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Biomedical subjects

T Seppala

Publications and source records attributed to T Seppala.

16 recordsLinked to original sources
PubMed1996

Comprehensive drug screening in blood for detecting abused drugs or drugs potentially hazardous for traffic safety.

A comprehensive drug screening procedure for detecting drugs in the blood samples of car drivers suspected of driving under the influence of drugs, is presented. Amphetamines, cannabinoids, opioids, cocaine and benzodiazepines were screened by an immunological EMIT ETS system after acetone precipitation. Gas chromatographic methods were used to screen and quantitate basic, neutral and acidic drugs. The free amino groups of basic drugs were derivatized with heptafluorobutyric anhydride. Analysis was performed by a dual channel gas chromatograph combined with a nitrogen phosphorus and an electron capture detector. Phenyltrimethylammonium hydroxide was used as a methylathing agent for acidic substances before analysis with a gas chromatograph connected to a nitrogen phosphorus detector. A gas chromatograph/mass spectrometry was used as a common confirmation method. Tetrahydrocannabinol was quantitated after bis(trimethylsilyl)trifluoroacetamide derivatization, opiates after pentafluoropropionic anhydride derivatization and benzoylecgonine after pentafluoropropionic anhydride and pentafluoropropanol derivatization. Excluding benzodiazepines, which were confirmed with a gas chromatograph connected to a nitrogen phosphorus and an electron capture detector, the other basic drugs as well as the acidic drugs were confirmed after the same derivatization procedures as in the screening methods. Alcohols were quantitated in triplicate by gas chromatography using three different kinds of columns. Although urine is the most important specimen for screening abused drugs, it has only limited use in forensic toxicology. The described system is most useful for analyzing a wide range of substances, including illicit drugs, benzodiazepines, barbiturates, antidepressants and phenothiazenes in forensic samples when urine is not available.

Accidents, Traffic↗
PubMed1996

The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation.

STUDY OBJECTIVE: To determine the pharmacokinetics of oxycodone and the excretion of oxycodone and its metabolites noroxycodone and oxymorphone in uremic patients undergoing renal transplantation. DESIGN: Open study of the pharmacokinetics and excretion of oxycodone. SETTING: IV Department of Surgery, Helsinki University Central Hospital. PATIENTS: 10 uremic patients undergoing renal transplantation and 10 ASA status I patients undergoing general surgery. INTERVENTIONS: Intravenous (IV) oxycodone chloride 0.07 mg/kg was administered 30 minutes before induction of standardized anesthesia. Sampling of blood and urine was conducted for 24 hours. MEASUREMENTS AND MAIN RESULTS: The concentrations of oxycodone and noroxycodone in plasma and the 24 hour urine recoveries of the conjugated and unconjugated forms of oxycodone, noroxycodone, and oxymorphone were measured. Mean elimination half-life was prolonged in uremic patients due to increased volume of distribution and reduced clearance. Interindividual variation was very great. Plasma concentrations of noroxycodone were higher in uremic patients. Significantly smaller quantities of free oxycodone and noroxycodone and both free and conjugated oxymorphone were excreted in the urine in the uremic than in the control patients. CONCLUSIONS: Elimination of oxycodone is impaired in end-stage renal failure.

Adult↗
PubMed1990

Actions and interactions of hypnotics on human performance: single doses of zopiclone, triazolam and alcohol.

Actions and interactions with ethanol (0.8 g/kg) of triazolam (TRZ, 0.25 mg) and zopiclone (ZOP, 7.5 mg) on performance and memory were studied with 12 healthy young subjects. The randomized double-blind and crossover test sessions were carried out at 1-week intervals. Each time a set of performance tests and self-assessments on visual analogue scales were done before the treatment and 1.5, 3, 4.5, 6 and 8 h after it. The clinical test for drunkenness (CTD) was done 2 and 5 h after drug intake. Venous blood was sampled after each set of tests. Both TRZ and ZOP impaired coordinative and reactive skills, but not peripheral attention or body balance. They also impaired cognitive test performance (digit substitution, symbol copying), and lowered flicker fusion threshold. The psychomotor effects of the two hypnotics and measures of subjective sedation peaked at 1.5 and 3 h. Spatial memory was impaired by TRZ at 4.5 h. Cognitive tests and tracking were most sensitive to alcohol. Furthermore alcohol impaired both motor and vestibular aspects of the CTD while both ZOP and TRZ alone had only minor effects. Alcohol enhanced and prolonged the effects of both hypnotics without modifying their plasma concentrations. Drug-alcohol interactions were mainly additive though more obvious with TRZ. Interactions were evident also on the CTD. The hypnotics were free from residual psychomotor and cognitive effects at 8 h even after the coadministration of alcohol. It is concluded that ZOP and TRZ have a mainly additive interaction with alcohol but pharmacokinetic mechanisms do not seem to contribute essentially to this.

Adult↗
PubMed1988

Anxiogenic effect of yohimbine in healthy subjects: comparison with caffeine and antagonism by clonidine and diazepam.

Three placebo-controlled double-blind and crossover trials were carried out to analyze the effects of oral yohimbine (YOH) 0.8 mg/kg on mood and performance in 16 healthy students. Subjective assessments (visual analogue scales, side-effects on questionnaire) and objective measurements (digit symbols, flicker fusion, tapping, heterophoria) were done at baseline, and post treatment. YOH shifted the healthy subjects' mood towards feeling panicked, elevated systolic blood pressure and plasma prolactin concentrations, reduced digit symbol substitution, and induced drowsiness and passiveness. Caffeine (CAF) 10 mg/kg raised plasma cortisol and rendered the subjects slightly panicked. Muzziness, clumsiness, tremor, chills and nausea were common after both YOH and CAF. Diazepam (DZ) 0.3 mg/kg given at 60 min antagonized some effects of CAF but failed to antagonize YOH. Clonidine (CLO) 100 micrograms counteracted YOH effects on blood pressure but less the subjective and hormonal effects. CLO 200 micrograms partly antagonized the pressor, sedative but not the hormonal responses of YOH. DZ counteracted YOH effects on plasma cortisol on panic but not on other subjective measures or plasma prolactin. Since CLO did not abolish YOH-induced prolactin increase, it is suggested that these effects of YOH are mediated not only via adrenergic alpha 2-receptors; other mechanisms made important contributions.

Adult↗
PubMed1986

Dopamine metabolism in the cerebrospinal fluid of drug-free schizophrenic patients with and without cortical atrophy.

Cortical atrophy measured with computed tomography was observed in ten of 53 schizophrenic patients. Levels of homovanillic acid, dihydroxyphenyl acetic acid (DOPAC), conjugated DOPAC, and dopamine sulfate (DASO4) were measured in the cerebrospinal fluid of these patients during a drug-free evaluation. Patients with cortical atrophy had lower cerebrospinal fluid levels of homovanillic acid, DOPAC, and conjugated DOPAC but higher DASO4 levels. Combined measures of dopamine utilization were significantly lower in patients with cortical atrophy. We did not find significant clinical or demographic differences between the patients with and without cortical atrophy. Patients without brain atrophy who had dopamine utilization above the mean showed more psychotic symptoms and shorter duration of illness, while those with dopamine below the mean had more negative symptoms. We propose that both state- and trait-dependent variables affect dopamine turnover.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

The effects of amiflamine on cerebrospinal fluid amine metabolites in the rhesus monkey.

Amiflamine, a drug reported to be a reversible inhibitor of monoamine oxidase type A (MAO-A) selective for serotonergic neurons in rodents, was administered to rhesus monkeys over a 12-fold dosage range (0.5-6 mg/kg). Amiflamine produced small, essentially equivalent reductions in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA, 1-28%), 3-methoxy-4-hydroxyphenylglycol (MHPG, 4-26%), and homovanillic acid (HVA, 7-29%), suggesting that the effects of amiflamine are approximately equal on serotonin, norepinephrine and dopamine metabolism in nonhuman primates. Concentrations of amiflamine were very low in CSF 3-6 h after drug administration (less than 7 nmol/l), while those of its two major, biologically active metabolites were higher (22-150 nmol/l) and varied in relative proportions among the monkeys. Further investigation is required of some preliminary observations of a possible association between drug metabolite variations and the substantial individual differences in the amine metabolite changes following amiflamine treatment. MAO-B in platelets was not inhibited by 6 mg/kg amiflamine, indicating that MAO-A selectivity was maintained. At low amiflamine doses, early and transient increases in CSF 5-HIAA and HVA concentrations were observed, suggesting an amine-releasing effect of the drug within brain serotonergic and dopaminergic neurons.

Animals↗
PubMed1985

Rhesus monkey cerebrospinal fluid amine metabolite changes following treatment with the reversible monoamine oxidase type-A inhibitor cimoxatone.

The effects of cimoxatone, a reversible inhibitor of monoamine oxidase type A (MAO-A), on the deaminated metabolites of norepinephrine, dopamine, and serotonin were examined in continuously collected rhesus monkey cerebrospinal fluid (CSF). Cimoxatone, 0.5-8 mg/kg given PO, produced dose-proportionate reductions of 24-h mean CSF 3-methoxy, 4-hydroxy phenylglycol (MHPG) concentrations of 21%-52%. Homovanillic acid (HVA) concentrations also decreased 27%-55%, while CSF 5-hydroxyindoleacetic acid (5-HIAA) decreases were somewhat smaller (7%-32% from baseline). All three metabolite concentrations reached a nadir approximately 6-10 h after drug administration, and required over 40 h to gradually return towards baseline following drug discontinuation. HVA concentration reductions in particular persisted during the entire 24-h period following treatment and were the slowest to return to baseline values. CSF concentrations of cimoxatone and its MAO-inhibiting O-demethyl metabolite showed a parallel time course, peaking 6-10 h after treatment and persisting for up to 24 h in the case of cimoxatone and over 48 h for its metabolite. Single simultaneous time point determinations revealed 10-to 20-fold lower concentrations of cimoxatone and its metabolite in CSF compared to plasma 2 h after treatment. MAO-B activity in platelet-rich plasma was not inhibited by 8 mg/kg cimoxatone, indicating that this drug maintains MAO-A selectivity in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Antidepressants and driving.

Although some impairment of skills due to antidepressants has been observed clinically, the impact of antidepressants on traffic safety is at present unknown.

Antidepressive Agents↗
PubMed1985

Cerebrospinal fluid and plasma monoamines and their metabolites in euthymic bipolar patients.

In a search for trait markers in manic-depressive illness, we studied cerebrospinal fluid (CSF) and plasma monoamines and their metabolites in 25 lithium-treated euthymic bipolar patients (12 of whom provided unmedicated samples) and 30 normal volunteers. No group differences were found. Lithium treatment showed a trend to increase CSF hydroxy-indoleacetic acid (HIAA) (p = 0.05). Dopaminergic and serotonergic metabolites were highly correlated in the CSF of all three groups. We found no evidence of a trait marker for manic-depressive illness among CSF monoamines and their metabolites.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Liquid chromatographic assay for CSF catecholamines using electrochemical detection.

A liquid chromatographic assay for noradrenaline (NA), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in human and monkey cerebrospinal fluid (CSF) is described. The limits of sensitivity vary between 0.1-0.3 pmol/ml of each catechol. Within-day precision as indicated by mean coefficient of variation (CV) of five days varied between 8.0-14.8 for NA (3.0-0.1 pmol/ml), 6.9-27.4 for DA (6.0-0.1 pmol/ml), and 4.1-17.6 for DOPAC (30-1 pmol/ml). Between-day precision (CV) was estimated to be 12.3, 14.9 and 16.6 for 4 pmol/ml of NA, DA and DOPAC, respectively. The method was reproducible enough for reliable quantitation of CSF free NA and DOPAC levels at physiological concentrations while the sensitivity for DA was too low to measure the free amine in less than 3 ml of human lumbar CSF. After acid hydrolysis total (free + conjugated) DA can, however, be quantified in CSF. Ranges for CSF NA and DOPAC levels were 0.13-2.0 and 0.43-14.6 pmol/ml in normal volunteers (n = 72), 0.19-3.19 and 0.7-7.09 pmol/ml in untreated chronic schizophrenic patients (n = 52), and 1.1-3.2 and 9.8-22.7 pmol/ml in rhesus monkeys (n = 8), respectively.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Determination of conjugated dopamine in cerebrospinal fluid from humans and non-human primates with high performance liquid chromatography using electrochemical detection.

A simple and reliable procedure for the determination of conjugated dopamine (DA) in cerebrospinal fluid (CSF) is described. The conjugate, presumably a sulfate, is conveniently hydrolyzed in 0.4 M sulfuric acid at 95 degrees. Thereafter, dopamine is quantitated using HPLC with electrochemical detection. Sensitivity (0.5 pmol/ml) is sufficient for clinical studies. Only 400 ul of CSF are required for the assay. The within assay coefficient of variation was 3.2% for conjugated DA (concentration of 11.8 pmol/ml). In a material consisting of 261 samples of lumbar CSF from unmedicated psychiatric patients and normal control subjects, a concentration range of 1.3-21.7 pmol/ml was found. No clear differences were evident between the major diagnostic groups.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Acute effects of buspirone and alcohol on psychomotor skills.

Acute psychomotor and psychological effects of oral buspirone (10 and 20 mg) with and without alcohol (1 g/kg) were studied in a double-blind crossover trial in 12 young males. Treatments were administered at 1-week intervals in balanced order. Buspirone failed to impair objective performance but caused drowsiness and fatigue. The reference drug lorazepam (2.5 mg) impaired skills objectively, with less subjective impairment. Lorazepam, but not buspirone, interacted with alcohol.

Adult↗
PubMed1980

Clomipramine and doxepin in depressive neurosis. Plasma levels and therapeutic response.

The therapeutic efficacy, plasma levels, and psychomotor effects of tryptophan (L-tryptophan), clomipramine hydrochloride, and doxepin were investigate in "neurotically" depressed outpatients. The tricyclic antidepressants were significantly more efficacious than tryptophan in inducing remission. The alleviation of depression was preceded by an improvement of the initially slow information-processing rates in the depressed patients. The plasma levels of the tricyclics that were associated with a therapeutic response were significantly lower than those reported in "endogenously" depressed inpatients.

Adult↗
PubMed1979

Drugs, alcohol and driving.

Driving a car is a complex psychomotor and perceptual task which is subject to impairment by many factors. Several workers have studied the potential effects of drugs and alchol in crash production by epidemiological and laboratory studies. Both types of studies have yielded useful data but their limitations must be borne in mind when applying the results in pratice. Alcohol is obviously the most common single cause of traffic accidents. A progessively increased risk with increasing blood alcohol levels is well documented; fatigue and/or drugs increase this risk. Drugs are related much more infrequently to traffic accidents although on the basis of statistics, there is a potential risk with drug use. However, drugs alone are not as important as alcohol. The most significant drugs as regards driving risk are obviously certain antianxiety agents, hypnotics, stimulants, hallucinogens, marihuana, lithium and narcotic analgesics, as well as ganglionic blocking agents, insulin and sulphonylurea derivates. Patients should not drive after taking these drug until they are objectively fully alert and capable. Anticholinergics, antihistamines, antidepressants, antipsychotics, phenybutazone, indomethacin, alpha-methyldopa, and beta-blockers may in some cases cause central side effects (e.g. drowsiness) strong enough to affect driving performance. After starting therapy with these drugs, or after a significant change in dose, driving should be avoided until it is known that unwanted effects do not occur. Psychotropic drugs may enhance the deleterious effect of alcohol, and with most hypnotics there is still an effect the next morning. Some drugs (e.g. anticonvulsants or antiparkinsonian drugs) may make driving safer, but the disease (epilepsy, Parkinsonism, cardiovascular diseases, psychic disorders, etc.) ofter precludes driving. Clinicians should warn their patients about an impairment of driving skills if this is likely to occur due to the drug or the illness concerned.

Alcohol Drinking↗