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Biomedical subjects

L Kangas

Publications and source records attributed to L Kangas.

At least 109 records · Page 6Linked to original sources
PubMed1982

Comparison of midazolam and flunitrazepam for night sedation. A randomised double-blind study.

In a double-blind randomized study midazolam 15 mg and flunitrazepam 2 mg caused a significantly better night's sleep than placebo. Midazolam had a moderate sedative effect the following morning but, in other respects studied, no residual effects were found. In contrast, flunitrazepam decreased both the degree of apprehension and excitement the following morning. Flunitrazepam also inhibited salivary secretion and caused less cardiovascular changes than placebo or midazolam. The dose of thiopentone needed for induction of anaesthesia was significantly lower in those given flunitrazepam. The results show that midazolam is a potent sedative agent with a short duration of action.

Adult↗
PubMed1982

Flunitrazepam as an induction agent in elderly, poor-risk patients.

Great interindividual variation was found in response to flunitrazepam when the latter was used as an induction agent for general anaesthesia in elderly, poor-risk patients. However, no significant changes in the pharmacokinetics of this nitrobenzodiazepine derivative were found, which suggests that there are pharmacodynamic alterations in response to the drug with advancing age. A sudden but transient drop in blood pressure was found in three out of 12 patients, even although flunitrazepam was given, i.v., in low 0.3-0.5 mg incremental doses. A marked amnesic effect was found. No analgesics were needed in the recovery room (2 h), supporting the evidence that flunitrazepam has an analgesic-sparing effect. Flunitrazepam resulted, in general, in smooth induction of anaesthesia, but a long time was needed for induction.

Age Factors↗
PubMed1982

Comparison of old and new types of premedications.

By random allocation 41 patients received 1 mg flunitrazepam orally the night before operation and 1 mg on the morning of operation (group 1), and another 41 received 100 mg pentobarbital orally the night before operation, followed by intramuscular scopolamine (0.006 mg/kg) + morphine (0.02 mg/kg) on the morning of operation (group 2). All patients received 0.5 mg atropine intravenously just before the induction of anesthesia. The patients in group 2 were better sedated and had less salivary secretion than those in group 1, but otherwise both were comparable. In group 2 the induction requirements of thiopentone were significantly decreased in comparison with group 1, again indicating a more potent sedative effect. Because even in the total scoring of the results there was no significant difference between the two groups, the easy oral route of administration of flunitrazepam offers a clinically relevant alternative to the conventional premedication. In some of these E.N.T. patients who received flunitrazepam, intravenous atropine given just before the induction of anesthesia was unable to prevent salivary secretion. Oral benzodiazepine derivatives (flunitrazepam) appear to be useful before surgery as the old type of premedication (oral pentobarbital + i.m. scopolamine and morphine).

Administration, Oral↗
PubMed1982

Tofizopam: a benzodiazepine derivative without sedative effect.

In a single-blind randomized study 47 patients received 100 mg tofizopam orally as a premedication before minor surgery, 50 patients received placebo, an 50 patients no premedication. Both tofizopam and placebo significantly increased the subjective sedative effect of the patients, but there was no significant difference in any of the measured parameters between tofizopam and placebo. In another double-blind randomized study, 49 patients received 100 mg tofizopam three times orally before gynecologic operations and 49 patients received placebo. Compared with placebo, tofizopam had a stimulant action and decreased the excitement of the patients. The effect of tofizopam on apprehension + excitement was significantly better than that of placebo. According to these results, the active component seems to be an unknown metabolite of tofizopam causing a clear drug effect only after repeated oral doses of the parent drug. A slow accumulation in the central nervous system is also possible. In the drug response a wide interindividual variation was found.

Adult↗
PubMed1982

A comparative study of the clinical effects of oral flunitrazepam, medazepam, and placebo.

In a double-blind randomized study 40 patients received 1 mg flunitrazepam, 40 patients received 10 mg medazepam, and 40 patients received placebo p.o. the night before surgery. On the morning of surgery each patient received another identical oral dose of the product or placebo taken the previous night. On the average, the flunitrazepam group slept better, was better sedated, and was less anxious than the medazepam or placebo groups. Similarly, as a reflection of diminished autonomic reactions, the patients receiving flunitrazepam had fewer cardiovascular changes. Flunitrazepam significantly decreased the amounts of thiopentone needed for induction of anesthesia. Medazepam did not. The pronounced sedative, sleep-inducing, and anxiolytic effects of flunitrazepam appear to be of great clinical importance for its use in anesthesiology. Repeated administrations of medazepam seem to be required to produce an evident clinical effect of the drug, possibly via the slow accumulation of metabolites. The main difference between these two benzodiazepine derivatives as regards clinical response therefore seems to be pharmacokinetic in origin.

Adult↗
PubMed1982

A pharmacokinetic and pharmacodynamic study of flunitrazepam.

Flunitrazepam was given as an induction agent i.v. to 12 patients undergoing otologic operations. Pharmacokinetics were evaluated from serum samples at 5 min-72 h by 63Ni-EC-GLC. Pharmacodynamic characteristics were estimated subjectively by simple questionnaire and objectively by the anesthetist during and after anesthesia. The dose of flunitrazepam required for anesthesia varied from 14 to 33 (mean 21) micrograms/kg and was not related to age. The mean distribution volumes of flunitrazepam, calculated by the three-compartment open model, were Vd1 0.61 (SD = 0.36) l/kg, Vd2 1.4 (SD = 0.70) l/kg, and Vd3 3.6 (SD = 1.39) l/kg. The mean elimination half-life was 25 h and serum clearance was 94 ml/min. The maximum decreases in blood pressure during anesthesia correlated with the age of the patients. The general assessment of the anesthetist about this form of anesthesia was positive in 75% of the 12 cases. A clear anterograde amnesia was found.

Adult↗
PubMed1981

Dialysability of benzodiazepines by haemodialysis and controlled sequential ultrafiltration (CSU) in vitro.

The efficacy of haemodialysis and controlled sequential ultrafiltration (CSU) for the elimination of three hypnotic and 6 benzodiazepine drugs was compared in vitro. In comparison to haemodialysis the efficacy of ultrafiltration by CSU was poor, as the mean per cent of CSU/haemodialysis (mg/hr) for 5 benzodiazepines was only 0.6-4.0% and for three hypnotics, phenobarbital 3.4%, pyrithyldione 8.2% and glutethimide 2.5% of the haemodialysis values. In haemodialysis in vitro phenobarbital, pyrithyldione, glutethimide and chlordiazepoxide were significantly and markedly more dialysable than 5 other benzodiazepines. The mean clearance of six benzodiazepine derivatives was about 2 to 3 times higher at blood flow rates of 200 ml/min. than 100 ml/min. In CSU experiments in vitro it was possible to remove approximately (as the mean percent of the initial dose) only the amount of five benzodiazepines corresponding to the per cent of the protein unbound fraction in the plasma (correlation r = 0.975, P less than 0.01). Only low amounts of three hypnotics, especially glutethimide, were removed by CSU in vitro.

Benzodiazepines↗
PubMed1981

Effect of age on the pharmacokinetics and sedative of flunitrazepam.

Flunitrazepam (0.015 mg/kg) was injected i.v. into 20 patients, ages 19-79 years, as a sedative agent prior to epidural anesthesia. The concentrations of unchanged flunitrazepam in sea were determined by 63Ni-EC-GLC, and the pharmacokinetic parameters were calculated using the two-compartment open model. Age as such had no effect on the kinetics of flunitrazepam, but its sedative effect was clearly increased in the group over 60. No correlation between the serum level or elimination half-life and sedation was found. Generally, flunitrazepam's strong and rapid sedative effect renders it a useful adjuvant in connection with epidural anesthesia.

Adult↗
PubMed1981

A comparative study on the clinical effects of flunitrazepam and oxazepam as oral premedication.

The clinical effects of flunitrazepam and oxazepam as oral premedicants were tested in a double-blind study of 69 otorhinolaryngologic patients. Flunitrazepam had a somewhat higher sedative effect (p less than 0.10) and moderated the increase in systolic blood pressure significantly (p less than 0.005) more than did oxazepam, but as regards the other parameters tested no significant differences were found (sleep, apprehension, excitement, dizziness, emetic effect, headache, increase in heart rate, venepuncture). In some patients a profuse salivary secretion was observed despite intravenous injection of atropine just before the induction of anesthesia. Our results support earlier claims of flunitrazepam's relatively strong sedative and anxiolytic properties, but on the whole the difference in clinical effects of these benzodiazepine derivatives was not marked.

Administration, Oral↗
PubMed1980

Determination of methenamine in biological samples by gas-liquid chromatography.

Methenamine (hexamethylenetetramine), a urinary disinfectant, was determined in human plasma and urine by gas-liquid chromatography with a short (10 m) open-bore glass capillary column (split ratio 1:20) and nitrogen-selective detector. An almost quantitative recovery (92.1%) was achieved by simple dilution of water-containing samples (0.5 ml) with acetone (4.5 ml). After centrifugation an aliquot (2 microliter) of the supernatant was injected into the gas chromatograph. Selectivity and sensitivity of the nitrogen detector allowed the quantitation of unchanged methenamine in plasma and urine up to 24 h after a single therapeutic dose of 1 g. Reproducibility of the method was 7.6 and 2.1% (C.V.) in serum and urine, respectively. The time required for the analysis of one sample was approx. 2 min. Due to the simple extraction and short analysis time it was possible to analyze the samples concurrently with sample taking. Absorption of standard tablets and an enterosoluble preparation of methenamine hippurate was compared.

Adult↗
PubMed1980

Comparative in vitro investigations on the dialysability of hypnotic and psychotropic drugs by hemodialysis and controlled sequential ultradiffusion.

The efficiency of hemodialysis and controlled sequential ultradiffusion (CSU) for the elimination of toxic drug concentrations was tested by in vitro-investigations. In the 6 benzodiazepin derivatives tested, the clearance is markedly higher at a blood flow of 200 ml/min than at 100 ml/min. Pyrithyldione, glutethimide and phenobarbital are better dialysed than the benzodiazepines with exception of chlordiazepoxide. In comparison with hemodialysis, hemofiltration by means of CSU was less effective because of the small amount of ultrafiltrate obtained.

Anti-Anxiety Agents↗
PubMed1980

Transfer of free and conjugated oxazepam across the human placenta.

Six women, 13 to 16 weeks pregnant, and 12 women at 38 to 40 weeks gestation, received oral oxazepam about 12 h before legal abortion, by hysterotomy in the former and before elective caesarean section in the latter group. The concentrations of free and conjugated oxazepam in maternal and fetal plasma were determined by gas-liquid chromatography. In early pregnancy the mean ratio between the plasma concentration of total (free + conjugated) drug in the umbilical cord and a maternal vein was 0.6 whereas in late preganancy the ratio vein was 1.1. Both in early and late pregnancy, the free and glucuronide conjugate of oxazepam were found in the fetus at concentrations which indicated transplacental passage of the parent drug and its metabolite. There was great interindividual variation in the plasma levels both of free and conjugated oxazepam.

Adult↗
PubMed1980

Comparative study of the clinical effects of tofizopam, nitrazepam and placebo as oral premedication.

In a double-blind randomized study 47 patients received tofizopam 100 mg orally the night before operation, and 100 mg on the morning of operation; 49 patients received nitrazepam 5 mg and 50 patients received placebo. On average the nitrazepam group slept better and were better sedated than the tofizopam or placebo groups. Compared with placebo or nitrazepam, tofizopam decreased the excitement of the patients. The effect tofizopam on apprehension and excitement was significantly better than those of placebo or nitrazepam. Nitrazepam, but not tofizopam, significantly decreased the induction requirements of thiopentone.

Administration, Oral↗
PubMed1980

A comparative study on the clinical effects of flunitrazepam and lorazepam.

The clinical effects of flunitrazepam and lorazepam as oral premedicants were tested in a double-blind study in 81 gynaecological patients. Flunitrazepam showed a higher sedative effect (p < 0.05), but in regard to other parameters tested, no significant differences were found (sleep, apprehension, excitement, dizziness, emetic effect, headache, increase or decrease in systolic blood pressure, increase in pulse rate, venipuncture). In 9 per cent of the patients treated with lorazepam, a prominent muscular relaxation with slurred speech was observed, but in none of the cases treated with flunitrazepam. Our results support the earlier claims of flunitrazepam's relatively specific sedative property, but on the whole the difference in the clinical effects of these benzodiazepine derivatives is not marked.

Adult↗
PubMed1980

A comparative study of the clinical effects of pentobarbital and diazepam given orally as preoperative medication.

The clinical effects of pentobarbital, 100 mg, and diazepam, 10 mg, given orally as preoperative medications before dental surgery were tested in a double-blind study in 50 adult patients. The concnetrations of pentobarbital and diazepam (plus its three active metabolites) in plasma, measured by gas chromatography, were correlated with their clinical effects as assessed both subjectively and objectively (sedation, apprehension, excitement, dizziness, pre- and post-operative emetic effect, increase or decrease in systolic blood pressure, pulse rate, and ease of venipuncture). No significant difference in the effects of these two agents was observed, nor was there any obvious relationship between the concentration in plasma and clinical effect.

Adult↗
PubMed1980

A comparative study on the clinical effects of rectal diazepam and pentobarbital on small children. Relationship between plasma level and effect.

In order to test the possible differences in the clinical effects between benzodiazepines and barbiturates, 5 mg of diazepam and 60 mg of pentobarbital were used in a double-blind study as rectal premedication in 75 small children before major surgery. There were no significant differences between the two groups in the six parameters tested (demeanour in the anaesthetic room, preoperative emetic effect, response to venepuncture, degree of salivary suppression, postoperative state in the recovery room, postoperative emetic effect). The concentrations of pentobarbital and diazepam (and its 3 active metabolites) in the plasma were determined by gas chromatography and correlated with the clinical effects. No significant correlation was found between the total active benzodiazepine concentrations and the clinical effects of rectal diazepam. In contrast to diazepam, a weak but significantly positive correlation between the plasma concentrations of pentobarbital and the total score was found. Similarly, the plasma level of pentobarbital and the response to venepuncture and the degree of salivary secretion were in correlation with each other. In the plasma concentrations of both pentobarbital and total benzodiazepines, a wide interindividual variation was observed, indicating irregular rectal drug absorption.

Child, Preschool↗
PubMed1979

Long-term nitrazepam treatment in psychiatric out-patients with insomnia.

Psychiatric patients (N = 26) were treated chronically (from 1 week to 12 years) with nitrazepam, because of insomnia. The patients gave their subjective estimations of the effects and side effects of nitrazepam. The concentrations of nitrazepam in the plasma were measured by 63Ni-EC-gas-liquid chromatography. The pharmacokinetics of nitrazepam were compared between the psychiatric patients and healthy volunteers (N = 11). The steady-state concentrations and the half-life of nitrazepam in the psychiatric patients were comparable to those of the healthy volunteers. The subjective hypnotic effect of nitrazepam was mostly good or satisfactory and remained unchanged during long-term treatment. Only a few, mild side effects were reported. Nitrazepam does not seem to cause enzyme induction with lowered plasma levels and may therefore be of special value in the treatment of chronic insomnia.

Adult↗