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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isoniazid (INH) is widely used in most prophylactic and therapeutic anti-tuberculosis regimens because of its effectiveness and low cost. Yet, INH poisoning appears to be rare. We report the first case of intentional INH overdosage in Singapore. A 26-year-old Filipino male presented with mental obtundation, recurrent seizures, metabolic acidosis and hepatic dysfunction. He was successfully treated with large doses of pyridoxine (vitamin B6). Recommendations for the management of acute INH toxicity are highlighted.
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PMID:Intentional overdosage with isoniazid: case report and review of literature. 894 71

Since isoniazid is increasingly being used to control the spread of tuberculosis, physicians must be aware of its potentially fatal effects. The ingestion of toxic amounts of isoniazid causes recurrent seizures, profound metabolic acidosis, coma and even death. In adults, toxicity can occur with the acute ingestion of as little as 1.5 g of isoniazid. Doses larger than 30 mg per kg often produce seizures. When ingested in amounts of 80 to 150 mg per kg or more, isoniazid can be rapidly fatal. The first signs and symptoms of isoniazid toxicity usually appear 30 minutes to two hours after ingestion and include nausea, vomiting, slurred speech, dizziness, tachycardia and urinary retention, followed by stupor, coma and recurrent grand mal seizures. The seizures produced by isoniazid toxicity are often refractory to anticonvulsant therapy. Given in gram-per-gram amounts of the isoniazid ingested, pyridoxine (vitamin B6) usually eliminates seizure activity and helps to correct the patient's metabolic acidosis. Isoniazid toxicity should be suspected in any patient who presents with refractory seizures and metabolic acidosis.
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PMID:Isoniazid overdose: recognition and management. 949 Sep 97

We report a case of a 10-year-old boy, being treated for seizures with carbamazepine, who developed acute liver failure within four days of initiation of therapy for suspected tuberculosis with isoniazid, rifampin, pyrazinamide, and ethambutol. Isoniazid-induced liver disease was diagnosed. The likely role of carbamazepine and rifampin in potentiating the hepatotoxicity of isoniazid, and the importance of early recognition of isoniazid-induced liver disease, are discussed.
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PMID:Acute liver failure caused by isoniazid in a child receiving carbamazepine. 966 30

Isoniazid-induced seizures respond poorly to anticonvulsants but well to pyridoxine (Vitamin B6); theophylline produces difficult-to-treat seizures with substantial morbidity and mortality. Theophylline therapy depresses plasma pyridoxal-5'-phosphate (PLP), the active metabolite of pyridoxine, suggesting that theophylline-induced seizures might be amenable to treatment with pyridoxine. Our study established the dose-response relationship for convulsions due to isoniazid and theophylline in mice and determined if pyridoxine antagonized such seizures. Female CD-1 outbred mice weighing 25 to 30 g were used. Clonic seizures had clonic activity lasting 5 sec; tonic seizures had loss of the righting reflex with tonic hindlimb extension. Groups of 10 mice received single doses of 50, 100, 150, 200, 250 or 300 mg aminophylline/kg i.p. or 100, 150, 200, 250, 300 or 350 mg isoniazid/kg i.p. and were observed for seizures or death. Pyridoxine or saline with aminophylline or isoniazid were administered simultaneously. The LD50 for aminophylline was 266 mg/kg; for isoniazid it was 160 mg/kg. Doses of 150 mg aminophylline/kg or 100 mg isoniazid/kg did not induce seizures. Pyridoxine with aminophylline or isoniazid did not alter the frequency or time of onset of seizures or death. This was unexpected because pyridoxine antagonizes theophylline-induced seizures in mice and reverses isoniazid-induced seizures in humans. We found no evidence that PLP depletion in mice is a mechanism for seizures induced by isoniazid or aminophylline in a fashion similar to isoniazid in humans.
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PMID:Seizures induced by theophylline and isoniazid in mice. 1050 46

Isoniazid (INH) is the most widely used of the antituberculosis drugs. An acute overdose is potentially fatal and is characterized by the clinical triad of repetitive seizures unresponsive to the usual anticonvulsants, metabolic acidosis with a high anion gap and coma. The diagnosis of INH overdose should be considered in any patient who presents with an unexplained metabolic acidosis and convulsions. The cornerstone of therapy consists in pyridoxine (vitamin B6) and the dose should be equal to the amount of INH ingested. When conservative therapy fails or in case of renal insufficiency, dialysis must be considered. Severe central nervous toxicity can also be caused by chronic ingestion of higher than therapeutic doses of INH. In those cases pyridoxine-therapy can be useful as well. In the present paper a case of acute overdose of INH is reported, followed by a review of the literature.
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PMID:Acute isoniazid intoxication: seizures, acidosis and coma. 1054 12

Isoniazid-induced seizures resulted in rhabdomyolysis and associated acute renal tubular necrosis in a dog. Rhabdomyolysis and myoglobinuric renal failure, although recognised in the dog, are reported infrequently as a consequence of seizures. The clinical presentation of isoniazid toxicity in a dog is described.
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PMID:Isoniazid-induced seizures with secondary rhabdomyolysis and associated acute renal failure in a dog. 1199 96

Isoniazid is an anti-tuberculosis drug, used commonly for treatment and prophylaxis of tuberculosis. Acute isoniazid intoxication is characterized by a clinical triad consisting of metabolic acidosis resistant to treatment with sodium bicarbonate, seizures which may be fatal and refractory to standard anticonvulsant therapy, and coma. Treatment requires admission to the intensive care unit for ventilatory support, management of seizures and metabolic acidosis. Pyridoxine, in a dose equivalent to the amount of isoniazid ingested, is the only effective antidote. We report the successful treatment of two isoniazid intoxication cases: the case of a child developing an accidental acute isoniazid intoxication and an adult case of isoniazid intoxication with the intent of suicide.
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PMID:Seizures, metabolic acidosis and coma resulting from acute isoniazid intoxication. 1611 96

Isoniazid (INH) has neurotoxic effects such as seizure, poor concentration, subtle reduction in memory, anxiety, depression and psychosis. INH-induced toxic effects are thought to be through increased oxidative stress, and these effects have been shown to be prevented by antioxidant therapies in various organs. Increased oxidative stress may be playing a role in these neurotoxic effects. N-methyl D-aspartat receptors (NMDA) are a member of the ionotropic group of glutamate receptors. These receptors are involved in a wide variety of processes in the central nervous system including synaptogenesis, synaptic plasticity, memory and learning. Erdosteine is a potent antioxidant and mucolytic agent. We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH. In the present study, compared to control group, NMDAR2A (NR2A) receptors were significantly decreased and malondialdehyde (MDA), end product of lipid peroxidation, production was significantly increased in INH-treated group. On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production. In conclusion, decreasing NR2A receptors in hippocampus and increasing lipid peroxidation correlates with the degree of oxidative effects of INH and erdosteine protects above effect of INH on NR2A receptors and membrane damage due to lipid peroxidation by its antioxidant properties.
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PMID:The effects of isoniazid on hippocampal NMDA receptors: protective role of erdosteine. 1613 24

A 25-year-old, 54-kg Hispanic man who had recently started multidrug therapy for pulmonary tuberculosis presented in status epilepticus after ingesting 9 g of isoniazid in a suicide attempt. Successful management of this patient required collaboration between several institutions to provide the large amount of necessary intravenous pyridoxine. Ultimately, this single overdose depleted the supply of intravenous pyridoxine for a significant region of the state of Nebraska. Isoniazid is commonly used to treat tuberculosis, but it is encountered relatively infrequently as the cause of an acute overdose. Severe isoniazid overdoses may present as seizure activity that is refractory to conventional antiepileptic therapy. Although intravenous pyridoxine is an effective antidote for isoniazid overdoses in patients presenting with status epilepticus, this agent has few indications and is typically stocked in limited quantities. In regions with large populations of patients who receive antituberculosis therapy, collaborative networks must be created to ensure that adequate supplies of intravenous pyridoxine (> or = 20 g) are available for effective treatment of isoniazid poisonings.
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PMID:Acute isoniazid toxicity and the need for adequate pyridoxine supplies. 1699 64

Tuberculosis has re-emerged as a significant public health threat over the last decade both globally and within Australia. This is thought to be largely due to the HIV epidemic, a growing itinerant population, and immigration. The antibiotic isoniazid remains an integral part of drug therapy. With the numbers of patients receiving isoniazid remaining high, the number of cases of acute poisoning is expected to be significant. This paper presents a series of two cases of isoniazid poisoning presenting to a tertiary referral centre in North Queensland. Isoniazid toxicity produces a triad of coma, metabolic acidosis and seizures. The seizures are often refractory to traditional antiepileptics. A specific antidote is available (pyridoxine [vitamin B6]) and both patients were administered this as part of their treatment. We also surveyed all hospitals in Australia with an accredited adult Emergency Department to assess the availability of pyridoxine.
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PMID:Isoniazid overdose : a case series, literature review and survey of antidote availability. 1753 59


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