Sedative and hypnotic drugs—Fatal and non-fatal reference blood concentrations

Jönsson, Anna K.; Söderberg, Carl; Espnes, Ketil Arne; Ahlner, Johan; Eriksson, Anders; Reis, Margareta; Druid, Henrik

doi:10.1016/j.forsciint.2014.01.005

Cited by 43 publications

(35 citation statements)

References 40 publications

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“…Alprazolam is the benzodiazepine with a high abuse liability [26], and it shows the highest FTI of all benzodiazepines in our material. Swedish researchers published FTI values for sedative and hypnotic drugs based either on fatal mono-intoxications or multi-drug intoxications [12].…”

Section: Discussionmentioning

confidence: 99%

“…For illicit drugs, fatal toxicity can be evaluated by relating the number of associated deaths to measures of availability such as seizures by law enforcement agencies [8]. Several recent studies have been published addressing the FTI for various classes of prescription drugs, such as antidepressants [9][10][11], sedative-hypnotic drugs [12], carisoprodol [13], and methadone [14,15]. Drug consumption has been expressed as the number of prescriptions, kilograms, or defined daily doses (DDD) dispensed.…”

Section: Introductionmentioning

confidence: 99%

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Fatal toxicity index of medicinal drugs based on a comprehensive toxicology database

2016

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The fatal toxicity index (FTI) is the absolute number of fatal poisonings caused by a particular drug divided by its consumption figure. Consequently, it is a useful measure in evaluating toxicity of the drug and its relevance in fatal poisonings. In this study, we assessed the FTI of medicinal drugs in 3 years (2005, 2009, and 2013) in Finland. As the measure of drug consumption, we used the number of defined daily doses (DDD) per population in each year. There were 70 medicinal drugs in Finland for which the mean FTI expressed as the number of deaths per million DDD over the three study years was higher or equal to 0.1. The Anatomical Therapeutic Chemical (ATC) classification system was used for the classification of the active ingredients of medicinal drugs according to the organ or system which they act on. Of these 70 drugs, 55 drugs (78.6 %) acted on the nervous system (denoted by ATC code N), 11 (15.7 %) on the cardiovascular system (C), three (4.3 %) on the alimentary tract and metabolism (A), and one (1.4 %) on the musculoskeletal system (M). The nervous system drugs consisted of 20 psycholeptics, (ATC code N05), 20 psychoanaleptics (N06), eight analgesics (N02), six antiepileptics (N03), and one other nervous system drug (N07). The highest individual FTIs were associated with the opioids methadone, dextropropoxyphene, oxycodone, tramadol, and morphine; the antipsychotics levomepromazine and chlorprothixene; and the antidepressants doxepin, amitriptyline, trimipramine, and bupropion. Buprenorphine was not included in the study, because most of the fatal buprenorphine poisonings were due to smuggled tablets. A clearly increasing trend in FTI was observed with pregabalin and possibly with bupropion, both drugs emerging as abused substances.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fatal toxicity index of medicinal drugs based on a comprehensive toxicology database

2016

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“…Higher-thantherapeutic concentrations were identified using the therapeutic intervals recommended by TIAFT (TIAFT, 2010). Difficulties related to determining therapeutic vs toxic blood concentrations of prescription drugs have been highlighted previously (Jönsson et al, 2014).…”

Section: Methodological Considerationsmentioning

confidence: 99%

Non-prescribed use of psychoactive prescription drugs among drug-impaired drivers in Sweden

Tjäderborn

Jönsson

Sandström

et al. 2016

Drug and Alcohol Dependence

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Aims: To determine the prevalence of non-prescribed drug use among subjects suspected of drug-impaired driving with a confirmed intake of a psychoactive prescription drug, and to identify associated factors. Methods:Subjects investigated for drug-impaired driving in Sweden during 2006-2009 with a confirmed intake of diazepam, flunitrazepam, tramadol, zolpidem or zopiclone were identified using the Swedish Forensic Toxicology Database. Information on dispensed prescription drugs was retrieved from the Swedish Prescribed Drug Register. Non-prescribed use was defined as a confirmed use of a psychoactive prescription drug intake confirmed by toxicological analysis in a subject by whom it was not dispensed in the 12 months preceding the sampling. Prevalence proportions were calculated for each drug and logistic regression was used to identify associated factors. Results: In total, 2225 subjects were included. The median age (range) was 34 (15-80) years and 1864 (83.8%) subjects were male. Non-prescribed use was found in 1513 subjects (58.7%); for flunitrazepam 103 (76.3%), diazepam 1098 (74.1%), tramadol 192 (40.3%), zopiclone 60 (29.7%), and zolpidem 60 (21.2%) subjects, respectively. Younger age and multiple-substance use were associated with nonprescribed use, whereas ongoing treatment with other psychoactive drugs was negatively associated with nonprescribed use. Conclusions: Non-prescribed use of psychoactive prescription drugs was common in subjects suspected of drug-impaired driving and was more frequent for benzodiazepines and tramadol compared to zolpidem and zopiclone. The young and multi-substance users were more likely, whereas subjects with ongoing prescribed treatment with other psychoactive drugs were less likely, to use non-prescribed drugs.

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“…Nonetheless, the use of alternative matrices may reduce the influence of these confounding factors, and brain tissue has previously proved to be a viable alternative to blood [21][22][23][24][25]. The primary disadvantage of using brain tissue is the scarcity of reference concentrations available for comparison, since only 4 case reports with brain concentrations of nitrobenzodiazepines have been found [26][27][28][29], while femoral blood concentrations are more abundant [10,21,26,[29][30][31][32][33][34][35]. Our purpose was to establish postmortem brain and femoral blood reference concentrations of clonazepam, flunitrazepam, and nitrazepam and their 7-aminometabolites to aid future evaluations of postmortem results.…”

Section: Introductionmentioning

confidence: 99%