Isoniazid (INH) poisoning
- Rama B Rao, MD
Rama B Rao, MD
- Assistant Professor Emergency Medicine and Medical Toxicology
- Weill Cornell Medical Center, Cornell University
- Section Editors
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Michele M Burns, MD, MPH
Michele M Burns, MD, MPH
- Section Editor — Pediatric Toxicology
- Assistant Professor of Pediatrics and Emergency Medicine
- Harvard Medical School
- Deputy Editor
- Jonathan Grayzel, MD, FAAEM
Jonathan Grayzel, MD, FAAEM
- Senior Deputy Editor — UpToDate
- Deputy Editor — Emergency Medicine (Adult and Pediatric)
- Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Assistant Professor of Emergency Medicine
- University of Massachusetts Medical School
Isoniazid (INH) is an antibiotic used to treat infection with Mycobacterium tuberculosis (TB). A large portion of the world's population is infected with TB. Although the disease is inactive in the majority, up to 10 percent of these persons may become infectious in their lifetime [1-3]. Many patients who are identified as being at risk of developing active, infectious TB or who suffer from active disease are treated with INH.
Acute INH toxicity frequently manifests as altered mental status or seizures. Poisoning may occur with unintentional ingestion in children, suicidal intent, or in patients taking extra tablets to compensate for missed doses [4-6]. Chronic INH toxicity frequently manifests as peripheral neuropathy or hepatotoxicity, although other chronic conditions are described.
The presentation and management of acute INH poisoning will be reviewed here. Chronic INH hepatotoxicity and the clinical use of INH are discussed separately. (See "Isoniazid hepatotoxicity" and "Isoniazid: An overview".)
PHARMACOLOGY AND CELLULAR TOXICOLOGY
The antimicrobial activity of Isoniazid (INH) is selective for mycobacteria, probably resulting from its ability to inhibit mycolic acid synthesis. This inhibition interferes with cell wall synthesis, producing a bactericidal effect. (See "Isoniazid: An overview".)
INH toxicity stems from several causes, including deficiencies of pyridoxine (vitamin B6) and gamma amino butyric acid (GABA). INH induces a state of functional pyridoxine deficiency by at least two mechanisms. First, INH metabolites directly attach to and inactivate pyridoxine species. Second, INH inhibits the enzyme pyridoxine phosphokinase; this enzyme is necessary to activate pyridoxine to pyridoxal 5' phosphate, the cofactor in many "pyridoxine-dependent" reactions. Functional pyridoxine deficiency is the likely mechanism of INH-induced peripheral neuropathy.
- World Health Organization. www.Who.int/mediacentre/factsheets/fs104/en/index.html (Accessed on July 18, 2009).
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- PHARMACOLOGY AND CELLULAR TOXICOLOGY
- CLINICAL FEATURES OF ACUTE TOXICITY
- CLINICAL FEATURES OF CHRONIC TOXICITY
- Peripheral neuropathy
- DIFFERENTIAL DIAGNOSIS
- LABORATORY EVALUATION
- MANAGEMENT OF ACUTE TOXICITY
- Airway management
- Gastrointestinal decontamination
- Seizure management
- - Pyridoxine
- - Benzodiazepines
- - Other sedative hypnotic medications
- - Phenytoin and fosphenytoin
- Metabolic acidosis
- Enhanced elimination
- Prolonged coma
- PEDIATRIC CONSIDERATIONS
- ADDITIONAL RESOURCES
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS