Isoniazid Poisoning

Isoniazid Poisoning is a topic covered in the 5-Minute Emergency Consult.

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Basics

Description

  • Complexes with and inactivates pyridoxal-5 phosphate, the active form of pyridoxine (vitamin B6)
  • Inhibits pyridoxine phosphokinase, hindering the conversion of pyridoxine to its active form
  • Yields a net decrease in γ-aminobutyric acid (GABA) production:
    • Depressed GABA causes cerebral excitability and seizures
  • Inhibits lactate dehydrogenase, decreasing the conversion of lactate to pyruvate:
    • Contributes to the profound anion gap metabolic acidosis
  • Chronic toxicity:
    • Interferes with synthesis of nicotinic acid (niacin)
    • May cause syndrome indistinguishable from pellagra after months of therapy (niacin deficiency)
  • Some actions similar to the monoamine oxidase inhibitors:
    • Reports of a tyramine-like reaction to isoniazid (INH)
    • Rare cases of mania, diaphoresis, depression, obsessive–compulsive disorder, and psychosis
  • Pharmacokinetics:
    • Rapidly absorbed, peak levels within 1–2 hr
    • Volume of distribution is 0.6 L/kg and protein binding is low (10%)
    • Renally excreted within 24 hr after acetylation in the liver
    • Half-life is <1 hr in fast acetylators and 2–4 hr in slow-acetylating individuals

Etiology

  • High-risk groups include:
    • Immigrants
    • Homeless
    • HIV infected
    • Alcoholics
    • Lower socioeconomic status populations
  • Slow acetylators (60% of African Americans and Whites compared to 20% of Asians) are more prone to chronic effects/toxicity
  • LD50 estimated at 80–150 mg/kg
  • Ingestions <1.5 g lead to mild toxicity, and those of 10 g or more often result in fatality

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Citation

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TY - ELEC T1 - Isoniazid Poisoning ID - 307467 Y1 - 2016 PB - 5-Minute Emergency Consult UR - https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307467/all/Isoniazid_Poisoning ER -