Antiarrhythmic agents

Iako danas postoje i druge metode liječenja aritmija (kateterska ablacija, elektrostimulacija srca i sl.), antiaritmici su i dalje najčešće upotrebljavana terapija u prevenciji i liječenju nepravilnog ritma srca. Kako bi uspjeh liječenja aritmija bio što veći, nužno je poznavati način na koji antiaritmici modificiraju i iniciraju provođenje impulsa kroz srce, kao i odrediti omjer koristi i rizika za svakog bolesnika posebno. Osobito je važno imati na umu nuspojave, proaritmogeno djelovanje i interakcije antiaritmika s drugim lijekovima.Although there are other methods of treating arrhythmias (catheter ablation, heart electro stimulation etc.), antiarrhythmic agents are used most often in the prevention and treatment of irregular heart rhythms. To ensure efficient treatment of arrhythmias, it is necessary to know the way antiarrhythmic agents modify and initiate cardiac impulse conduction, as it is to determine the risk-benefit ratio for each patient. It is particularly important to be aware of side effects, proarrhythmogenic effects and the interaction of antiarrhythmic agents with other medicaments

Drugs in Pregnancy

Na području kliničke farmakologije trudnoće vrlo je malo pravih, kontroliranih kliničko-farmakoloških istraživanja zbog etičkih razloga. Budući da potrošnja lijekova u trudnoći raste, racionalna farmakoterapija nameće se kao imperativ. Većina lijekova može proći kroz placentu uz mogućnost farmakološkog i teratogenog učinka na embrio i fetus. Uzrok malformacija nepoznat je u 70% slučajeva, a lijekovi, kemikalije i zračenje čine 2% uzroka. Danas je poznato manje od 30 teratogena. Lijekovi mogu djelovati štetno na plod u bilo kojem razdoblju trudnoće. Budući da je čak 50% trudnoća neplanirano, tu je činjenicu važno imati na umu prilikom propisivanja lijekova ženama generativne dobi. Pri izboru lijeka treba se odlučiti za lijekove koji su do sada često propisivani u trudnoći i za koje se pokazalo da su neškodljivi. Takvim lijekovima treba dati prednost pred novim ili neispitanim lijekovima, a uvijek treba primijeniti najnižu djelotvornu dozu. Trudnice treba upozoriti da ne uzimaju lijekove bez recepta i bez prethodnog dogovora s liječnikom. Liječnici i trudnice mogu zatražiti konzultaciju kliničkog farmakologa o uzimanju lijekova u trudnoći. Neobično je važno da se trudnicama objasni tzv. normalna učestalost malformacija u trudnoći koja iznosi oko 3% te rizik povezan sa samom bolešću, kako bi se izbjegao nepotreban pobačaj ili neliječenje bolesti trudnice.As it is not ethical for pregnant women to be included in clinical trials there are very few controlled clinical trials with pregnant women. The fact is that drug consumption in pregnancy continuously rises, so rational pharmacotherapy becomes an imperative. Majority of drugs pass the placental barrier, carrying potential pharmacological and/or teratogenic activity on embryo and fetus. In 70% of fetal malformations causative factor remains unknown while drugs, various chemicals and radiation make just 2% of causes. Generally, in everyday use are less than 30 drugs with absolutely proved teratogenic activity. Drugs can harm a fetus in any period of pregnancy. About 50% of pregnancies are not planned and that information is very important when prescribing drugs to the women in generative phase. Drugs which have been widely prescribed and which have been shown to be safe in pregnancy should be a first line in prescribing to pregnant women. Those drugs should, certainly have an advantage in comparison to the new drugs with incompletely defined safety profile. It is also recommended to use the lowest efficient dose. Pregnant women should be warned to contact their physician any time when they need some drug, despite if the drug is on the OTC regimen. If dilemma regarding the use of certain drugs in pregnancy exists physicians and pregnant women should contact a clinical pharmacologist. Finally, to avoid unnecessary abortions or lack of adequate treatment, pregnant women should be informed on, so called, normal frequency of malformations which is about 3%, and on risk associated with the disease as well

Oxycodone: a strong opioid in the treatment of patients with arthritis

Smanjenje boli je vrlo važan dio liječenja reumatoloških bolesnika. Peroralni proizvodi s kontroliranim otpuštanjem omogućuju bolesnicima bolju kontrolu boli zbog pogodnijeg doziranja i održane koncentracije u krvi. U studijama je dokazano da je jaki opioid, oksikodon učinkovit u smanjenju umjerene do jake perzistirajuće boli u bolesnika s degenerativnim i upalnim reumatskim bolestima. Osim značajne kontrole boli i bolje fizičke funkcije, oksikodon s kontroliranim otpuštanjem je poboljšao podnošenje boli u bolesnika s osteoartritisom.Reducing pain is a major goal in treating patients with arthritis. Oral controlled-release opioid products enable patients to better maintain pain control due to convenient dosing intervals and sustained blood concentration. Oxycodone is a strong opioid that has proved to be efficacious in analgesic studies of persistent moderate to severe pain in patients with degenerative and inflammatory rheumatic diseases. Beyond significant pain control and better physical function, controlled-release oxycodone improved coping with pain in patients with osteoarthritis

Use of gastroprotective agents in recommended doses in hospitalized patients receiving NSAIDs: a drug utilization study

OBJECTIVE: In recent years, studies investigated to what extend recommendations for co-prescribing gastroprotective agents in prevention of NSAID-induced gastrointestinal complications are followed in clinical practice. However, only a few studies have also taken into consideration the recommended dose of gastroprotectives prescribed in NSAID-induced ulcer prophylaxis. The aim of our study was to evaluate the prevalence of concomitant use of gastroprotectives with NSAIDs in hospitalized patients, with emphasis on the recommended dose of gastroprotectives for ulcer prophylaxis. - - - - - METHOD: This observational, cross-sectional, drug utilization study included all adult patients receiving NSAIDs hospitalized in the Clinical Hospital Center Zagreb on the day of the study. Data on age, sex, comorbidities, indications for NSAID use, type/dose of NSAIDs and gastroprotectives, history of gastrointestinal events, active gastrointestinal symptoms and risk factors were evaluated. - - - - - MAIN OUTCOME MEASURE: Study outcomes were: (1) prevalence of prescription of gastroprotectives among NSAID-users at risk; (2) prevalence of prescription of gastroprotective in recommended dose; (3) association between risk factors and prescription of GPAs. - - - - - RESULTS: The rates of gastroprotectives prescription were significantly higher in NSAID-users with concomitant risk factors as compared to patients without risk factors [47/70 (67.1%) and 8/22 (36.4%), respectively; p = 0.01072]. However, gastroprotection in recommended ulcer-preventive dose was low in both groups [8/70 (11.4%) and 9/92 (9.8%), respectively]. The number of concomitant risk factors did not increase the odds of receiving anti-ulcer therapy (odds ratio 0.7279). Thirty-three percent of patients with concomitant risk factors were not prescribed gastroprotectives. Ibuprofen, NSAID with the lowest risk of inducing gastrointestinal complications, was prescribed in only two patients. - - - - - CONCLUSION: The results indicate high awareness among hospital physicians about possible NSAID-induced gastrointestinal complications, but insufficient knowledge about risk factors related to NSAID-induced gastrointestinal toxicity, recommended dose of gastroprotectives in NSAID-induced ulcer prophylaxis and gastrointestinal toxicity of different types of NSAIDs

The Association of Uric Acid with Glucose and Lipids in General Population: Croatian Cross-Sectional Study

Hyperuricemia may have an important role in metabolic syndrome, cardiovascular diseases and stroke. Elevated serum uric acid concentration has been shown to be the strong predictor of cardiovascular mortality in several recently published studies. Our aim was to determine the prevalence of hyperuricemia in general Croatian population and to investigate the association of serum uric acid with glucose and lipids. This was a retrospective cross-sectional study on 6,476 consecutive adults. Prevalence of hyperuricemia was 13.9% in general population and it was significantly higher in males, than in females (26% vs. 6%; p<0.001). Median uric acid concentration was higher in males than in females (343 vs. 238 mmol/L; p<0.001). Age, glucose and lipid parameters did not correlate with uric acid. In hyperuricemic subjects, increased concentrations of glucose (33.1% vs. 13.1%; p<0.001), triglycerides (46.9% vs. 17.6%; p<0.001), total cholesterol (69.6% vs. 51.9%; p<0.001), LDL-cholesterol (64.5% vs. 46.4%; p<0.001) and decreased concentration of HDL- -cholesterol (24.3% vs. 13.0%; p<0.001) were more prevalent than in subjects with normal serum concentrations of uric acid. Hyperuricemia is highly prevalent in Croatian general population and it aggregates with hyperglycemia and dyslipidemia

Učinci simvastatina i fenofibrata na malondialdehid i reducirani glutation u plazmi, jetri i mozgu normolipidemičnih i hiperlipidemičnih štakora

The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains.Cilj ovog istraživanja bio je istražiti učinke različitih doza simvastatina i fenofibrata na malondialdehid (MDA) i reducirani glutation (GSH) u plazmi, jetri i mozgu mužjaka normolipidemičnih (Wistar) i hiperlipidemičnih (Zucker) štakora. Na prvim dvjema eksperimentalnim skupinama normolipidemičnih štakora simvastatin je primijenjen u dozama 10 ili 50 mg/kg dnevno, a fenofibrat na trećoj i četvrtoj skupini u dozama od 30 i 50 mg/kg/dan. Prva eksperimentalna skupina hiperlipidemičnih štakora primala je simvastatin 50 mg/kg/dan, a druga fenofibrat 30 mg/kg/dan. Kontrolne skupine normolipidemičnih i hiperlipidemičnih štakora primale su fiziološku otopinu. Simvastatin, fenofibrat i fiziološka otopina primjenjivani su oralno tijekom tri tjedna. U plazmi i mozgu normolipidemičnih štakora simvastatin I fenofibrat pokazali su slične i o dozi neovisne učinke na koncentracije MDA i GSH. Općenito, MDA je bio smanjen, a koncentracija GSH bila je povećana. U hiperlipidemičnih štakora simvastatin nije utjecao na koncentraciju MDA i GSH, ali je prouzročio značajno smanjenje GSH u jetri. Fenofibrat je smanjio MDA u plazmi i jetri te povećao MDA u mozgu. U oba soja štakora fenofibrat je značajno smanjio koncentraciju GSH u jetri, vjerojatno zbog konjugacije GSH s nekim metabolitima fenofibrata. Prema našim rezultatima, simvastatin djeluje antioksidacijski samo u normolipidemičnih štakora, a antioksidacijski učinak fenofibrata prisutan je u oba soja

Učinci simvastatina i fenofibrata na aktivnost butirilkolinesteraze u mozgu, plazmi i jetri normolipidemičnih i hiperlipidemičnih štakora

The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14–17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity.Cilj ispitivanja bio je u normolipidemičnih i hiperlipidemičnih štakora potvrditi pretpostavku da simvastatin (SIMV) I fenofibrat (FENO) ne uzrokuju samo povećanje aktivnosti butirilkolinesteraze (BuChE) u plazmi i jetri nego i povećavaju aktivnosti BuChE u mozgu. Katalitička aktivnost enzima mjerena je upotrebom acetiltiokolina (ATCh) i butiriltiokolina (BTCh) kao supstrata. Normolipidemični i hiperlipidemični štakori raspoređeni su u eksperimentalne skupine, koje su tri tjedna primale SIMV 50 mg/kg na dan ili FENO 30 mg/kg na dan, dok su kontrolne skupine primale fiziološku otopinu. I SIMV i FENO uglavnom su izazvali povećanje aktivnosti BuChE u mozgu obaju sojeva štakora bez obzira na korišteni supstrat. Aktivnosti BuChE mjerene BTCh kao supstratom bile su značajno veće u odnosu na kontrolne vrijednosti u mozgu normolipidemičih štakora nakon primjene SIMV te u mozgu hiperlipidemičnih štakora nakon primjene obaju agensa (14‒17%, p<0,001). Povećanje aktivnosti BuChE u plazmi i jetri nakon primjene SIMV i FENO izmjeren je u oba soja štakora bez obzira na to je li korišten ACTh ili BTCh. U većini slučajeva povećanje aktivnosti BuChE u plazmi i jetri bilo je značajno. S obzirom na važnu ulogu BuChE u kolinergičnom prijenosu te na njezinu farmakološku funkciju, potrebno je nastaviti istraživanja utjecaja antilipidnih lijekova na aktivnost BuChE

Antibiotic Use Optimization Program in the Largest Croatian University Hospital – Benefits of Restrictions on Unlimited Antibiotic Use

The aim of this study was to obtain the relevant information on antibiotic use in a 750-bed Croatian university hospital. The study has been designed as a 2-point prevalence interventional analysis. For each patient on antibiotic therapy, diagnosis, indication for treatment, antibiotic therapy, dosage and route of administration together with the results of microbiological studies (if available) were obtained. After the first prevalence analysis in 2001, a restriction on unlimited antibiotic use was introduced. The second analysis, performed in 2002, after restrictions on antibiotic use, revealed reductions in the rates of restricted release antibiotics and overall antibiotic use with decreases from 38.6% to 36.9% and 23.4% to 23.2% respectively (p=0.87). The first survey showed that the 5 most often prescribed antibiotics in the therapy of bacterial infections were: gentamicin, other aminoglycosides, carbapenems, amoxycillin+clavulanate and vancomycin with proportions of 14.8%, 10.3%, 8.2%, 7% and 7% respectively. In the year 2002, the most prescribed antimicrobial drugs in the therapy of bacterial infections were: gentamicin, quinolones, vancomycin, carbapenems and cefuroxime with proportions of 18.6%, 11.4%, 9.7%, 9.3% and 8% respectively. A reduction in the proportions of doubtful antibiotic therapy, from 24.6% before the intervention, to 24.2% after the restrictions, accompanied by a 0.4% rise in the rates of indicated antibiotic therapy was also observed (p=0.93). Our study shows that restrictions on formerly unlimited use of antimicrobials, even when leading to an improvement in their prescribing, do not necessarily cause rapid and significant reduction in the overall use of antibiotics or explicit positive financial effects

The effects of simvastatin and fenofibrate on malondialdehyde and reduced glutathione concentrations in the plasma, liver, and brain of normolipidaemic and hyperlipidaemic rats

The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains