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Biomedical subjects

O Dale

Publications and source records attributed to O Dale.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of hypothermia on the elimination of ethanol, diazepam and oxazepam in rat liver slice incubations.

The elimination of ethanol, diazepam and oxazepam which are metabolised by different enzymes, has been studied for 30, 60, 90 and 120 min at 37, 27, 17 and 7 degrees C in rat liver slice incubations. Ethanol elimination followed zero-order kinetics at all temperatures, while the benzodiazepines consistently displayed first-order kinetics. No sign of phase transition was observed in the respective Arrhenius-plots. Ethanol elimination was more temperature dependent than the elimination of diazepam, while the elimination of oxazepam was little influenced by temperature. This is shown by the temperature ratios (Q10) and energies of activation (Ea) of 1.76, 1.56, 1.24 and 40.5, 31.9, 15.2 for ethanol, diazepam and oxazepam, respectively. This means that ethanol, diazepam and oxazepam elimination was reduced by 25, 22 and 14%, respectively, for each 10 degrees C of temperature reduction, which is considerably lower than the commonly observed 50% reduction of enzyme activity. We conclude that observations made for one drug on temperature dependent elimination may not apply to other drugs.

Animals↗
PubMed1994

A prospective study of fertility and outcome of pregnancy after discontinuation of oral contraception in relation to elective orthopedic surgery.

OBJECTIVE: To evaluate the risk of unwanted pregnancies, their outcome and the rate of resuming contraception after discontinuation of oral contraception (OC) prior to elective surgery. DESIGN: A six months prospective follow-up study. SETTING: Orthopedic unit, operating on a total of 897 women during a period of 24 months. SUBJECTS: Seventy-eight healthy women in whom OC was stopped prior to elective orthopedic surgery. OUTCOME: Pregnancy rate, pregnancy outcome and reinstitution rate of OC. RESULTS: Complete outcome data are available for 73 (93.5%) of 78 women who were asked to participate in the study. Five pregnancies were reported, giving a cumulated six month pregnancy rate of 6.8%. Three pregnancies were completed to term, one was ectopic and one terminated by induced abortion. Within six months after the operation the cumulative user rate of oral contraceptives was 74.2%. None of the women were readmitted to hospitals for severe illness during the study period. CONCLUSIONS: The women resumed oral contraceptives relatively soon after their first post-operative menstrual cycle. This may explain why the pregnancy rate during the first six postoperative months appears low.

Abortion, Induced↗
PubMed1994

Biphasic time-course of serum concentrations of clomipramine and desmethylclomipramine after a near-fatal overdose.

A 27-y-old male was admitted deeply comatosed 5-6 h after taking approximately 15 g clomipramine. The prominent feature of the case was a biphasic course of clomipramine and desmethylclomipramine serum concentrations, possibly caused by delayed drug absorption. Clinically, 2 serious episodes requiring mechanical ventilation and aggressive pressor agent infusions occurred as the serum concentrations declined. However, the severe adult respiratory distress syndrome--related inflammatory process that required 4 w of intensive care may also be an explanation, although blood cultures were negative and neither liver nor renal functions were severely compromised.

Adult↗
PubMed1993

Hepatic elimination of diazepam: interactions with albumin, desflurane and sevoflurane.

We have studied the effect of sevoflurane and desflurane on the hepatic elimination of diazepam, by incubating slices of rat livers in a closed system. Protein free and protein containing (albumin 10 g litre-1) buffers were used to examine the effect of the anaesthetics on enzyme activity and diazepam binding to albumin. Both anaesthetics (in concentrations of 0.5, 1.5 and 3.0 mmol litre-1) reduced the elimination of diazepam slightly in the absence of albumin, while the presence of the protein increased elimination to a maximum of 30% at the greatest concentration of the anaesthetics. These data support previous observations that volatile anaesthetics may interact pharmacokinetically with both liver enzyme activity and drug binding to albumin.

Albumins↗
PubMed1993

Ovulation induction with low-dose follicle-stimulating hormone in women with the polycystic ovary syndrome.

Fifty infertile women with the polycystic ovary syndrome (PCOS) were treated for 66 cycles with low-dose FSH stimulation starting with 75 IU FSH for two weeks before eventual stepwise increases in the gonadotropin dose occurred. An unifollicular response was observed in 35 (53%) cycles and in 20 (30%) cycles there were two-three mature follicles. A multifollicular response (> 3 mature follicles) resulted in 11 (17%) cycles. One of the 66 cycles was complicated with the ovarian hyperstimulation syndrome. Twelve (22%) pregnancies were obtained following 55 completed cycles. All ongoing pregnancies were singleton gestations. The obese PCOS women required a longer period of stimulation and a higher amount of gonadotropin to achieve follicular maturation. However, there was no difference in cycle cancellation or pregnancy rate between obese and non-obese PCOS women. Thus low-dose FSH administration seems a safe stimulation regimen with a satisfactory conception rate in PCOS women.

Adult↗
PubMed1992

Single dose pharmacokinetics of trazodone in healthy subjects.

Eight healthy subjects were administered trazodone-HCl orally (100 mg) with and without food and by infusion in a three way cross-over study. Unchanged trazodone was determined in serum and urine by high performance liquid chromatography after an alkaline extraction. Absorption of trazodone was irregular in fasting subjects and improved after food intake. Food intake significantly decreased the maximum serum concentrations of trazodone from 1.88 +/- 0.42 to 1.47 +/- 0.16 micrograms/ml, and increased the time for reaching maximum concentration from 1.3 +/- 0.8 hr to 2.0 +/- 1.5 hr. No differences were observed in the total amount of trazodone absorbed with or without food with bioavailability values of 65 +/- 6 and 63 +/- 4 per cent, respectively. The apparent volume of distribution and total body clearance for trazodone were estimated to 0.84 +/- 0.16 l/kg and 5.3 +/- 0.9 l/hr, respectively. The terminal elimination half-life of 7.3 +/- 0.8 hr showed no significant differences between the different ways of administration. Urinary excretion of unchanged trazodone during 26 hr was less than 0.13 per cent of the administered dose, suggesting a high degree of trazodone metabolism. Earlier statements of enterohepatic circulation of trazodone and pharmacokinetic differences between males and females were not confirmed by the present study. Due to the irregular absorption in fasting subjects, trazodone should preferably be administered after food.

Absorption↗
PubMed1991

[Anesthetic gases, the ozone layer and the greenhouse effect. How harmful are the anesthetic emissions for the global environment?].

During the last decade, world society has acknowledged the harmful effects on the environment of the greenhouse effect and of depletion of the ozone layer, caused by industrial emissions of man-made compounds. Ozone depletion is caused mainly by chlorine compounds or nitrogen oxides released by degradation in the stratosphere. The greenhouse effect is caused by increased trapping of terrestrial heat radiation. Degradation of the anaesthetic vapours halothane, enflurane and isoflurane releases chlorine, and nitrous oxide degradation produces reactive nitrogen oxides. Nitrous oxide in particular, but also the vapours, absorb terrestrial radiation. The total discharge of anaesthetic vapours contributes to less than 0.01% of the total atmospheric chlorine load, and the annual Norwegian release of approximately two tons accounts for 0.2% of the world total. It is estimated that the total amount of nitrous oxide released from anaesthetics accounts for 0.05% of the greenhouse effect, while annual Norwegian emissions of nitrous oxide (less than 160 tons) comprise 0.2-0.4% of world total. Because of their favourable clinical properties and their modest contribution to ozone depletion and the greenhouse effect, medical use of inhalational anaesthetic agents should not be banned. However, low flow anaesthetic techniques should be employed, in order to reduce their negative impacts on the atmosphere.

Air Pollutants↗
PubMed1991

Metabolism and alkylating activity of thio-TEPA in rat liver slice incubation.

Precision-cut rat-liver slices were used to study the metabolism of the alkylating agent N,N',N''-triethylenethiophosphoramide (thio-TEPA). Exposure to high concentrations (1-10 mM) of thio-TEPA for 6 h did not prove to be toxic to the liver slices as indicated by insignificant leakage of potassium from the cells. The time course of the disappearance of thio-TEPA (initial concentration, 5.2 microM) from the buffer during incubation followed first-order kinetics. Formation of N,N'N''-triethylenephosphoramide (TEPA) apparently accounted for the elimination of thio-TEPA. Pretreatment of the rats with phenobarbital significantly increased the reaction rate. Conversely, pretreatment with the cytochrome P-450 inhibitor allylisopropylacetamide significantly reduced the metabolic rate. The elimination of thio-TEPA and formation of TEPA occurred independently of thio-TEPA concentration, which ranged from 5.2 to 104 microM. Thio-TEPA's oxo-analogue TEPA, which was not further metabolized, was the only metabolite identified. However, a significantly time-related increase in 4-(nitrobenzyl)-pyridine (NBP) alkylating activity was observed following incubation of liver slices with thio-TEPA but not after their incubation with TEPA. This may possibly indicate the formation of unknown active metabolites.

Alkylation↗
PubMed1988

Rat liver slices and diazepam metabolism: in vitro interactions with volatile anaesthetic drugs and albumin.

The influence of the volatile anaesthetic agents enflurane, isoflurane, halothane and the halothane metabolite trifluoroacetic acid was studied on the hepatic elimination of diazepam, by incubating precision-cut slices of rat liver in a closed system. The impact of anaesthetic-induced action on enzyme activity and diazepam binding to human serum albumin (HSA) was assessed in protein free and protein containing buffers, respectively. Human serum albumin reduced the elimination of diazepam by 12 and 50% at concentrations of 1 and 10 mg ml-1, respectively. In the absence of albumin, halothane 1 mmol litre-1 reduced the elimination of diazepam by 13%, whereas enflurane at 1.5 mmol litre-1 caused a reduction of 8%. No effect was seen from isoflurane 1 mmol litre-1 and trifluoroacetic acid 4 mmol litre-1. In the presence of the highest concentration of albumin, however, an increased elimination of diazepam of 24% resulted from exposure to enflurane and trifluoroacetic acid, while no statistically significant changes were seen for isoflurane and halothane. The present work supports the view that volatile anaesthetic agents may cause pharmacokinetic drug interactions by interference with both enzyme activity and drug protein binding.

Anesthetics↗
PubMed1987

Clinical pharmacokinetics of the inhalational anaesthetics.

At present, the most widely used inhalational anaesthetics are the halogenated, inflammable vapours halothane, enflurane, isoflurane and the gas nitrous oxide. The anaesthetic effect of these agents is related to their tension or partial pressure in the brain, represented at equilibrium by the alveolar concentration. The minimum alveolar concentration for a specific agent is remarkably constant between individuals. The uptake and distribution of inhalational anaesthetics depends on inhaled concentration, pulmonary ventilation, solubility in blood, cardiac output and tissue uptake. Inhalational anaesthetics are mainly eliminated by pulmonary exhalation, but significant amounts of halothane are removed by hepatic metabolism. Inhalational agents currently in use have acceptable pharmacokinetic characteristics, and clinical acceptance depends on their potential for adverse effects. Induction of anaesthesia with halothane is rapid and relatively pleasant and it is the agent of choice for paediatric anaesthesia. Between 20 and 50% is metabolised, and the parent drug is a potent inhibitor of drug metabolism. Post-operatively enzyme induction may follow. The major disadvantages of halothane are myocardial depression, propensity to evoke cardiac arrhythmias and the rare but serious halothane hepatitis. Induction and recovery from enflurane anaesthesia is rapid. Metabolism accounts for 5 to 9% of the elimination. The metabolic product inorganic fluoride may in rare cases cause renal toxicity. Enflurane is a weak inhibitor of drug metabolism at anaesthetic concentrations. Enflurane depresses circulation more than halothane by reducing both myocardial contractility and systemic vascular resistance, but cardiac rhythm is stable. Enflurane anaesthesia may, unlike the other agents, induce epileptic activity. Enflurane is widely used as replacement for halothane in adults. Despite its low blood-gas solubility, the airway irritability of isoflurane precludes a faster induction of anaesthesia than with halothane. Isoflurane is almost resistant to biodegradation. Myocardial contractility is maintained during isoflurane anaesthesia and cardiac rhythm is stable except for the occurrence of tachycardia in some patients. Isoflurane is the inhalational agent of choice for neurosurgical operations. Sevoflurane is an experimental ether vapour: induction and recovery is fast and pleasant. It is metabolised to the same extent as enflurane and subnephrotoxic concentrations of inorganic fluoride may result. Sevoflurane has fewer respiratory and cardiovascular depressant effects than halothane and may be a future alternative for paediatric anaesthesia.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, Inhalation↗
PubMed1986

The interaction of enflurane, halothane and the halothane metabolite trifluoroacetic acid with the binding of acidic drugs to human serum albumin. An in vitro study.

The interaction of the volatile anaesthetics enflurane, halothane and the halothane metabolite trifluoroacetic acid with the binding of two highly bound acidic drugs (warfarin, phenytoin) to albumin has been studied in vitro by equilibrium dialysis. Trifluoroacetic acid (TFA) inhibited the binding of both drugs to human serum albumin (HSA). Halothane, on the other hand, increased the binding of warfarin to HSA, while enflurane inhibited only the binding of phenytoin. It seems that the binding of the acidic drugs warfarin and phenytoin to HSA is more sensitive to the structures of the gases than for the basic drug diazepam which was previously shown to be equally affected by both gases. Furthermore, it seems that drugs competing for the same binding site (warfarin, phenytoin) may respond differently to conformational changes of the site. It is suggested that drugs bound to the "diazepam site" are more easily affected by the volatile anaesthetics than drugs bound to the "warfarin site".

Binding Sites↗