Publications by authors named "Joachim Frost"

23 Publications

  • Page 1 of 1

Pitfalls of rapid testing for drugs of abuse.

Tidsskr Nor Laegeforen 2020 10 25;140(14). Epub 2020 Sep 25.

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http://dx.doi.org/10.4045/tidsskr.20.0696DOI Listing
October 2020

Severe Neurological Sequelae after a Recreational Dose of LSD.

J Anal Toxicol 2020 Oct 8. Epub 2020 Oct 8.

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim.

A young man with an unremarkable medical history suffered a seizure with subsequent cardiorespiratory arrest and severe neurological sequelae after ingesting a blotter. Analysis of a similar blotter and a serum sample obtained 3 hours after the event detected lysergic acid diethylamide (LSD) at the amount of 300 μg in the blotter and at a concentration of 4.0 ng/mL (12.4 nmoles/L) in serum. No other drugs were present in concentrations which may confer significant effects. In addition, no individual traits which would make the patient particularly susceptible to adverse LSD effects have subsequently been identified. This suggests that LSD may confer toxic effects in previously healthy individuals.
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http://dx.doi.org/10.1093/jat/bkaa145DOI Listing
October 2020

Post mortem tissue distribution of quetiapine in forensic autopsies.

Forensic Sci Int 2020 Oct 24;315:110413. Epub 2020 Jul 24.

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Clinical Pharmacology, St. Olav University Hospital, NO-7006, Trondheim, Norway.

The antipsychotic drug quetiapine is widely used, and increasingly prescribed off-label. Furthermore, quetiapine use has been linked to increased mortality rates, most likely due to a range of cardiovascular and metabolic adverse effects. This makes quetiapine a relevant substance in forensic toxicology casework. Quetiapine is believed to undergo significant post mortem redistribution. Herein, we present tissue distribution and concentration levels of quetiapine in post mortem whole blood, brain tissue, skeletal muscle, and liver tissue in a series of 14 quetiapine-implicated forensic autopsy cases along with the quetiapine concentrations determined in femoral whole blood in conjunction with the autopsies. Quantification was performed using liquid-liquid extraction and a validated UPLC-MSMS method. Six deaths were attributed to intoxication with quetiapine in combination with other substances; there were no quetiapine monointoxications. In eight cases, death was attributed to other causes than drug toxicity. In a majority of the cases, liver tissue contained the highest quetiapine concentrations, while whole blood levels were the lowest. Central (heart) blood concentrations were generally higher than peripheral (femoral) blood levels. Quetiapine concentrations in femoral blood correlated most strongly with concentrations in skeletal muscle. Otherwise, there was no consistent hierarchy of quetiapine tissue concentrations, and the tissue distribution showed no clear relationship with the length of the post mortem interval.
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http://dx.doi.org/10.1016/j.forsciint.2020.110413DOI Listing
October 2020

Post-mortem toxicological analyses of blood samples from 107 patients receiving opioid agonist treatment: substances detected and pooled opioid and benzodiazepine concentrations.

Addiction 2020 Aug 1. Epub 2020 Aug 1.

National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Department of Mental Health, P.O. Box 104, 2381, Brumunddal, Norway.

Aims: To present the substances and their concentrations detected post-mortem in patients receiving opioid agonist treatment (OAT) stratified by cause of death, estimate the pooled opioid and benzodiazepine concentrations using established conversion factors for blood concentrations from the Norwegian Road Traffic Act, and explore the association between drug-induced cause of death and the pooled opioid and benzodiazepine concentrations.

Design: Cross-sectional nationwide study.

Setting: Norway.

Participants: One hundred and seven patients who died during OAT (i.e. within 5 days after the last intake of OAT medication) between 1 January 2014 and 31 December 2015, with post-mortem femoral blood available for toxicology. Data were collected from hospital records, the Norwegian Cause of Death Registry and autopsy reports.

Measurements: Presence of alcohol and non-alcohol substances in the bloodstream at time of death, determined through records of toxicology of post-mortem femoral blood.

Findings: A median of four substances was detected across the causes of death. At least one benzodiazepine was detected in 81 (76%) patients. The median pooled opioid concentration was significantly higher in drug-induced deaths compared with other causes of death (362 ng/mL versus 182 ng/mL, P < 0.001), in contrast to the pooled benzodiazepine concentration (5466 versus 5701 ng/mL, P = 0.353). The multivariate regression analysis showed that only increasing pooled opioid concentration (ng/ML) was associated with increased odds of a drug-induced cause of death (odds ratio, 1.003; 95% confidence interval: 1.001-1.006).

Conclusions: In Norway, overall opioid concentration seems to play an important role in drug-induced deaths during opioid agonist treatment in patients prescribed methadone or buprenorphine. Patients prescribed buprenorphine tend to replace their agonist with full agonists, while patients prescribed methadone tend to have high opioid concentrations from methadone as the only opioid.
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http://dx.doi.org/10.1111/add.15211DOI Listing
August 2020

A Validated Method for the Simultaneous Determination of Quetiapine, Clozapine and Mirtazapine in Postmortem Blood and Tissue Samples.

J Anal Toxicol 2020 Apr;44(5):440-448

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway.

Psychotropic drugs are regularly present in cases of sudden, unexpected death. Such drugs also tend to express significant postmortem redistribution. To facilitate further investigation of this phenomenon, reliable quantitative methods applicable to multiple biological matrices are needed. We present a validated ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of quetiapine, clozapine and mirtazapine in postmortem whole blood, skeletal muscle, brain tissue and liver tissue using high-performance liquid chromatography-tandem mass spectrometry. Sample preparation was performed using liquid-liquid extraction. The validated ranges were 3.8-1534, 16-1960 and 13-1060 μg/L for quetiapine, clozapine and mirtazapine, respectively. Within-run and between-run accuracy (87.4-122%) and precision (CV 1.5-8.9%), matrix effects (95-101%) and recovery (35.7-92%) were validated at two concentration levels; 5.8 and 1227 μg/L for quetiapine, 25 and 1568 μg/L for clozapine and 20 and 849 μg/L for mirtazapine. Stability in a 10°C environment was assessed for treated samples of brain, liver and muscle tissue, showing deviations in analyte concentrations ranging from -8% to 9% after 3 days. The analyte concentrations in treated samples of whole blood stored at 4°C deviated by <5% after 5 days. The method was applied in three forensic autopsy cases implicating quetiapine, clozapine and mirtazapine, respectively, in supratherapeutic concentrations.
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http://dx.doi.org/10.1093/jat/bkaa002DOI Listing
April 2020

A woman in her forties who used addictive drugs in very high doses.

Tidsskr Nor Laegeforen 2020 01 2;140(1). Epub 2020 Jan 2.

Background: Following a surgical procedure, a female patient in her forties was prescribed opioids (oxycodone). The prescription escalated into doses that were extremely high, and at a level beyond any experienced previously, either at the various hospital units that were involved in the treatment or in the medical literature.

Case Presentation: The patient had no known history of substance abuse. After the surgical procedure, her general practitioner continued to prescribe the drug. The prescriptions escalated over the course of a couple of years, and at the time of our first contact with her, the doses had reached 11 000 mg oxycodone per day.

Interpretation: The high doses were tapered down over the course of around nine months. The spiralling prescriptions had several causes: the oxycodone treatment was initiated without a set plan for withdrawal; the patient had a change of general practitioner during the early stage; and she was a patient without any history of substance abuse. The costs escalated to the extent that the Norwegian Health Economics Administration eventually refused further payments. In such cases there is a need for close cooperation between the inpatient drug rehabilitation care unit and medical and pharmacological units.
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http://dx.doi.org/10.4045/tidsskr.19.0287DOI Listing
January 2020

Quetiapine is not a sleeping pill.

Tidsskr Nor Laegeforen 2019 Sep 16;139(13). Epub 2019 Sep 16.

Use of the antipsychotic drug quetiapine to treat sleep disorders has become widespread, also in Norway. Its efficacy is poorly documented, and even low doses may have substantial side effects. There is thus reason to warn against prescribing quetiapine for sleep.
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http://dx.doi.org/10.4045/tidsskr.19.0205DOI Listing
September 2019

Driver-related risk factors of fatal road traffic crashes associated with alcohol or drug impairment.

Accid Anal Prev 2019 Oct 12;131:191-199. Epub 2019 Jul 12.

Oslo University Hospital, Department of Forensic Sciences, P.O. Box 4950 Nydalen, NO-0424 Oslo, Norway.

Fatal road traffic crashes are often related to speeding, non-use of a seatbelt, and alcohol/drug-impaired driving. The aim of this study was to examine associations between driving under the influence of drugs and/or alcohol and driver-related risk factors that have been reported as significantly contributing causes of fatal road traffic crashes. The data were extracted from Norwegian road traffic crash registries and forensic toxicology databases. Drug/alcohol investigated car and van drivers and motorcycle riders fatally injured in road traffic crashes in Norway during 2005-2015 were included in this study (n = 772). Drug and alcohol concentrations corresponding to 0.5 g/kg alcohol in blood were used as the lower limits for categorising drivers/riders as impaired; 0.2 g/kg was the upper limit for being categorised as sober. Associations between driver-related risk factors and impairment from specific substance groups were calculated using multivariable logistic regression, adjusted for other substance groups, age, and sex, and were reported when the confidence intervals did not contain the value 1 or lower. Substances found in concentrations above the impairment limits were mainly alcohol (20%), medicinal drugs (10%: benzodiazepines, opioids, z-hypnotics), stimulants (5%: amphetamines, methylphenidate, and cocaine), and cannabis (4%: THC). The drug/alcohol-impaired drivers had compared to the sober drivers more often been speeding (68% versus 32%), not used a seatbelt (69% versus 30%), and been driving without a valid driver license (26% versus 1%). Logistic regression analysis showed that impairment from alcohol or stimulants (mainly amphetamines) was associated with all three risk factors, medicinal drugs with all except speeding, and impairment from cannabis (THC) with not having a valid driver license. Among motorcycle riders, drug/alcohol impairment was associated with not having a valid driver license and non-use of a helmet. At least one of the risk factors speeding, non-use of a seatbelt/helmet, and driving without a valid license were present among the vast majority of the drug/alcohol-impaired fatally injured drivers and riders, and also among more than half of the fatally injured sober drivers.
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http://dx.doi.org/10.1016/j.aap.2019.06.014DOI Listing
October 2019

Fatally injured drivers in Norway 2005-2015-Trends in substance use and crash characteristics.

Traffic Inj Prev 2019 6;20(5):460-466. Epub 2019 Jun 6.

a Department of Forensic Sciences , Oslo University Hospital , Oslo , Norway.

Norway introduced a "Vision Zero" strategy in 2001, using multiple approaches, aiming toward a future in which no one will be killed or seriously injured in road traffic crashes (RTCs). Official statistics show that the number of fatally injured road users has declined substantially from 341 deaths in 2000 to 117 in 2015. In-depth crash investigations of all fatal RTCs started in Norway in 2005. The aim of this study was to investigate whether fatal crash characteristics, vehicle safety features, and prevalence of drugs and/or alcohol among fatally injured drivers and riders has changed during 2005-2015, accompanying the reduction in road fatalities. Data on all car/van drivers and motorcycle/moped riders fatally injured in RTCs during 2005-2015 were extracted from Norwegian road traffic crash registries and combined with forensic toxicology data. The proportion of cars and motorcycles with antilock braking systems and cars with electronic stability control, increased significantly during the study period. The prevalence of nonuse of seat belts/helmets and speeding declined among both fatally injured drivers and riders. In addition, the prevalence of alcohol declined, though no significant change in the total prevalence of other substances was noted. The observed changes toward more safety installations in cars and motorcycles and lower prevalence of driver-related risk factors like alcohol use, speeding, and nonuse of seat belts/helmets among fatally injured drivers/riders may have contributed to the decrease in road traffic deaths.
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http://dx.doi.org/10.1080/15389588.2019.1616700DOI Listing
July 2020

Corrigendum to "Differences in combinations and concentrations of drugs of abuse in fatal intoxication and driving under the influence cases" [Forensic Sci. Int. 281 (2017) 127-133].

Forensic Sci Int 2018 02 30;283:219. Epub 2017 Dec 30.

Department of Forensic Sciences, Oslo University Hospital, Post Box 4950, Nydalen, N-0424 Oslo, Norway; Norwegian Centre of Addiction Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Post Box 1039, Blindern, N-0315 Oslo, Norway.

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http://dx.doi.org/10.1016/j.forsciint.2017.12.040DOI Listing
February 2018

Differences in combinations and concentrations of drugs of abuse in fatal intoxication and driving under the influence cases.

Forensic Sci Int 2017 Dec 6;281:127-133. Epub 2017 Nov 6.

Department of Forensic Sciences, Oslo University Hospital, Post Box 4950, Nydalen, N-0424 Oslo, Norway; Norwegian Centre of Addiction Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Post Box 1039, Blindern, N-0315 Oslo, Norway.

Background: In toxicology, international classification systems focus on single intoxicants as the cause of death. It is, however, well known that very few drug related deaths are caused by a single substance and that information concerning the drug concentrations as well as the combinations of drugs are essential in order to ascertain the cause of death. The aim of the study was to assess whether those prone to fatal intoxications differ significantly from chronic drug users - in terms of demographics and drug exposure patterns.

Material And Methods: Fatal psychoactive drug intoxications in Norway during 2012, where a forensic autopsy including toxicological analysis were performed, were included. Analytical findings in blood were compared with concentrations in blood from apprehended drivers under the influence of drugs and ethanol (DUID) during the same time period. The opioid and benzodiazepine concentrations were assessed as morphine and diazepam equivalents, respectively, in order to compare concentrations across the different groups.

Results: A total of 194 autopsy cases and 4811 DUID cases were included. Opioids were detected in around 90% of the drug intoxication cases, but in only 16% of the DUID cases. The number of substances detected in fatal intoxications was 4.9 compared to 2.6 in the DUID cases. The total opioid concentrations were significantly higher in the fatal intoxication cases compared to DUID cases (229ng/mL versus 56.9ng/mL morphine equivalents, respectively). Benzodiazepines were detected in 90% of the fatal cases. Only one fatal opioid mono-intoxication was found; a case with a very high methadone concentration (1238ng/mL).

Discussion: Mono-intoxication with heroin was not seen in any of the fatal intoxications in Norway, and single drug intoxications were rare (1.5%). Fatal intoxications were caused by a combination of drugs with significantly more substances as well as higher total drug concentrations among the fatal cases compared to the DUID cases. The combination of opioids and benzodiazepines seemed to represent an increased risk of death.

Conclusion: The total load of drugs influence the degree of intoxication and the total concentration level must be considered, including the total number of substances. Our findings imply that international statistics regarding an opioid being the main intoxicant should have a shift in focus towards combinations of drugs (especially opioids and benzodiazepines) as a major risk factor for fatal drug overdoses.
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http://dx.doi.org/10.1016/j.forsciint.2017.10.045DOI Listing
December 2017

Ingen grunn til å savne kodein!

Authors:
Joachim Frost

Tidsskr Nor Laegeforen 2017 10 2;137(18). Epub 2017 Oct 2.

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http://dx.doi.org/10.4045/tidsskr.17.0770DOI Listing
October 2017

Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, norcodeine, morphine and morphine glucuronides in a series of codeine-related deaths.

Forensic Sci Int 2016 May 4;262:128-37. Epub 2016 Mar 4.

Department of Laboratory Medicine, Children's and Womens's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

This article presents levels and tissue distribution of codeine, codeine-6-glucuronide (C6G), norcodeine, morphine and the morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem blood (peripheral and heart blood), vitreous fluid, muscle, fat and brain tissue in a series of 23 codeine-related fatalities. CYP2D6 genotype is also determined and taken into account. Quantification of codeine, C6G, norcodeine, morphine, M3G and M6G was performed with a validated solid phase extraction LC-MS method. The series comprise 19 deaths (83%) attributed to mixed drug intoxication, 4 deaths (17%) attributed to other causes of death, and no cases of unambiguous monointoxication with codeine. The typical peripheral blood concentration pattern in individual cases was C6G≫codeine≫norcodeine>morphine, and M3G>M6G>morphine. In matrices other than blood, the concentration pattern was similar, although in a less systematic fashion. Measured concentrations were generally lower in matrices other than blood, especially in brain and fat, and in particular for the glucuronides (C6G, M3G and M6G) and, to some extent, morphine. In brain tissue, the presumed active moieties morphine and M6G were both below the LLOQ (0.0080mg/L and 0.058mg/L, respectively) in a majority of cases. In general, there was a large variability in both measured concentrations and calculated blood/tissue concentration ratios. There was also a large variability in calculated ratios of morphine to codeine, C6G to codeine and norcodeine to codeine in all matrices, and CYP2D6 genotype was not a reliable predictor of these ratios. The different blood/tissue concentration ratios showed no systematic relationship with the post-mortem interval. No coherent degradation or formation patterns for codeine, morphine, M3G and M6G were observed upon reanalysis in peripheral blood after storage.
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http://dx.doi.org/10.1016/j.forsciint.2016.02.051DOI Listing
May 2016

Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

Clin Ther 2016 Jan 3;38(1):222-6. Epub 2015 Nov 3.

Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway.

Purpose: More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis.

Methods: The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification.

Findings: All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway.

Implications: The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries.
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http://dx.doi.org/10.1016/j.clinthera.2015.10.015DOI Listing
January 2016

Sudden Cardiac Death Following Use of the Synthetic Cannabinoid MDMB-CHMICA.

J Anal Toxicol 2016 Jan-Feb;40(1):86-7. Epub 2015 Sep 9.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway

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http://dx.doi.org/10.1093/jat/bkv110DOI Listing
August 2016

A validated method for simultaneous determination of codeine, codeine-6-glucuronide, norcodeine, morphine, morphine-3-glucuronide and morphine-6-glucuronide in post-mortem blood, vitreous fluid, muscle, fat and brain tissue by LC-MS.

J Anal Toxicol 2015 Apr 3;39(3):203-12. Epub 2015 Jan 3.

Department of Laboratory Medicine, Children's and Womens's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway Department of Clinical Pharmacology, St. Olav University Hospital, NO-7006 Trondheim, Norway.

The toxicodynamics and, to a lesser degree, toxicokinetics of the widely used opiate codeine remain a matter of controversy. To address this issue, analytical methods capable of providing reliable quantification of codeine metabolites alongside codeine concentrations are required. This article presents a validated method for simultaneous determination of codeine, codeine metabolites codeine-6-glucuronide (C6G), norcodeine and morphine, and morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem whole blood, vitreous fluid, muscle, fat and brain tissue by high-performance liquid chromatography mass spectrometry. Samples were prepared by solid-phase extraction. The validated ranges were 1.5-300 ng/mL for codeine, norcodeine and morphine, and 23-4,600 ng/mL for C6G, M3G and M6G, with exceptions for norcodeine in muscle (3-300 ng/mL), morphine in muscle, fat and brain (3-300 ng/mL) and M6G in fat (46-4,600 ng/mL). Within-run and between-run accuracy (88.1-114.1%) and precision (CV 0.6-12.7%), matrix effects (CV 0.3-13.5%) and recovery (57.8-94.1%) were validated at two concentration levels; 3 and 150 ng/mL for codeine, norcodeine and morphine, and 46 and 2,300 ng/mL for C6G, M3G and M6G. Freeze-thaw and long-term stability (6 months at -80°C) was assessed, showing no significant changes in analyte concentrations (-12 to +8%). The method was applied in two authentic forensic autopsy cases implicating codeine in both therapeutic and presumably lethal concentration levels.
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http://dx.doi.org/10.1093/jat/bku145DOI Listing
April 2015

Lethal poisonings with AH-7921 in combination with other substances.

Forensic Sci Int 2014 Nov 26;244:e21-4. Epub 2014 Aug 26.

Norwegian Institute of Public Health, Division of Forensic Sciences, Box 4404 Nydalen, 0403 Oslo, Norway.

AH-7921 is a synthetic μ-opioid agonist, approximately equipotent with morphine. We report the death of two young individuals after ingestion of AH-7921 in combination with other psychoactive drugs. In the first case a young man died shortly after ingesting Internet drugs. Toxicological analysis of post mortem peripheral blood revealed AH-7921 (0.43 mg/L), 2-FMA (0.0069 mg/L) and 3-MMC (0.0021 mg/L) as well as codeine (0.42 mg/L), codeine-6-glucuronide (0.77 mg/L) and acetaminophen (18.7 mg/L). The second case involved a young female found dead at home. The only positive finding at medicolegal autopsy was needle marks. Toxicological analysis revealed AH-7921 (0.33 mg/L), methoxetamine (MXE) (0.064 mg/L), etizolam (0.27 mg/L), phenazepam (1.33 mg/L), 7-aminonitrazepam (0.043 mg/L), diazepam (0.046 mg/L), nordiazepam (0.073 mg/L), and oxazepam (0.018 mg/L) in blood. In both cases intoxication with AH-7921 in combination with other psychoactive drugs was considered to be the cause of death.
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http://dx.doi.org/10.1016/j.forsciint.2014.08.013DOI Listing
November 2014

Forensic autopsies in a naturalistic setting in Norway: autopsy rates and toxicological findings.

Forensic Sci Int 2012 Nov 3;223(1-3):353-8. Epub 2012 Nov 3.

Department of Laboratory Medicine, Children's and Womens's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Autopsies can give valuable information about the cause of death, and represent an important tool for obtaining valid cause of death statistics. In particular, they may shed light on the circumstances of death in ambiguous and criminal cases. To address the need for information on current autopsy practices, forensic autopsy rates in two counties in Central Norway over the period 2007-2009 were assessed. To investigate toxicological findings that could possibly remain undisclosed without the performance of an autopsy, the impact of alcohol and drugs in forensic autopsy cases from this material was evaluated. The total forensic autopsy rate in this material was 3%. The forensic autopsy rates were low for natural deaths (1%), accidental falls (12%) and the heterogeneous category "other accidents" (21%), relatively high for accidental poisonings (84%), and less than adequate for road traffic accidents (57%). For suicides the forensic autopsy rate was 63%, and for recognized homicides 100%. The total forensic autopsy rate was higher for men than for women (5% vs. 2%), and decreased with age, being 38% in the age group <30 years, 23% in the age group 30-59 years, and 1% in the age group >59 years. Despite that Norwegian legislation and regulations regarding forensic autopsy requests are national, the forensic autopsy rates were generally lower in the county of Nord-Trøndelag than in Sør-Trøndelag, with most striking differences in suicide deaths (11% vs. 91%) and road traffic accidents (46% vs. 67%). This illustrates how autopsy rates, and possibly cause of death registries, might be susceptible to the influence of regional variations in law enforcement, with possible consequences for the quality and validity of cause of death statistics. Of the forensic autopsy cases where toxicological analysis was performed (361 of 364 cases) a total of 71% had positive toxicology results; 12% were positive for alcohol only, 44% were positive for drugs only, and 15% were positive for both alcohol and drugs. The toxicology results suggest that alcohol and drugs are important factors in sudden unexpected deaths, and that a thorough and comprehensive toxicological analysis is called for when investigating these deaths. Mean BAC in alcohol positive forensic autopsy cases was 1.7‰ (median 1.6‰, range 0.29-4.1‰). The average number of substances detected in toxicology positive cases was 2.6 (median 2, range 1-10). The by far most frequently detected classes of substances were (1) benzodiazepines, (2) opioids and (3) alcohol.
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http://dx.doi.org/10.1016/j.forsciint.2012.10.023DOI Listing
November 2012

[Opioid-induced pruritus].

Tidsskr Nor Laegeforen 2012 Oct;132(19):2180-1

Avdeling for klinisk farmakologi, St. Olavs hospital, Norway.

Pruritus is a common adverse effect of opioids, particularly after spinal and epidural administration. Although not harmful in itself, pruritus can be troublesome and affect patients' quality of life and motivation to continue opioid treatment. Several mechanisms have been postulated, but the pathogenesis of opioid-induced pruritus is still not fully understood. The µ-opioid receptor system seems to play a central role. Many treatment strategies have been tried in the management of opioid-induced pruritus, but none have proven to be completely satisfactory. Treatment with the µ-opioid receptor antagonist naloxone or the serotonin 5-HT(3) receptor antagonist ondansetron has documented effect.
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http://dx.doi.org/10.4045/tidsskr.12.0539DOI Listing
October 2012

Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine-related deaths.

Forensic Sci Int 2012 Jul 28;220(1-3):6-11. Epub 2012 Jan 28.

Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Compared to morphine and morphine-6-glucuronide (M6G), codeine and its other major metabolites codeine-6-glucuronide and norcodeine have weak affinity to opioid μ-receptors. Analgesic effects of codeine are thus largely dependent on metabolic conversion to morphine by the polymorphic cytochrome P450 isoenzyme 2D6 (CYP2D6). How this relates to toxicity and post-mortem whole blood levels is not known. This paper presents a case series of codeine-related deaths where concentrations of morphine, M6G and morphine-3-glucuronide (M3G), as well as CYP2D6 genotype, are taken into account. Post-mortem toxicological specimens from a total of 1444 consecutive forensic autopsy cases in Central Norway were analyzed. Among these, 111 cases with detectable amounts of codeine in femoral blood were identified, of which 34 had femoral blood concentrations exceeding the TIAFT toxicity threshold of 0.3mg/L. Autopsy records of these 34 cases were retrieved and reviewed. In the 34 reviewed cases, there was a large variability in individual morphine to codeine concentration ratios (M/C ratios), and morphine levels could not be predicted from codeine concentrations, even when CYP2D6 genotype was known. 13 cases had codeine concentrations exceeding the TIAFT threshold for possibly lethal serum concentrations (1.6 mg/L). Among these, 8 individuals had morphine concentrations below the toxic threshold according to TIAFT (0.15 mg/L). In one case, morphine as well as M6G and M3G concentrations were below the limit of detection. A comprehensive investigation of codeine-related fatalities should, in addition to a detailed case history, include quantification of morphine and morphine metabolites. CYP2D6 genotyping may be of interest in cases with unexpectedly high or low M/C ratios.
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http://dx.doi.org/10.1016/j.forsciint.2012.01.019DOI Listing
July 2012

[Sexual dysfunction induced by antidepressants].

Tidsskr Nor Laegeforen 2010 Oct;130(19):1930-1

Avdeling for klinisk farmakologi, St. Olavs hospital, 7006 Trondheim, Norway.

Sexual dysfunction is often concurrent with depressive disorders. Antidepressants may induce or augment sexual dysfunction as an adverse effect. About 40% of all patients treated with selective serotonin reuptake inhibitors, or other serotonergic agents, report such effects. If sexual dysfunction is not adequately dealt with it may contribute to noncompliance and thus compromise treatment. For the norepinephrine and dopamine reuptake inhibitor bupropion, the incidence of sexual adverse effects is equal to that for placebo. Additional treatment with bupropion, or switching to mirtazapin or bupropion, may be effective. Studies in men have documented positive effects of concomitant treatment with sildenafil or tadalafil.
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http://dx.doi.org/10.4045/tidsskr.10.0438DOI Listing
October 2010