Background The aim of this study was to analyze the total outpatient utilization of antibacterials for systemic use (ATC class J01) and the outpatient utilization of antibiotics on the reimbursable medication list of the Health Insurance Fund, in the Republic of Srpska, in 2007 and 2008. Methods In the retrospective study outpatient utilization of prescription-only antibacterials for systemic use dispensed in pharmacies was analyzed. Anatomical therapeutic chemical/defined daily dose methodology was used to monitor drug utilization. Results It was observed that penicillins accounted more than 50% of both total and reimbursable antibiotic use, and that broad-spectrum penicillins were more prescribed than narrow-spectrum. Amoxicilline was the most prescribed antibiotic. Cephalosporins, namely cefalexin, were widely prescribed as well as tetracyclines and combination of sulfametoxazole and trimethoprim. Increased utilization of a macrolide antibiotic claritromycin was observed. The list of reimbursable antibiotics was comprised of the first-generation antibiotics. Utilization of all reimbursable antibiotics increased in 2008, except phenoxymethylpenicillin, due to marketing authorization renewal process. Conclusions The outpatient utilization of antibiotics was comparable with trends worldwide. Utilization increase of almost all reimbursable antibiotics suggested that more patients were able to achieve their rights deducible form the health insurance, and that the spending out-of pocket for medicines was reduced. Utilization of amoxicillin, solely or in combination with clavulanic acid, as the most prescribed antibitotic was similar to other countries. Antibiotics are important and widely used medicines.1,2 In human medicine, about 80-90% of antibiotics are used in outpatient and the rest in hospitalized patients.3 Overuse and/or misuse of antibiotics have significant consequences, such as increased costs, therapeutic failure, drug toxicity, drug interactions, and bacterial resistance. In developing countries, on average, 35 per cent of the total health budget is spent on antibiotics.4 Antimicrobial drug resistance is a rapidly increasing global problem.5,6 Prevalence of resistance is positively correlated with prescribed outpatient antibiotic use at national level. Although antibiotics are prescription-only medicines, actual consumption may also include self-medication.2,6,7 Cultural factors to play important role in the consumption of antibiotics.8,9 Thus, information on the trends, patterns, and determinants of antibiotic consumption is essential to determine areas where improvement is needed. Until recently, information on outpatient antibiotic consumption in various countries was limited. In 2001, Cars et al.3 published comparable outpatient antibiotic use in fifteen European countries. A compulsory reporting of health institutions to Drug Regulatory Agency of the Republic of Srpska (DRA) on drugs utilization started in year 2006, when a related by-law came into action.10 Up to 2006, there were no comprehensive data available for analysis of total outpatient antibiotic utilization in the Republic of Srpska. Therefore, only the data on utilization of drugs on the reimbursable medication list of the Republic of Srpska Health Insurance Fund (HIF) were available and reliable source for analysis on drugs utilization and prescribing patterns.11,12 The aim of this study was to analyze the total outpatient utilization of antibiotics classified in ATC group J01 and the outpatient utilization of antibiotics on the reimbursable medication list of the Health Insurance Fund, in 2007 and 2008. Methods The outpatient utilization of all prescription-only drugs and the outpatient utilization of drugs on the reimbursable 23 Marković-Peković et al. medication list of the Health Insurance Fund was analyzed (Table 2), using anatomical therapeutic chemical/defined daily dose methodology (ATC/DDD methodology). The ATC system classifies the drugs into different groups according to the organ or system on which they act and their chemical, pharmacological and therapeutic properties. The drugs were classified into ATC groups by its international non-proprietary name (INN), and the results were expressed as a DDD per thousand inhabitants per day (DDD/ TID). The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults, and its use in DDD/TID is to enable a study of the extent of medicine utilization in a defined area and its changes over certain time period. The DDD/TID is a useful indicator for national and international comparisons, especially when areas to be compared have different number of inhabitants.13, 14 Hereafter in this article, the acronym DDD should be taken to indicate DDD/TID. Utilization of antibacterials for systemic use (ATC class J01) dispensed in the pharmacies in 2007 and 2008 was analyzed, excluding antifungals, antibacterials for tuberculosis, antitumoral and topical antibiotics. According to the Law on Medicines, antibiotics are prescriptiononly medicines, prescribed by family practitioners and dispensed in the pharmacies by pharmacists, through individual prescription forms.15 Utilization statistics were retrieved from the DRA16 and HIF database, unpublished data are available upon request. List of medicines reimburesd by the HIF is published in the Republic of Srpska Official Gazzette.17,18 Results The obtained results were presented in a systematic way using different ATC levels, starting with the utilization data of the main anatomical groups (Table 1), followed with the pharmacological subgroups of the antiinfectives for systematic use (group J) (Fig. 1), and subsequently presenting the results of the chemical subgroups (Table 2) and active substances (Table 3). Both total outpatient drugs utilization and utilization of the reimbursable drugs were increased in this period, for 10% and 26%, respectively. Total utilization of antibacterials for systemic use (J01) in 2008 decreased for 18%, while the utilization of reimbursable antibiotics increased for 2% (Table 1). In total antibiotic utilization, beta-lactam penicillins were the most prescribed subgroup, followed by the subgroups of other beta-lactam antibacterials (cephalosporins), and tetracyclines. An increase in utilization of sulfonamides and trimethoprim and quinolones subgroups was observed, while the utilization of macrolides, lincosamides and streptogramins subgroup decreased. The most prescribed reimbursable antibiotic subgroup also belongs to beta-lactam penicillins. An increase in utilization was noted in subgroup of tetracyclines, while the utilization decreased in subgroups of macrolides, lincosamides and streptogramins and quinolone antibiotics (Fig.1). TOTAL DRUGS UTILIZATION REIMBURSABLE DRUGS UTILIZATION ATC 2007 2008 ATC 2007 2008 DDD Percentage DDD Percentage DDD Percentage DDD Percentage C 174,54 37,37 213,67 41,45 C 159,77 65,54 201,55 65,61 N 72,45 15,51 70,05 13,59 A 26,76 10,98 38,21 12,44 A 57,05 12,22 66,49 12,90 N 19,61 8,04 22,46 7,31 B 51,94 11,12 59,03 11,45 R 12,71 5,21 12,44 4,05 M 22,00 4,71 24,42 4,74 J 9,60 3,94 9,78 3,18 R 20,23 4,33 21,60 4,19 B 2,76 1,13 6,27 2,04 S 17,41 3,73 20,91 4,06 H 4,03 1,65 6,14 2,00 J 22,06 4,72 17,72 3,44 S 3,37 1,38 4,32 1,41 Other groups 29,33 6,28 21,62 4,19 Other groups 5,15 2,11 6,04 1,97 Total utilization 467,01 100 515,51 100 Total utilization 243,76 100 307,21 100 Key: C, cardiovascular system; N, nervous system; A, alimentary tract and metabolism; B, blood and blood forming organs; M, musculo-skeletal system; R, respiratory system; S, sensory organs; J, antiinfectives for systemic use; H, systemic hormonal preparations; DDD=DDD/TID, defined daily dose per thousand inhabitants per day. table 1. Outpatient utilization of drugs dispensed in pharmacies: total utilization of all prescription-only drugs and utilization of reimbursable drugs, in terms of DDD/TID and percentage, ranked by 2008 24 Scripta Medica Vol. 41 • No 1 • May 2010. It was observed that penicillins accounted for more than 50 per cent of both total and reimbursable antibiotic use. Broad-spectrum penicillins were four to five times more prescribed than the narrow-spectrum penicillins. In 2008, the total utilization broadand narrow-spectrum penicillins decreased for 19% and 44%, respectively. The use of broad-spectrum reimbursable penicillins rose for 3 per cent, while the use of narrow-spectrum decreased for 4% (Table 2). Combination of amoxicillin with clavulanic acid, accounted for about 3% of the total antibiotic use, with utilization decrease. This combination was not available at the reimbursable drugs list (Table 2 and Table 3). Subgroup of tetracyclines represented about 10% of both the total and the reimbursable antibiotic utilization. Doxycycline accounted for 90% of the total tetracycline utilization, and was the only tetracycline reimbursed by the HIF (Table 2 and Table 3). The utilization of sulfonamides and trimethoprim combination accounted for 10% of the total antibiotic utilization, and about 16% of reimbursed antibiotics, with an increased use noted (Table 2 and Table 3). In 2008, total utilization of cephalosporins subgroup decreased, and first-generation was the most prescribed, with a noted decrease of 4%. Utilization of the secondand third-generation of cephalosporins decreased in 2008 (Table 3). Cefalexin was the only cephalosporin antibiotic reimbursed by HIF, with 8% utilization increase in 2008 (Table 3). In 2008, total use of macrolides decreased for 19% and the fluoroquinolones increased for 12%, while reimbursable utilization of these both subgroups decreased (Table 2). As shown in Table 3, amoxicilline was the most used antibiotic, and ten times more prescribed than ampicilin in 2007. We noticed that in 2008 total amoxicilline use decreased, while the reimbursed one increased for 21% and 3%, respectively. The total use of benzathine phenoxymethylp

The objective of this study was to analyse cardiovascular medicines utilisation patterns in Republic of Srpska (Bosnia and Herzegovina) over the 2002–2006 period.

Sažetak. Infekcije tmdnice su relativno česte, tako da je često i propisivanje antibiotika и trudnoći. Vrsta antibiotika, doza, trajanje, način i učestalost primjene zavise od uzročnika i težine bolesti. U Sjedinjenim Američkim Državama, prema Upravi za hranu i lijekove (engl., Food and Drug Administration, FDA) svi lijekovi, prema riziku za oštećenje ploda, svrstavaju se и 5 grupa (А, В, C, D, X). Najmanji rizik imaju lijekovi iz grupe A i B, a najveći iz grupe X. Cilj rada je bio da se ispita učestalost primjene antibiotika kod trudnica, koje su najčešće indikacije za njihovu primjenu, koji se antibiotici najčešće koriste i и koju grupu rizika po plod spadaju, te koliko je antibiotska terapija trajala. ® Studija je obuhvatila 694 trudnice. Ispitivanje je provedeno tokom 2004. i 2005. godine. Podaci su prikupljeni modifikovanim upitnikom za trudnice Svjetske zdravstvene organizacije, originalno urađenom na Institutu za farmakološka istraživanja “Mario Negri ”, Milano, ltalija. U toku trudnoće, lijekove je uzimalo 574 (82,71%) žene. U prosjeku, uzimano je 2,84 lijeka po trudnici. Najčešće su korišćeni preparati željeza (69,9%) i vitamini (56,1%), a slijede sistemski antibiotici (33,9%), antimikotici u obliku vaginaleta (22,3%), simpatikomimetici za spriječavanje prijevremenog porođaja (22,0%), polni hormoni (progesteron) (13,9%), te benzodiazepini (12,0%>). Od sistemskih antibiotika najčešće su korišćeni beta laktamski antibiotici (penicilini i cefalosporini, FDA grupa B). Najčešće indikacije za terapiju sistemskim antibioticima su bile: infekcije urinarnog trakta, a zatim respiratornog. Utvrđeno je da su antibiotici primjenjivani i kod virusnih infekcija uz opravdanje da se trudnice zaštite od bakterijske superinfekcije. Oko 3% trudnica bilo je na hroničnoj terapiji, koja je započeta prije i trajala je tokom čitave trudnoće (epilepsija, oboljenja štitne žlijezde, i slično). Antibiotike za sistemsku primjenu je koristila treéina trudnica, a najčešće su korisćeni beta laktamski antibiotici, amoksicilin i cefaleksin. Antibiotici su najčešće korišćeni za liječenje infekcija urinarnog i respiratornog trakta. Kod veéine trudnica, liječenje infekcija bilo je neodgovarajuée.

Sažetak. U trendu porasta ukupnih troškova za zdravstvo, kontinuirano praćenje upotrebe lijekova и zdravstenom sistemu omogućava sagledavanje zdravstvenog stanja stanovništva, farmakoterapijskih navika doktora i trendova и propisivanju, stepena racionalnosti upotrebe lijekova, te upoređivanja istih sa svjetskim kretanjima. Cilj ovog rada je bio da se analizira upotreba lijekova koji se izdaju na teret Fonda zdravstvenog osiguranja Republike Srpske и periodu 2003-2004. godina. Retrospektivnom studijom analizirana je upotreba lijekova sa pozitivne liste Fonda zdravstvenog osiguranja Republike Srpske 2003-2004. godine. Podaci su obrađeni prema ATC/DDD metodologiji, a rezultati izraženi brojem DDD/1.000 osiguranih lica/dan. Prikazana su i materijalna izdvajanja za lijekove sa pozitivne liste, izraženo и milionima konvertibilnih maraka. U 2004. godini je došlo do porasta upotrebe lijekova od 21% izraženo brojem DDD, a materijalna izdvajanja su porasla za 25% и odnosu na prethodnu godinu. Najveéa je upotreba lijekova и grupama za kardiovaskularne bolesti (ACE inhibitori i Ca blokatori), lijekova koji djeluju na sistem za varenje i metabolizam (antidijabetici i antiulkusici), koji djeluju na nervni sistem (antiepileptici i anksiolitici), te sistemski antiinfektivi. U obe godine najveéi su troškovi bili izdvojeni za lijekove и liječenju kardiovaskularnih oboljenja. Porast upotrebe lijekova, kao i povećanje troškova и zdravstvu zahtijeva detaljnu analizu, primjenom farmakoekonomskih metoda koje bi trebalo da pomognu pri donošenju odluka о raspodjeli raspoloživih sredstava. Na osnovu ovakvih podataka država тога kontinuirano da prilagođava zdravstevnu politiku и skladu sa standardnim kliniâkim smjernicama i medicini zasnovanoj na dokazima, kako bi farmakoterapiju učinila racionalnom i dostupnom cjelokupnom stanovništvu.

Using spectrophotometric assay, we have studied the distribution of α-D-mannosidase, β-D-galactosidase, and N-acetyl-β-D-glucosaminidase in hog serum, the aqueous humor, optic nerve, retina, and uvea (iris, ciliary body, choroid). N-acetyl-β-D-glucosaminidase was the most active gycosidase in all tissues that we studied. The highest activity of α-D-mannosidase was found in the extracts prepared from the iris, while β-D-galactosidase and N-acetyl-β-D-glucosaminidase were the most active in the extracts of the choroid and ciliary body, respectively. The aqueous humor and serum had several times lower specific activity of glycosidases than did the extracts of ocular tissues or optic nerve. There was no significant difference between the activity of these enzymes in the aqueous humor and serum. High activity of glycosidases in the optic nerve suggests their role for intrinsic axonal repair. Retinal extracts had the smallest glycosidase activity of all ocular extracts prepared. The physiological role of these findings is discussed.

INTRODUCTION Using the Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology, we analyzed utilization of prescription-only drugs in Banja Luka region in 2000-2001. MATERIAL AND METHODS A retrospective study on drug utilization, according to ATC classification, was conducted on the basis of data received from Central City Pharmacy Banja Luka, and results were presented in terms of DDD/1000 inhabitants/day. RESULTS Pharmaco-epidemiological analysis showed that the list of 20 most frequently prescribed drugs in 2000 included 8 cardiovascular drugs and 6 anti-infective drugs. In 2001, 20 most frequently prescribed drugs, included 9 cardiovascular drugs, and 4 anti-infective drugs. Regarding anti-infective agents, the most frequently prescribed antibiotics were amoxicillin, doxycyline, co-trimoxazole and gentamicin. The most frequently prescribed drug in 2000 was diazepam (5.33 DDD/1000 inhabitants/day). The use of this drug significantly increased in 2001 (7.95 DDD/1000 inhabitants/day). DISCUSSION AND CONCLUSION Based on total analysis, it can be concluded that the positive drug list, defined by the Health Insurance Fund, significantly affected the drug utilization profile, but some drugs are considered to be irrationally prescribed.