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PubMed · 8634931

Acute isoniazid intoxication: a case report.

Abstract

Since its introduction in 1952, isoniazid has remained one of the drugs of choice in the treatment and prophylaxis of tuberculosis. In populations with a high prevalence rate of tuberculosis or suicide rate, acute ingestion of isoniazid has occasionally been reported. Acute intoxication by isoniazid is known to cause symptoms of seizures, metabolic acidosis, coma, and even death. These clinical symptoms, however, are not well recognized by physicians in Taiwan, even though the prevalence rate of tuberculosis is relatively high here. This report concerns the case of a 25-year-old female with a past history of tuberculosis who presented with the symptoms of refractory seizures, metabolic acidosis and deep coma after intentional ingestion of some unknown drug. Although implicating agents were not recognized initially, she was successfully revived with basic resuscitation, anticonvulsants and correction of metabolic acidosis. A review of her history revealed that her ingestion of five grams of isoniazid in this case was responsible for the entire clinical spectrum. Given easy access to isoniazid in Taiwan, a diagnosis of isoniazid poisoning should always be considered in patients who present with the classical symptoms of refractory seizures, metabolic acidosis and coma.

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BibTeXRIS

Y D Chang, C C Yang, T J Lin, J Ger, J F Deng. 1996. Acute isoniazid intoxication: a case report.. https://pubmed.ncbi.nlm.nih.gov/8634931/

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[Isoniazid intoxication].

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Mitogen-activated protein kinase-dependent activation of the Na+/H+ exchanger is mediated through phosphorylation of amino acids Ser770 and Ser771.

We investigated regulation of the type 1 isoform of the Na(+)/H(+) exchanger by phosphorylation. Four specific groups of serine and threonine residues in the regulatory carboxyl-terminal tail were mutated to alanine residues: group 1, S693A; group 2, T718A and S723A/S726A/S729A; group 3, S766A/S770A/S771A; and group 4, T779A and S785A. The proteins were expressed in Na(+)/H(+) exchanger-deficient cells, and the activity was characterized. All of the mutants had proper expression, localization, and normal basal activity relative to wild type NHE1. Sustained intracellular acidosis was used to activate NHE1 via an ERK-dependent pathway that could be blocked with the MEK inhibitor U0126. Immunoprecipitation of (32)P-labeled Na(+)/H(+) exchanger from intact cells showed that sustained intracellular acidosis increased Na(+)/H(+) exchanger phosphorylation in vivo. This was blocked by U0126. The Na(+)/H(+) exchanger activity of mutants 1 and 2 was stimulated similar to wild type Na(+)/H(+) exchanger. Mutant 4 showed a partially reduced level of activation. However, mutant 3 was not stimulated by sustained intracellular acidosis, and loss of stimulation of activity correlated to a loss of sustained acidosis-mediated phosphorylation in vivo. Mutation of the individual amino acids within mutant 3, Ser(766), Ser(770), and Ser(771), showed that Ser(770) and Ser(771) are responsible for mediating increases in NHE1 activity through sustained acidosis. Both intact Ser(770) and Ser(771) were required for sustained acidosis-mediated activation of NHE1. Our results suggest that amino acids Ser(770) and Ser(771) mediate ERK-dependent activation of the Na(+)/H(+) exchanger in vivo.

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