Isoniazid Poisoning

Basics

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

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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