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)

Accidental or intentional isoniazid (INH) overdose is not uncommon. Two patients suffering from pulmonary tuberculosis ingested INH (9 g and 12 g respectively) intentionally following acute personal stress. One patient presented with oliguria and coma whereas seizures were the dominant feature in the second case. Serum levels of INH were high in both cases. Satisfactory clinical recovery followed after the administration of intravenous pyridoxine. Literature on the subject was reviewed and the manifestations and recommendations for the management of acute INH toxicity are highlighted.
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PMID:Acute isoniazid toxicity--report of 2 cases and review of literature. 359 52

The pharmacokinetics of isoniazid following overdose in two patients is described. One patient was treated with haemodialysis for seizures and persistent coma without obvious immediate clinical improvement. In addition, three volunteer subjects were given isoniazid orally on two separate occasions. Isoniazid elimination pharmacokinetics were determined with and without concominant charcoal. Oral activated charcoal totally prevented the absorption of isoniazid. Current recommendations for treatment of isoniazid overdoses include intravenous pyridoxine (one gram IV pyridoxine for each gram of ingested isoniazid), intravenous diazepam or phenobarbital for continued seizures, and gastric decontamination with lavage and activated charcoal (1 g/kg). Extraordinary measures such as early haemodialysis and haemoperfusion should be reserved for those patients with persistent coma or refractory seizures.
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PMID:Isoniazid overdose: pharmacokinetics and effects of oral charcoal in treatment. 369 94

Sprague-Dawley rats with interictal and ictal spike activity induced by intraperitoneally injected isoniazid (INH) were treated, 5 min before or 30 min later, with liposome-entrapped gamma-aminobutyric acid (GABA) (LEG) or GABA or phosphatidylserine. Crossover injections were given in random sequence and INH alone ws also injected in every animal as a control. LEG inhibited either seizures or interictal spikes in both groups. No decrease of epileptogenic activity was seen after GABA or phosphatidylserine treatment alone. It is suggested that LEG could contribute to the reconstitution of the GABA pool decreased by INH.
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PMID:Liposome-entrapped gamma-aminobutyric acid inhibits isoniazid-induced epileptogenic activity in rats. 395 56

The effect of halothane on cerebellar control of motor activity and on cerebellar cyclic 3',5'-guanosine monophosphate (cGMP) content was studied in mice. Isoniazide and picrotoxin were used to increase motor activity and induce seizures associated with an increase in cerebellar cGMP content. Halothane markedly decreased the cerebellar cGMP content (by 60 per cent at 0.61 per cent, the concentration at which 50 per cent of mice lost righting reflex) and prevented the isoniazide-induced increase in cGMP content. Halothane, 0.61 per cent, significantly reduced both isoniazide- and picrotoxin-induced motor activity; the ED50 convulsive dose of isoniazide (137.7 +/- 7.04) and of picrotoxin (1.9 +/- 0.2 mg x kg-1, sc) was about three times higher (402.2 +/- 17.9 and 5.8 +/- 0.6 mg x kg-1, sc, respectively) in mice exposed to halothane. In contrast, halothane did not alter the ED50 convulsive dose of strychnine, which has a different site and mechanism of action, blockade of glycine receptors, a mechanism not involving the cerebellar system. These results indicate that halothane has a significant effect on the cerebellar control of motor activity and that cGMP plays an important role in the alteration of cerebellar function by halothane.
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PMID:Halothane effect on cGMP and control of motor activity in mouse cerebellum. 625 59

Caerulein, cholecystokinin octapeptide (CCK-8) and diazepam delayed the onset of seizures produced by harman and thiosemicarbazide (TSC). Caerulein had the potency of diazepam, whereas CCK-8 was less active by a factor of four. The convulsions induced by isoniazid (INH) were very resistant to both caerulein and diazepam; CCK-8 was not tested against isoniazid. Haloperidol did not influence the effect of TSC; it enhanced isoniazid-induced seizures, and antagonized the convulsant effect of harman.
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PMID:Anticonvulsant effects of caerulein, cholecystokinin octapeptide (CCK-8) and diazepam against seizures produced in mice by harman, thiosemicarbazide and isoniazid. 626 41

Acute toxicity from ingestion of isoniazid (INH) is manifested by coma and seizures unresponsive to conventional therapy. Though small doses of pyridoxine can reverse the seizure activity of acute isoniazid toxicity, large doses of pyridoxine (B6) are needed to completely reverse the symptoms. A case report is presented demonstrating the need for large doses of pyridoxine to reverse the symptoms of isoniazid intoxication and the literature of isoniazid toxicity in the pediatric age group is reviewed.
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PMID:Acute isoniazid intoxication: reversal of CNS symptoms with large doses of pyridoxine. 649 43

Of 53 patients with drug-induced seizures seen in the last decade, 45% had single seizures, 40% had multiple convulsions, and 15% had status epilepticus. Generalized seizures with focal features were common, but simple partial (motor) seizures occurred in only two patients. Isoniazid, insulin, lidocaine, and psychotropic medications were the most common drugs that caused seizures. Forty-nine patients recovered without ill effects, but 4 patients died of cardiovascular complications. The combined cardiovascular toxicity of the convulsants, antidotes, and anticonvulsants was more important than the number or duration of seizures in determining outcome.
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PMID:Drug-induced seizures: a 10-year experience. 650 30

Isoniazid is a useful chemical convulsant in that metabolic events associated with the preseizure state can be easily examined. In the present study, net levels of glucose, glycogen, ATP, and phosphocreatine were measured using enzymatic techniques in control mice, and in those injected with isoniazid. Results from this study showed a differential effect of isoniazid on cells from the cerebral cortex and the cerebellum. In the preseizure stage, the high energy phosphates ATP and phosphocreatine were decreased in layer 1 and the pyramidal cell layer of the cerebral parietal cortex, but were unchanged in the cerebellum. At the onset of seizures, metabolites were decreased not only in cortical layers, but in the molecular layer and Purkinje cell rich layer of the cerebellum as well. The somewhat delayed response of the cerebellum emphasizes the differential nature of metabolism in various brain regions. Such a delay in cerebellar energy response to perturbation may be conducive to the seizure state. In another series of mice, either sodium valproate or clonazepam was administered prior to isoniazid, and metabolite studies repeated. Results showed that at a time when each anticonvulsant acted to eliminate overt seizure activity, the reduction in ATP and phosphocreatine was not as great as it was in seizing mice treated with isoniazid alone.
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PMID:Isoniazid induced seizures and cerebral cortical and cerebellar energy metabolism. 681 36

This study investigated the ability of hyperbaric exposure to antagonize ethanol's anticonvulsant effect on isoniazid (INH)-induced seizures. Drug-naive, male C57BL/6 mice were injected intraperitoneally with saline, 1.5, 2.0, or 2.5 g/kg ethanol followed immediately by an intramuscular injection of 300 mg/kg of INH. The mice were then exposed to either 1 atmosphere absolute (1 ATA) air, 1 ATA helium-oxygen gas mixture (heliox), or 12 ATA heliox at temperatures that offset the hypothermic effects of helium. Ethanol increased the latency to onset of myoclonus in a dose-dependent manner. Exposure to 12 ATA heliox antagonized ethanol's anticonvulsant effect at 2.0 and 2.5 g/kg, but not at 1.5 g/kg. Ethanol also increased the latency to onset of clonus in a dose-dependent manner beginning at 2.0 g/kg. Exposure to 12 ATA heliox antagonized this anticonvulsant effect. When exposed to 12 ATA heliox, the blood ethanol concentrations at time to onset of myoclonus were significantly higher in mice treated with 2.5 g/kg of ethanol as compared with blood ethanol concentrations of mice exposed to 1 ATA air. These findings extend the acute behavioral effects of ethanol known to be antagonized by hyperbaric exposure and support the hypothesis that low-level hyperbaric exposure blocks or reverses the initial action(s) of ethanol leading to its acute behavioral effects.
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PMID:Low-level hyperbaric antagonism of ethanol's anticonvulsant property in C57BL/6J mice. 784 5

The National Animal Poison Control Center received 28 calls of isoniazid (INH) exposures in dogs and cats between 1987 and 1993. The ingestion of a single 300 mg INH tablet was the most common complaint. Isoniazid has a low therapeutic margin and produces life threatening signs in dogs ingesting single 300 mg human tablets. The LD50 of INH in dogs is estimated at 50 mg/kg bw, which is probably similar to that for humans. However, rodents are among the species most resistant to INH and thus are not good animal models for toxic dose extrapolation. The more consistent clinical signs reported were recurrent clonic-tonic seizures followed by a stuporous state with poor response to stimulus. Ideal treatment combines vitamin B6 given as a single i.v. bolus at an equivalent dose to the amount of INH ingested and anticonvulsants such as 1 mg diazepam/kg bw. This combination acts synergistically to improve GABAergic transmission in the CNS and has proved effective in protecting animals from further convulsions and death, even after several seizure episodes, as often encountered in clinical situations.
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PMID:Treatment of acute isoniazid overdose in dogs. 859 42


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