Vesna Mijatović

The influence of essential oil of aniseed (Pimpinella anisum, L.) on drug effects on the central nervous system

Anise (Pimpinella anisum L.; Apiaceae) and its essential oil have been widely used in folk medicine, pharmacy and food industry. Since there are some data about the impact of anise on functions of central nervous system (CNS), the issue of possible interactions with drugs acting in CNS should be considered. This survey aimed to examine the influence of aniseed essential oil (EO) intake on the effects of drugs that act in CNS. The chemical profile of essential oil determined by GC-MS revealed as the main components: trans-anethole (88.49%), γ-himachalene (3.13%), cis-isoeugenol (1.99%), and linalool (1.79%). The effects of codeine, diazepam, midazolam, pentobarbital, imipramine and fluoxetine were tested in mice after 5days of peroral pretreatment with human equivalent dose of aniseed EO (0.3mg/kg). The intake of EO led to significant increase of analgesic effect of codeine. The motor impairment caused by midazolam was enhanced in the group treated by EO. The application of diazepam decreased the number and percentage of entries in open arm in elevated maze plus test in the group pretreated with EO indicating augmented effect of drug on motor activity. EO pretreatment caused significant shortage of pentobarbital induced sleeping time when compared to control. The decrease in antidepressant effect of imipramine and fluoxetine was diminished by the pretreatment with aniseed EO. Based on the results of this study we conclude that concomitant intake of aniseed EO preparations and drugs that act on CNS should be avoided due to potential herb-drug interactions, which also need further clinical confirmation.

Consumption of non-steroidal anti-inflammatory drugs in Serbia: a comparison with Croatia and Denmark during 2005–2008

PurposeTo analyze the amount and pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) in Serbia and to compare these parameters with those in Croatia and Denmark. The prescribing pattern of NSAIDs in Serbia as a direct indicator of physicians’ knowledge of these agents was also assessed.MethodsThe use of NSAIDs in Serbia, Croatia, and Denmark was analyzed during a 4-year period (2005–2008). Data were retrieved from the annual reports of the Agency for Drugs and Medical Devices of Serbia, Croatia, and Denmark. Data on prescribing behavior were obtained from the Health Insurance Fund of Serbia and represent NSAIDs issued by prescription between 2005 and 2008. Results were expressed as the number of defined daily doses/1000 inhabitants/day. The drug utilization 90% method was also used.ResultsThe total consumption of NSAIDs in Serbia was higher than that in Croatia and Denmark. Diclofenac accounted for approximately 50% of NSAID consumption during the observation period, followed (in much smaller quantities) by ibuprofen. The most commonly prescribed medicine was diclofenac, followed, in much smaller amounts, by ibuprofen. There was no trend of a reduced consumption of diclofenac or of an increased use of ibuprofen during the study periodConclusionsThese data suggest that factors other than evidence-based medicine have a dominant effect on the use of NSAIDs in Serbia. Targeted education from independent sources in the prescribing, dispensing, and use of drugs is important to improve the quality of the prescribing behavior and the use of NSAIDs.

The outpatient utilization of non-steroidal anti-inflammatory drugs in South Bačka District, Serbia.

Objective To evaluate the utilization of non-steroidal anti-inflammatory drugs (NSAIDs) in South Bačka District (SBD), Serbia. Setting State-owned and private pharmacies in SBD, a northern district of Serbia, with 605,720 inhabitants (according to the 2008 census). Method Data on the number of packages, size of packages, and retail price of NSAIDs (Anatomical Therapeutic Chemical (ATC) group M01A) from 1 January to 31 March 2008 were obtained from all state-owned and private pharmacies in SBD. This included NSAIDs bought without prescription and those issued by prescription (on the Health Insurance Companies List for Reimbursement). The number of defined daily doses/1000 inhabitants/day (DDD/1000 inh/day) was calculated. Within the DU90% (drug utilization 90%) segment, the proportion of high-, medium- and low-risk NSAIDs with respect to the risk of gastrointestinal (GI) bleeding was determined. Price/DDD was also calculated. Main outcome measure Consumption of drugs expressed as DDD/1000 inh/day. Results The total consumption of NSAIDs over a 3-month period was 48.31 DDD/1000 inh/day. Only four drugs were within DU90%: diclofenac, ibuprofen, nimesulide and meloxicam (62.14, 19.87, 5.77, and 5.73% of total NSAID consumption, respectively). All dispensed NSAIDs within the DU90% segment except nimesulide (which was exclusively purchased without prescription) were nearly equally purchased without prescription and issued by prescription. The average price per DDD within the DU90% segment was 0.17 Euro/DDD, whereas it was 0.30 Euro/DDD for NSAIDs beyond the DU90% segment. The pattern of use of NSAIDs according to their GI risk showed that medium-risk diclofenac accounted for 66.45%, whereas low-risk ibuprofen was estimated to be 21.25% within the DU90% segment. Conclusion Factors other than evidence-based medicine (such as poor health education in the past that led to long-lasting consequences on the cultural behaviour of the general population as well as on the prescribing habits of physicians) have a dominating impact on the use of NSAIDs in SBD. Targeted education from independent sources in the prescribing, dispensing and use of drugs is required to improve the quality of prescription and use of NSAIDs in Serbia.

Drug Addiction as Risk for Suicide Attempts.

Introduction: Suicide is closely linked to the substances use. Therefore it is very important to confirm the factors that affect the possibility of suicidal behavior. Methodology: The survey included 200 respondents; 100 heroin addicts on the substitution program that attempted suicide and 100 opiate addicts who have not attempted suicide. The evaluation included a questionnaire with socio-demographic, hereditary and addiction data, legal problems and then the Minnesota Multiphasic Personality Inventory–MMPI-2. Results: The results showed a statistically significant difference compared to the personality structure, especially pronounced in hypersensitive structures, in relation to the duration of addictive experience and duration of heroin by intravenous route, as well as in relation to the presence of psychotic disorders, drug abuse and suicidal behavior in the family. Conclusion: As risk factors among opiate addicts are indentified interfered biological and psychological factors and the effects of the substances themselves.

Acquired prolongation of QT interval as a risk factor for torsade de pointes ventricular tachycardia: a narrative review for the anesthesiologist and intensivist

More than 70% of intensive care unit (ICU) patients experience heart rhythm disturbances, and these patients have correspondingly higher mortality rates. Consequently, one of the standards of care in ICUs is continuous electrocardiography monitoring. One of the potentially preventable dysrhythmic events is the occurrence of torsade de pointes ventricular tachycardia in the setting of acquired prolonged QT interval. This type of ventricular tachycardia can be malignant because it often progresses to ventricular fibrillation. Many factors predispose to lengthening of the QT interval, the most important of which are electrolyte abnormalities and the administration of specific medications. In this review, we discuss the pathophysiology of acquired long QT interval, stressing the medication-induced acquired long QT-interval and factors present in ICU patients that promote prolongation of the QT interval. We also propose guidelines to avoid the occurrence of torsade de pointes ventricular tachycardia.

Pharmacokinetic Herb-Drug Interaction between Essential Oil of Aniseed (Pimpinella anisum L., Apiaceae) and Acetaminophen and Caffeine: A Potential Risk for Clinical Practice.

Aniseed (Pimpinella anisum L., Apiaceae) and its essential oil (EO) have been widely used. Because there are some data about the impact of aniseed EO on drug effects, this survey aimed to assess the potential of pharmacokinetic herb–drug interaction between aniseed EO and acetaminophen and caffeine in mice. The chemical analysis (gas chromatography–mass spectrometry) of aniseed EO has confirmed trans‐anethole (87.96%) as the main component. The pharmacokinetic studies of intraperitoneally (i.p.) and orally applied acetaminophen (200 mg/kg) and caffeine (20 mg/kg) were performed in mice after 5 days of oral treatment with human equivalent dose of aniseed EO (0.3 mg/kg/day). The analysis of pharmacokinetic data showed that in the group treated by aniseed EO, the significant decrease in the peak plasma concentration of acetaminophen after oral application (p = 0.024) was revealed when compared with control group and the reduction of systemic exposure to the drug after oral application (74 ± 32% vs. 85 ± 35% in the control) was noted. The bioavailability of orally applied caffeine was also significantly decreased (p = 0.022) after the EO treatment in comparison with the control (57 ± 24% vs. 101 ± 29%). Therefore, the compromised therapeutic efficacy of acetaminophen and caffeine during the usage of aniseed EO preparations should be considered. Copyright

Are There Striking Differences in Outpatient Use of Antibiotics Between South Backa District, Serbia, and Some Scandinavian Countries?

There is little published information about antibiotic utilization in outpatients in Serbia. The objective of this study was to determine the amount and structure of outpatient antibiotic use in South Backa District (SBD) in Serbia, to assess prescibing quality of antibiotics and to compare with results from Scandinavian countries. Data on the antibiotic use were collected from all private and state-owned pharmacies from January through March 2008 in SBD. Results were expressed as the number of defined daily doses/1,000 inhabitants/day. The drug utilization 90% method was also used. Penicillins were the most frequently used antibiotic subgroup in SBD (35.20%), followed by cephalosporins (19.16%) and macrolides (13.18%). Thirteen drugs accounted for 90% of total antibiotics consumption (DU90% segment). The average cost/DDD within the DU90% segment was 0.95 euros, whereas the average cost/DDD beyond the DU90% segment was 1.89 euros, indicating that less expensive antibiotics were more frequently used. High use of ampicillin, third-generation cefalosporins, co-trimoxazole, and gentamicin, will aggravate the alarming problem of resistance in Serbia. Differences in the amount and structure of antibiotic consumption between SBD and Scandinavian countries indicate the need of updated national guidelines for rational antimicrobial drug use in Serbia.

Cardiovascular effects of methadone and concomitant use of diazepam during methadone maintenance treatment induction: low concentration risk

ABSTRACT Background: The aim is to evaluate the role of diazepam concentrations in development of low-concentration-methadone-associated QTc prolongation in patients with opioid use disorder during methadone maintenance treatment (MMT) induction. Research design and methods: Individuals with addiction disorder on MMT were studied before the beginning of MMT and after one and six months of MMT. Serum concentrations of methadone, diazepam, electrolytes and ECG were analyzed. Results: Thirty patients were enrolled. The mean methadone concentration at time points was 177 ± 119 ng/ml and 343 ± 182 ng/ml, while the mean diazepam concentration was 561 ± 437 ng/ml and 1045 ± 933 ng/ml. The QTc interval before the introduction of MMT, after 1 and 6 months of MMT were 412 ± 27 ms, 425 ± 18 ms and 424 ± 15 ms, respectively, showing statistically significant increase in the length of QTc interval after 1 and 6 months of MMT. Statistically significant correlation between the concentration of methadone and QTc interval length at observed time points (R2 = 0.239, p = 0.018; R2 = 0.513, p = 0.006) was shown, and it remained so if the concentration of diazepam was included (R2 = 0.347, p = 0.026, R2 = 0.513, p = 0.009). Conclusions: The prolongation of QTc below the risk threshold in low methadone therapeutic doses has been recorded and concomitant use of diazepam could be a co-factor in such issue.

Methadone-drugs interactions: possible causes of methadone-related deaths

Background Methadone is an effective analgesic and it is widely used to suppress withdrawal symptoms from other opiates. Its consumption is usually associated with concomitant drug use in heroin addicts, and this combination is a possible risk factor for lethal outcome. The aim of this study was to analyze characteristics of methadone-related deaths (MRDs), and to evaluate the concomitant use of the drugs that can contribute to methadone toxicity.