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Biomedical subjects

J Mørland

Publications and source records attributed to J Mørland.

At least 19 recordsLinked to original sources

Rearrest rates among Norwegian drugged drivers compared with drunken drivers.

The rearrest rates among Norwegian drugged (n=1102) and a group of drunken drivers (n=850) (BAC: 0.16-0.19%) apprehended during 1992, were 57% (n=629) and 28% (n=238), respectively, when followed prospectively for 7 years. The most important risk factors for recidivism among drugged drivers were previous arrests for drugged or drunken driving (rearrest rate among previous arrests: 73%, no previous arrest: 42%), multi-drug detection at selection (multi-drug: 62%, single drug: 41%), sex (male: 61%, female: 35%) and age (below 36 years: 60%, 36 years and older: 44%). Most of the recidivist drugged drivers were rearrested during the year of selection (21%), followed by 13, 7 and 6%, retrospectively, during the following years. When followed both retrospectively and prospectively for a period extending from 1984 to 1998, 71% (n=779) and 40% (n=344) of the selected drugged and drunken drivers, respectively, were arrested two or more times.

Adolescent↗

Urinary excretion of diazepam metabolites in healthy volunteers and drug users.

Urinary excretion profiles of diazepam metabolites were investigated. The subjects were healthy volunteers receiving one single 10-mg dose of diazepam or drug abusers starting a prison sentence. Urinary excretion of metabolites was analysed by immunological screening, liquid chromatography and gas chromatography-mass spectrometry. Relating the metabolite concentration to creatinine concentration in the specimens decreased sample-to-sample variations. In some cases such correction could protect a subject from erroneous accusations of a new intake.

Adult↗

[Centrally acting muscle relaxants and traffic hazards].

BACKGROUND: An increasing number of the centrally acting muscle relaxants were withdrawn from the Norwegian market during the 1988-98 period. The only drug in this group now marketed in Norway is carisoprodol. The National Institute of Forensic Toxicology in Norway analyses all blood samples from suspected drugged drivers. In later years there has been a marked increase in the number of blood samples testing positive for carisoprodol or meprobamate (the major metabolite). MATERIAL AND METHODS: 480 cases testing positive for central muscle relaxants in the years 1984-1998 were further studied. RESULTS: Compared with blood samples positive primarily for benzodiazepines, there were more women in the group (39% vs. 15%), and fewer drugs and less alcohol were detected. INTERPRETATION: The positive samples may indicate misuse or abuse due to the fact that high drug concentrations and concomitant use of benzodiazepines were frequent. This knowledge should have implications for doctors prescribing centrally acting muscle relaxants.

Accidents, Traffic↗

Toxicity of drug abuse--amphetamine designer drugs (ecstasy): mental effects and consequences of single dose use.

MDMA (3,4-methylendioxymethamphetamine) is the most commonly used substance within the 'ecstasy' group of drugs. MDMA interferes with serotonin and catecholamine transporters in the central nervous system to increase monoamine synaptic levels and thereby mediate the majority of its central nervous effects. These range from wanted effects like euphoria, central nervous stimulation, and feeling of closeness to mild hallucinations, impairment of cognition and co-ordination and further to serious reactions like agitation, disturbed and bizarre behaviour, and possibly psychosis. The full picture of the consequences of these transitory changes is not known. It has been assumed that the risk of being involved in fatalities and accidents during the state of MDMA influence is increased, but this possible risk increase has so far not been determined. Observations of the prevalence of MDMA involvement in cases of reckless driving and the MDMA blood concentrations measured indicate a risk increase comparable to that observed after use of amphetamines.

Accidents, Traffic↗

Lack of crosstolerance between morphine and morphine-6-glucuronide as revealed by locomotor activity.

Morphine-6beta-glucuronide is a major metabolite of morphine. We wanted to examine whether the effects related to opiate CNS stimulation could be mediated by different receptors for morphine and M6G by studying the development of crosstolerance between these two drugs. The effect studied was locomotor activity in C57BL/6JBom mice. We observed a dose-dependent development of tolerance to daily injections of morphine, with 20 micromol/kg giving the most rapid development of tolerance, apparent already on the second day of treatment. This was also observed for the same dose of M6G. Crosstolerance to M6G was measured both after 1 day pretreatment and 7 days pretreatment with morphine 20 micromol/kg, while the crosstolerance to morphine was tested only after 1 day pretreatment with M6G (20 micromol/kg). Lack of crosstolerance towards M6G after 1 day of morphine pretreatment was observed, whereas crosstolerance to M6G was observed after 7 days of exposure to morphine pretreatment. Crosstolerance after M6G pretreatment to morphine was observed. It was concluded that the main part of the effect caused by M6G was mediated through a specific M6G receptor.

Animals↗

[Detection of zopiclone in many drivers--a sign of misuse or abuse].

In 1998 zopiclone had a 42% share of the prescribed hypnotic drug market in Norway. The National Institute of Forensic Toxicology analyses all blood samples from suspected drugged drivers. The rise in zopiclone prescription was partly reflected in an increase in the number of drivers with zopiclone detected in the blood. We looked closer at the test results from 101 drivers with zopiclone detected in their blood in the January 1994 to April 1999 period. 60% had blood concentrations of zopiclone above the concentration observed after intake of therapeutic doses; 80% had higher blood concentrations than those expected 8 hours after intake of therapeutic doses. The majority of the drivers also tested positive for illegal drugs, prescription drugs with abuse potential, or alcohol. This indicates that zopiclone is misused or abused. Therefore the same caution should be applied when prescribing zopiclone as is applied when prescribing e.g. benzodiazepines.

Automobile Driving↗

[Repeated driving under influence].

Many drivers arrested for driving under the influence have earlier been arrested and convicted for a similar type of violation. The article reviews Norwegian studies on car drivers influenced by alcohol, other drugs than alcohol, and also drivers influenced by amphetamine. The results show that between 10 and 30% of drivers convicted for driving under the influence of alcohol, are rearrested two or more times for the same violation during a subsequent three year period. The recurrence rate is dependent on blood alcohol concentration at the selection time. The recurrence rate among drivers under the influence of drugs other than alcohol is significantly larger (up to 54%), when studied over the same three year period. The number of drivers influenced by amphetamine has increased dramatically during recent years. The recurrence rate among drivers influenced by amphetamine is on part with that of drivers using other drugs than alcohol. There are indications that an increasing number of drunken drivers have changed their abuse pattern during recent years from alcohol to illegal drugs such as amphetamine.

Alcohol Drinking↗

Urinary excretion of 11-nor-9-carboxy-delta9-tetrahydrocannabinol and cannabinoids in frequent and infrequent drug users.

Urinary excretion of 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH) and cannabinoids was monitored in prison inmates. Urinary specimens were collected up to five times per day. EMIT (cutoff 20 ng/mL; EMIT20) and gas chromatography (GC) (cutoff 10.3 ng/mL, LOD 1.4 ng/mL) were used for cannabinoid screening and THCCOOH confirmation, respectively. Urinary creatinine concentrations were recorded. Of the samples with positive EMIT screens, 78% were confirmed by GC analysis. The plotting of THCCOOH/creatinine ratios (THCCOOH/C) versus time gave smoother excretion curves than THCCOOH concentrations alone. Based on THCCOOH/C the first 5 days after the last reported intake, the mean urinary excretion half-life was 1.3 days in infrequent users, and a median of 1.4 days was found in frequent users. In the latter group, apparent terminal urinary excretion half-lives up to 10.3 days were observed. The last positive specimens were found after 4 days for THCCOOH with cutoff 15.0 ng/mL (NIDA/SAMSHA), 5 days for THCCOOH with cutoff 10.3 ng/mL, and 12 days for cannabinoids (EMIT20) in infrequent users and after 17, 22, and 27 days, respectively, in frequent users. Increases in urinary cannabinoids were sometimes found without concomitant increase in THCCOOH or THCCOOH/C. One subject admitted new cannabis intake, after which marked increases in THCCOOH and THCCOOH/C were observed. In others, new intake was suspected. Considerable variations between consecutive specimens were also observed in THCCOOH concentration and THCCOOH/C ratio without suspicion of a new intake.

Adolescent↗

The extent of postmortem drug redistribution in a rat model.

The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together with a specimen from the minced carcass. Drugs were analyzed by high performance liquid or gas chromatography. For phenobarbital, acetaminophen and carbamazepine the postmortem to antemortem blood drug concentration ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely related to the apparent volume of distribution for the drugs studied (p < 0.001). Accordingly, an apparent volume of distribution of more than 3-4 L/kg is a good predictor that a drug is liable to undergo postmortem redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.

Animals↗

Postmortem drug redistribution--human cases related to results in experimental animals.

Femoral blood is widely accepted as the most reliable postmortem specimen for drug analysis in forensic toxicology. There is considerable evidence that the drug concentrations in peripheral blood samples are closer to the antemortem level than the concentration in cardiac blood. In the present study drug concentrations measured in postmortem femoral and/or heart blood samples from eight cases were compared with the concentration found in serum samples from the same subject collected antemortem or perimortem. The drugs involved were amitriptyline, nortriptyline, imipramine, verapamil and chloroquine. Two additional cases with very early postmortem blood samples, as well as femoral blood samples from later autopsy, involved amphetamine and tetrahydrocannabinol. The results from the human cases were compared with results from rat experiments on similar drugs. The samples were analyzed by high performance liquid or gas chromatography. The cases with tricyclic antidepressants had a median postmortern femoral blood to antemortem serum drug concentration ratio of 3.3, the 95% reference range being from 1.1 to 6.0 (pooled data). Large variations of the ratios were seen. The extremes noted were a postmortem femoral blood to antemortem serum drug concentration ratio of 0.9 in a case with nortriptyline and 49 in the case with chloroquine. The low ratio in the former case could be due to attempted resuscitation, while the high ratio in the latter case is probably due to the extremely high apparent volume of distribution and a high blood to plasma concentration ratio for chloroquine. Accordingly, it is dubious whether the drug concentration found in femoral blood at autopsy can be accepted as being representative for the antemortem level. The results obtained from the human cases in the present study were generally in reasonable agreement with previous rat experiments, confirming that the animal studies when interpreted carefully, are indicative of the changes observed in man as well as a previous study in pigs. Studies on drug concentrations in pigs are not necessarily more representative for the findings in humans than experiments with a smaller animal like the rat. The postmortem concentration changes observed for tetrahydrocannabinol in man were found to be unpredictable, while in the accompanying experimental rat study there was a significant postmortem decrease in the tetrahydrocannabinol blood concentration measured in blood from the inferior vena cava. In special cases where the diagnosis of overdose is to be used as judicial evidence, a single sample of blood may prove insufficient. In such cases, analyses of several samples of blood and tissue will increase the possibility of reaching a correct conclusion, but reference values on drug concentrations in tissues are often missing.

Adolescent↗

Study of rearrests for drunken driving in Norway.

The National Institute of Forensic Toxicology (NIFT) in Oslo receives blood samples from all Norwegian drivers suspected of driving under the influence of alcohol. It is well known that a large proportion of the arrested drunken drivers are repeat offenders. The purposes of this investigation was to find the arrest rates (the percentage of subjects arrested once or more) among drunken drivers followed retrospectively and prospectively during the 11-year period 1984-1994 and the probability of 'abstaining' from becoming a recidivist during the 9 years subsequent to the year of selection. By examining the rearrest rates during the 3 following years for drivers selected in 1986, 1989, 1991 and 1992 we tried to look for major effects due to the change in the Norwegian road traffic act of 1988. Altogether 45% of the selected drunken drivers were arrested two or more times. Totally the '9-year survival rate' (i.e. not being rearrested) was 60% for drivers with blood alcohol concentration (BAC) selected from the interval 0.06-0.09%; 56% from BAC 0.13-0.16% and 51% from 0.26-0.29%. The data were further evaluated with respect to frequency of rearrest during 3 years after selection, and was around 30% in 1986, while it was lower for drivers selected in 1992 (19%). An explanation for the reduction in rearrest rate may be the changes in the road traffic act which took place in 1988.

Adolescent↗

Morphine-6-glucuronide-induced locomotor stimulation in mice: role of opioid receptors.

Morphine-6beta-glucuronide is a major metabolite of morphine with potent analgesic actions. To explore the importance of this opiate when administered as a drug by its own or in morphine action, we studied the locomotor activity response to morphine and morphine-6-glucuronide in drug-naive C57 BL/6JBom mice. The effects of administration of the two opiates on a battery of 7 different locomotor activities were studied and compared to saline controls. A dose of 20 micromol/kg morphine-6-glucuronide resulted in more locomotion than the same dose of morphine, while at higher doses (up to 120 micromol/kg), similar increases for most locomotor behaviours were recorded for both drugs. Pretreatment with naltrindole indicated that the delta-receptors play an equivalent but minor role in mediating both morphine-6-glucuronide and morphine hyperlocomotion. Administration of high naltrexone doses (10 mg/kg) completely abolished the locomotor stimulation induced by both opiates. However, at intermediate naltrexone doses of 0.25 and 0.5 mg/kg, morphine-induced behaviours was completely inhibited while morphine-6-glucuronide induced behaviours demonstrated partial resistance to naltrexone inhibition. The mu1-specific receptor antagonist naloxonazine caused 75% reduction of morphine induced behaviours and only 50% inhibition of morphine-6-glucuronide induced behaviors. Taken together our observations indicated general similarity but also marked differences between morphine and morphine-6-glucuronide with respect to opiate receptors mediating the locomotor stimulatory effect.

Analgesics, Opioid↗

Differential inhibition of morphine glucuronidation in the 3- and 6-position by ranitidine in isolated hepatocytes from guinea pig.

The influence of ranitidine on morphine metabolism, with special emphasise on the ratio between morphine-3-glucuronide and morphine-6-glucuronide was studied in isolated guinea pig hepatocytes. Ranitidine reduced the Kel of morphine dose-dependently with a maximum effect of 50%, and increased the relative concentration of morphine-6-glucuronide to morphine-3-glucuronide. These effects could be due to a direct or indirect effect on the conjugation enzymes involved, or an effect on the transport of morphine or glucuronides across cell membranes. The latter explanation was rejected on the basis of the observation that the ratios between intra- and extracellular concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide were not influenced by ranitidine. Increasing concentrations of ranitidine gradually decreased the morphine-3-glucuronide/morphine-6-glucuronide ratio by up to 21%. This could stem from interference of energy or co-substrate supply, or through direct effects on the different UDPGTases involved. The observation that the present effect on morphine glucuronidation was the opposite of that observed when administering a known co-substrate (UDPGA) depletor, indicated that in all probability the effect of ranitidine was a direct inhibition on the uridine 5'-diphosphate glucuronyltransferases involved, with a more pronounced effect for the isoenzymes responsible for the 3'-glucuronidation.

Animals↗

Postmortem amitriptyline pharmacokinetics in pigs after oral and intravenous routes of administration.

In this study we have evaluated the postmortem pharmacokinetics of amitriptyline (Ami) and metabolites in pigs after oral and intravenous administration, and the results are compared with previous studies in rats and humans. In addition a meticulous investigation of blood and tissue concentrations after postmortem intravenous infusion of Ami was undertaken. Of a total of 9 over-night fasted pigs, 3 were given 25 mg/Kg Ami orally, and another 3 pigs received an intravenous infusion lasting 1 h of 3.3 mg/Kg Ami prior to death. The final 3 pigs were sacrificed and then given the intravenous infusion after death. After approximately 5 h at room temperature, all carcasses were subsequently stored at 4-5 degrees C. Postmortem blood samples were collected at 0.25, 1, 2, 4, 8, 24, 48, and 96 h through an indwelling intracardial needle. Postmortem examination with blood and tissue sampling was performed 96 h after death. Analysis was carried out by high performance liquid chromatography with ultraviolet detection. Postmortem blood samples from the heart of the orally dosed animals revealed large and variable concentration increases of 99(30-243)% for Ami and 96(52-429)% for the main metabolite 10-OH-Ami at 96 h. In the intravenously infused live pigs heart blood Ami increased by 55(33-69)% and 10-OH-Ami increased by 232(76-240)%. Blood from the atria had significantly higher Ami concentrations than blood from both ventricles in the animals dosed while alive, and the drug concentration in femoral blood was higher than in heart blood (p < 0.01). In the orally dosed pigs the left lobe of the liver had significantly higher Ami levels than the right lobe. Tissue/blood Ami concentration ratios were generally lower than previously reported in rats and approximating the levels reported in humans. The animals infused intravenously after death demonstrated high drug levels in blood samples from central vessels, heart, lungs as well as cerebrospinal fluid and vitreous humour. This implies that the presence of a lethal concentration of a drug in just one sample of heart blood can prove worthless in a case where agonal drug infusion may have occurred.

Administration, Oral↗

Drugged driving, a review based on the experience in Norway.

Since 1959, the Norwegian Road Traffic Act has prohibited driving under the influence of drugs other than alcohol. On suspicion, the police request a clinical examination from any driver, as well as blood analyses for illegal and prescribed drugs affecting driving performance. During the last few years, there has been a marked increase in the number of drivers suspected of be influenced by drugs (1983, n = 900; 1995, n = 3329). The most commonly detected drugs are tetrahydrocannabinol, amphetamine, benzodiazepines and opiates. Multi-drug use is frequently found (> 60%). The occurrence of amphetamine (1991, n = 216; 1995, n = 937) and heroin (1991, n = 19; 1995, n = 172) has increased considerably. The frequency of drugged drivers apprehended in roadside traffic appears to be at least 10-fold higher in Norway than most other countries. This is probably mainly due to differences between national road traffic acts and the level of attention to the problem, and not to national differences in the prevalence of drugged driving.

Accidents, Traffic↗