Biomedical subjects

J Kanto

Publications and source records attributed to J Kanto.

At least 55 records · Page 3Linked to original sources

PubMed1991

A comparison of dexmedetomidine, and alpha 2-adrenoceptor agonist, and midazolam as i.m. premedication for minor gynaecological surgery.

The effects of i.m. dexmedetomidine 1.0 micrograms kg-1, a new alpha 2-adrenoceptor agonist, were compared with those of i.m. midazolam 0.08 mg kg-1 and placebo on vigilance, anaesthetic requirements, haemodynamic state and plasma catecholamine concentrations in a double-blind placebo-controlled study in 107 healthy (ASA physical status I-II) women undergoing cervical dilatation and uterine curettage. The premedicants were administered i.m. 60 min before induction of anaesthesia with thiopentone. Nitrous oxide 70% in oxygen and thiopentone were used for maintenance. Both premedicants were tolerated well and no serious haemodynamic or other adverse events occurred. Dexmedetomidine caused moderate reductions in arterial pressure (maximally by 20%) and heart rate (maximally by 15%). Atropine was administered to two dexmedetomidine-premedicated patients because of bradycardia less than 45 beat min-1. Both premedicants decreased the plasma concentrations of noradrenaline by about 50%, but only dexmedetomidine attenuated the catecholamine response to anaesthesia and surgery. The thiopentone requirements were decreased significantly (P = 0.003) by both dexmedetomidine (17%) and midazolam (19%). Recovery times were 11.3 (SD 4.2) min after midazolam, 8.5 (5.2) min after dexmedetomidine and 5.6 (11.4) min after placebo (P = 0.006 between midazolam and placebo groups, other differences ns).

Adrenergic alpha-Agonists↗

PubMed1991

Intramuscular dexmedetomidine, a novel alpha 2-adrenoceptor agonist, as premedication for minor gynaecological surgery.

The effects of three different doses (0.5, 1.0 and 1.5 micrograms/kg) of dexmedetomidine, a novel alpha 2-adrenoceptor agonist, on vigilance, anaesthetic requirements, haemodynamics, and plasma catecholamine levels were investigated in a double-blind placebo-controlled study in 20 healthy (ASA physical status I-II) women scheduled for uterine dilatation and curettage (UD&C). The drug was administered intramuscularly 60 min before induction of anaesthesia with thiopentone, N2O/O2 (70/30%) and thiopentone was used for maintenance. There were no significant differences between the groups in thiopentone requirements, plasma adrenaline concentrations, or subjective or objective assessment of sedation before anaesthesia and UD&C. Blood pressure, heart rate, and plasma noradrenaline levels were reduced after dexmedetomidine, with three patients receiving atropine for excessive bradycardia (less than 45 beats min-1). The haemodynamic as well as the sedative effects of dexmedetomidine after surgery lasted until the end of the observation period, 4 h after the injection of the drug, indicating that intramuscular administration of this premedication agent may result in a longer than optimal duration of pharmacological actions in connection with short surgical procedures.

Adrenergic alpha-Agonists↗

PubMed1991

Pharmacokinetics and clinical response of hyoscine plus morphine premedication in connection with cardiopulmonary bypass surgery.

Plasma hyoscine and morphine levels and various pharmacodynamic responses have been examined in seven patients scheduled for a coronary-artery bypass graft. Hyoscine 0.006 mg kg-1 and morphine 0.20 mg kg-1 were administered intramuscularly as routine premedication. Surgery was performed using high-dose fentanyl anaesthesia (100 micrograms kg-1). The clinical responses followed were heart rate, blood pressure, subjective sedation and antisialogogue effect. The plasma hyoscine levels were determined by radioreceptor assay, and plasma morphine levels by liquid chromatography, both up to 24 h. The maximum levels of plasma hyoscine (6.6 micrograms l-1) and morphine (158 micrograms l-1) and the time they were reached (13.0 and 9.7 min, respectively) were comparable with the values obtained in earlier studies using young healthy subjects. After the start of cardiopulmonary bypass, significant decreases in plasma levels of both hyoscine and morphine were found. The elimination half-life of hyoscine in the plasma was 2.4 h, which is somewhat greater than obtained in earlier studies with young healthy patients under regional anaesthesia. Elimination of plasma morphine (t1/2el = 3.3 h) was not significantly altered by the procedure. The sedative and antisialogogue effects of the drugs appeared quickly and were significant, but no tachycardia or other side effects were observed. In conclusion, the kinetic properties of both hyoscine and morphine are suitable for routine use as premedicants before cardiac surgery.

Anesthesia, Intravenous↗

PubMed1990

Extradural administration of bupivacaine: pharmacokinetics and metabolism in pregnant and non-pregnant women.

We found a similar time (about 0.4 h) to maximum serum concentration after extradural administration of bupivacaine 1.78 (SD 0.27) mg kg-1 to six pregnant patients at term, 1.58 (0.13) mg kg-1 to six women younger than 65 yr and 1.50 mg kg-1 to six women older than 65 yr. There were no significant differences in terminal half-life. No unconjugated 4'-hydroxy-bupivacaine was detected in the serum and urine of pregnant patients, in contrast with the other groups. The pregnant patients had significantly greater serum concentrations of the N-dealkylated metabolite, N-desbutyl-bupivacaine (DBB), than the non-pregnant groups. In contrast with 4'-hydroxy-bupivacaine, no conjugated forms of bupivacaine and desbutyl-bupivacaine were detected in urine. The mean total urinary excretion of bupivacaine and its metabolites and their conjugates varied between 2.46 and 3.22% of the total dose administered in the three patient groups, indicating that both 4'-hydroxylation and N-dealkylation are minor metabolic pathways in man.

Adult↗

PubMed1990

Pharmacokinetics of i.m. glycopyrronium.

A sensitive radioreceptor assay was used to determine the pharmacokinetics of glycopyrronium following a single i.m. injection of 8 micrograms kg-1 in nine surgical patients. Rapid absorption was found, with a mean peak plasma concentration after 16.1 min and mean elimination half-life of 75.4 min. Almost half (49.3%) of the drug was excreted in pharmacologically active form in the urine within 3 h. A significant increase in heart rate (P less than 0.05) occurred in 15 min, lasting up to 60 min, and an antisialagogue effect in 10 min, lasting up to 8 h (P less than 0.05). There was no measurable glycopyrronium in lumbar cerebrospinal fluid samples (n = 9) taken 40 min after administration of drug.

Blood Pressure↗

PubMed1990

Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery.

The effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, on vigilance, thiopental anesthetic requirements, and the hemodynamic, catecholamine, and hormonal responses to surgery were investigated in healthy (ASA physical status 1) women scheduled for dilatation and curettage (D & C) of the uterus. Fifteen minutes before induction they received single iv doses of either dexmedetomidine (0.5 micrograms/kg; n = 19) or saline (n = 20) in a double-blind fashion. Anesthesia was induced with thiopental and maintained with N2O/O2 (70/30%) and thiopental. Dexmedetomidine was well tolerated and no serious drug-related subjective side-effects or adverse events were observed. The most prominent subjective effects were fatigue and decreased salivation. The total amount of thiopental needed to perform D & C of the uterus was reduced approximately 30% (from 456 +/- 141 mg [mean +/- SD] after saline to 316 +/- 79 mg after dexmedetomidine). This was mostly due to a smaller induction dose in the group receiving dexmedetomidine. Dexmedetomidine appeared to improve the recovery from anesthesia as measured by visual analogue scales (VAS) on fatigue and nausea. The plasma concentration of norepinephrine was decreased by 56% after dexmedetomidine implying decreased sympathetic nervous activity. Systolic and diastolic blood pressure were moderately reduced after dexmedetomidine administration. The authors conclude that dexmedetomidine preanesthetic medication decreases thiopental anesthetic requirements and improves the recuperation from anesthesia with no serious hemodynamic or other adverse effects. Further studies in patients undergoing more stressful surgery are indicated.

Adrenergic alpha-Agonists↗

PubMed1990

Pharmacokinetics of glycopyrronium in parturients.

A sensitive radioreceptor assay was used to determine the pharmacokinetics of glycopyrronium 6 micrograms/kg after intramuscular (deltoid muscle) administration in eight Caesarean section patients. A fast absorption rate was found with a mean maximum plasma concentration (Cmax) of 6.3 (SD 1.5) ng/ml, a mean time to Cmax (Tmax) of 10.0 (3.8) minutes and the elimination half-life (t1) of 33.4 (1.92). The respective AUC0-8 h value was 5.61 (1.27) hours ng/ml. This dose produced a significant increase in the maternal heart rate after 10 minutes (p less than 0.05) and an antisialogogue effect after 30 minutes (p less than 0.05) of the drug injection. Almost half of drug (48.3%) was excreted into the urine within 3 hours. There were no measurable levels of glycopyrronium in the lumbar cerebrospinal fluid (CSF) after 60 minutes of drug injection. The concentrations of glycopyrronium in the umbilical venous (0.28 (0.25) ng/ml) and in the umbilical arterial (0.18 (0.11) ng/ml) plasma after 86 minutes of drug injection were low and clinically insignificant, as was the case in the amniotic fluid (0.15 (0.08) ng/ml).

Adult↗

PubMed1990

Anticholinergic premedication in Finland 1988.

In order to investigate the present use of anticholinergic drugs in premedication, a questionnaire was sent to Finnish anaesthesiologists. The results indicate that there is significant variation between different parts of the country regarding the usage of these drugs. A decrease in routine use has taken place over the past 5 years. Half of the anaesthesiologists now routinely use anticholinergic drugs in premedication, while 69% were using them 5 years ago. Glycopyrrolate has gained popularity and was the most used drug. Most anaesthesiologists gave the anticholinergic premedication intravenously, briefly before induction.

Administration, Oral↗

PubMed1990

Biological correlates of mental stress related to anticipated caesarean section.

The relationships between self-reported assessments of acute anxiety and several biochemical and physiological indicators of stress reaction were investigated in pregnant women at term in connection with spinal analgesia for caesarean section. Fear and apprehension were statistically significantly associated only with blood pressure and with an increase in heart rate from the previous day. The subjective estimate of the quality of the preoperative night's sleep was negatively associated with biochemical plasma and cerebrospinal fluid (CSF) measures of sympatho-adrenal activity. The previously reported negative correlation between body height and 5-hydroxyindoleacetic acid (5-HIAA, an indicator of serotonin metabolism) in lumbar CSF was confirmed. The concentration of 5-HIAA in CSF was positively correlated with the levels of other acidic monoamine metabolites and cortisol in CSF. It is concluded that hormone and monoamine metabolite measurements in CSF and plasma have only limited usefulness as quantitative indicators of the intensity of preoperative fear and anxiety.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Radioreceptor assay for pharmacokinetic studies of glycopyrrolate.

A sensitive radioreceptor assay for the determination of glycopyrrolate concentrations in human plasma, urine and cerebrospinal fluid (CSF) is described. The applicability of the assay for kinetic studies in human was studied by determining the plasma concentrations and the renal excretion in three gynaecological surgical patients, who received 8 micrograms/kg of glycopyrrolate as a premedication intramuscularly. Tritiated N-methyl scopolamine was used to label the muscarinic cholinergic receptors in the membrane preparation obtained from the rat brain. The limit of detection of the assay was 70 ng/l in plasma, 2 micrograms/l in urine and 140 ng/l in CSF. There was no evidence of cross-reactivity of glycopyrrolate derivatives in clinical concentrations. A very rapid absorption was found with a mean maximum plasma concentration (Cmax) of 14.26 (range 12.02-16.97) micrograms/l and mean Tmax (time to Cmax) of 13.3 (range 10-15) min. and almost 50% of the dose administered was excreted into the urine within 3 hr. The CSF levels of glycopyrrolate were under detection limit. It is concluded that the sensitivity of the method is sufficient for pharmacokinetic studies of glycopyrrolate after therapeutic dosing.

Aged↗

PubMed1990

Propofol in cesarean section. A pharmacokinetic and pharmacodynamic study.

The induction properties and pharmacokinetics of propofol, 2.5 mg/kg i.v., were studied in twelve unpremedicated healthy pregnant patients at term. The onset of anesthesia was rapid (27.7 +/- 7.3 sec) and the quality of induction, maintenance of and rapid recovery from anesthesia were clinically very acceptable. On the basis of Apgar scores and blood gas analyses of the feto-placental unit, propofol appears to be a safe alternative to other available induction agents. The pharmacokinetics of propofol in pregnant women (n = 8) were described by a high value for total body clearance (mean 2189.6 ml/min) and a short elimination half-life (mean 24.1 min). There was no correlation between the pharmacokinetic parameters determined for propofol and some pharmacodynamic observations during the induction of anesthesia (n = 8), nor was there any correlation between drug levels of propofol in the feto-placental unit and blood-gas tensions and pH values or Apgar scores (n = 12).

Adult↗

PubMed1990

Intramuscular atropine in healthy volunteers: a pharmacokinetic and pharmacodynamic study.

In a randomized, double-blind, placebo controlled crossover study, the pharmacokinetics and some clinically important pharmacodynamic effects of intramuscular atropine (dl-hyoscyamine) were studied in 6 healthy male volunteers. The plasma concentrations of l-hyoscyamine were analyzed by radioreceptor assay (RRA) and the plasma concentrations of dl-hyoscyamine by radioimmunoassay (RIA). The absorption rate and the elimination rate of dl-hyoscyamine and l-hyoscyamine were comparable (tmax = 8.40 vs 8.67 min, t1/2el = 2.95 vs 2.43 h, dose 0.02 mg/kg) but the mean maximum plasma concentration of dl-hyoscyamine was 2.9 times and the mean AUC value 6.0 times higher than that of l-hyoscyamine which indicates a kinetic difference between the enantiomers. The concentrations of d-hyoscyamine calculated from the dl- and l-hyoscyamine concentrations reached maximum between 1 and 2 h after drug injection. The renal excretion of l-hyoscyamine occurred mostly in 6 h (34% of the dose) and no conjugated drug forms were detected. The increase in heart rate was observed only after the higher dose (0.02 mg/kg) and it was significant between 30 min and 2 h. The plasma concentrations of l-hyoscyamine and the change in heart rate expressed as percentages showed a linear correlation: concentrations under 0.5 micrograms/l caused slowing of rate, higher concentrations caused acceleration. Also, the antisialagogue effect (30 min-3 h) correlated with plasma concentrations.

Adult↗

PubMed1990

beta-Glucuronide and sulfate conjugation of scopolamine and glycopyrrolate.

The metabolism of scopolamine and glycopyrrolate was studied in 11 healthy parturients undergoing cesarean section. After a single intramuscular injection of scopolamine (5 micrograms/kg, n = 7) or glycopyrrolate (6 micrograms/kg, n = 4), the concentrations of the drugs in the urine were determined up to 8-12 h using a radioreceptor assay. This assay measures scopolamine and glycopyrrolate with their possible active metabolites. The effect of beta-glucuronidase and sulfatase incubation on the drug concentrations was also studied. The concentrations of scopolamine and/or its active metabolites were on the average 7 times higher after incubation indicating that beta-glucuronide or sulfate conjugation is an important metabolic pathway for scopolamine. On the contrary, the glycopyrrolate concentrations increased only slightly between 1 and 3 hours after the drug injection. Thus, beta-glucuronide or sulfate conjugation plays only a minor part in the metabolism of glycopyrrolate.

Female↗

PubMed1989

Comparison of propofol and thiopentone for induction of anaesthesia for elective caesarean section.

Propofol 2.5 mg/kg was compared with thiopentone 5 mg/kg as an induction agent for elective Caesarean section. Thirty-two healthy women with cephalopelvic disproportion were included in an open randomised study. The placental transfer of propofol was also studied in 10 other mothers given a single dose of 2.5 mg/kg. The induction characteristics and haemodynamic response to propofol and thiopentone were similar. Side effects were rare with both agents, but propofol caused more discomfort on injection compared to thiopentone. Recovery times were shorter after propofol as evaluated by time to orientation, recovery scoring after anaesthesia and measurements with the Maddox wing. Rapid placental transfer and significant fetal uptake were detected for propofol. There was no significant neonatal depression as assessed by Apgar scores and blood gas analyses. Propofol appears to be a suitable alternative to thiopentone as an induction agent for anaesthesia in elective Caesarean section.

Anesthesia Recovery Period↗

PubMed1989

Temazepam or midazolam for night sedation. A double-blind study.

The effects of oral temazepam (20 mg), oral midazolam (15 mg) and a placebo were compared for night sedation on the evening prior to surgery in a double-blind study. Patients in the placebo group had significantly worse sleep than those in the temazepam (p = 0.004) or midazolam groups (p = 0.04). There was no significant difference between the two drug groups, nor between the residual effects of the three treatments. Temazepam appears to be somewhat more effective than the ultrashort-acting midazolam in pre-operative transient insomnia.

Administration, Oral↗

PubMed1989

Propofol as an induction agent in children: pain on injection and pharmacokinetics.

The efficacy of lignocaine (1%) mixed with propofol in reducing pain on injection with propofol was studied in 40 children undergoing elective surgery in a double-blind, randomized comparison with glucose (5%). The pharmacokinetics of propofol in a single dose of 2.5 mg/kg was also studied in eight children participating in the same study. Lignocaine (1 mg) significantly reduced pain on injection compared to the control group (P less than 0.001). The induction characteristics of propofol were not affected by the lignocaine, and no undesirable interaction was found between the two drugs. The first-stage elimination half-life (t1/2 beta) of propofol in children was shorter (mean 9.3 +/- 3.8 (s.d.) min) than the values found in adults. This pharmacokinetic alteration may have clinical significance following repeated administration or continuous infusion of propofol.

Anesthetics↗

PubMed1989

Pharmacokinetics of scopolamine during caesarean section: relationship between serum concentration and effect.

The pharmacokinetics (radioreceptor assay, RRA) and some of the clinical effects of the anticholinergic agent, scopolamine, were studied in 16 parturients during caesarean section. Following a single 0.005 mg/kg intramuscular injection (deltoid muscle), a very fast rate of absorption was found with mean peak serum concentrations occurring after only 10 min (n = 6). Due to severe bradycardia, 0.5 mg of atropine i.v. had to be given in addition to the i.m. scopolamine treatment to one parturient. The RRA measured the total concentration produced by the two anticholinergic agents in both serum and urine. There was a fundamental difference in the diffusion of scopolamine through the placenta and the blood-lumbar (CSF-barrier (n = 15). There was significant drug penetration in the foeto-placental unit, indicating an efficient drug transfer to the child, but there were measurable levels of the drug in the lumbar CSF in only three cases. The apparent elimination phase half-life of scopolamine in serum was only around 1 h. The urinary excretion of scopolamine and/or its antimuscarinic metabolites lasted only for 6 h (2.63 +/- 1.14% of the dose). The onset of the clinical effects of scopolamine appeared to be delayed, but long-lasting in contrast to the rapid absorption and quick disappearance from the serum. Both the heart rate changes, sedative and antisialogogue effects and serum concentrations did not show any correlation. There appears to be a surprisingly great difference between the pharmacokinetic parameters and the clinical effects of scopolamine.

Absorption↗

PubMed1989

Glycopyrrolate: pharmacokinetics and some pharmacodynamic findings.

In the present study, a sensitive and reproducible radioreceptor assay (RRA) was used to evaluate the basic pharmacokinetic properties of glycopyrrolate, a quaternary amine with peripheral antimuscarinic activity. Based on the plasma levels after a single intravenous injection, 6 micrograms/kg (n = 6), the distribution phase half-life (2.22 +/- 1.26 s.d. min) and the elimination phase half-life (0.83 +/- 0.29 h) of glycopyrrolate were short due to the low distribution volume during the elimination phase (0.64 +/- 0.29 l/kg) and to the respectively high total plasma clearance value (0.54 +/- 0.14 l/kg/h). An intramuscular injection, 8 micrograms/kg (n = 6), was followed by a fast and predictable systemic drug absorption and clinical effects (heart rate increase, dry mouth). In this group the time to maximum plasma concentration (tmax) was 27.48 +/- 6.12 min and the maximum plasma concentration (Cmax) was 3.47 +/- 1.48 micrograms/l. After oral drug intake, 4 mg (n = 6), an apparently low and variable gastrointestinal absorption was found (tmax = 300.0 +/- 197.2 min, Cmax = 0.76 +/- 0.35 microgram/l), thus indicating that the oral route of drug administration is of no value as a routine premedication. The correlation between the plasma concentration of glycopyrrolate and the drug effects appears to be variable. Because of its sensitivity, the RRA method proved to be quite useful in evaluating the kinetics of glycopyrrolate and its relationship to various clinical effects.

Absorption↗