Isoniazid Toxicity Medication

Updated: Jul 14, 2016
  • Author: Joseph L D'Orazio, MD, FAAEM; Chief Editor: BS Anand, MD  more...
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Medication

Medication Summary

Pyridoxine is the drug of choice for isoniazid (INH)-induced seizure or coma. If pyridoxine is not available, lorazepam or phenobarbital may be administered as a temporary measure to control seizures until sufficient pyridoxine is available.

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Vitamins, Water-Soluble

Class Summary

Vitamins are organic substances that are required by the body in small amounts for various metabolic processes, such as synthesis of gamma-aminobutyric acid (GABA) within the central nervous system (CNS). They may be synthesized in small or insufficient amounts in the body or may not be synthesized at all; supplementation thus may be required. Vitamins are used clinically for the prevention and treatment of specific vitamin deficiency states.

Pyridoxine (Vitamin B6)

Pyridoxine, also known as vitamin B-6, is the drug of choice for managing INH-induced seizures, metabolic acidosis, and mental status changes. It is involved in the synthesis of GABA within the CNS. INH depletes pyridoxine, thus decreasing the synthesis of GABA and increasing the potential for seizures.

For each 1 g of INH ingested, 1 g of parenteral pyridoxine should be given (max 5 g). If the quantity of INH ingested is unknown, empiric dosing of 70 mg/kg (max 5 g) is recommended.

If the parenteral form is not available, tablets can be crushed and given as a slurry; gram-for-gram replacement can also be carried out with pyridoxine tablets.

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Anticonvulsants, Other

Class Summary

Anticonvulsants are used to prevent seizure recurrence and terminate clinical and electrical seizure activity. Standard anticonvulsants, when used alone, may be ineffective in controlling seizures. Phenytoin should be used with caution, because INH may inhibit phenytoin metabolism.

Lorazepam (Ativan)

Lorazepam is the drug of choice for status epilepticus. It enhances the activity of GABA centrally to control seizures. Lorazepam may be administered intramuscularly (IM) if vascular access cannot be obtained.

Diazepam (Valium, Diastat)

Diazepam acts similarly to lorazepam, as it enhances GABA activity and causes sedation. It can also be administered rectally if vascular access cannot be obtained rapidly.

Midazolam

Midazolam is used as an alternative in the termination of refractory status epilepticus. Because it is water-soluble, it takes approximately 3 times longer to achieve peak electroencephalographic (EEG) effects than diazepam does. Thus, clinicians must wait 2-3 minutes to evaluate sedative effects fully before initiating procedures or repeating doses. It may be administered IM if vascular access cannot be obtained.

Phenobarbital

Phenobarbital works at the CNS GABA receptors to potentiate CNS inhibition. It exhibits anticonvulsant activity in anesthetic doses independently of GABA. Phenobarbital is the best-studied barbiturate in the treatment of status epilepticus. With phenobarbital, it is important to achieve therapeutic levels as quickly as possible. The intravenous (IV) dose may require approximately 15 minutes to attain peak levels in the brain. If the drug is injected continuously until convulsions stop, brain concentrations may continue to rise and can exceed that which is required to control seizures. It is important to use the minimal amount required and to wait for the anticonvulsant effect to develop before giving a second dose.

Propofol (Diprivan)

A phenolic compound unrelated to other types of anticonvulsants, propofol has general anesthetic properties when administered IV and acts independently of GABA. Propofol is a third-line agent and should be used for refractory status epilepticus. Intubation and ventilation are often required.

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