Browsing by Subject "benzodiazepines"

Screening of drugs of abuse has to combine sensitivity, selectivity and repeatability. The conventional screening methods include immunoassay screening followed by a more sensitive confirmation method. The aim of the study was to develop a simple, yet sensitive sample preparation method for screening of benzodiazepines and amphetamine derivatives in urine samples with silicon micropillar array electrospray ionization chip (µPESI) coupled to mass spectrometric analysis. Another aim was to evaluate the suitability of µPESI in biological sample analysis. Ideally, the developed method would provide an alternative to immunoassay screening method in forensic urine analysis. The sample preparation methods were separately optimized for benzodiazepines and amphetamine derivatives. Methods used included solid- phase extraction with Oasis HLB cartridge and C18-phase containing ZipTip®-pipette tip, liquid-liquid extraction, and dilution and filtering without prior extraction. Optimization focused, however, on ZipTip®-extraction. The compounds were spiked in blank urine to their cut-off levels, 200 ng/ml for benzodiazepines and 300 ng/ml for amphetamine derivatives. For benzodiazepines, every extraction phase was optimized. The sample pH was adjusted to 5, the ZipTip® phase was conditioned with acetonitrile and washed with a mixture of water (pH 5) and acetonitrile (10 % v/v) and the sample was eluted with a mixture of acetonitrile, formic acid and water (95:1:4 v/v/v). For amphetamine derivatives, pH values of sample and solvents were optimized. The sample pH was adjusted to 10, the ZipTip® phase was conditioned with a mixture of water and ammoniumbicarbonate (pH 10, 1:1 v/v), washed with a mixture of water and acetonitrile (1:5 v/v) and the sample was eluted with methanol. The optimized methods were tested with authentic urine samples obtained from Yhtyneet Medix Laboratories and compared to the results of quantitative GC/MS analysis. Benzodiazepine samples were hydrolyzed prior to extraction to improve recovery. All samples were measured with Q-TOF Micro apparatus and hydrolyzed benzodiazepine samples additionally with microTOF apparatus in Yhtyneet Medix Laboratories. Based on the results the developed method needs more optimization to function properly. The main problems were lack of reproducibility and poor sample ionization. Manual sample preparation and adding to the chip sample introduction spot increased variation. Authentic benzodiazepine samples gave false negative and authentic amphetamine derivative samples false positive results. False negatives may be due to the lack of sensitivity and false positives due to the contamination of sample cone, chips or solvents.

The body changes its response to medicine by age. Thus, medicines information for the elderly needs to differ from information targeted to younger adults. Package leaflets (PLs) are among the key sources of medicines information among general public. Although not generally recommended, benzodiazepines are commonly used by the elderly. The aim of this study was to evaluate the usability of benzodiazepine PLs and their information content from the elderly perspective. Additionally, the study aimed to explore how medicines information targeted to elderly in PLs aligns with the information targeted to health care professionals (HCPs). The study focused on PLs of benzodiazepines and their derivatives (diazepam, alprazolam, oxazepam, zopiclone and temazepam) that are commonly used but not recommended for the elderly. The usability of PLs was evaluated by using the Medication Information Design Assessment Scale (MIDAS). The informational content of PLs was studied by identifying all references for the elderly and comparing them to information targeted to HCPs in Database of medication for the elderly, Beer's criteria, Kapseli 35 publication, Martindale, Current Care Guideline for insomnia and the Summaries of Product Characteristics. The usability of the PLs in this study required several improvements. The mean of MIDAS-credits was 6,22 (n = 27; range 5,00-7,00), the scale maximum being 13. Sufficient line spacing and highlighting of important information were among the poorly represented elements. The occurrence of different font-sizes also varied. The most proficiently represented features included headings, contrast and the usage of upper and lower case in text. The PLs included in the content-analysis contained references to the elderly in all cases except one (n = 35). The references were categorized to general warnings, side effects and dose recommendations. They were in line with the information targeted to HCPs, but relatively short and often inadequate. Most PLs did not give an adequate overall picture of the medicine use among the elderly. The PLs for benzodiazepines need to be improved from the elderly perspective both in terms of information content and usability. Attention both from the medicine authorities and the pharmaceutical industry is required. Alternatively, separate drug-specific information leaflets for the elderly may be developed.

Many mental disorders, such as anxiety, mood and substance use disorders, become prevalent in adolescence and continue into young adulthood. Anxiety disorders are among the most common mental disorders in adolescents and approximately 6-13 % of adolescents and young adults suffer from them. Benzodiazepines have been used for the treatment of anxiety and sleep disorders for several years but they are not recommended for young patients due to risk of dependence and abuse. Nevertheless, benzodiazepines are also prescribed to treat mental disorders in children and adolescents under 18 -years of age. There is limited population-based evidence on the use of benzodiazepines among children and adolescents. The aim of this study was to investigate the use of benzodiazepines and benzodiazepine related drugs as anxiolytics and hypnotics in the Finnish population aged 0-25 years during 2006-2014. Data of this study were obtained from the Prescription Register of the Social Insurance Institution of Finland covering reimbursed drug purchases of benzodiazepines (N03AE, N05BA, N05CD, N06CA01) and benzodiazepine related drugs (N05CF) dispensed to 0-25 year olds. Purchases of orally administered dosage forms were included in this study. The majority (97 %) of anxiolytic and hypnotic users in the group of 0-25 year olds were 16-25-year-old adolescents and young adults. Use of anxiolytics and hypnotics among 16-25-year-olds decreased from the prevalence 19.9 / 1 000 to 15.9 / 1 000 inhabitants during the years 2006-2014. There were also decrease in incidence and prevalence of long-term use. The prevalence of long-term use among young adults decreased from 5.5 / 1 000 in 2006 to 3.3 / 1 000 young adults in 2014. The majority of anxiolytic and hypnotic users were females but long-term use was more common in males than in females. There was a decrease in use of almost every studied drug. Oxazepam was the only drug with increased number of users during the study period. Use of benzodiazepines as anxiolytics and hypnotics has decreased among adolescents and young adults since 2008 in Finland. Furthermore, long-term use of these drugs has decreased among young adults. Results indicate that rational drug therapy has been paid more attention in recent years which was reflected in decreased use of benzodiazepines.