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131.
Bromazepam, a relatively newly benzodiazepine with marked anxiolytic effects, was compared in a randomised, double-blind manner with diazepam for its effectiveness as an oral premedicant drug. A scoring system was used to assess sedation, relief of anxiety, nausea, and cardiovascular effects in two groups of women having gynaecological operations. No difference was demonstrated between the effectiveness of the two drugs. 相似文献
132.
Sixty children, aged 1—12 years, were investigated with regard to gastric pH and volume before general anaesthesia. Thirty children (group D) received diazepam 0.75 mg/kg b.w. rectally 1 h before anaesthesia. Thirty children (group L) received a "lytic cocktail" (pethidine 28 mg, promethazine 7 mg, chlorpromazine 7 mg per ml) 0.05 ml/kg b.w. intramuscularly 1 h before anaesthesia. The pH values were significantly higher and the amount of gastric juice was significantly lower in group L compared to group D. The number of children in group L with gastric juice volume exceeding 0.4 ml/kg and the number of children with pH less than 2.5 was significantly smaller compared to group D. The number of children with both gastric pH less than 2.5 and gastric juice volume greater than 0.4 ml/kg was significantly smaller in the group receiving "lytic cocktail" intramuscularly compared to the group receiving diazepam rectally. Bile-stained gastric contents was not related to the gastric pH. 相似文献
133.
Fifty healthy female patients scheduled for surgery were randonly allocated into two groups in a double-blind study. One group received lorazepam 2.5 mg orally at 2200 h on the evening before surgery as night sedation, and again at 0800 h on the morning before surgery as premedication. The second group received diazepam 10 mg orally at the samte times. The quality of sleep the night before surgery was superior in the lorazepam group (p less than 0.02). The frequency of effective sedation produced pre-operatively was similar in both groups. Although the incidence of amnesia for visual stimuli following lorazapam was higher (p less than 0.05) than with diazepam, there was no difference in the recall of auditory and painful stimuli. The overall incidence of side effects was similar for each drug and at the dosage used no difference was found in the time to awaken from anaesthesia. 相似文献
134.
Dental treatment in young handicapped patients 总被引:1,自引:0,他引:1
A trial was undertaken to assess the suitability of oxygen/nitrous oxide sedation (relative analgesia) for dental treatment in unmanageable handicapped young patients. Fifty patients with chronological ages 5-22 years and mental ages 1 1/2-14 years participated in the double blind trial to see if premedication with diazepam 0.2 mg/kg would be a useful adjunct. After the trial, previous dental histories and behaviour at regular recall visits over the next 12-18 months were studied. Seventeen of 19 patients previously treated with general anaesthesia and 27 of 31 formerly untreated patients accepted treatment in the trial; of the 50 patients, 33 are continuing treatment with oxygen/nitrous oxide sedation, seven need general anaesthesia and 10 have moved from the district. It appears that the use of diazepam premedication improves patient demeanour and operating conditions although this improved effect is not carried over to recall visits. The results obtained indicate that routine dental procedures can be safely carried out by an experienced operator-sedationist in young handicapped patients using oxygen/nitrous oxide sedation. The frequency with which potentially hazardous techniques need to be used can be reduced, as can hospital admissions. 相似文献
135.
Diazepam effects on striatal met-enkephalin levels following long-term pharmacological manipulations
As measured by highly specific radioimmunoassay, long-term treatment of rats for 28 days with benzodiazepines resulted in a significant increase in the striatal met-enkephalin content, which was opposite to the decrease in this area observed after acute administration. Other areas investigated i.e. the hypothalamus, the medulla oblongata/pons and the midbrain, were unchanged after chronic benzodiazepine treatment. Acute diazapam challenge of these animals revealed a considerable degree of tolerance towards the acute drug effect. In rats chronically treated with morphine for 28 days, acute diazepam administration no longer decreased striatal met-enkephalin, in contrast to rats receiving ethanol for the same time, in which the diazepam-induced decrease was potentiated. 相似文献
136.
Data obtained from anxious outpatients treated with either chlordiazepoxide or diazepam (n= 533) or placebo (n= 285) were used to explore the impact of coffee/tea and cigarette consumption upon the frequency of reporting of drowsiness after 2 weeks of treatment. Strong evidence was provided that both cigarette smoking and coffee drinking afiect the frequency with which drowsiness is reported by patients receiving the two benzodiazepines. However, not only the magnitude but also the direction of the impact of coffee consumption upon drowsiness depends upon the level of cigarette smoking and vice versa. For patients smoking ≦ 1 pack of cigarettes/day, drowsiness is reported less frequently by heavy coffee users while for patients smoking > 1 pack of cigarettes/day, drowsiness is reported more frequently by heavy coffee users. Similarly, for patients drinking ≦ 2 cups of coflee/day, drowsiness occurs less frequently among heavier smokers while for patients drinking > 2 cups of coffee/day, drowsiness occurs more frequently among heavier smokers. These results are consistent with reports that particular substances contained in coffee and tea and in cigarette smoke stimulate the synthesis of hepatic enzymes which metabolize both the benzodiazepines here studied and the substances which have stimulated enzyme synthesis. 相似文献
137.
Midazolam and diazepam for gastroscopy 总被引:2,自引:0,他引:2
Midazolam 0.1 mg/kg was compared with diazepam 0.15 mg/kg intravenously in patients undergoing gastroscopy. The patients receiving midazolam were more sedated at the end of the procedure. The mean discharge times from the clinic for diazepam and midazolam patients were 85 and 102 minutes, respectively. The principal differences between the two drugs were that midazolam had a faster rate of onset, was virtually free from venous complications, provided much better amnesia (90% compared with 50%), and although the recovery time was longer with midazolam, the rate of recovery during the period of observation was faster. Neither drug caused any significant cardiorespiratory depression. 相似文献
138.
Å. Bliding 《European journal of clinical pharmacology》1974,7(3):201-211
Summary Two benzodiazepins with different rates of absorption have been compared in a double-blind cross over study in six healthy subjects using single doses of diazepam (Valium) 2, 5 and 10 mg and oxazepam (Sobril) 15, 25 and 50 mg. Further, oxazepam formulations with different rates of absorption have been compared in 8 healthy subjects. Lastly, the diurnal variation in serum levels during long-term therapy with the benzodiazepins has been followed up in a pilot study in hospital. Drug influence was assessed at intervals and showed that the quantitative and qualitative subjective effects as well as the alteration of reaction time and hand steadiness were more pronounced during the rising phase than in the constant plateau or falling phase of serum drug concentrations. Rapidity of increase in concentration appeared more important than the absolute level. Diazepam has the faster rate of absorption and had a significantly (p<0.05–0.001) greater influence at 30 min, and usually at 90 min, too, than oxazepam or the placebo. Oxazepam, even when administered as a formulation with near-maximal absorption rate, still had not high enough a rate of absorption to produce the distinctly identifiable onset of reactions characteristic of diazepam and did not give noticeable prolongation of reaction time or increased hand unsteadiness even at its maximal serum concentrations. The separate pilot study showed that relatively large diurnal variations in serum concentrations might occur during continuous treatment for more than four weeks and that a preparation with a high rate of absorption (diazepam) could still produce a subjectively apparent experience after each individual dose. It seems reasonable to assume that the risk of abuse, and equally also one of the factors increasing the risk of habituation to psycho-pharmaceutical drugs, is related to subjectively experienced effects, which, as shown above, depend to a large extent on the rate of absorption. For maintenance treatment a steady serum level adapted to the individual is probably to be preferred, while in acute treatment, for example, of attacks of anxiety, a compound with rapid absorption is required, and the therapeutic advantages must then be weighed against the greater risk of abuse. 相似文献
139.
Gueorguieva I Nestorov IA Rowland M 《Journal of pharmacokinetics and pharmacodynamics》2006,33(1):1-27
Abtract There are situations in drug development where one may wish to reduce the dimensionality and complexity of whole body physiologically
based pharmacokinetic models. A technique for formal reduction of such models, based on global sensitivity analysis, is suggested.
Using this approach mean and variance of tissue(s) and/or blood concentrations are preserved in the reduced models. Extended
Fourier amplitude sensitivity test (FAST), a global sensitivity technique, takes a sampling approach, acknowledging parameter
variability and uncertainty, to calculate the impact of parameters on concentration variance. We used existing literature
rules for formal model reduction to identify all possible smaller dimensionally models. To discriminate among those competing
mechanistic models extended FAST was used, whereby we treated model structural uncertainty as another factor contributing
to the overall uncertainty. A previously developed 14 compartment whole body physiologically based model for diazepam disposition
in rat was reduced to three alternative reduced models, with preserved arterial mean and variance concentration profiles. 相似文献
140.
Gueorguieva I Aarons L Rowland M 《Journal of pharmacokinetics and pharmacodynamics》2006,33(5):571-594
Modelling is an important applied tool in drug discovery and development for the prediction and interpretation of drug pharmacokinetics. Preclinical information is used to decide whether a compound will be taken forwards and its pharmacokinetics investigated in human. After proceeding to human little to no use is made of these often very rich data. We suggest a method where the preclinical data are integrated into a whole body physiologically based pharmacokinetic (WBPBPK) model and this model is then used for estimating population PK parameters in human. This approach offers a continuous flow of information from preclinical to clinical studies without the need for different models or model reduction. Additionally, predictions are based upon single parameter values, but making realistic predictions involves incorporating the various sources of variability and uncertainty. Currently, WBPBPK modelling is undertaken as a two-stage process: (i) estimation (optimisation) of drug-dependent parameters by either least squares regression or maximum likelihood and (ii) accounting for the existing parameter variability and uncertainty by stochastic simulation. To address these issues a general Bayesian approach using WinBUGS for estimation of drug-dependent parameters in WBPBPK models is described. Initially applied to data in rat, this approach is further adopted for extrapolation to human, which allows retention of some parameters and updating others with the available human data. While the issues surrounding the incorporation of uncertainty and variability within prediction have been explored within WBPBPK modeling methodology they have equal application to other areas of pharmacokinetics, as well as to pharmacodynamics. 相似文献