Rational pharmacotherapy training for fourth-year medical students

OBJECTIVES: In this study we aimed to evaluate the impact of Rational Pharmacotherapy (RPT) course program, reinforced by video footages, on the rational pharmacotherapy skills of the students. MATERIALS AND METHODS: RPT course program has been conducted in Dokuz Eylul University School of Medicine since 2008/9. The course has been organised in accordance with World Health Organisation (WHO) Good Prescribing Guide. The aim of the course was to improve the problem solving skills (methodology for selection of the (p)ersonel-drug, prescription writing and informing patient about his illness and drugs) and communication skills of students. The impact of the course has been measured by pre/post-test design by an objective structured clinical examination (OSCE). In academic year 2010/11, to further improve OSCE score of the students we added doctor-patient communication video footages to the RPT course programme. During training, the students were asked to evaluate the doctor-patient communication and prescription on two video footages using a checklist followed by group discussions. RESULTS: Total post-test OSCE score was significantly higher for 2010/11 academic year students (n = 147) than it was for 2009/10 year students (n = 131). The 2010/11 academic year students performed significantly better than the 2009/10 academic year students on four steps of OSCE. These steps were “defining the patient's problem”, “specifying the therapeutic objective”, “specifying the non-pharmacological treatment” and “choosing a (drug) treatment, taking all relevant patient characteristics into account”. CONCLUSIONS: The present study demonstrated that the implementation of video footages and group discussions to WHO/Good Prescribing Method improved the fourth-year medical students’ performance in rational pharmacotherapy skills

The outcomes of favipiravir exposure in pregnancy: a case series.

Purpose As in vitro and in vivo studies reported antiviral efficacy against RNA viruses, favipiravir, a pyrazinecarboxamide derivative, has become one of the treatment options for COVID-19 in some countries including Turkey. Preclinical studies demonstrated the risk for teratogenicity and embryotoxicity. Hence, the drug is contraindicated during pregnancy. Although limited in numbers, case-based evaluations indicate that favipiravir might not be a major teratogen in human pregnancies. This study aimed to present and analyze the outcomes of favipiravir exposure during pregnancy

Effect of repeated low-dose organophosphorothionate pesticide exposure on digoxin pharmacokinetics in rats; a possible interaction involving P-glycoprotein

Aside from acute occupational exposure, an important part of the population may be chronically exposed to the trace amounts of organophosphorothionate pesticides (OPTs) via residues in nutrients and drinking water. P-glycoprotein (P-gp) is a transmembrane protein responsible for the efflux of numerous drugs. OPTs were shown to inhibit P-gp function in vitro and increase its expression in vivo. Digoxin is a probe drug for the investigation of P-gp. To evaluate the effect of repeated low-dose OPT exposure on P-gp, commercial formulations of diluted OPT or tap water were administered to female Wistar rats for 8 consecutive days. On the ninth day each group was further divided into two groups and digoxin was administered either intraduodenally ( ID) or intravenously (IV). Blood sampling and bile and urine collection were taken during 6 h at various intervals. The peak concentration in serum (C-max) of digoxin was found to be decreased and the mean absorption time (MAT) was significantly increased in the digoxin OPT group. The mean residence time was significantly elevated in the digoxin(ID) OPT group. The biliary excretion% digoxin was significantly increased in the digoxin OPT group, while the renal excretion% digoxin rose only in the digoxinID OPT group. No significant differences in time to reach C-max (t(max)), area under the plasma concentration-time curve (AUC)(0-360), area under the moment curve (AUMC) 0-360, and bioavailability (F) were detected. In our study, repeated low-dose OPT exposure reduced the absorption and increased the excretion% digoxin, which may be related to enhanced P-gp expression. However, alterations of digoxin pharmacokinetic parameters did not change the systemic availability of digoxin

Interactions between Verapamil and Digoxin in Langendorff-Perfused Rat Hearts: The Role of Inhibition of P-glycoprotein in the Heart

WOS: 000283093100001PubMed ID: 22545967P-glycoprotein (P-gp) is expressed in tumour cells as well as normal tissues including heart. Modulation of P-gp transport in vivo may lead to increased drug penetrance to tissues with resulting increases in toxicity. We aimed to investigate the effects of P-gp on the isolated heart by digoxin infusion in the absence and presence of verapamil. The study was performed in Langendorff isolated perfused rat hearts. After a 20 min. stabilisation period with Tyrode Buffer, digoxin (125 mu g/5 mL) was infused for 10 min. in the control group (n = 7). The same dose of digoxin was infused during perfusion with verapamil (1 nm) containing Tyrode Buffer (n = 8) in the study group. Outflow concentration and cardiac parameters of digoxin were measured at frequent intervals for 40 min. AUEC((0-40 min)) for left ventricular developed pressure was significantly increased in the presence of verapamil (4260 +/- 39.37 mmHg min versus 4607 +/- 98.09 mmHg min; 95% CI -587.7 to -105.8; p = 0.0083). The significant increases in left ventricular developed pressure were at 20, 25, 30, 35 and 40 min. AUC((0-40 min)) value for outflow digoxin concentration-time curve was significantly lower in the presence of verapamil. Verapamil increased the positive inotropic effect of digoxin, probably through the inhibition of P-gp, which effluxes digoxin out of cardiac cells.Dokuz Eylul University Research FoundationDokuz Eylul University [2009. KB. SAG. 080]This work was supported by Dokuz Eylul University Research Foundation (2009. KB. SAG. 080)

A New Application Route of Nitrofurantoin: Preparation and Characterization of Novel Transdermal Formulations

WOS: 000400497400011PubMed ID: 27480119Objectives: Nitrofurantoin is widely used in the prophylaxis of urinary-tract infections. The aim of this study was to develop and characterize innovative transdermal formulations of nitrofurantoin, to increase the patient compliance and decrease the adverse effects such as nausea and vomiting which limit the drug use in long-term. Methods: Nitrofurantoin loaded microemulsion, gel (hydrogel, lipogel and DMSO gel) and film formulations were prepared and characterized via several parameters. Ex-vivo drug permeation studies were performed to determine the amount of drug permeated through the rat skin. In in-vivo studies, in order to detect nitrofurantoin in urine, the selected formulations were applied to male Wistar rats transdermally. Also, skin irritation tests (transepidermal water loss and erythema) were performed. Results: All nitrofurantoin loaded formulations were prepared successfully and were stable at +4 degrees C for 3 months. 13%, 16%, 32.5%, 36.5% and 39% of drugs permeated through the rat skin in the 168th hour for hydrogel, lipogel, film, microemulsion and DMSO gel, respectively. Only with film and DMSO gel formulations, nitrofurantoin was detected in urine. Transepidermal water loss was increased compared to basal level in film type formulations (p0.05). Conclusion: There is no approved transdermal formulation of nitrofurantion on the market. Therefore, the prepared film formulations could be an alternative due to their high penetration through the rat skin, the presence of nitrofurantoin in urine and because they cause no irritation on the skin.Dokuz Eylul University Research FoundationDokuz Eylul University [2011.KB.SAG.004]This present study was supported by Dokuz Eylul University Research Foundation (2011.KB.SAG.004)

Evaluation of Legal Legislation Compliance and Readability of Clinical Trial Informed Consent Forms

Background: The volunteers approached for participation in a clinical trial should be given detailed and understandable information about the study through an informed consent form (ICF) before enrollment. In this study, we evaluated clinical trial files submitted to the Turkish Medicines and Medical Devices Agency (TITCK) to investigate the compliance to legal legislation and readability of ICFs as well as the factors affecting them. Methods: This is a descriptive, cross-sectional study. We evaluated 160 ICFs in the phase II-IV clinical trial files submitted to TITCK in 2016 to determine their compliance to legislation (n = 160) and to assess their readability (n = 152) using Atesman formula. Overall compliance score was calculated. ICFs were also evaluated in terms of written format (font size, line spacing, section headings) and page count. Statistical analysis was performed with chi-square, Student's t test, analysis of variance, Mann-Whitney U, and Kruskal Wallis analysis. Results: Compliance to legislation and suitability of written format of international trial ICFs were significantly higher than those of national trial ICFs. Most of the national trials were investigator initiated. Readability was low in both national and international trial ICFs where the text was longer in the latter. Conclusion: Results showed that researchers need easy-to-read ICF writing training that fits legal regulations

Health profiles of methyl bromide applicators in greenhouses in Turkey.

Introduction: Methyl bromide is a toxic substance that has hazardous effects on human health with acute and chronic exposure. Our previous study showed that methyl bromide applicators frequently use large amounts of methyl bromide haphazardly in greenhouses in the prefectures of Narlidere and Balcova in the Aegean city of Izmir. This study aims to evaluate the health conditions of these workers. Materials and Methods: Our previous study showed that there are 38 methyl bromide applicators in our study area. After the informed consent of methyl bromide applicators was obtained, a questionnaire was used for a survey of demography and symptoms. Each subject was examined before and after application of the compound. Blood and urine samples were collected and stored. Blood samples were analysed for methyl bromide and bromide ion, kidney and liver function tests and lipid profile. Results: The age range of subjects was 19 to 53 years (mean age: 41 +/- 8.57). This study showed that methyl bromide applicators use large amounts of methyl bromide disregarding legal regulations and that some of them had nonspecific complaints. Subjects had been working as methyl bromide applicators for approximately 9.7 +/- 4.15 years. A total of 69.7% of methyl bromide applicators reported that they did not use protective equipment while 33.3% of them had a history of acute methyl bromide intoxication. A statistically significant relationship was found between the usage of protective equipment and the level of blood bromide ion in the blood (P<0.05). Conclusion: Usage of methyl bromide, training, screening and follow-up of applicators must be rigorously controlled in accordance with national legal arrangements and international protocols. Greater efforts are required in the implementation of controls to achieve the targets set by the legal regulations and to ensure continual improvement in the limitation of the risks of this environmental hazard