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Toxicology – Isoniazid (INH) Toxicity
Source
Isoniazid (INH) is a first-line antitubercular medication used to treat both latent and active tuberculosis. It is structurally related to pyridoxine (vitamin B6).
Typical Presentation
Acute overdose classically presents with severe, refractory seizures and metabolic acidosis. Children are particularly vulnerable, and toxicity may occur rapidly after ingestion. Chronic use is associated with liver injury and neurological complications.
Clinical Features
Acute Toxicity
Symptoms may begin within 30 minutes of ingestion and include:
Long-term exposure may cause:
INH interferes with pyridoxine (vitamin B6) metabolism, impairing pyridoxine-dependent enzymatic pathways. This leads to depletion of GABA and excess glutamate activity, predisposing patients to seizures.
Management
Treatment focuses on seizure control, airway stabilization, and reversal of vitamin B6 depletion:
Key Points
Source
Isoniazid (INH) is a first-line antitubercular medication used to treat both latent and active tuberculosis. It is structurally related to pyridoxine (vitamin B6).
Typical Presentation
Acute overdose classically presents with severe, refractory seizures and metabolic acidosis. Children are particularly vulnerable, and toxicity may occur rapidly after ingestion. Chronic use is associated with liver injury and neurological complications.
Clinical Features
Acute Toxicity
Symptoms may begin within 30 minutes of ingestion and include:
- Refractory seizures
- Altered mental status or coma
- Vomiting
- Slurred speech
- Hyperreflexia or hyporeflexia
- Tachycardia
- Oliguria
- High anion gap metabolic acidosis
- Elevated lactate levels
Long-term exposure may cause:
- Elevated liver enzymes and hepatitis
- Hepatocellular necrosis
- Peripheral neuropathy
- Optic neuritis
- Vitamin B6 deficiency
- Autoimmune manifestations (e.g., anemia, arthritis, eosinophilia)
INH interferes with pyridoxine (vitamin B6) metabolism, impairing pyridoxine-dependent enzymatic pathways. This leads to depletion of GABA and excess glutamate activity, predisposing patients to seizures.
Management
Treatment focuses on seizure control, airway stabilization, and reversal of vitamin B6 depletion:
- Benzodiazepines, propofol, or barbiturates for seizures
- Sodium bicarbonate for severe acidosis
- Supportive airway and hemodynamic management
- Ideally given gram-for-gram equal to the amount of INH ingested
- If the dose is unknown, an initial 5 g IV dose is recommended and may be repeated if seizures continue
Key Points
- Consider INH poisoning in patients with seizures unresponsive to standard anticonvulsants.
- Refractory seizures plus metabolic acidosis is highly suggestive.
- Pyridoxine is the definitive antidote.
- Chronic therapy may cause neuropathy and hepatotoxicity.
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