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| {{drugbox | | {| style="margin: 0 0 3em 3em; border: 1px solid #696969; float: right; width:20em" cellpadding="0" cellspacing="0"; |
| | IUPAC_name = pyridine-4-carbohydrazide | | ! style="padding: 0 5px; font-size: 100%; background:#F8F8FF" align=center | '''''[[Isoniazid|{{fontcolor|#6C7B8B|Isoniazid}}]]''''' |
| | image = Isoniazid skeletal.svg
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| | width =
| | ! style="padding: 0 5px; font-size: 85%; background:#F5F5F5" align=left |RIFATER (<sup>®</sup> FDA Package Insert |
| | CAS_number = 54-85-3
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| | ATC_prefix = J04 | | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid description|Description]] |
| | ATC_suffix = AC01 | | |- |
| | ATC_supplemental = | | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid clinical pharmacology|Clinical Pharmacology]] |
| | PubChem = 3767 | | |- |
| | DrugBank = APRD01055 | | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid microbiology|Microbiology]] |
| | C=6 | H=7 | N=3 | O=1
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| | molecular_weight = 137.139 g/mol
| | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid indications and usage|Indications and Usage]] |
| | bioavailability = | | |- |
| | protein_bound = Very low (0-10%)
| | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid contraindications|Contraindications]] |
| | metabolism = liver; CYP450: 2C19, 3A4 inhibitor
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| | elimination_half-life = 0.5-1.6h (fast acetylators), 2-5h (slow acetylators)
| | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid warnings and precautions|Warnings and Precautions]] |
| | excretion = urine (primarily), feces
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| | pregnancy_category = C
| | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid adverse reactions|Adverse Reactions]] |
| | legal_status = prescription only (US) | | |- |
| | routes_of_administration = oral, intramuscular, intravenous }}
| | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid overdosage|Overdosage]] |
| {{SI}}
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| | | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid clinical studies|Clinical Studies]] |
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| '''Isoniazid''' is also called '''isonicotinyl hydrazine''' or '''INH'''. Isoniazid is a first-line antituberculous medication used in the prevention and treatment of [[tuberculosis]]. Isoniazid is never used on its own to treat active tuberculosis because resistance quickly develops.
| | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid dosage and administration|Dosage and Administration]] |
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| Isoniazid is used in the treatment of mycobacterial infection. It was discovered in 1952, when for the first time, a cure for tuberculosis was considered reasonable. It is available in tablet, syrup, and injectable forms (given intramuscularly or intravenously). Isoniazid is available world-wide, is inexpensive to produce and is generally well tolerated.
| | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid how supplied|How Supplied]] |
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| ==Mechanism of action== | | ! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left |[[Isoniazid labels and packages|Labels and Packages]] |
| Isoniazid is a [[prodrug]] and must be activated by bacterial catalase. It is activated by catalase-peroxidase enzyme katG to form isonicotinic acyl anion or radical. These forms will then react with a [[NADH]] radical or anion to form isonicotinic acyl-NADH complex. This complex will bind tightly to ketoenoylreductase known as InhA and prevents access of the natural enoyl-AcpM substrate. This mechanism inhibits the synthesis of [[mycolic acid]] in the [[mycobacterium|mycobacterial]] cell wall.
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| Isoniazid reaches therapeutic concentrations in serum, [[cerebrospinal fluid]] (CSF), and within caseous granulomas. Isoniazid is metabolized in the liver via [[acetylation]]. There are two forms of the enzyme responsible for acetylation, so that some patients metabolize the drug quicker than others. Hence, the [[half-life]] is [[Bimodal_distribution|bimodal]] with peaks at 1 hour and 3 hours in the US population. The metabolites are excreted in the urine. Doses do not usually have to be adjusted in case of [[renal failure]].
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| Isoniazid is [[bactericidal]] to rapidly-dividing [[mycobacterium|mycobacteria]], but is [[bacteriostatic]] if the mycobacterium is slow-growing.
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| ==Dosing== | |
| The standard dose of isoniazid is 3-5mg/kg/day (max 300mg daily).
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| When prescribed intermittently (twice or thrice weekly) the dose is 15mg/kg (max 900mg daily).
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| ==Side effects== | |
| Adverse reactions include [[rash]], abnormal [[liver function tests]], [[hepatitis]], [[sideroblastic anemia]], [[peripheral neuropathy]], mild [[central nervous system]] (CNS) effects, and drug [[interaction]]s resulting in increased [[phenytoin]] (Dilantin) or [[disulfiram]] (Antabuse) levels.
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| [[Peripheral neuropathy]] and [[Central nervous system|CNS]] effects are associated with the use of isoniazid and are due to [[pyridoxine]] (vitamin B6) depletion, but are 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.
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| Hepatoxicity can be avoided with close clinical monitoring of the patient, specifically nausea, vomiting, abdominal pain and appetite.
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| Headache, poor concentration, poor memory and depression have all been associated with isoniazid use. The frequency of these side effects is not known, and the association with isoniazid is not well validated. The presence of these symptoms is not frequently disabling and is certainly ''not'' a reason to stop treatment with isoniazid; the patient should be strongly encouraged to continue treatment despite these symptoms. It must be explained to the patient that the harm done from not taking isoniazid far outweighs the problems arising from these symptoms.
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| INH therapy will decrease the efficacy of hormonal birth control when combined with Rifampin.
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| ==Synonyms and abbreviations==
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| * Isonicotinyl hydrazine
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| * Isonicotinic acid hydrazide
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| * INH
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| * H (for "hydrazide", and also the [[World Health Organisation|WHO]] standard abbreviation)
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| ==Wikipedia links== | |
| *[[Tuberculosis treatment]]
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| *[[Tuberculosis]]
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| *''[[Mycobacterium tuberculosis]]''
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| ==References== | |
| *[http://www.cdc.gov/nchstp/tb/pubs/corecurr/default.htm Core Curriculum on Tuberculosis (2000)] Division of Tuberculosis Elimination, Centers for Disease Control and Prevention
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| See Chapter 6, Treatment of LTBI Regimens - [http://www.cdc.gov/nchstp/tb/pubs/corecurr/Chapter6/Chapter_6_Regimens.htm Isoniazid]
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| <br>See Chapter 7 - Treatment of TB Disease Monitoring - [http://www.cdc.gov/nchstp/tb/pubs/corecurr/Chapter7/Chapter_7_Monitoring.htm Adverse Reactions to First-Line TB Drugs - Isoniazid]
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| <br>See Table 5 [http://www.cdc.gov/nchstp/tb/pubs/corecurr/Tables/table5.htm First-Line Anti-TB Medications]
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| *[http://www.aafp.org/afp/980215ap/romero.html Isoniazid Overdose: Recognition and Management] American Family Physician 1998 Feb 15
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| {{Antimycobacterials}}
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| [[Category:Antibiotics]]
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| [[Category:Hydrazines]] | |
| [[Category:Prodrugs]]
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| [[Category:Pyridines]]
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| [[Category:Tuberculosis]]
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| [[ar:إيزونيازيد]]
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| [[de:Isoniazid]] | |
| [[es:Isoniacida]]
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| [[fa:ایزونیازید]]
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| [[fr:Isoniazide]]
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| [[nl:Isoniazide]]
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| [[nn:Isoniazid]] | |
| [[pl:Izoniazyd]]
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| {{WH}}
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| {{WS}}
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