Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thiopental was administered for seizure control in 2 patients with uncontrollable seizures. Serum samples were collected from each patient and assayed for thiopental, and the resulting serum concentration--time data were analyzed pharmacokinetically. The biologic half-life in both patients was significantly longer than previously reported values. Based on the limited number of patients studied, it would appear that half-life and volume of distribution increase with the degree of obesity, while clearance remains unchanged. These pharmacokinetic characteristics would be worthy of consideration in cases where there may be prolonged use of thiopental, eg., for the control of uncontrollable seizures.
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PMID:Pharmacokinetic properties of thiopental in two patients treated for uncontrollable seizures. 10 93

Electroencephalographic activity and extracellular discharges from neurons in deep temporal lobe structures were recorded from fine wire microelectrodes chronically implanted in seven psychomotor epileptic patients for diagnostic localization of seizure foci. In four patients, inhalation of 80 per cent nitrous oxide resulted in loss of consciousness without change in firing rates of temporal lobe neurons (n = 22). In all seven patients, thiopental (400 or 200 mg, iv) decreased limbic neuronal firing rates (n = 38) until the return of wakefulness. In only three of these patients, however, did the firing rates of the neurons (n = 19) decrease significantly (P less than .05). Thiopental suppression of unit activity was not related to systemic hypoxia. This study demonstrates that anesthetic induction with nitrous oxide-oxygen does not significantly affect the firing of neurons in various regions of the human limbic system, which may explain the incidence of patient awareness reported when nitrous oxide-oxygen is administered alone. Thiopental depresses the firing of limbic neurons, and this may account in part for the temporary confusion and amnesia often manifested by patients recovering from the effects of thiopental.
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PMID:Limbic neuronal firing rates in man during administration of nitrous oxide--oxygen or sodium thiopental. 17 77

The effect on arterial pressure, EEG, preganglionic sympathetic nervous activity and pulse rate of repeated intravenous administrations of lidocaine (3 mg/kg) was investigated in cats anaesthetized with nitrous oxide. A continuous high voltage, burst-suppression EEG indicating constant seizure activity was found, whereas arterial pressure and sympathetic nervous activity did not change significantly. Although the onset of EEG seizure activity did not change the mean sympathetic activity level, the pattern of firing changed dramatically as every EEG seizure triggered a burst of sympathetic impulses. Barostatic reflexes were active after lidocaine administration unless seizure activity occurred. Thiopental 5 mg/kg given intravenously to cats during continuous lidocaine-induced EEG seizures always abolished the seizure activity without excessive depression of arterial pressure.
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PMID:Sympathetic nervous system response to lidocaine induced seizures in cats. 69 18

The effects of oral administration of clonazepam, a new benzodiazepine derivative (F. Hoffmann-La Roche), on the central nervous system were compared with those of diazepam and several anticonvulsants in mice and rats. 1) Clonazepam exhibited a moderate inhibitory effect on the locomotor activity observed with open-field situation in mice and no effect in rats, while it inhibited markedly the rearing behavior in both animals, the duration of action being approximately six hours. 2) Clonazepam potentiated the methamphetamine-induced hyper-locomotor activity in mice whereas trimethadione had no effect. 3) Clonazepam inhibited with a moderate potency the conditioned avoidance response and response to a fixed-ratio (FR 20) schedule of food reinforcement in rats, the potency being a little weaker than that of diazepam. 4) The muscle relaxant effect of clonazepam determined by the traction test was slightly more potent as compared with that of diazepam. Thiopental hypnosis was markedly potentiated after clonazepam. 5) The clonic (CL), tonic-flexor (TF) and extensor convulsions (TE) induced by pentetrazol were strongly inhibited after clonazepam in mice, anticonvulsant potency against CL and TE of clonazepam being approximately 23 and 21 times stronger than that of diazepam, 3333 and 3846 times that of trimethadione, and over 3047 and 178 times that of phenytoin, respectively. Clonazepam reduced markedly CL and TE elicited by bemegride with about 12 to 14 times stronger potency than diazepam. On the contrary, the anticonvulsant effect of clonazepam against TE of maximal electroshock seizure evoked by supramaximal current was weak, the potency being 0.71 times weaker than that of phenacemide, 0.14 times than phenytoin and 0.24 times than phenobarbital. By the combined administration of clonazepam with other anticonvulsants such as trimethadione and phenytoin against pentetrazol convulsion, and phenacemide, phenytoin and phenobarbital against maximal electroshock seizure, the antagonistic effect of these anticonvulsants was potentiated by 4 to 5 times. 6) The acute toxicity (LD50) of clonazepam was weak but that of phenacemide or phenytoin was potentiated to a certain degree by combined administration with clonazepam. The results suggest that clonazepam has a psychopharmacological profile similar to that of benzodiazepines with a particularly potent anticonvulsant effect on pentetrazol and bemegride convulsions, and the anticonvulsant effect is synergic with that of other anticonvulsants.
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PMID:[Central effects of clonazepam]. 98 89

Four different convulsant barbiturates and also thiopental, methohexital and pentobarbital were tested for in vitro contractor effects on rabbit jejunal segments, aortic strips and tracheal chains. The two convulsants that elicited lethal, tonic seizures in vivo contracted all three types of isolated preparation; however, two other convulsants that elicited intense but nonlethal, clonic seizures lacked contractor effect. Methohexital and pentobarbital also lacked contractor effect. In aortic strips, contractions induced by the two convulsants were not impaired by concentrations of phenoxybenzamine (10(-5) M) that blocked all contractor response to 10(-4) M norepinephrine, acetylcholine or histamine. Thiopental also contracted aortic strips but the effect differed from that of the convulsants in that it was much less intense, was partially antagonized by pretreatment with phenoxybenzamine, and was greatly potentiated by the presence of norepinephrine. Intense contractor effects, independent of adrenergic mechanisms, seem characteristic of a particular group of convulsant barbiturates; there are also similar with respect to structure, stimulant potency, and seizure pattern.
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PMID:Contractor effect of barbiturates on smooth muscle. 119 Sep 16

The effect of intravenous ciprofloxacin (CPX) pretreatment on the kinetics and brain sensitivity for thiopental was studied in male rats using a previously developed electroencephalographic (EEG) threshold method. Thiopental was administered intravenously with constant infusion rate. Immediately after the appearance of the first burst suppression of 1 sec. or more (the "silent-second") in the EEG the infusion was stopped and the rats were killed by decapitation. The dose of thiopental needed to reach the criterion of silent-second was slightly reduced in ciprofloxacin pretreated rats when compared with saline pretreated controls. One rat that developed seizures after CPX pretreatment needed a considerably reduced dose of thiopental to induce the silent-second. The serum concentrations of thiopental were markedly reduced in the experimental group while no significant differences were found in the concentrations of thiopental in the different parts of the central nervous system (CNS), fat or muscle tissue. The kinetics of CPX were also affected. The experimental group (CPX + thiopental treated) had significant higher brain concentrations of CPX than the corresponding only CPX treated control group while no differences were found in the serum concentrations of CPX between the groups. As previously suggested, the distribution of thiopental in the CNS is not only dependent on its lipid solubility, but also as a weak organic acid, on the transport system for organic acids out of the CNS which both thiopental and ciprofloxacin seem to use and mutually compete for it.
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PMID:Interaction between ciprofloxacin and thiopental in the central nervous system of the male rat. 144 48

The authors investigated the hemodynamic, metabolic, electroencephalographic (EEG), and electromyographic (EMG) characteristics of narcotic-induced rigidity during induction of anesthesia with alfentanil (175 micrograms/kg) in 10 patients. Thiopental (4 mg/kg) was administered to a ten-patient control group. Rigidity was quantified in eight muscle groups (sternocleidomastoid, deltoid, biceps, forearm flexors, intercostal, rectus abdominus, vastus medialis/lateralis, and gastrocnemius). Marked rigidity was observed in all muscle groups in all patients receiving alfentanil and in none receiving thiopental. Central venous pressure increased with onset of rigidity, while mean arterial pressure and cardiac index remained unchanged. Manual ventilation was extremely difficult during alfentanil-induced rigidity. Arterial oxygen tension decreased more rapidly during rigidity than during the same time interval in the control group, while patients experiencing rigidity were more acidotic, as reflected by greater increases in base deficit. The EEG demonstrated an anesthetic state without seizure activity. The immediate increase in central venous pressure with the onset of rigidity, along with occasional simultaneous parallel variations in central venous pressure and the EMG, strongly suggest a mechanical mechanism for the change in central venous pressure. The metabolic changes during rigidity may be partly related to the absence of the normal cardiovascular reflexes that are reported to occur during voluntary isometric muscle contractions. A neurochemical mechanism of narcotic-induced rigidity is briefly reviewed.
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PMID:Physiology of alfentanil-induced rigidity. 300 95

A 5 years old girl with status epilepticus refractory to treatment with Diphenylhydantoin at a dose of 30 mg/kg/day and Thiopental in continuous IV perfusion at a dose of 4 mg/kg/h is presented. Control of status was achieved by continuous IV perfusion of Chlormethiazole at a dose of 10 mg/kg/h which also caused respiratory depression. Seizure activity reappeared after IV perfusion of Chlormethiazole was retired, and could be controlled only with Sodium Valproate. Mechanisms of action of Chlormethiazole and its effectiveness in treatment of refractory status epilepticus are revised.
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PMID:[Treatment of refractory status convulsivus with chlormethiazole]. 314 89

The possible cerebral sparing effect of thiopental was evaluated in 32 severely asphyxiated neonates randomly assigned to either a thiopental treatment or control group. All infants had neurologic manifestations of asphyxia and required assisted ventilation. Thiopental was begun at a mean age of 2.3 hours and was given as a constant infusion that delivered 30 mg/kg over 2 hours. Treatment was continued at a lower dose for 24 hours. Seizure activity occurred in 76% of infants given thiopental and 73% of control infants at a mean age of 1.5 and 2.5 hours, respectively. Although initial arterial blood pressure was similar in both groups, hypotension occurred in 88% of treated and 60% of control infants. The amount of blood pressure support required was significantly greater (P less than 0.005) in the thiopental treatment group. Three infants died in the control group, and five in the treatment group. Developmental assessment was performed at a minimum of 12 months of age in 22 infants. There were no significant differences in neurologic, cognitive, or motor outcome between groups. Deteriorating performance over time was a consistent trend in both groups. These findings indicate that treatment of severe perinatal asphyxia with thiopental does not appear to have a cerebral sparing effect and may be associated with significant arterial hypotension.
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PMID:Use of barbiturate therapy in severe perinatal asphyxia: a randomized controlled trial. 353 1

High-dose thiopental was administered in 8 children with uncontrollable seizures or hypoxic encephalopathy (group A) and 7 full-term neonates with neonatal asphyxia (group B). All of them were submitted to artificial hyperventilation to maintain pCO2 near 3.5 kPa. Rectal temperature was kept at about 35 degrees C. Thiopental was infused with a rate of 2-4 mg X h-1 X kg-1, with treatment lasting 32-192 h for group A (mean 103 h), and 36-48 h for group B (mean 38.5 h). Plasma concentration-time data were analysed pharmacokinetically. Thiopental elimination half-life was 14.5 h (group A) and 20.9 h (group B). The clearance of thiopental was 0.27 liters X h-1 X kg-1 (group A) and 0.32 liters X h-1 X kg-1 (group B). The volume of distribution at steady-state was 5.41 liters X kg-1 (group A) and 8.26 liters X kg-1 (group B). These results show that high-dose thiopental pharmacokinetics is not very different for full-term newborns, children and adults. Elimination half-life and volume of distribution are changed when compared to single-dose studies, while clearance is only slightly modified. The time for disappearance of thiopental from blood is also very long (2 to 5 days). These pharmacokinetic characteristics would be worthy of consideration in cases where there may be prolonged use of thiopental, considering the risk of accumulation and toxicity.
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PMID:High-dose thiopental pharmacokinetics in brain-injured children and neonates. 360 52


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