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)

Several interactions involving antiepileptic drugs are based on changes in the rate of their metabolism and elimination, with concomitant rise or fall of plasma levels. Thus, phenobarbital generally induces the production of the DPH metabolizing enzyme, but its presence inhibits the action of that enzyme. The net result depends upon the balance between these factors in individual patients. Either a decline, a rise, or no change of the DPH plasma level may occur after the onset of administration of phenobarbital. Drugs that may cause elevation of the DPH plasma level include disulfiram, sulthiame, bishydroxycoumarin, chloramphenicol, phenyramidol, benzodiazepines, sulfamethizole, and isoniazid. Isoniazid has been shown experimentally to be a strong inhibitor of DPH metabolism. The extent of DPH plasma level elevation by INH is related to the genetic make-up of individual patients. The highest and frequently toxic DPH plasma levels were seen in very slow INH inactivators. The incidence of clinically significant interactions is not high with most drug combinations; marked changes of antiepileptic drug levels occur only in apparently susceptible individuals. The effects of interactions are not necessarily detrimental; elevation of a low ineffective level may improve seizure control. A rise to a toxic level range requires reduction of the dose of primary drug or elimination of interfering drugs. Monitoring the blood levels of anti-epileptic drugs provides the best means to anticipate interactions and to regulate the doses when multiple medications have to be used.
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PMID:Interactions of antiepileptic drugs. 5 Feb 32

Isoniazid inhibited the metabolism of primidone in a patient with focal seizures. The steady-state serum level of primidone rose when the patient received both drugs simultaneoulsy. The serum levels of the primidone metabolites, phenobarbital and phenylethylmalonamide, fell and the rate of metabolism of primidone decreased. The results are similar to those observed when isoniazid is adminstered with diphenylhydantoin.
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PMID:Isoniazid as an inhibitor of primidone metabolism. 81 7

Incubation of rat brain synaptosomes and mitochondria with LPO inducers (Fe2+ and ascorbate) was accompanied by a decrease of deamination of serotonin (substrate of MAO-A) in mitochondria, but not in synaptosomes, with simultaneous stimulation of GABA and GLCA deamination, apparently owing to modification of catalytic properties of brain membrane-bound MAO. Oxidation of PEA (substrate of MAO-B) was insignificantly altered in both fractions. Reactions of deamination of serotonin, GABA, and GLCA (but not PEA), were highly sensitive to a selective inhibitor of MAO-A pyrazidol (pyrlindole). Isoniazid and hydrazides of quinoline carbonic acids (inhibitors of both modified MAO and copper-containing amine oxidases) strongly inhibited deamination of GABA and GLCA. During epileptiformic seizures in rats, genetically selected for high incidence of audiogenic epilepsia, stimulation in brain synaptosomes and mitochondria of LPO was observed. This was accompanied by a marked decrease in serotonin and PEA deamination, with a simultaneous increase in GABA and GLCA deamination in both fractions. The data obtained suggest that appearance of GABA-deaminating activity owing to modification of catalytic properties of MAO, might be an essential pathogenetic component in the development of epileptic seizures.
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PMID:The role of lipid peroxidation in the possible involvement of membrane-bound monoamine oxidases in gamma-aminobutyric acid and glucosamine deamination in rat brain. Focus on chemical pathogenesis of experimental audiogenic epilepsy. 152 Apr 3

We report earlier that isoniazid and foot-shock stress individually increase the maximal number of [35S]TBPS binding sites (Bmax) measured "ex vivo" in unwashed membranes from rat cerebral cortex and that the increase due to both treatments are prevented by pretreatment "in vivo" with diazepam which alone induced a significant decrease in the total number of [35S]TBPS binding sites. In the present paper, the effect of stress was studied on both the increase in [35S]TBPS binding and the convulsant activity induced by isoniazid in unstressed rats. Isoniazid induced a time dependent increase in [35S]TBPS binding. The isoniazid-induced increase in [35S]TBPS binding was markedly potentiated by foot-shock stress. Moreover, foot-shock stress markedly reduced the latency to the appearance of generalized seizures induced by isoniazid (300 mg/kg s.c.). The results provide evidence that the "in vivo" inhibition of GABAergic transmission elicited by isoniazid results in an increase of [35S]TBPS binding in the rats cerebral cortex. The finding that stress, like isoniazid, enhances [35S]TBPS binding suggests that this treatment also inhibits the function of GABAergic synapses.
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PMID:Foot-shock stress enhances the increase of [35S]TBPS binding in the rat cerebral cortex and the convulsions induced by isoniazid. 205 36

Isoniazid overdose is known to result in the rapid onset of seizures, metabolic acidosis, and prolonged obtundation. Pyridoxine has been reported to be effective in treating isoniazid-induced seizures. We report three cases of obtundation secondary to isoniazid overdose that was immediately reversed by intravenous pyridoxine. In two of these cases, status seizures were stopped by intravenous pyridoxine administration, but the patients remained comatose for prolonged periods. The comas were immediately reversed by the administration of additional pyridoxine. In the third case, the patient's lethargy was treated by intravenous pyridoxine on presentation and was followed by immediate awakening. Pyridoxine is effective in treating not only isoniazid-induced seizures, but also the mental status changes associated with this overdose. The dose required to induce awakening may be higher than that required to control seizures.
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PMID:Reversal of prolonged isoniazid-induced coma by pyridoxine. 129 May 58

Isoniazid (INH) poisoning is a known cause of metabolic acidosis and seizures. The following case report describes a 14-year-old boy with an INH overdose who suffered profound metabolic acidosis (pH of 6.69) and who completely recovered with no obvious sequelae.
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PMID:Complete recovery from severe metabolic acidosis associated with isoniazid poisoning in a young boy. 260 6

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

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

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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