Intravenous pyridoxine is used in high doses to control the metabolic acidosis and seizures associated with isoniazid overdose and poisoning from other hydrazine compounds (Gyromitra mushrooms and jet/rocket fuel). It is also used as a adjunct to ethylene glycol toxicity
Mechanism of action:
Vitamin B6 or pyridoxal-5-phosphate (P5P) is the active form of pyridoxine. P5P is essential for many enzymatic reactions but importantly for the conversion of L-glutamic acid to GABA. In an hydrazine overdose (typically isoniazid) P5P is inhibited, effectively inhibiting the production of GABA and promoting seizures. Large doses of P5P (vitamin B6) are required to overcome the inhibition.
- 1 g of pyridoxine for each gram of isoniazid ingested up to a maximum go 5 g (70mg/kg in children).
- Give this dose at 0.5 g/minute until the seizures stop or the infusion is complete. The remainder of the dose is administered over 4 hours.
- If the ingested dose of isoniazid is unknown, give 5 g of pyridoxine empirically.
- Benzodiazepines are also given for their synergistic effect on seizure control and also as a temporising measure while multiple vials are procured (they are usually in 50mg vials therefore a large overdose will require 100 vials).
Hydrazine or monomethylhdrazine poisoning:
- Administer an initial bolus of 25 mg/kg IV.
Ethylene glycol poisoning:
- Give 50 mg IV every 6 hours.
- Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. European Journal of Emergency Medicine 2005; 12:78-85.