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02-07-11 How does pyridoxine work as the antidote for INH poisoning?

Question of the Week
February 7, 2011
 
 
How does pyridoxine work as the antidote for INH poisoning?
 Isoniazid (INH) is used for the treatment of active and latent tuberculosis because of its interaction with mycobacterial enzymes; however, INH also creates a net deficiency of pyridoxine. INH and its metabolites bind to pyridoxine and pyridoxal 5’ phosphate (the activated form) and enhance their renal elimination. One of the metabolites of INH also inhibits the enzyme which converts pyridoxine to its active form.  Pyridoxine’s activated form, pyridoxal 5’ phosphate, is the cofactor needed for production of GABA, an inhibitory neuron in the brain. GABA is actually created from glutamic acid which is one of the most excitatory neurotransmitters in the brain.  With an INH overdose, there is less GABA and more excitatory glutamic acid. Convulsions occur and do not cease with administration of typical anticonvulsant therapies, most of which rely on GABA being present in order for them to work. Treatment with high dose pyridoxine will stop the convulsions.
Once adequate dosing of the pyridoxine is given, additional anticonvulsant therapy is not needed; however, many patients remain sedated from the dosage of benzodiazepines they received.
 
 
This question prepared by:  Saralyn Williams, MD  Medical Toxicologist
 

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