Isoniazid acute toxicity

Hepafotoxicity from chronic paracetamol (acetaminophen) therapy in adults have been reported in the literature, but compared to the acute toxicity seen with deliberate or accidental overdoses, these are very few. The majorify of fhese are associafed wifh chronic efhanol intake, smoking, isoniazid, rifampin, phenobarbifal and phenyfoin (inducers of the cytochrome P450 system). Short-term fasting and... 

A. Acute overdose. Isoniazid produces acute toxic effects by reducing brain pyridoxal 5-phosphate, which is the active form of vitamin Bg and an essential cofactor for the enzyme glutamic acid decarboxylase. This results in lower CNS levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which leads to uninhibited electrical activity manifested as seizures. INH may also Inhibit the hepatic conversion of lactate to pyruvate, exacerbating the lactic acidosis from seizures. 

A. Specific levels. Isoniazid Is not usually detected in routine toxicology screening. Specific levels may be obtained but are rarely available or helpful for management of acute overdoses. A 5 mg/kg dose produces a peak INH concentration of 3 mg/L at 1 hour (1-7 mg/L is considered antitubercular). Semm levels higher than 30 mg/L are associated with acute toxicity. 

Acute poisoning with isoniazid in children (48) and adults (13,26,35) 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/kg often produce seizures and 80-150 mg/kg or more can be rapidly fatal. The first signs and symptoms of isoniazid toxicity usually appear 0.5-2.0 hours after ingestion, by which time peak absorption occurs (49), and include nausea, vomiting, slurred speech, dizziness, tachycardia, and urinary... 

Gilhotra R, Malik SK, Singh S, Sharma BK. Acute isoniazid toxicity—report of 2 cases and review of literature. Int J Clin Pharmacol Ther Toxicol 1987 25(5) 259-61. 

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