Statins, such as simvastatin, lower circulating cholesterol levels and are widely prescribed for the treatment of hypercholesterolaemia. Several studies have shown unexpected effects of statins on inflammation. We studied the anti-inflammatory effect of simvastatin using a standard model of an acute local inflammation, the carrageenan-induced footpad oedema. Experimental groups (n = 6-8) were given simvastatin in a dose range 5-30 mg/kg, indomethacin 1-8 mg/kg and methylcellulose (control) per os. Footpad volume was measured with a plethysmograph and compared with the pre-injection volume of the same paw. Swelling (in microlitres) was then calculated, and in drug-treated animals, per cent inhibition was derived through comparison with the control group. Histopathological examination of the skin biopsies was performed to examine severity of paw skin lesions and to confirm the simvastatin-induced inhibition of acute inflammation. Both simvastatin and indomethacin administered orally, 1 hr before carrageenan injection, significantly reduced the extent of footpad oedema. Indomethacin dose-dependently blocked the swelling; the maximal effect was obtained with 8 mg/kg by 48.3% (P < 0.05). Simvastatin produced a comparable anti-inflammatory activity at a dose of 5 mg/kg (32%), while 10 and 30 mg/kg caused a 47.6% and 51.7% reduction, respectively, with the maximal effect observed at 20 mg/kg by 57.2% (P < 0.05). The comparison of the ED(50) of these agents on molar basis showed equipotent anti-inflammatory activity. Histopathological examination of the footpad skin biopsies revealed that simvastatin, dose-dependently and comparablly to indomethacin, reduced polymorphonuclear leucocyte infiltration. These data support the hypothesis that simvastatin has an acute anti-inflammatory activity.

The effect of simvastatin applied in a short-term pretreatment on proinflammatory cytokines production in acute systemic inflammation induced by endotoxin - lipopolysaccharide (LPS) in rats was investigated. Both LPS and simvastatin doses were established in separate experiments in which increasing doses of both compounds were given to obtain the LD(50) LPS and the maximally protective dose of simvastatin against LD(50) LPS. To determine the anti-inflammatory effect, simvastatin was given orally for 5 days, followed by a single intraperitoneal non-lethal dose of LPS (0.25 LD(50)). Plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 were measured by enzyme-linked immunosorbent assay. The acute i.p. LD(50) LPS amounted to 22.15 mg/kg. Simvastatin of 20 mg/kg p.o. was maximally protective against LD(50) LPS, and this dose was used for studying its effects on LPS-induced cytokines production. Cytokines concentrations were significantly increased upon challenge of non-lethal dose of LPS. The peak levels of TNF-alpha and IL-1beta were significantly suppressed by simvastatin, compared to control rats only treated with dimethylsulfoxide before LPS. In contrast, simvastatin did not affect IL-6 levels at all timepoints. Simvastatin pretreatment given orally produced acute anti-inflammatory effects by inhibiting TNF-alpha and IL-1beta, but no IL-6 production.

Saietak. Akutne respiratorne infekcije (ARI), predstavljaju najčešće infekcije uopšte. ARI, naročito one lokalizovane и gornjim respiratornim putevima, čest su razlog posjete Ijekaru porodične medicine i pedijatru. Cilj rada je bio da se ispita učestalost ARI gomjih respiratornih puteva kod pacijenata и ordinaciji Ijekara porodične medicine, primjenjene dijagnostičke procedure i način liječenja sa posebnim osvrtom na propisivanje antibiotika. Podaci su uzeti iz medicinskih dokumenata pacijenta, a odnosili su se na starost, pol, dijagnostičke procedure, indikaciju, način i uspjeh liječenja. Od 294 pregledana pacijenta sa znacima i simptomima ARI, akutna infekcija gomjih respiratornih puteva je dijagnostikovana kod njih 197 (67,0%). Utvrđeni su akutni faringitis i tonzilitis, kao i akutne respiratorne infekcije multiplih i nespecifičnih lokalizacija. Kod većine, dijagnoza je postavljena samo kliničkim pregledom koji je uradio Ijekar porodične medicine. Antibiotici su propisani kod 150 (76,1%) pacijenata sa ARI gomjih respiratornih puteva. Najčešće je propisivan amoksicilin, fenoksimetil penicilin, amoksicilin sa klavulanskom kiselinom, cefahlor i azitromicin. Simptomatska teapija je preporučena svim pacijentima. Utvrdena je prekomjema primjena antibiotika и liječenju akutnih infekcija gomjih respiratornih puteva i ukazano je na neophodan racionalniji pristup и njihovom liječenju. Naročito je neracionalna primjena antibiotika utvrđena и liječenju akutnog nekomplikovanog sinuzitisa, akutnih faringitisa i tonzilitisa.

Sažetak. Prekomjemo propisivanje benzodiazepina je problem и mnogim zemljama, sto zahtijeva proširenje znanja i stavova о njihovom racionalnom propisivanju. U Domu zdravlja Banja Luka, tokom šest mjeseci, pomoéu upitnika ispitano je poznavanje benzodiazepina i način njihovog propisvanja među doktorima porodične medicine. Na pitanja iz upitnika odgovorio je i 981 pacijent. Rezultati su pokazali da je 341 pacijentu (34,76%) od ukupnog broja ispitanih, propisan benzodiazepin, uglavnom diazepam (252 pacijenata, 73,90%). Benzodiazepini su najčešće propisivani za nepsihijatrijske, organske bolesti i to za esencijalnu hipertenziju i druge kardiovaskularne bolesti (66,27%). Značajan broj pacijenata je benzodiazepin uzimao prema potrebi, duže od godine (69,79%) Hi nekoliko mjeseci (26,39%). Većina pacijenata nije poznavala moguća neželjena dejstva benzodiazepina (87,68%). Postoji neracionalano propisivanje benzodiazepina kod organskih bolesti, naročito kod kardiovaskulranih bolesti, tako da je neophodno uticati na propisivačke navike doktora, radi njihovog racionalnog propisivanja.

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.

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.

Using ATC/DDD methodology, we analyzed antibiotic utilization in the Clinical Centre of Banja Luka, one of the largest clinical centres in Bosnia and Herzegovina, during the war and postwar period (1994-2000), as well as the role of drug donations on doctors' prescribing decisions. The retrospective analysis of antibiotic utilization (group J according to the Anatomical Therapeutical Chemical - ATC classification) was based upon the data provided from the hospital computer centre and calculated as the number of defined daily doses (DDD) per 100 bed days. The pharmacoepidemiological analysis showed that the total use of antibiotics changed markedly; in the war year of 1994, as well as in 1998, antibiotics were the second most frequently used group of drugs (19.7% and 14.1% of total drug utilization respectively), while in the following years antibiotics were considerably less used. These dynamics were significantly influenced by drug donations, the percentage of which in the overall antibiotic supply in 1996 was 91.5%, while in 1999 and in 2000 it decreased considerably to 46.8% and 45.6%, respectively. The most widely prescribed antibiotics were penicillins, aminoglycosides, sulphonamides and tetracyclines. Among these, the aminopenicillins, co-trimoxazole, gentamicin and tetracyclines were mainly (70-100%) supplied as a drug donations. However, macrolides, cephalosporins and quinolones were less used due to fact that they were considerably less often delivered through drug donations. It can be concluded that the drug donations had a significant impact on prescribing practice and the rational use of antibiotics in the Clinical Centre studied.