Ethanol and the absorption of barbiturate
25
Citation
6
Reference
10
Related Paper
Keywords:
Barbiturate
Coma (optics)
Meprobamate
The effects of pentobarbital on electroencephalogram (EEG) and auditory brain-stem response (ABR) were evaluated in 13 Japanese white male rabbits, divided into two groups, 7 and 6, respectively. After baseline evoked responses were obtained, pentobarbital was infused intravenously at 60 mg/kg/h in both groups. EEGs and ABR were recorded with 15 min intervals. When the blood concentration of pentobarbital reached therapeutic levels (2.0-5.0 mg/dL), cortical and hippocampal EEGs became isoelectric. Although the appearance of ABR waves was significantly delayed, each wave was clearly observed in spite of isoelectric EEG levels. The rabbits in one group were killed at that time, and their brains were removed to determine the concentration of pentobarbital in the brain tissue. In another group, pentobarbital was additionally infused at the rate of 120 mg/kg/h. Although the waves (II-IV) of the ABR gradually disappeared with increasing dosage, wave I was present until just prior to cardiac arrest. It is considered that the persistency of ABR at high doses of barbiturates is characteristic of patients in deep barbiturate coma. Therefore, at the diagnosis of brain death, there is no necessity to consider the half-life of the barbiturate, even if an excessive amount of barbiturate remains in the brain. In this study, pentobarbital concentration in the brain was nearly equal to the concentration in the blood. However, it is estimated that a large amount of barbiturate is accumulated in the brain of a patient after brain death because the blood flow in the brain is stagnant.
Barbiturate
Coma (optics)
Cite
Citations (10)
Diazepam (DZP) pretreatment (100 mg/kg, ip) of rats 6 h before pentobarbital administration (45 mg/kg, ip) prolonged the barbiturate-induced narcosis. The concentrations of [ 14 C]pentobarbital and total pentobarbital derivatives in blood or brain showed no differences between control and DZP-pretreated animals. The brain and blood concentrations of pentobarbital, when measured at a time corresponding to the respective arousal times from pentobarbital narcosis, were lower in the DZP-pretreated group. These results indicate that acute DZP pretreatment increases the sensitivity of the rat brain to pentobarbital rather than inducing changes in the disposition of the barbiturate.
Barbiturate
Cite
Citations (2)
The effects of pentobarbital on survival times of mice exposed to oxygen, 5 per cent, were studied over a large dosage range in normal mice and in mice made tolerant to the effect of barbiturates. Tolerance was induced by pretreatment with phenobarbital, 210 mg/kg, for three days, which increased the median anesthetic dose (AD50) for pentobarbital from 34 to 53 mg/kg. In nontolerant mice there was a dose-related increase in mean survival times for doses between 35 and 60 mg/kg, with a maximum increase to 303 per cent above control. At doses of more than 60 mg/kg survival times progressively decreased toward control. For tolerant mice survival time as a function of pentobarbital dosage was shifted to the right, i.e., protection necessitated higher doses. This shift was not explained by lower brain concentrations of pentobarbital in tolerant animals, but rather parallelled the increased tolerance to the anesthetic effect of the barbiturate. The authors conclude that in this model the protective effect of barbiturate is a function of the anesthetic effect rather than the barbiturate concentration in brain per se. Hypothermia (29 C) resulted in an increase in mean survival time comparable to that in barbiturate-treated animals. This supports the hypothesis that protection is ultimately a function of decreased cerebral metabolism, whether produced by anesthesia or by hypothermia. This model measures only the effect on spontaneous respiration during hypoxia. It is possible that other mechanisms are involved if barbiturates protect in other situations, such as during or after periods of complete ischemia.
Barbiturate
Phenobarbital
Hypoxia
Cite
Citations (55)
Three subsequent doses of pentobarbital (5, 15, and 40 mg/kg) were applied intraperitoneally in acute experiments in rats with a cortical epileptogenic focus. Histograms of intervals between individual focal discharges were shifted towards longer intervals even after the smallest dose of pentobarbital; the prolongation of intervals was clearly visible after the third dose also in the EEG recording. Shape of primary as well as projected cortical focal discharges after pentobarbital resembled that seen after local application of GABA. Barbiturate spindles which were present after the first and second dose of pentobarbital were regularly triggered by focal discharges. The mechanism of this triggering was probably a thalamocortical one, because marked projected discharges were recorded from various thalamic nuclei from the very beginning of focal activity.
Barbiturate
Cite
Citations (2)
Barbiturate
Phenobarbital
Cite
Citations (36)
The i.p. administration of pentobarbital using an escalating drug-dose schedule for an 11-day period resulted in the establishment of dependence on pentobarbital in male rats. Mean plasma pentobarbital levels were approximately 5 micrograms/ml during the first 3 days of the infusion period. Subsequently, there was observed a dose-responsive increase in plasma pentobarbital levels for the next 5 days, with a decline in pentobarbital levels noted during the final 3 days of the pentobarbital infusion period. Removal of pentobarbital from the infusate resulted in a rapid decline in plasma levels to less than 50% by 8 hr into the drug-free period and to barely detectable levels by 24 hr. This was correlated with a steadily increasing occurrence of withdrawal signs, with a peak occurrence by 7 to 9 hr after initiation of the drug-free period. Spontaneous locomotor activity was significantly greater in pentobarbital-dosed animals during withdrawal than in saline-infused control rats. The i.p. infusion of pentobarbital is a quick and reliable method for the study of barbiturate dependence in the rat.
Barbiturate
Intravenous Infusions
Plasma levels
Cite
Citations (18)
Acetylsalicylic acid was administered orally in doses from 0.2 to 1.9 g/kg with pentobarbital or thiopental, given intraperitoneally 1 h later, in doses ranging from 25 to 55 mg/kg, to overnight-fasted, male, albino rats. Both sleeping time and mortality were significantly increased with acetylsalicylic acid – barbiturate combinations. A dose-response relationship was observed in both sleeping time and mortality after acetylsalicylic acid and thiopental but only with the former after acetylsalicylic acid and pentobarbital. Starvation prolonged thiopental sleeping time. At equal doses, thiopental was more toxic than pentobarbital, when given separately and in combination with acetylsalicylic acid.
Barbiturate
Cite
Citations (5)
The basic principles in treatment of patients suspected of, or known to be, physically dependent on barbiturates, nonbarbiturate sedatives, and/or "minor tranquilizers" are: stabilization on pentobarbital in daily amounts and frequency of dosage sufficient to completely suppress barbiturate-type abstinence phenomena and produce minimal signs of barbiturate intoxication; and progressive reduction of pentobarbital dosage at the rate of not more than 100 mg. a day after three to five days of stabilization.
Barbiturate
Abstinence Syndrome
Cite
Citations (63)
Barbiturate
Gamma-Aminobutyric Acid
Cite
Citations (39)