2020年10月31日 星期六

Isoniazid Intoxication

Substance

 Isoniazid (one of the anti-TB regimen, some are accidental. Some are intentional)

-       Accounts for 5% of Intoxication related seizure


Common name or Trade name

INH

 

Involving system

- In adults, toxicity can occur with the acute ingestion of as little as 1.5 g of isoniazid. [1]

- ingested in amounts of 80 to 150 mg per kg or more, isoniazid can be rapidly fatal. [1]

- CNS: Doses larger than 30 mg per kg often produce seizures. [1]

Mechanism: This reduction in GABA levels increases the susceptibility to seizures. [1]

 

 Presentation

-       nausea, vomiting, slurred speech, dizziness, tachycardia, and urinary retention

-       stupor [1]

-       seizure [1, 2]

-       intractable seizure, acidosis, metabolic acidosis and coma [1, 3, 4]

-       dementia [5]

-       status epilepticus in children [6]

-       elevated anion gap and metabolic acidosis, hyperglycemia, hypokalemia, glucosuria, and ketonuria [1]

 

Antidote and Treatment 

-       Decontamination, irrigation, Charcoal 50 gm, 1gm/ kg

-       BZD for seizure, valium IV.

-       pyridoxine intravenously [6]

-       If the amount of ingested isoniazid is unknown, 5 g of pyridoxine is given intravenously over five to 10 minutes [1]

(Dose: Given in gram-per-gram amounts of the isoniazid ingested, pyridoxine (vitamin B6) usually eliminates seizure activity and helps to correct the patient's metabolic acidosis. [1])

Mechanism: -      pyridoxine is a necessary cofactor for the production of the neurotransmitter gamma-aminobutyric acid (GABA). Pyridoxine must be activated to produce GABA. [1]

-       NaHCO3-, if the ABG pH is less than 7.1. A good starting dose is 1 to 3 mEq per kg

-       continuous veno-venous hemodiafiltration [2]

Disposition 

-       consult social worker, psychiatrist, suicide prevention unit.

-       Depends individualized.

  

REFERENCES

 

[1] Romero JA, Kuczler FJ Jr. Isoniazid overdose: recognition and management. Am Fam Physician. 1998 Feb 15;57(4):749-52. PMID: 9490997.

 

[2]. Skinner K, Saiao A, Mostafa A, Soderstrom J, Medley G, Roberts MS, Isbister GK. Isoniazid poisoning: Pharmacokinetics and effect of hemodialysis in a massive ingestion. Hemodial Int. 2015 Oct;19(4):E37-40. doi: 10.1111/hdi.12293. Epub 2015 Mar 16. PMID: 25779481.

 

[3]. Khoharo HK, Ansari S, Abro A, Qureshi F. Suicidal Isoniazid poisoning. J Ayub Med Coll Abbottabad. 2009 Apr-Jun;21(2):178-9. PMID: 20524502.

 

[4] Kürşad H, Kizilkaya M, Sahin M, Dogan N, Ilgaz A. Treatment of acute isoniazid toxicity of unknown dose. South Med J. 2003 Jan;96(1):101. doi: 10.1097/01.SMJ.0000049841.49028.41. PMID: 12602731.  

 

[5]. McLay RN, Drake A, Rayner T. Persisting dementia after isoniazid overdose. J Neuropsychiatry Clin Neurosci. 2005 Spring;17(2):256-7. doi: 10.1176/jnp.17.2.256. PMID: 15939987.

 

[6] Caksen H, Odabas D, Erol M, Anlar O, Tuncer O, Atas B. Do not overlook acute isoniazid poisoning in children with status epilepticus. J Child Neurol. 2003 Feb;18(2):142-3. doi: 10.1177/08830738030180021101. PMID: 12693784.


~~~~~~~ edited by Yu-Jang Su Oct 31, 2020 ~~~~~~