Isoniazid
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Isoniazid is a first-line antituberculous medication used in the prevention and treatment of tuberculosis. It is often prescribed under the name INH. The chemical name is isonicotinyl hydrazine or isonicotinic acid hydrazide.
It is available in tablet, syrup, and injectable forms (given via intramuscular injection), available world-wide, inexpensive to produce, and is generally well tolerated.
Mechanism of action
Isoniazid inhibits the mycolic acid cell wall synthesis via oxygen-dependent pathways, such as the catalase-peroxidase reaction. It reaches therapeutic concentrations is serum, cerebrospinal fluid (CSF), and within caseous granulomas.
Isoniazid is metabolized in the liver via acetylation and hydrolysis. Metabolites are excreted in the urine. Doses do not usually have to be adjusted in case of renal failure.
Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.
Side effects
Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects, and drug interactions resulting in increased phenytoin (Dilantin) or disulfiram (Antabuse) levels.
Peripheral neuropathy and CNS effects are associated with the use of isoniazid and is due to pyridoxine (vitamin B6) depletion, but is uncommon at doses of 5 mg/kg. Persons with conditions in which neuropathy is common (e.g., diabetes, uremia, alcoholism, malnutrition, HIV-infection), as well as pregnant women and persons with a seizure disorder, may be given pyridoxine (vitamin B6) (10-50 mg/day) with isoniazid.
Reference
- Core Curriculum on Tuberculosis (2000) (http://www.cdc.gov/nchstp/tb/pubs/corecurr/default.htm) Division of Tuberculosis Elimination, Centers for Disease Control and Prevention
See Chapter 6, Treatment of LTBI Regimens - Isoniazid (http://www.cdc.gov/nchstp/tb/pubs/corecurr/Chapter6/Chapter_6_Regimens.htm)
See Chapter 7 - Treatment of TB Disease Monitoring - Adverse Reactions to First-Line TB Drugs - Isoniazid (http://www.cdc.gov/nchstp/tb/pubs/corecurr/Chapter7/Chapter_7_Monitoring.htm)
See Table 5 First-Line Anti-TB Medications (http://www.cdc.gov/nchstp/tb/pubs/corecurr/Tables/table5.htm)
- Isoniazid Overdose: Recognition and Management (http://www.aafp.org/afp/980215ap/romero.html) American Family Physician 1998 Feb 15