Abstract
Background
Pyridoxine (vitamin B6) is used as an antidote for isoniazid (INH) overdose, especially
in intentional ingestions. The active form of pyridoxine is pyridoxal 5′-phosphate
(P5P), a cofactor for glutamic acid decarboxylase in gamma aminobutyric acid (GABA)
synthesis. INH inhibits this enzymatic pathway causing a decrease in brain levels
of GABA, the major inhibitory neurotransmitter in the central nervous system, with
resultant increase in susceptibility to seizures. The aim of this study was to evaluate
and document the role of pyridoxine in the treatment of patients with intentional
ingestion of INH and to report our experience.
Methods
Medical records of affected patients were reviewed; data collected included exposure
history, clinical manifestations, physical examination, laboratory values and clinical
outcomes.
Results
There were 16 cases of INH intoxication associated with intentional ingestions, 11
were associated with substantial ingestions with the maximum dose ingested being 15 g.
In 9 cases the patients suffered seizures while other clinical manifestations included
hypertension, drowsiness and vomiting. Pyridoxine was administered prophylactically
in only 3 patients, none of whom developed seizures.
Conclusion
Intentional ingestion of INH is one of the causes of drug-induced seizures. Early
recognition and specific treatment with pyridoxine can prevent mortality. Our series
suggests that patients with large-dose intentional ingestions have a substantial risk
of multiple seizures that can be treated successfully with 1 g of pyridoxine intravenously
or 1 g of pyridoxine per gram of isoniazid ingestion. This antidote is safe and effective.
Consideration can be given to administering pyridoxine prophylactically in some circumstances.
Keywords
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References
- Pyridoxal-5′-phosphate-dependent enzymes involved in biotin biosynthesis: structure, reaction mechanism and inhibition.Biochim Biophys Acta - Proteins Proteomics. 2011; 1814: 1459-1465https://doi.org/10.1016/j.bbapap.2010.12.004
- Hydrosoluble vitamins.Handb Clin Neurol. 2014; 120: 891-914https://doi.org/10.1016/B978-0-7020-4087-0.00059-0
- Near fatal poisoning by isoniazid and rifampicin.J Assoc Physicians India. 2016; 64: 88-89https://doi.org/10.5958/0973-9130.2016.00034.7
- Isoniazid-induced status epilepticus in a pediatric patient after inadequate pyridoxine therapy.Pediatr Emerg Care. 2010; 26: 380-381https://doi.org/10.1097/PEC.0b013e3181db24b6
- Convulsive seizures with a therapeutic dose of isoniazid.Intern Med. 2014; 53: 239-242https://doi.org/10.2169/internalmedicine.53.1303
- Poisoning due to raw Gyromitra esculenta (false morels) west of the Rockies.Can J Emerg Med. 2007; 9: 127-130
- Pyridoxine in clinical toxicology: a review.Eur J Emerg Med. 2005; 12: 78-85https://doi.org/10.1097/00063110-200504000-00007
- The utilization of intravenously infused pyridoxine in humans.Clin Chim Acta. 1994; 229: 27-36https://doi.org/10.1016/0009-8981(94)90226-7
- Isoniazid: a review of characteristics, properties and analytical methods.Crit Rev Anal Chem. 2017; 47: 298-308https://doi.org/10.1080/10408347.2017.1281098
- Isoniazid overdose treated with high-dose pyridoxine.Ann Emerg Med. 1983; 12: 303-305https://doi.org/10.1016/S0196-0644(83)80514-9
- Suicidal psychosis secondary to isoniazid.Pediatr Emerg Care. 2002; 18: 25-27https://doi.org/10.1097/00006565-200202000-00008
- Isoniazid-induced reduction in GABAergic neurotransmission alters the function of the cerebellar cortical circuit.Neuroscience. 2008; 154: 710-719https://doi.org/10.1016/j.neuroscience.2008.02.024
- Treatment of drug-induced seizures.Br J Clin Pharmacol. 2016; 81: 412-419https://doi.org/10.1111/bcp.12720
- Seizures, metabolic acidosis and coma resulting from acute isoniazid intoxication.Anaesth Intensive Care. 2005; 33: 518-520
- Acute isoniazid intoxication: an uncommon cause of convulsion, coma and acidosis.Tuberk Toraks. 2013; 61: 50-53https://doi.org/10.5578/tt.1897
- Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids.Int J Tuberc Lung Dis. 1999; 3: 703-710
- Rhabdomyolysis in isoniazid poisoning.J ToxicolClinToxicol. 2001; 39: 143-151https://doi.org/10.1081/CLT-100103830
- Treatment of acute isoniazid toxicity.Am J Hosp Pharm. 1975; 32: 202-206https://doi.org/10.1097/01.SMJ.0000049841.49028.41
- Pyridoxine responsive seizures secondary to isoniazid prophylaxis in an infant.Neurol India. 2017; 65: 94
- Coma caused by isoniazid poisoning in a patient treated with pyridoxine and hemodialysis.Adv Ther. 2008; 25: 1085-1088https://doi.org/10.1007/s12325-008-0098-7
- Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome.N Engl J Med. 1983; 309: 445-448https://doi.org/10.1056/NEJM198308253090801
- Acute sensory neuropathy-neuronopathy from pyridoxine overdose.Neurology. 1987; 37: 1729-1732https://doi.org/10.1212/WNL.37.11.1729
Article Info
Publication History
Published online: February 03, 2018
Accepted:
January 25,
2018
Received in revised form:
January 25,
2018
Received:
November 22,
2017
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
