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Biomedical subjects

J Kanto

Publications and source records attributed to J Kanto.

At least 217 records · Page 12Linked to original sources

Nitrazepam premedication for minor surgery.

Sixty-one patients received nitrazepam 5 mg by mouth on the night before operation, followed by 2.5 mg given on the morning of operation and were compared with 60 patients who received no premedication. All were undergoing either therapeutic abortion, by dilatation and curettage, or explorative curettage. The plasma concentrations of nitrazepam were determined by gas chromatography and compared with the clinical effects of the drug. The premedicated patients slept better on the night before operation, and were more sedated and less apprehensive. Headache was more frequent following nitrazepam. There was no significant difference between the groups in respect of dizziness and nausea. The unpremedicated patients had a faster average heart rate. There was no obvious relationship between the plasma concentration of nitrazepam and the quality of sleep, degree of sedation, apprehension, excitement or headache.

Administration, Oral↗

Plasma nitrazepam concentrations after an acute intake and their correlation to sedation and serum growth hormone levels.

Concentrations of nitrazepam in plasma were determined by gas chromatography in healthy volunteers after an acute peroral administration of nitrazepam (5 and 10 mg). Placebo tablets were also used, and an assessement of subjective drug effects was made during each medication. In addition serum growth hormone levels were determined. The peak plasma nitrazepam concentration was achieved at 120 minutes (46.9 +/- 3.2 ng/ml, mean +/- S.E.M.) after 5 mg of nitrazepam and at 180 minutes (82.8 +/- 10.5 ng/ml) after the dose of 10 mg. The half-life of nitrazepam in plasma ranged from 16.5 to 48.3 (mean 28.8) hours. A significant positive correlation was seen between the subjective sedative effects and the magnitude of the peak nitrazepam concentrations in plasma. This drug effect was highly significant when the plasma levels of nitrazepam were rising. The subjective sedative effects were more prominent after 10 mg than after 5 mg dose of nitrazepam. The plasma nitrazepam concentration was not significantly correlated with the subjective sedative effect the next morning, 12 hours after the drug intake. Serum growth hormone levels rose significantly during the study both after 5 mg and 10 mg nitrazepam doses (peak levels 16.3 +/- 4.0 and 12.7 +/- 3.1 ng/ml) and were significantly higher than after placebo administration (3.7 +/- 0.7 ng/ml).

Administration, Oral↗

Cerebrospinal-fluid concentrations of nitrazepam in man.

The concentrations of nitrazepam in the plasma and cerebrospinal-fluid (CSF) of 38 neurological patients were determined by gas chromatography 2-36 hours after a single 5 mg oral dose. The percentage ratio between the mean CSF and the plasma concentrations increased from 8.0% at 2 hours to 15.6% at 36 hours. This percentage rise was significant (P less than 0.001). The maximum concentration of nitrazepam in the plasma was 36.7 +/- 5.7 ng/ml (at 2 hours) and CSF 3.0 +/- 0.3 ng/ml (at 4 hours). During the beta-phase the half-life of nitrazepam in plasma was about 27 hours and in the CSF markedly longer about 68 hours, indicating a very slow elimination of nitrazepam from the CSF.

Administration, Oral↗

Passage of digoxin into cerebrospinal fluid in man.

The passage of digoxin into the cerebrospinal fluid (CSF) was studied in 8 infants on maintenance therapy with digoxin, 11 adult patients on long-term digoxin therapy, and 15 patients, previously non-digitalized, who were given 0.5 mg digoxin orally 1 hr to 12 hrs prior to lumbar puncture. Digoxin in the serum and CSF was determined by radioimmunoassay. In the infants a mean serum concentration of 1.5 ng/ml (range 0.7-2.3 ng/ml) was found, and a simultaneous mean CSF concentration of 0.5 ng/ml (range 0.3-1.1 ng/ml). In the adults on long-term therapy, the corresponding figures were 1.1 ng/ml (range 0.5-2.2 ng/ml) and 0.3 ng/ml (range 0-0.6 ng/ml). Among the 15 patients given a single oral dose of digoxin, detectable CSF concentrations (0.2-0.3 ng/ml) were found in five, 1-12 hrs after the administration of the drug. In three paediatric patients with hydrocephalus (3 months-5 years) digoxin therapy was started as an attempt to decrease CSF production. In these patients, the production of CSF was reduced by 17, 25 and 30%, respectively.

Aged↗

Carbamazepine: placental transport, tissue concentrations in foetus and newborn, and level in milk.

The pharmacokinetics of carbamazepine were studied during pregnancy and early childhood by investigating the extent of its placental penetration and its distribution in the foetal and neonatal tissues at autopsy. In foetuses the liver and kidney contained high levels of carbamazepine, whereas brain and lungs had low values. Carbamazepine-10,11-epoxide was also detected in the foetal circulation. At autopsy material, carbamazepine was localized mostly in the cerebral cortex, heart, liver and kidney. The concentration of carbamazepine in the milk was found to be 60 per cent of the respective plasma value.

Adolescent↗

Selective and non-selective beta-blockade in renin release.

The effects of two beta-adrenergic receptor blocking drugs, the non-selective propranolol and the beta1selective metoprolol, were studied on hemodynamics and plasma renin activity (PRA) of healthy volunteers in an ergometric exercise test. Oral doses of 160 mg of propranolol and 200 mg of metoprolol were tested against placebo. The drug plasma concentrations were determined. Heart rate and systolic blood pressure were equal and significantly lower during treatment with both active drugs when compared to placebo. The effect of drugs on exercise heart rate was correlated with the logarithm of drug plasma concentration with both propranolol and metoprolol. Propranolol, but not metoprolol, decreased the basal level of PRA. The ergometric exercise induced a significant rise in PRA after placebo but this increase was partially inhibited by the both active drugs. On the basis of these findings it is suggested that in man the basal level of PRA could be decreased mainly by blocking the beta2-adrenoceptors. Instead the exercise induced increase of PRA could be inhibited by blocking the beta1-adrenergic receptors.

Administration, Oral↗

Inotropic action and myocardial uptake of digoxin and betamethyldigoxin in isolated guinea pig atria.

The chronotropic and inotropic effects as well as the tissue levels of digoxin and methyldigoxin were studied in isolated guinea pig atria. Higher concentrations of methyldigoxin than of digoxin were required to cause arrhythmias. The inotropic potencies of the two glycosides did not differ from each another in equimolar concentrations in the organ bath. The increase in contractility correlated with the level of the glycoside in the organ bath and in the tissue. Digoxin was more effectively taken up by the heart tissue than methyldigoxin. Thus, when the tissue levels of the glycosides were the same, the contractility was greater after methyldigoxin than after digoxin.

Animals↗

Pharmacokinetics of methylergometrine (methylergonovine) in the rabbit and man.

Methylergometrine concentrations in human and rabbit plasma were determined by a new radioimmunoassay after a single intravenous injection (0.2 mg in man and 0.05, 0.1 and 0.2 mg/kg in rabbits). Both in man and in the rabbit methylergometrine disappeared quickly from the plasma with a mean T1/2alpha of 1.8 and 1.2-1.7 min. respectively. Similarly, the T1/2beta-values were 32.1 and 27.3-93.2 min. tthe mean maximal response in the rabbit uterus in situ after 0.05, 0.1 and 0.2 mg/kg intravenously dose was found at 40 sec., 26 sec., and 26 sec. after the drug administration, respectively, and the dose response curve was quite steep. A significant correlation was found between the dose and response.

Adult↗

Cardioselective (metoprolol) and non-selective (propranolol) beta-blockade and glucose homeostasis.

The effects of two beta-adrenergic receptor blocking drugs, the non-selective propranolol and the cardioselective metoprolol, on the concentrations of blood glucose, serum insulin (IRI) and growth hormone (GH) were studied in 8 healthy male volunteers both at rest and on exercise. The tablets of 160 mg of propranolol and 200 mg of metoprolol were tested against a placebo. The heart rate and systolic blood pressure were significantly lower during treatment with the active substances than with placebo. There were no significant differences between the blood glucose and serum IRI levels after the compounds and the placebo. A decreased insulin/blood glucose ratio after exercise was seen during metoprolol. The serum GH levels were of about the same magnitude after the three different treatments but the peak values were seen 30 and 40 minutes earlier after propranolol and metoprolol than after the placebo. The concentrations of the drugs in plasma did not correlate significantly with the changes in serum levels of IRI and GH in the exercise test. In the present acute test situation propranolol and metoprolol did not significantly affect glucose homeostasis and there were no apparent differences between the drugs.

Adult↗

Feto-maternal concentrations of diazepam and W-demethyldiazepam after intra-amniotic diazepam injection.

Ten milligrams of diazepam were injected intraamniotically in 8 mothers prior to therapeutic abortion between 12 and 19 weeks. The diazepam concentrations in the maternal plasma were comparable to those found after the same intramuscular diazepam dose to the mother. The concentration of diazepam in the amniotic fluid 12 to 18 hours after the injection was no longer significantly higher than in the maternal plasma. The concentrations of diazepam in the fetal plasma, liver and brain were comparable to the concentrations resulting from a 10 mg intramuscular diazepam dose to the mother about 2 hours before legal abortion. The feto-maternal ratio of diazepam was of same magnitude as after the intramuscular application to the mother. The results indicate that the disappearance of diazepam from the amniotic fluid in this stage of pregnancy occurs extraplacentally, through the mambranes into the uterine circulation. In the treatment of a fetus with drugs having properties similar to diazepam, intra-amniotic administration is no better than intramuscular administration to the mother.

Adolescent↗

Halothane anaesthesia in caesarean section.

The safety and efficacy of halothane anaesthesia were investigated in 97 caesarean sections using 0.4-0.6% halothane added to a mixture of 61 N2O/3-4 1 O2. The administration of halothane was initiated before intubation and terminated immediately prior to delivery. Only one patient reported memories from the operation. The mean Apgar score 1 min after delivery (8.5) was significantly better than that (8.2) in 100 caesarean sections in which a mixture of 71 N2O/3 1 O2 was used. In 17 caesarean sections, the halothane concentrations were examined after 0.9% halothane had been given for exactly 1 min after intubation. It was found that halothane reached and passed the placenta after only 1 min. The levels in the maternal artery and umbilical vein were comparable. The levels in the maternal artery, maternal vein and umbilical vein were markedly higher than in the umbilical artery, which indicated an accumulation of halothane in the foetal tissues. However, due to the vigour of the newborn, halothane concentrations 10 min after birth were very low. The half-life of halothane in the maternal circulation was approximately 1 min with the described method of administration. Blood gas determinations, which were made in seven newborns, proved satisfactory.

Anesthesia, Inhalation↗

[First aid at medical congresses].

The sixth International Congress of Pharmacology in Helsinki, July 1975, was held on a campus area 5 km from the nearest hospital. The congress was attended by 2 600 active participants and one thousand social members, traveling from 54 countries. The equipment at the Congress first aid station allowed for all kinds of emergency treatments, ranging from the care of minor complaints to cardiopulmonary resuscitation. A mobile intensive care unit was kept outside the station throughout the day and was also available at the major social events in the evening. The great majority of the symptoms necessitating a visit to the station were minor complaints. Most participants received their medication direct from the first aid station, the most common drugs being mild analgesics, anticholinergics and antibiotics. According to our experience, at a congress with 3 500 participants it is sufficient to have one physician present at the first aid station, or at least on call, and one to three additional first aid assistants. In general, it is of utmost importance to make adequate plans for the provision of medical as well as dental care at large congresses.

Congresses as Topic↗

The protein binding of diazepam and N-demethyldiazepam in patients with poor renal function.

The plasma protein binding of diazepam and of its main metabolite, N-demethyldiazepam, was measured in patients with renal disease and in healthy volunteers by ultracentrifugation. The total and non-protein bound concentrations of diazepam and N-demethyldiazepam, and the concentration of unconjugated oxazepam in the plasma were determined by gas chromatography after an oral 10 mg dose of diazepam. In the volunteers 98% of diazepam and N-demethyldiazepam were bound to the plasma proteins. In patients with renal disease the corresponding values were 92% and 95%, respectively. In the patients with renal disease no correlation could be found between the percent protein binding of diazepam or N-demethyldiazepam in the plasma and the serum creatinine concentration. Considerable variations in diazepam concentrations at 1 and 24 hours and in N-demethyldiazepam concentrations at 24 hours were found in the patients with renal disease. In contrast to the volunteers, 5 patients out of 28 with renal disease had measurable amounts of unconjugated oxazepam in the plasma. The deficient ability of the plasma proteins of patients with renal disease to bind diazepam may increase its clinical effect.

Adolescent↗

Spectrophotofluorometric method for quantitative determination of sulpiride in human plasma and urine.

A new spectorophotofluorometric method for the determination of sulpiride (S) in the human plasma and urine is described. The plasma concentrations (0--24 hours) and renal excretions (0--48 hours) of sulpiride were measured after Dogmatil forte (Schürholtz), or Sulpiril (Leiras) tablets both containing 200 mg of sulpiride, after two Sulpiril capsules (Leiras) containing 50 mg of sulpiride in each capsule, and after 20 ml Dogmatil saft (Schürholtz) and 20 ml Sulpiril mixt. (Leiras) both containing 5 mg/ml of sulpiride. There were no significant differences in the sulpiride concentrations in plasma or cumulative urinary excretion of sulpiride after Dogmatil forte (200 mg S) or Sulpiril tablet (200 mg S). Two Sulpiril capsules (100 mg S) produced significantly lower plasma concentrations of sulpiride at 3 hours than a Sulpiril tablet (200 mg S) and these were also lower at 4 and 6 hours than with either a Dogmatil forte (200 mg S) or a Sulpiril tablet (200 mg S). Two Sulpiril capsules (100 mg S) gave significantly higher plasma sulpiride concentrations from 1 to 6 hours than 20 ml Sulpiril mixt. (100 mg S) and from 2 to 6 hours higher than 20 ml Dogmatil saft (100 mg S). The plasma half-life of sulpiride measured after two Sulpiril capsules, 20 ml Dogmatil saft and 20 ml Sulpiril mixt., was 9.4 hours, 9.5 hours, and 10.2 hours, respectively. The renal excretion of sulpiride after two Sulpiril capsules (100 mg S) was significantly lower than after a Sulpiril tablet (200 mg S) from 8 to 48 hours, and also significantly lower than after a Dogmatil forte tablet (200 mg S) from 24 to 48 hours. Two Sulpiril capsules (100 mg S) gave significantly higher sulpiride urine concentrations from 8 to 24 hours than 20 ml Sulpiril mixt. (100 mg S) and from 24 to 48 hours than 20 ml Dogmatil saft (100 mg S). There was no significantly differences in this respect between either a Dogmatil forte tablet (200 mg S) and a Sulpiril tablet (200 mg S) or between Dogmatil saft (100 mg S) and Sulpiril mixt. (100 mg S). Comparied with a Dogmatil forte tablet, the bioavailability, calculated by the AUC24 for a Sulpiril tablet was 159%, for a Sulpiril capsule 118%, for Dogmatil saft 77%, and for Sulpiril mixt. 89%. The same values calculated from the sulpiride urine concentrations were 118%, 114%, 71%, and 67%, respectively. There were no significant differences in the blood pressure or heart rate of the volunteers during the experiment. 2 volunteers reported a sedative effect after a Dogmatil forte tablet.

Adult↗