Biomedical subjects

J Kanto

Publications and source records attributed to J Kanto.

At least 109 records · Page 6Linked to original sources

PubMed1985

Tofisopam and midazolam: differences in clinical effects and in changes of CSF monoamine metabolites.

The effect of two repeated oral doses of 100 mg tofisopam 15 mg midazolam and placebo on the concentrations of monoamine metabolites (MHPG, 5-HIAA, HVA) in lumbar CSF were studied in general surgical patients operated on under spinal analgesia (n = 12 in each group). Midazolam, but not tofisopam, improved the quality of sleep the night before surgery. Both active agents reduced preoperative anxiety of the patients, but tofisopam was without subjective sedative action. In the placebo group, in contrast to the active drug groups, there was a slight positive correlation between the MHPG concentration and degree of anxiety before surgery. The only significant difference in the monoamine metabolites in lumbar CSF was found in the concentrations of HVA between tofisopam and placebo treated patients. The lower HVA concentrations suggest that the curious 3,4-benzodiazepine derivative, tofisopam, modifies central dopaminergic activity.

Aged↗

PubMed1985

Serum concentrations and urinary excretion of lidocaine and its two desethylated metabolites after spinal anaesthesia using lidocaine or lidocaine with phenylephrine.

In 13 patients undergoing transurethral prostatic resection under spinal anaesthesia with heavy lidocaine or with heavy lidocaine plus phenylephrine hydrochloride, the serum concentrations of lidocaine, monoethylglycinexylidide and glycinexylidide and their renal excretion were measured with a HPLC method. Seven patients were given lidocaine alone 1.25 mg/kg and six lidocaine 1.25 mg/kg mixed with phenylephrine hydrochloride 3 mg. There was no significant difference between the two groups either in the serum levels of lidocaine or in the renal excretion rate of lidocaine and its metabolites. This finding gives support to the opinion that phenylephrine in low doses has no prolonging effect on spinal anaesthesia performed with heavy lidocaine.

Aged↗

PubMed1985

The usefulness of radioreceptor assay and gas liquid chromatography in pharmacokinetic studies on midazolam.

The usefulness of radioreceptor assay (RRA) in the pharmacokinetic studies on midazolam - the first benzodiazepine with water-soluble salts - was compared with that of gas liquid chromatography (GLC) in 18 patients operated on under local anesthesia in supine position. There were no significant differences observed in the serum levels determined with these two methods after a single i.v. injection of midazolam 0.075 mg/kg although considerable variability was manifest. Similarly, the pharmacokinetic parameters did not differ from each other in view of the concentrations determined by RRA or GLC. The pharmacokinetics of midazolam were compared in three patient groups on the basis of the GLC determined concentrations: a) in pregnant patients operated on at term under epidural analgesia (group 1, n = 6), b) in nonpregnant women operated on under epidural analgesia (group 2, n = 6), and c) in 3 male and female subjects operated on under brachial plexus blockade (group 3). The total serum clearance, the most important pharmacokinetic parameter, was highest in group 1 patients and lowest in group 3. However, these significant differences were not reflected so clearly in the elimination half-life of midazolam. There were no differences in tissue distribution (Vd alpha, Vd beta) between the three patient groups. A highly significant correlation was observed between the serum concentrations and sedative effects of midazolam. Midazolam is a short-acting sedative-anxiolytic agent with a rapid onset of action especially useful for patients operated on under local anesthesia. Apparently, the pharmacokinetic differences observed in this study are of no great clinical significance in single dose administration.

Adult↗

PubMed1985

Midazolam kinetics before, during and after cardiopulmonary bypass surgery.

Gas-chromatographically determined serum concentrations of midazolam were recorded before, during and after cardiopulmonary bypass in patients scheduled for a coronary artery bypass grafting operation. Following single 0.075 mg/kg (n = 6) and 0.15 mg/kg (n = 6) intravenous injections of midazolam, a mean distribution phase half-life of 3.4 and 4.4 min respectively was calculated. At the establishment of the bypass, a rapid drop in the concentration of midazolam was observed followed by a significant increase in concentration during the postperfusion period. The apparent mean elimination phase half-life (281 min) of midazolam was longer than that (about 120 min) measured in earlier works in young, healthy subjects. Thus the metabolism of midazolam during the postperfusion period appears to be slower.

Benzodiazepines↗

PubMed1985

Optimum dosage of lidocaine.

Lidocaine dosage recommendations vary widely. Severe heart failure adds to risk factors when attempting to reach the optimal therapeutic blood level. Fifty-two coronary care unit (CCU) patients, who were treated with lidocaine infusion after an initial bolus injection of 100 mg, were randomly selected for the study. Blood samples were drawn at 2, 6 and 18 h. The material was divided into four groups according to infusion rates: Group A (n = 15) 4 mg/min for 3 h and then 3 mg/min for 15 h, Group B (n = 10) 4 mg/min for 3 h and then 2 mg/min for 15 h, Group C (n = 9) 2 mg/min for 18 h and Group D (n = 18) according to clinical situation by a mean rate of 3.3 mg/min for 2 h, 2.5 mg/min for 4 h and 2.15 mg/min for 12 h. The mean serum lidocaine concentrations were in optimum therapeutic range of 2-4 mg/l in Groups A, B and D at every sampling time point. Percentage of the patients whose lidocaine concentrations at each sampling time were within the optimum range as follows: Group A 72, 67 and 52, Group B 70, 70 and 56%, Group C 0, 38 and 63% and Group D 38, 38 and 30%. Our material indicates that the optimal lidocaine infusion rate for CCU patients should be as in Group B.

Aged↗

PubMed1985

Epidural morphine as postoperative analgesic following cesarean section under epidural analgesia.

Low dosage epidural morphine (4 mg) provided adequate postoperative pain relief in patients undergoing elective cesarean section under epidural analgesia. In the control group (n = 11), all but one patient needed opiates postoperatively, but 9 patients out of the 11 receiving epidural morphine needed only mild analgesics or no analgesics at all, postoperatively. Slight nausea and facial itching were the most common unwanted effects in the epidural morphine group. Low dosage epidural morphine is a useful tool in postoperative pain treatment following cesarean section.

Adult↗

PubMed1985

Neurosecretory response of hypothalamic-hypophyseal axis to spinal anesthesia, minor gynecological surgery and irradiation.

The effect of spinal anesthesia, dilatation and curettage plus the first intracavitary radiotherapy or only that of intracavitary radiotherapy on growth hormone (HGH = the response of anterior pituitary) and arginine vasopressin (AVP = the response of posterior pituitary) levels was studied in 10 patients suffering from cervical or endometrial uterine cancer. Differing from earlier animal studies, irradiation had no effect on GH or AVP secretion, nor was there any change in the hormone levels following spinal anesthesia and dilatation and curettage. The neurosecretory response of hypothalamic-hypophyseal axis to spinal anesthesia and minor gynecological surgery appears to be minimal.

Adult↗

PubMed1984

Comparison of radioreceptor assay and radioimmunoassay for atropine: pharmacokinetic application.

A membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist quinuclidinyl benzilate (QNB). The KD for binding was 0.48 nM and Bmax was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine has been compared with a radioimmunoassay (RIA) for atropine. The RRA measures only the active component of atropine, 1-hyoscyamine and in this respect it differs from the RIA. As little atropine as 1.25 ng/ml (4.33 nmol/l) in a 25 microliters serum sample could be reliably assayed by the RRA. Using both assay techniques the pharmacokinetics of atropine was studied after a single 0.02 mg/kg i.v. dose given to 8 anaesthetized patients. The half-life calculated by the RRA was 3.7 +/- 2.3 h (m +/- SD) and by the RIA 4.3 +/- 1.7 h. Both the volume of distribution and the total clearance were higher according to the RRA than the RIA: 3.9 +/- 1.5 vs 1.7 +/- 0.71/kg and 15.4 +/- 10.3 vs 5.9 +/- 3.6 ml/min/kg, respectively. The AUC measured by the RRA and RIA was 29.8 +/- 18.9 and 103.9 +/- 110.7 micrograms X h/l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.

Adult↗

PubMed1984

Delayed cord clamping in cesarean section with general anesthesia.

Delay in cord clamping after vaginal delivery increases the blood volume of the newborn. Similar effects have also been observed in cesarean section births. Other effects of delayed cord clamping in cesarean section have not been investigated. In a group of nineteen healthy mothers having elective cesarean sections the cord clamping time was increased from 0 minutes to 1.5 and 3 minutes. Significantly lowered PO2 and pH and elevated plasma lactate levels were observed in infants with 3 minutes' delay when compared with the early clamping group. We conclude that, when healthy mature newborns are considered, early clamping of umbilical cord in cesarean section with general anesthesia is preferable to late clamping.

Adult↗

PubMed1984

Flunitrazepam as an induction agent in children. A clinical and pharmacokinetic study.

Flunitrazepam was studied as an induction agent in paediatric patients. The onset of action was slow and its efficacy uncertain following single doses of 0.03 mg kg-1(n = 4), or 0.04 mg kg-1 (n = 6) i.v. Long-lasting sedative effects were observed following operation. A strong anterograde but not retrograde amnesic effect was obtained, and a possible analgesic sparing property. Flunitrazepam has a faster and more extensive tissue distribution and a more rapid elimination (half-life about 12 h) in children than in adults.

Anesthesia, General↗

PubMed1984

Midazolam versus atropine plus pethidine as premedication in children.

The effects of oral midazolam or intramuscular atropine and pethidine used as premedication in two groups of 35 children over 5 years of age were studied. There was some evidence that the anxiolytic effect of midazolam was rather better than that of atropine plus pethidine, but, in other respects, subjective assessments in the two patient groups were similar. Intramuscular atropine caused tachycardia and subjective side-effects, nevertheless children appear to require anticholinergics during premedication because of excessive salivary secretion, especially during extubation. Oral midazolam is a new anxiolytic drug which can be used as an alternative to existing premedicant drugs, but, in children, it should still be combined with an anticholinergic agent. No correlation between serum levels of midazolam or atropine and their clinical effects was found.

Administration, Oral↗

PubMed1984

Pharmacokinetics and sedative effect of midazolam in connection with caesarean section performed under epidural analgesia.

Midazolam, the new investigational 1,4-benzodiazepine derivative with highly water-soluble salts, was studied as an anaesthesiological adjuvant in 11 patients undergoing elective caeserean section under epidural analgesia. I.v. administered midazolam, 0.075 mg/kg after delivery, caused a rapid and marked sedative effect, lasting for about 2-3 h. Short-lasting anterograde amnesia of about 30 to 60 min was reported as well. The serum levels of the parent drug and its active metabolites were determined in six cases by a radioreceptor assay and pharmacokinetic parameters were calculated on the basis of these levels by a two-compartment open model. Up to 3 h after midazolam administration, good correlation between the sedative effect and serum drug levels was found. The rapid but short-lasting action can be explained by the pharmacokinetic parameters of midazolam: a short distribution phase half-life (4.19 min), and a short elimination phase half-life (67.85 min) due to a high clearance value (13.18 ml/min/kg) and a moderate distribution volume (1.20 l/kg).

Adult↗

PubMed1984

Midazolam as adjunct to high-dose fentanyl anaesthesia for coronary artery bypass grafting operation.

The usefulness of midazolam as an adjunct during high-dose fentanyl anaesthesia was studied by following the changes in the haemodynamics and total body oxygenation after an intravenous injection of 0.075 mg/kg and 0.15 mg/kg of midazolam during the induction of fentanyl (75 micrograms/kg)-oxygen anaesthesia for a coronary artery bypass operation. These responses were then compared to the changes seen in patients receiving the same fentanyl anaesthesia without the midazolam. A rapid decline after the midazolam injection was seen in the mean systemic arterial pressure (24-32%--the lowest individual value was 45 mmHg (6.0 kPa)) and in the systolic and diastolic pulmonary arterial pressures (29-33% and 30-31%) in 1-3 min. As measured 10 min after the midazolam injection, a decrease from the baseline was seen in the stroke index (25-30%), in the left ventricular stroke work index (46-42%) and in the right ventricular stroke work index (48-61%). These haemodynamic variables remained on a lower level throughout the study period (40 min) in the midazolam patients as compared to the controls. The tissue oxygenation seemed to be sufficient in all groups during the study period. An intravenous injection of a relatively low dose of midazolam during the induction of high-dose fentanyl anaesthesia seems to be followed by rapidly increased venous pooling and a moderately to severely decreased systemic arterial pressure. Based on the results of this study, midazolam cannot be recommended as an adjunct during high-dose fentanyl anaesthesia.

Adult↗

PubMed1984

Obstetric analgesia: pharmacokinetics and its relation to neonatal behavioral and adaptive functions.

The neonatal pharmacokinetic and neurobehavioral properties of certain agents used in obstetric analgesia are reviewed (local anesthetics, opiates, inhalation agents, benzodiazepines). Fetal and neonatal pharmacokinetic alterations partly explain the neurobehavioral differences observed between different drug groups and ways of drug administration. The most effective and safest method with fewest neonatal neurobehavioral effects appears to be regional epidural analgesia performed with plain bupivacaine. The use of epidural opiates remains problematic. Inhalation agents and parenteral pethidine (meperidine) are still clinically useful alternative compounds in circumstances where epidural analgesia is not possible. Pharmacokinetically and according to neurobehavioral assessments, inhalation agents appear to be more attractive than pethidine. Benzodiazepines, especially after high or repeated doses, may cause the so-called floppy-infant syndrome, at least partly, due to a slow neonatal drug elimination.

Adaptation, Physiological↗

PubMed1984

Epidural and intrathecal opiates in obstetrics.

The use of epidural and intrathecal opiates in obstetrics is reviewed. Opiate receptors in the substantia gelatinosa of the spinal cord appear to be the main site of drug action after both epidural and intrathecal modes of drug administration. However, an additional systemic effect for this selective spinal analgesia cannot be excluded, especially after epidural drug administration. Contrary to that of general surgery patients, the response of pregnant women at term to epidural opiates is unpredictable. The action of the opiates is of short duration. There are at least three anatomical reasons for this phenomenon: an extensive epidural venous blood flow during pregnancy, visceral fibers (uterine contraction pain) located deeper in the substantia gelatinosa than somatic fibers (skin and peritoneal pain), and A delta fibers (uterine pain) which bypass opiate receptors in the substantia gelatinosa. After intrathecal injection of opiates, there was a strong analgesic action during delivery, but an unacceptable amount of side effects prevents their routine use. In post-cesarean patients, epidurally administered opiates are quite effective analgesics, but they still have one serious unwanted effect: respiratory depression of delayed onset. Thus, in routine obstetric practice, epidural or intrathecal opiates play only a limited role.

Analgesics, Opioid↗

PubMed1984

Use of atropine in connection with oral midazolam premedication.

The clinical significance of intramuscular premedication with 0.01 mg/kg of atropine in a procedure involving oral benzodiazepine premedication (15 mg midazolam the evening before surgery and on the morning of surgery) was investigated in a double-blind study. As far as sedation, apprehension, excitement, dizziness, emesis, and headache were concerned, there were no significant differences between group 1 (atropine) and group 2 (placebo) patients; however, both during and after anesthesia patients in group 1 had less excessive salivary secretion (especially during extubation). As a result of sympathetic overactivity, patients in group 1 had an increased heart rate and an increased incidence of supraventricular tachycardia. In group 1 intravenous infusion proved more difficult, and in addition, the patients complained more of subjective side effects (dry mouth). There was no significant correlation between the radioimmunologically measured serum concentrations and the clinical effects of atropine measured just before the induction of anesthesia. Substantial interindividual differences were found in these serum levels. From the anesthetist's viewpoint, atropine has both beneficial effects (antisecretory) and unwanted effects (cardiovascular effects). For the patient atropine caused only subjective unwanted effects. Midazolam, a new short-acting, sedative benzodiazepine derivatives, can be used without atropine as an oral premedicant.

Administration, Oral↗

PubMed1984

[Comparative study of the oral administration of flunitrazepam with oral pentobarbital and intramuscular administration of atropine and pethidine (meperidine) as premedication].

Thirty-four patients were allocated at random to treatment with 1 mg of flunitrazepam, orally, the night before operation, and 1 mg on the morning of operation (Group 1), and another 34 to treatment with 100 mg of pentobarbital, orally, the night before operation, followed by intramuscular atropine (0.01 mg/kg)+pethidine (meperidine 1 mg/kg) on the morning of operation (Group 2). The patients in both groups slept equally well. As far as apprehension and excitement (= anxiolytic effect) just before induction of anaesthesia were concerned, oral flunitrazepam proved to be markedly better than i.m. atropine+pethidine. There were no significant differences in cardiovascular variables between the two groups. From the anaesthesiologist's point of view, atropine had beneficial antisecretory effects, but, from the patients point of view, it caused only a subjective unwanted effect (dry mouth). In our opinion, oral flunitrazepam is a useful alternative agent for routine premedication. However, when used without i.m. atropine, excessive salivary secretion in some patients may occur and be disturbing, especially during extubation.

Administration, Oral↗

PubMed1983

Penetration of lidocaine and its active desethylated metabolite into cerebrospinal fluid in man.

Penetration into lumbar cerebrospinal fluid (CSF) of lidocaine and its active desethylated metabolite, monoethylglycinxylidide (MEGX), has been studied in 10 neurological patients after a single subcutaneous injection of 2 mg/kg prior to lumbar puncture. An HPLC method was used to assay lidocaine, MEGX and glycinxylidide (GX) in serum and CSF. The serum protein unbound fraction of lidocaine was determined by equilibrium dialysis. The mean peak serum lidocaine concentration was found 25 minutes after injection, and the corresponding peak CSF level occurred after 70 min. A similar slow penetration of MEGX into CSF was observed, which indicates low membrane permeability for these two agents. No GX was found. The steadily increasing CSF lidocaine/serum total lidocaine ratio throughout the period of study up to 120 min and the higher level in CSF than the corresponding unbound fraction of the total serum lidocaine indicate that serum protein binding is not the sole determinant of the penetration of lidocaine into lumbar CSF. Rapid accumulation in brain tissue and diffusion back into cerebral extracellular fluid and to lumbar CSF may also occur. The apparent slow membrane penetration of lidocaine and its desethylated metabolite may be one reason for the difficulty of controlling lidocaine infusion rates according to therapeutic effectiveness and side-effects.

Adult↗