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Vanja Piljak, Selma Škrbo, Naida Omerović, A. Trnka, Dina Lagumdžija, N. Smajic

Background: Adolescents are a susceptible population in terms of medication use. They are not only inclined to abuse illegal substances but are also prone to nonmedical medication use, which exposes them to a significant risk of various adverse drug reactions (ADR). Objective: This research aims to assess medication use among adolescents in Sarajevo Canton. Methods: This paper features information about the most frequently used medications, reasons for their use, sources of their procurement, ADR and concurrent use with other medications and/or alcohol. To obtain this data, a questionnaire with open- and close-ended questions was created. The survey was conducted online and 444 participants were included. Results: Medications were used by 90.1% of adolescents. The most commonly used medications were non-opioid analgesics, antibiotics, dietary supplements, antihistamines and benzodiazepines. Mild to moderate pain was the most frequent reason for medication use. Participants were at risk of ADR, drug-drug interactions (DDI), and drug-alcohol interactions. Conclusion: It is up to healthcare workers, especially pharmacists, to educate and guide adolescent patients on rational medication use and inform them about potential dangers following the use of these medications.

Background: The pathophysiology and therapy of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are a dilemma for scientists and health professionals, and the fact that patients show different symptoms and severity of the clinical picture also contributes to that. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of immunomodulators) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring inflammatory markers (ESR and CRP), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Inflammatory markers [ESR (erythrocyte sedimentation rate), CRP (C-reactive protein)] were examined on three occasions: twice during hospitalization and once after hospital discharge. Immunomodulators used intrahospital were corticosteroids (methylprednisolone, dexamethasone, methylprednisolone + dexamethasone), tocilizumab or metenkefalin/tridecactide. Posthospital, patients were taking either methylprednisolone or did not use any immunomodulators. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis and Wilcoxon Signed-Rank) were applied and effect size (ES) was calculated. Results: Three corticosteroid therapies used intrahospital caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture, but the ES was the biggest with methylprednisolone + dexamethasone, then dexamethasone, and lastly methylprednisolone. Posthospital, methylprednisolone caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture. The most common comorbidity in all patients, as well as in patients with a severe clinical picture, was hypertension. There was no statistically significant impact of the number of comorbidities patients had on ESR and CRP, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of immunomodulators, especially methylprednisolone + dexamethasone intrahospital and methylprednisolone posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease’s pathophysiology and the immune response. There is also a positive correlation between the number of comorbidities patients have and the severity of the clinical picture.

Background: Patients infected by coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), display various symptoms and severity of the clinical picture. Thus, the therapy and pathophysiology of this disease are a dilemma for health professionals and scientists. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of anticoagulants) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring coagulation markers (PT, INR, aPTT and D-dimer), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Coagulation markers [PT (prothrombin time), INR (international normalized ratio), aPTT (activated partial thromboplastin time), D-dimer] were examined on three occasions: twice during hospitalization and once after hospital discharge. Anticoagulants used intrahospital were fraxiparine, rivaroxaban or unfractionated heparin. Posthospital, patients were taking either rivaroxaban or did not use any anticoagulants. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis, Wilcoxon Signed-Rank and Bonferroni) were applied and effect size (ES) was calculated. Results: Three anticoagulants used intrahospital caused a significant decrease in PT, INR and D-dimer and a significant increase in aPTT, especially in patients with a severe clinical picture, but the ES was the biggest with fraxiparine, then rivaroxaban, and lastly unfractionated heparin. Posthospital, rivaroxaban caused a significant decrease in PT, INR and D-dimer and a significant increase in aPTT, especially in patients with a severe clinical picture. Hypertension was the most common comorbidity in all patients, as well as in patients with a severe clinical picture. There was a statistically significant impact of the number of comorbidities patients had on D-dimer, and none on PT, INR and aPTT, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of anticoagulants, especially fraxiparine intrahospital and rivaroxaban posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease’s pathophysiology and the coagulation process. There is also a positive correlation between the severity of the clinical picture and the number of comorbidities patients have.

Selma Škrbo, Semir Mehović, Naida Omerović, A. Trnka, N. Smajic, B. Pehlivanovic, Dina Lagumdžija

Aims: This study aimed to investigate whether the place of the survey makes a significant impact on the responses regarding the process of self-medication, as well as the present pharmacists’ engagement in this process in the Sarajevo Canton. Study Design: An anonymous questionnaire-based survey. Place and Duration of Study: One public pharmacy and various public places in the Sarajevo Canton, Bosnia and Herzegovina, for five months, February–June 2019. Methodology: A total of 312 respondents was included. The first group (165 respondents) was surveyed in the pharmacy after buying an over-the-counter (OTC) drug, and the second group (147 respondents) was surveyed outside the pharmacy. Results: Pharmacists instructed 65% of respondents (72.73% in the first group and 57.14% in the second group) on how to take the purchased OTC drug and checked whether 55% of respondents (70.91% in the first group and 38.1% in the second group) bought an appropriate drug for their health problem. Only 25% of respondents (36.36% in the first group and 12.24% in the second group) was informed about the adverse effects, whereas 29% of respondents (41.82% in the first group and 14.97% in the second group) was informed about the potential contraindications or interactions of the purchased OTC drug. The statistical analysis showed a significant relationship between the responses to the questions and the place of the survey about providing information on the adverse effects (P = .03), comorbidities (P = .049), and general information about the purchased OTC drug (P = .04). Conclusion: In the Sarajevo Canton, pharmacists should be more actively involved in the process of self-medication and provide the necessary advice to patients consuming OTC drugs. Further research is needed so general conclusions could be drawn.

Hyperuricemia is a potential marker of cardiovascular diseases, and its relation to hypertension and arteriosclerosis, as well as the outcomes of certain cardiovascular events, is interesting. The research was carried out a sample of 50 subjects of both sexes, who were either on allopurinol or febuxostat treatment. Effects of allopurinol and febuxostat on concentrations of uric acid and some lipid fractions (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol) were observed in 25 subjects on allopurinol treatment, and in 25 subjects on febuxostat treatment, who were chosen by defined criteria, with each patient serving as his or her control. The total observation period was six months and the cut was made after the first three Original Research Article Ziga Smajic et al.; JPRI, 32(35): 44-54, 2020; Article no.JPRI.63434 45 months and at the end of the research. Evaluating the effectiveness of allopurinol in subjects with hyperuricemia, it was established that concentrations of uric acid decreased by 126.28±20.36 μmol/L, at the end of the research, compared to the initial concentration. In subjects who used febuxostat, at the end of the research, concentrations of uric acid decreased by 252.80±94.17 μmol/L, compared to the initial concentration. Evaluating the effectiveness of febuxostat on concentrations of lipid fractions, a statistically significant increase of 0.17±0.02 mmol/L in concentrations of HDL and a statistically significant decrease of 0.37±0.14 mmol/L in concentrations of LDL were noted. Subjects with gout treated with allopurinol had significantly lower average concentrations of cholesterol compared to subjects with gout and metabolic syndrome (p=0.001). Subjects with gout and metabolic syndrome had significantly higher concentrations of LDL at the beginning and the end of the research, regardless of therapy (p=0.045;p=0.049, respectively). Both drugs showed effectiveness in the treatment of hyperuricemia, and a certain effect on concentrations of lipid fractions.

The kinetics of passive transport of ketoprofen and metformin, as model substances for high and low permeability, respectively, across the artificial membrane under the influence of the pH of donor solution was investigated. There was an upward trend in the apparent permeation coefficient (Papp) of ketoprofen with the decrease in pH to a value close to pKa. At the pH value below pKa the permeation coefficient had lower value, due to the higher retention of ketoprofen in the artificial membrane. Metformin is a low permeable compound, and the highest permeation values were recorded at pH 7.4. Two dissociation constants determine that metformin at physiological pH exists as a hydrophilic cationic molecule, i.e. predominantly in ionized form. At pH values below 2.8, metformin mainly exists in diprotonated form, and it was, thus, very poorly permeable. The highest retention, i.e. affinity of both ketoprofen and metformin to the membrane, was at the lowest pH values, which is explained by different mechanisms. At higher pH values of donor compartment the substances showed significantly less affinity to the membrane. The obtained values of apparent permeation coefficients at studied pH values showed good correlation with the obtained experimental values by other in vitro methods.

Selma Škrbo, Semir Mehović, Naida Omerović, Anela Hadžifejzović-Trnka, Nermina Žiga-Smajić, B. Pehlivanovic, Dina Lagumdžija

Introduction: Self-medication has been very popular and globally prevalent for a long time. Aim: This research aims to present pharmacists’ engagement in the process of self-medication in the Sarajevo Canton. Methods: A total of 312 respondents completed an anonymous questionnaire-based survey. The first group (165 respondents) was surveyed in the pharmacy after buying a non-prescription drug, and the second group (147 respondents) outside the pharmacy. Results: The most commonly purchased drug was paracetamol, whereas headache was dominant amongst health conditions for which treatment respondents intended to use the purchased drug. A belief that respondents could cure themselves was the most common answer when asked why they had not visited a doctor, whereas previous experience with the purchased drug prevailed as an answer when asked from whom they had gotten information about the adequacy of the purchased drug for their health problem. Respondents mostly bought drugs for themselves. Pharmacists instructed 65% of respondents on how to take the purchased drug and checked whether 55% of respondents bought an appropriate drug for their health problem. Only 25% and 29% of respondents were informed about the adverse effects and potential contraindications or interactions of the purchased drug, respectively. According to 45% of respondents, pharmacists spent up to one minute in a conversation with them about the purchased drug. Conclusion: In the Sarajevo Canton, pharmacists should be more actively involved in the process of self-medication and provide the necessary advice to patients consuming non-prescription drugs. Further research is needed to create a clearer picture.

Introduction: Hyperuricemia is an independent risk factor for the development of many diseases. Aim: The aim of this paper is to compare the effects of allopurinol and febuxostat on the values of triglycerides and uric acid in hyperuricemic patients. Methods: This was a pharmacological-clinical retrospective-prospective study. The research sample comprised 50 examinees of both genders and different ages who were undergoing allopurinol (100 mg/day) or febuxostat (80 mg/day) therapy. Statistical Product and Service Solutions (SPSS) Software and Microsoft Excel were used for statistical analysis. Results: Examinees who were treated with allopurinol had a statistically significant decrease in uric acid concentrations (by 126.28 ± 20.36 μmol/l) at the end of the observation compared to the initial values (p = 0.006). Examinees who were treated with febuxostat had a statistically significant decrease in uric acid concentrations (by 252.80 ± 94.17 μmol/l) at the end of the observation compared to the initial values (p = 0.001). The initial value of triglycerides was 1.58 ± 0.64 mmol/l in allopurinol-treated examinees, and 1.60 ± 0.52 mmol/l in febuxostat-treated examinees. After three and six months of allopurinol use, there was a statistically significant increase in triglyceride values (p = 0.046 and p = 0.042, respectively). A statistically significant decrease in triglyceride values (by 0.16 ± 0.10 mmol/l) was noted after three months of febuxostat use (p = 0.012). Conclusion: The results of this research confirmed the previous findings and pointed out the positive pharmacological effects of allopurinol and febuxostat.

S. Špirtović-Halilović, A. Osmanović, D. Završnik, Aida Selmanagić, Selma Škrbo, Nihada Škrijelj, S. Trifunović, S. Roca et al.

Four 4-hydroxycoumarin derivatives were synthesized and the structure was confirmed by NMR spectroscopy and Mass spectrometry. Tested compounds have shown significant antimicrobial activity against Bacillus subtilis subsp. spizizenii, Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis, and the effect of more halogens on the benzene nucleus, as well as the combination of halogen and alkyl groups, on the antimicrobial activity, was investigated. According to the docking study, these compounds can operate simultaneously on two enzymes, amylase and gyrase (1BAG and 1KZN), which are known to play an important role in bacterial life. Obtained docking study parameters for tested compounds showed an association with the in vitro results of the antimicrobial activity of these compounds. In silico tests of molecular properties of the tested compounds showed that the compounds met Lipinski's rule of five. In this paper, the ADME parameters of tested compounds were also calculated: Caco2 (in vitro Caco2 cell permeability), HIA (human intestinal absorption), MDCK (in vitro Mandin Darby Canine Kidney (MDCK) cell permeability), TPSA (topological polar surface area), etc.

Aim To analyse the long-term impact of altered metabolism on the level of mediators of inflammatory response in female patients with type 2 diabetes. Methods This study included 97 female patients with type 2 diabetes and 107 female, nondiabetic control subjects, who were recruited at the Clinical Centre University of Sarajevo and the General Hospital Tešanj. The effects of glycaemic control on markers of inflammatory response represented by C-reactive protein (CRP), fibrinogen, leukocytes, sedimentation rate, and cytokine IL-6 were tested. All subjects were free of evidence of infections, surgery, thyroid disease, polycystic ovarian syndrome, active liver and kidney damage. All biochemical analyses were performed according to standard International Federation of Clinical Chemistry (IFCC) protocols. Results A significant increase of fibrinogen (p<0.001), CRP (p=0.001), interleukin-6 (p=0.013), leukocytes (p<0.001) and sedimentation rate (p=0.008) in diabetic female population compared to control subjects was found. A significant correlation between CRP and haemoglobin A1c (p=0.035), interleukin-6 and glucose (p=0.032), IL-6 and body mass index (p=0.007) was found. Conclusion Our data suggest that inflammation plays an important role in the pathogenesis of diabetes in female diabetic population. A more detailed study on a far larger number of subjects is needed if they were to be used effectively as biomarkers in the primary prevention of type 2 diabetes in this population.

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