the possible causes is the disruption of the autoimmune system leading to the disappearance of hypocretin-releasing neurons. Currently, multicenter studies on synthesizing hypocretin-like proteins that may be the basis of causal narcolepsy treatment are conducted. As yet pharmacotherapy contributes only to reduce the symptoms of the disease. Commonly used medications are amphetamine derivatives, modafinil, pitolisant and γ-hydroxybutyric acid sodium salt (GHB)

New Medicine Service as support for medication adherence by chronically ill patients

Effective management of the treatment for chronically ill patients is a multifactorial process. The crucial is an accurate diagnosis, appropriate and well-designed pharmacotherapy, as well as patient medication adherence. Adherence is defined as the extent to which patients are able to follow the general practitioner's recommendations for the prescribed treatments. Patients’ reasons for deviating from the treatment plan are diverse and may be intentional or unintentional. They may be non-adherent during different stages of their treatment. Some patients may decide not to fill physician prescriptions and not start their treatment at all. Patients may use more or less than the prescribed medication or use their treatments at the wrong time. They may also discontinue therapy prematurely. The common reasons for medication non-adherence may include lack of symptoms, improvement in health, in patients’ subjective opinion, fear of potential side effects, long-term conditions, multimorbidity, and polypharmacy. Poor knowledge about medicines can also lead to severe consequences such as non-adherence. Several interventions may contribute to improved adherence. The current legislation in pharmaceutical care enables registered pharmacists to intervene successfully when a medicine is prescribed, increase effective medicine taking for the treatment of a long-term condition, and optimize the therapy; they also may offer the patient, opportunistic advice on healthy living or public health topics in line with the promotion of healthy lifestyles. One of the proposed pharmaceutical care services for Polish patients – the New Medicine Service, was introduced in England in 2011 as support for subjects starting a newly initiated medication for long-term treatment. The article presents the assumptions and goals for this pharmaceutical consultation in polish system of health care, discusses the interview schedule and forms, and describes the service's beneficial contribution to better medication adherence by chronically ill patients

Approved and Commercialized Antidiabetic Medicines (Excluding Insulin) in Seven European Countries—A Cross-Sectional Comparison

Diabetes mellitus is a complex, multifactorial, progressive condition with a variety of approved therapeutic options. The purpose of this study was to offer an overview of the authorized antidiabetic medicines (excluding insulin) compared with marketed products in seven European countries. Data were obtained from primary sources, including the websites of national authorities and directly from specialists in the countries of interest. The range of marketed medicines compared with the authorized group was assessed in terms of active pharmaceutical ingredients (>60% in Bulgaria, France, Serbia), brand names (>70% in Bulgaria, the Czech Republic, Romania, Serbia, Spain), pharmaceutical forms (>60% in all countries), strengths (>60% in Bulgaria, the Czech Republic, Romania, Serbia, Spain), marketing authorization holder (≥50% in all countries) and the status of medicine. Spain was found to have the highest number of products based on most of these attributes. Over 90% of authorized medicines had a pharmacy price in Serbia. Regarding the newer class of GLP-1 receptor agonists, a retail price for all approved substances was available in Bulgaria, Romania, Serbia, and Spain. Only one brand name with one concentration was found available for some agents, being susceptible to drug shortages: glibenclamide (Romania, Serbia, Spain), glipizide (the Czech Republic, Poland, Romania, Spain), glisentide (Spain), acarbose (the Czech Republic), sitagliptin (Bulgaria, Poland), vildagliptin (the Czech Republic, Poland) and saxagliptin (the Czech Republic, France, Romania, Serbia). An overview of the national and international therapeutic options may allow competent authorities and health professionals to take rapid measures in case of supply problems or health crises

Factors facilitating and hindering development of a medication use review service in Eastern Europe and Iran - cross-sectional exploratory study

Funding Information: European Association of Faculties of Pharmacy PRD 2019 grant for the project ?Develop-ment and Implementation of Medication Use Review Services at Community Pharmacy in Eastern European countries?. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Polypharmacy is a common issue in patients with chronic diseases. Eastern-European countries and Iran are exploring possibilities for implementing the Medication Use Review (MUR) as a measure for optimizing medication use and ensuring medication safety in polypharmacy patients. The aim of this study was to gain insights into the development of the community pharmacy sector and map facilitators and barriers of MUR in Eastern Europe and Iran. The representatives of the framework countries received a questionnaire on community pharmacy sector indicators, current and future developments of pharmacies, and factors encouraging and hindering MUR. To answer the questionnaire, all representatives performed document analysis, literature review, and qualitative interviews with key stakeholders. The socio-ecological model was used for inductive thematic analysis of the identified factors. Current community pharmacist competencies in framework countries were more related to traditional pharmacy services. Main facilitators of MUR were increase in polypharmacy and pharmaceutical waste, and access to patients’ electronic list of medications by pharmacists. Main barriers included the service being unfamiliar, lack of funding and private consultation areas. Pharmacists in the framework countries are well-placed to provide MUR, however, the service needs more introduction and barriers mostly on organizational and public policy levels must be addressed.publishersversionPeer reviewe

Evaluation of medication safety assessment tools for pharmacist-led medication reviews: the Eastern European pilot project

Background: Pharmacist-led medication reviews (MR) are one of the key methods to support medication safety in polypharmacy patients. The aims of this study were to pilot MRs in Eastern European community pharmacies, describe medication use in polypharmacy patients, and evaluate the usability of medication safety assessment tools.Methods: The MR pilot was undertaken in Estonia, Latvia, Poland, Hungary, Romania, and Bulgaria. Patients who used at least five medicines were directed to the service by their GPs. Data on drug-related problems (DRPs) and adherence were collected by pharmacists through structured patient interviews. Databases for identification of potential drug-drug interactions (pDDIs) and adverse drug reactions (ADRs) named Inxbase/Riskbase, as well as an integrated tool comprising potentially inappropriate medicines (PIMs) lists EU(7)-PIM and EURO-FORTA, were applied retroactively to the MR pilot data to investigate possibilities for their use and to describe medication use and potential risks in the study population.Results: A total of 318 patients were included in the study, 250 of them elderly (≥65 years). One hundred and eighty (56.6%) participants had a total of 504 pDDIs based on Inxbase analysis. On average, there were 1.6 pDDIs per participant. Twenty-five (5.0%) of the 504 pDDIs were in a high-risk category. A total of 279 (87.7%) participants had a potential ADR in at least one of 10 Riskbase categories. One hundred and fifty-four (20.8%) of the potential ADRs were in a high-risk category. Twenty-seven pDDIs and 68 ADRs documented as DRPs during the service were not included in the databases. Using the integrated EU(7)-PIM/EURO-FORTA PIM list, a total of 816 PIMs were found in 240 (96%) of the 250 elderly participants (on average 3.4 PIMs per elderly participant). Seventy-one (29.6%) of the participants were using high-risk PIMs. Twenty-one percent of high-risk PIMs and 13.8% of medium-risk PIMs were documented as DRPs by the pharmacists during the pilot.Conclusion: Medication safety assessment tools can be useful in guiding decision-making during MRs; however, these tools cannot replace patient interviews and monitoring. Tools that include a thorough explanation of the potential risks and are easy to use are more beneficial for MRs

The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens