Statins exhibit their pharmalogical effects by competitive inhibition trough binding with active sites of enzymes. Rosuvastatin, of all statines, has the most binding interactions with the enzyme, and being the most potent statin, it is presumed that the strength of enzyme binding directly influences its potency. Reduction of derivatives of mevalonic acids results with decreased risk of cardiovascular diseases and very significant pleotropic effect of statins. Rosuvastatin comes in the form of calcium salt. During the clinical trial it has been marked as superstatin with its proven activity in lowering cholesterol levels. Aim of this paper was to examine the antiinflammatory and antioxidant activity

Background: In this clinical pharmacological research, we dealt with the action of allopurinol on triglyceride levels in hyperuricemic patients.Methods: The study included 40 hyperuricemic patients, of both genders and different age groups, that were sorted by comorbid diagnoses in several subgroups. All patients were clinically treated in the period of three years both at UCC Sarajevo, and P.I. General Hospital "Abdulah Nakaš" Sarajevo. All clinical measurements were carried out using standard IFCC methods with the appropriate analysers.Results: The study was based on mean triglyceride levels before and after three and six months of treatment with allopurinol. It was found out that the mean triglyceride levels were not significantly different from the reference values prior to treatment (p = 0.846) and after three months of therapy (p=0.153). In contrast, after six months of treatment, triglyceride levels significantly increased compared to the reference values. In patients with a diagnosis of gout and metabolic syndrome, triglycerides were statistically significantly increased during the six months of observation. A statin group of patients showed a statistically significant increase in triglyceride levels after three months of therapy (p = 0.032), while, after six months their levels had decreased (p = 0.029). In patients with diabetes mellitus type II, triglycerides rose after three months of treatment (p = 0.039) and retained the same level after six months of observation.Conclusions: The analysis shows that the use of allopurinol has an effect on triglyceride levels in hyperuricemic patients.

The subject of the study in this pharmacological-clinical paper was the effect of allopurinol on the values of HDL and LDL in hyperuricemic patients. The research sample included 40 clinically treated patients of both sexes (UKC Sarajevo and JU General Hospital "Abdulah Nakaš" Sarajevo) and various age groups, which according to the diagnosis of the disease were classified into several subgroups (gout, diabetics, patients with metabolic syndrome). In subjects with established gout diagnosis, who were on the treatment with statins and allopurinol, it was found that the value of uric acid decreased after three and six months of use of allopurinol (p <0.05). It was found that the values of LDL fraction were statistically significantly decreased after 3 and 6 months of therapy (p <0.05), while the HDL fraction decreased after 3 months of therapy, but maintained the same to the sixth month of therapy. Also, in the treatment with allopurinol, subjects with metabolic syndrome with severe heart disease (hypertension present), the mean values of uric acid statistically decreased significantly, the values of LDL fractions were statistically significantly increased (p <0.05), while the values of HDL fraction increased after 3 months of therapy, so that later this value remained constant.

Introduction: Pharmacovigilance is an arm of patient care. No one wants to harm patients, but unfortunately any medicine will sometimes do just this. Underreporting of adverse drug reactions by healthcare professionals is a major problem in many countries. In order to determine whether our pharmacovigilance system could be improved, and identify reasons for under-reporting, a study to investigate the role of health care professionals in adverse drug reaction (ADR) reporting was performed.Methods: A pretested questionnaire comprising of 20 questions was designed for assessment of knowledge, perceptions, practice and barriers toward ADR reporting on a random sample of 1000 healthcare professionals in Bosnia and Herzegovina.Results: Of the 1000 respondents, 870 (87%) completed the questionnaire. The survey showed that 62.9% health care professionals would report ADR to the Agency for Medicinal Products and Medical Device of Bosnia and Herzegovina (ALMBIH). Most of surveyed respondents has a positive perception towards ADR reporting, and believes that this is part of their professional and legal obligation, and they also recognize the importance of reporting adverse drug reactions. Only small percent (15.4%) of surveyed health care professionals reported adverse drug reaction.Conclusions: The knowledge of ADRs and how to report them is inadequate among health care professionals. Perception toward ADR reporting was positive, but it is not reflected in the actual practice of ADRs, probably because of little experience and knowledge regarding pharmacovigilance. Interventions such as education and training, focusing on the aims of pharmacovigilance, completing the ADR form and clarifying the reporting criteria are strongly recommended.

Introduction: Non-critical and irrational use of antibiotics is the most important reason for the ever faster development of infectious diseases causative agents’ resistance to those drugs. The aim of this study was to determine the most frequent bacterial causative agents of urinary infections and their resistance to antibiotics. Methods: The study was carried out in the Microbiological Laboratory of the Institutefor Public Health of Canton Sarajevo, during the period of January-March 2007, 2008, and 2009. The identification of the causative agents was conducted with classical biochemical series and the sensitivity test to antimicrobial drugs with the disc-diffusion method. The CLSI protocols that precisely define the kind of antibiogram discs used for particular bacteria were used. Results: The most common causative agents of urinary infections were E scherichia coli , Gr. Klebsiella-Enterobacter , Proteus mirabilis and Pseudomonas spp. The highest prevalence of the studied infections was at the age of 71-90 years for all four bacterial species. Women are more exposed to E. coli and Proteus mirabilis infections, and men to Pseudomonas spp . infections. The highest resistance of E. coli was to ampicillin and to trimethoprim+sulfomethoxazole, and the least towards cefixime. For Proteus mirabillis , there was significantly more nonresistant strains than resistant ones toall tested antibiotics except to nitrofurantoin. The least was shown in case of cefixime and gentamicin. Gr. Klebsiella-Enterobacter showed generaly high resistance towards all antibiotics, the least to gentamicin. Documented resistance of Pseudomonas spp . to all antibiotics was also very high. Key words: urine culture, antibiotics, antibiogram, sensitivity,resistance

Introduction : One of the most important priorities in therapy is pain control. Therefore, many different groups of drugs are being used for this purpose, primarily opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Opioid analgesic tramadol, by binding to specific receptors, modulates the perception and response to painful stimuli and inhibits transmitting and further processing of pain impulses. Lornoxicam, which belongs to the oxicam class of NSAIDs, is a non-selective cyclooxygenase inhibitor with strong analgesic and anti-inflammatory effects, and better tolerance profile. Preliminary research, which requires further verification, suggests that lornoxicam may be a better alternative or adjunctive therapy to opioid analgesics in the treatment of moderate to severe pain. The aim of this study was to investigate antinociceptive effects of lornoxicam, as well as the combination of lornoxicam with tramadol. Methods : Analgesic effect of combination of lornoxicam and tramadol or lornoxicam applied alone was examined on female albino mice, using a hot plate method. Measurements were made 30, 60, 90 and 120 minutes after intraperitoneal and subcutaneous administration, in dose of 10 mg/kg. Results: Combination of lornoxicam and tramadol, applied intraperitoneally, increases the threshold of sensitivity to painful stimuli, which was not the case with subcutaneous administration. Conclusions: Lornoxicam significantly increases analgesic effect when applied intraperitoneally in combination with tramadol. On the other hand, lornoxicam in combination with tramadol, did not increase the threshold of sensitivity to painful stimuli with significant difference, after subcutaneous administration

Subject: The concentration of serum uric acid (SUA) is one of the potential markers of cardiovascular and cerebrovascular diseases, as well as some other severe diseases. In this pharmacological – clinical study we evaluated allopurinol effect on certain values of lipid profile fractions in hyperuricemic patients diagnosed with metabolic syndrome that had pronounced cardiovascular problems, also with diagnosed hypertension. Methods: Research sample comprised 40 clinically treated hyperuricemic patients of both sexes, different ages, classified into several subgroups according to the disease diagnoses. The methods used in the study included: assay analysis, statistical and comparative methods. All clinical measurements were performed with standard IFCC methods on suitable biochemical analyzers. Results: Study established that after the first three months of allopurinol use, there was statistically significant difference in the average value of uric acid compared to the patients’ initial state. During the next three months of therapy no further statistically significant difference in average values of uric acid (p = 0,936) was detected, meaning that the desirable effects of drug use were achieved. Simultaneously, the values of triglycerides, cholesterol and LDL fractions in test subjects increased significantly (p > 0,05). The values of HDL fractions increased after three month therapy with allopurinol, but later their value remained constant. Atherogenic index increased significantly after three and six months of therapy, therewith retaining at upper limit of reference value. Conclusion: The study results confirmed the primary hypothesis, which was that the allopurinol use affects the values of lipid profile fractions in hyperuricemic patients.

GOAL Inappropriate prescribing of a multiple therapeutic agents to patients with chronic conditions is very common in everyday practice. Adverse drug reactions (ADRs) are still considered as one of the main problems of drug therapy. We investigated idiosyncratic symptoms and signs of adverse drug reactions (ADRs) of the most frequent used combination of drugs among hospitalized patients prescribed polypharmacy. METHODOLOGY A cross sectional study (design) was performed in Pharmacies "Eufarm Edal" in Tuzla from 2010 to 2011. Polypharmacy was defined as using > or =4 drugs. The total study sample of 166 examiners was interviewed with a questionnaire about ADRs which was developed special for study. Linear regression analyses was used to evaluate predictors of idiosyncratic signs of adverse drug reactions of the most prevalent drug combinations; using length of drugs in cases polypharmacy more than 6 months as independent variable. Age, sex, index of cumulative morbidity, drug number in polypharmacy, type of drug combination related pharmacological effects, type of hospital clinics were used as possible confounders. RESULTS The most common exposures to various drug combinations were: medication for high blood pressure and heart (62%), psychotropic drugs (59%), antacids (47%) and antibiotics (46%) among hospitalized patients with polypharmacy. Our results indicated that from 9.6% to 90.4% of hospitalized patients with polypharmacy had at least one suspicious long-term idiosyncratic drug combination use symptoms. The ADRs prevalence often used psychotropic drug combination was initiated suspected idiosyncratic adverse reactions: confusion, depression, anxiety, decreased libido and insomnia. Linear regression analyses also showed that it remains a very strange, and negative idiosyncratic and lacking therapeutic effects of use of antacids in conditions of polypharmacy. CONCLUSION The toxicity of some drug combinations may sometimes be synergistic and be greater than the sum of the risks of toxicity of either agent used alone. In order to recognize and to prevent ADRs (including drug interactions), good communication between pharmacist and patient and/or physicians and patient is crucial, and prescribers should develop an effective therapeutic partnership with the patient and with fellow health professionals.

Goal: Polypharmacy and drug-related problems (DRPs) have been shown to prevail in hospitalized patients. We evaluated the prevalence of polypharmacy; and investigated relationship between polypharmacy and: symptoms of DRPs, number of drugs and OTC, index of cumulative morbidity, length of exposure to polypharmacy and the number of days of hospital stay among hospitalized patients. Methodology: A study was performed in Pharmacies „Eufarm Edal“ Tuzla from 2010 to 2011. Polypharmacy was defined as using ≥ 3 drugs. The total study sample of 226 examiners were interviewed with special constructed questionnaires about DRPs. Experimental study group consisted of hospital patients with polypharmacy (n=166) and control group hospital patients without polypharmacy (n=60). Mann-Whitney test was used to test for significant self-reported symptom differences between groups and cross sectional subgroups, t- test and χ2- test for age, gender and treatment data in hospital. Results: The prevalence of polypharmacy was 74% among 226 hospitalized patients. The vulnerable age subgroup of hospitalized patients was men and hospitalized patients aged from 46 to 50 years (not geriatric patients). The prevalence of index of cumulative morbidity was 65%. The most common exposures varied by patient age and by hospital type, with various antibiotics, antidepressants, analgesics, sedatives, antihypertensives, flixotide, ranitidine and others. The prevalence of exposure to OTC and self- treatment was 80%. The prevalence of symptoms of drug-related problems were significantly differed among patients of experimental in relationship of control study group patients (P<0.001). Conclusion: In addition to helping to resolve the above mentioned issues, the results from this study could provide baseline information quantifying the problem of drug- related problems among hospitalized patients receiving polypharmacy and contribute to the formulation and implementation of risk management strategies for pharmacists and physicians in primary care health.

AIM To evaluate differences in the treatment quality between often used oral anticoagulants, warfarin and acenocoumarol in patients with nonvalvular atrial fibrillation (NVAF). METHODS This was an observational, comparative, one-year clinical study, conducted in the Blood Transfusion Institute of Sarajevo, Bosnia & Herzegovina. All patients who were using warfarin/ acenocoumarol and monitored were eligible. Patients who met inclusion criteria (the age of 40-80, diagnosed NVAF, CHADS index score > or = 2, the planned long-term treatment) were includes in two parallel groups of 60 patients, composed according to the warfarin/acenocoumarol treatment as well as the gender and age. Routinely measured International normalised ratio (INR) values were the basic parameter for individual quality and stability assessment. RESULTS All average, monthly INR values were in therapeutic range (2.0-3.0) in both therapeutic groups. There were no significant differences either in the number of therapeutic INR values per patient (50.53 +/- 23.72% vs. 51.74 +/- 26.68%, P = 0.795) or in individual quality of treatment: > 50% therapeutic INR values (60.0% vs. 64.9%, P = 0.721) and > 75% therapeutic INR values (18.3% vs. 22.8%, P = 0.714) in the warfarin and acenocoumarol group, respectively. Significantly better stability was determined for acenocoumarol as compared with warfarin treatment in terms of a longer period of the total observed time during which therapeutic INR values were stable (37.6% vs. 35.7%, P = 0.0002). CONCLUSION Both drugs have shown similar quality of individual anticoagulation control, but acenocoumarol have shown significantly better anticoagulation stability with therapeutic INR values covering significantly longer time of treatment.

Alpha lipoic acid is important intramolecular redox system. It is coenzyme of piruvate dehydrogenase and ketoglutarate dehydrogenase. Alpha lipoic acid has enzymatic and cytoprotective effect. It has key role in citric acid cycle, as a coenzyme. Therapeutic efficacy of alpha lipoic acid in diabetic neuropathy is based on reaction with free radicals and lipophylic antioxydans properties. Clinical studies results showed efficacy and safety of alpha liponic acid application in patients with diabetic neuropathy.

PURPOSE Combination FAR4 consists from two peptide components: met-enkephalin and alpha adrenocorticotropine 1-13 (ACTH 1-13) named before as alpha-melanocyte-stimulating hormone-like (alpha-MSH-like). Met-enkephalin and alpha-MSH exhibited cytoprotective effects individually and statistically significant additive effect was registered when both peptides were applied in combination on the model of ethanol induced gastric lesions in rats. We performed subacute toxicity study with subcutaneous application. WORK METHOD Wistar rats were randomized in 3 test groups (treatments) consisted of 10 male and to female rats and one control group consisted of 20 male and 20 female rats. One daily dose was applied 3 days a week. Three dose ranges as multiplication of expected maximal human therapeutic dose (10 mg of met-enkephalin and 2 mg of alpha-ACTH 1-13) were estimated: equivalent dose, dose that was 5 times higher and 10 times higher dose. Animals were treated during 4 weeks with 10-days long observation period without the treatment after. After the planned scarification at the end of study, necropsy with histopathology examination was performed. RESULTS No lethality, toxic signs or histopathological changes were observed during the subacute toxicity testing. Variation of laboratory animals body mass was observed through six terms of body mass deternimation. Increase in body mass was noted in all test and control groups. Statistical analysis with Kruskal Wallis single variance test showed statisticaly significant difference in the number of respirations between the groups of ma-. les for the first measurement (p = 0.040332) and second measurement (p = 0.016852), but multiple comparation with control group showed statisticaly significant difference. Afterthe planned scarification at the end of the study, necropsy did not reveal changes in macroscopic structure of organs and tissues. Histopathology examination was performed on the samples of liver, kidneys, lungs, heart, brain, spleen and thymus and no pathological changes were noted, while microscopic structure of tissues was perserved. The changes regarding postmortem organ mass as percentual ratio towards total group mass were not noted nor for males, nor for females. DISCUSSION Study was conducted following the rules of the Guide for the Care and Use of Laboratory Animals made by the U.S. National Institutes of Health. Methodologicaly our study complys with rutine design of thistipe of studies. Subacute toxicity studies usually last for fourweeks and the way of test substance application to laboratory animals should comply to future way of application in human use. In our study no lethality was registered and low toxicity