Isoniazid (INH), a hydrazide derivative of isonicotinic acid, is an inexpensive and effective treatment for tuberculosis. INH is well-known for its propensity to cause hepatitis with chronic use. Acute INH overdose is a well-known cause of drug-induced seizures and metabolic acidosis.

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   Mechanism of toxicity

   
   
   
   
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      Acute overdose. INH produces acute toxic effects by reducing brain pyridoxal 5-phosphate, which is the active form of vitamin B6 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 electric activity manifested as seizures. INH may also inhibit the hepatic conversion of lactate to pyruvate, exacerbating the lactic acidosis resulting from seizures.

      
      
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      Chronic toxicity. Peripheral neuropathy, presenting in a stocking-glove distribution, is thought to be related to pyridoxine deficiency. It is the most common complication of chronic INH therapy. The mechanism of INH-induced hepatitis involves two pathways: an autoimmune mechanism and, more commonly, direct hepatic injury by INH and its metabolites. Hepatocellular necrosis is the most alarming adverse effect of chronic therapeutic INH.

      
      
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      Pharmacokinetics.

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