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    ISONIAZID

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    Isoniazid is the first-line medication used for preventing and treating tuberculosis. It was first discovered in 1912 and found to be effective against tuberculosis in 1951. Isoniazid is a prodrug that must be activated by the bacterial enzyme KatG to inhibit the synthesis of mycolic acid, a key component of the mycobacterial cell wall. Common side effects include rash, hepatitis, and peripheral neuropathy, which can be prevented by supplemental pyridoxine. Isoniazid is metabolized in the liver and excreted in urine, with slow acetylators having a higher risk of toxicity due to higher blood concentrations.

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    ISONIAZID

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    Isoniazid is the first-line medication used for preventing and treating tuberculosis. It was first discovered in 1912 and found to be effective against tuberculosis in 1951. Isoniazid is a prodrug that must be activated by the bacterial enzyme KatG to inhibit the synthesis of mycolic acid, a key component of the mycobacterial cell wall. Common side effects include rash, hepatitis, and peripheral neuropathy, which can be prevented by supplemental pyridoxine. Isoniazid is metabolized in the liver and excreted in urine, with slow acetylators having a higher risk of toxicity due to higher blood concentrations.

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    Isoniazid is the first-line medication used for preventing and treating tuberculosis. It was first discovered in 1912 and found to be effective against tuberculosis in 1951. Isoniazid is a prodrug that must be activated by the bacterial enzyme KatG to inhibit the synthesis of mycolic acid, a key component of the mycobacterial cell wall. Common side effects include rash, hepatitis, and peripheral neuropathy, which can be prevented by supplemental pyridoxine. Isoniazid is metabolized in the liver and excreted in urine, with slow acetylators having a higher risk of toxicity due to higher blood concentrations.

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    298 views2 pages

    ISONIAZID

    Uploaded by

    Poet POet PoEt
    Isoniazid is the first-line medication used for preventing and treating tuberculosis. It was first discovered in 1912 and found to be effective against tuberculosis in 1951. Isoniazid is a prodrug that must be activated by the bacterial enzyme KatG to inhibit the synthesis of mycolic acid, a key component of the mycobacterial cell wall. Common side effects include rash, hepatitis, and peripheral neuropathy, which can be prevented by supplemental pyridoxine. Isoniazid is metabolized in the liver and excreted in urine, with slow acetylators having a higher risk of toxicity due to higher blood concentrations.

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    ISONIAZID

    Isoniazid (Laniazid, Nydrazid), also known as isonicotinylhydrazine (INH), is an


    organic compound that is the first-line antituberculosis medication in prevention
    and treatment. It was first discovered in 1912, and later in 1951 it was found to
    be effective against tuberculosis. Isoniazid is never used on its own to treat
    active tuberculosis because resistance quickly develops. Isoniazid also has an
    antidepressant effect, and it was one of the first antidepressants discovered.

    The compound was first synthesised in the early 20th century,[1] but its activity
    against tuberculosis was first reported in the early 1950's and three
    pharmaceutical companies attempted unsuccessfully to simultaneously patent
    the drug[2] (most prominently, Roche, who launched their version, Rimifon, in
    1952). With the introduction of isoniazid, a cure for tuberculosis was first
    considered reasonable.

    Isoniazid is available in tablet, syrup, and injectable forms (given intramuscularly


    or intravenously). Isoniazid is available worldwide, is inexpensive and is generally
    well tolerated. It is manufactured from isonicotinic acid, which is produced from
    4-methylpyridine.[3]

    Mechanism of action

    Isoniazid is a prodrug and must be activated by a bacterial catalase-peroxidase


    enzyme called KatG.[5] KatG couples the isonicotinic acyl with NADH to form
    isonicotinic acyl-NADH complex. This complex binds tightly to
    ketoenoylreductase known as InhA, thereby blocking the natural enoyl-AcpM
    substrate and the action of fatty acid synthase. This process inhibits the
    synthesis of mycolic acid, required for the mycobacterial cell wall. A range of
    radicals are produced by KatG activation of Isoniazid, including nitric oxide[6]
    which has also been shown to be important in the action of another
    antimycobacterial prodrug PA-824.[7]

    Isoniazid is bactericidal to rapidly-dividing mycobacteria but is bacteriostatic if


    the mycobacterium is slow-growing.[citation needed] Isoniazid inhibits the P450
    system.Template:Pharmacology,Harvey 4th edition

    Dosing

    The standard dose of isoniazid in adults is 5 mg/kg/day (max 300mg daily). When
    prescribed intermittently (twice or thrice weekly) the dose is 15mg/kg (max
    900mg daily). Patients with slow clearance of the drug (via acetylation as
    described above) may require reduced dosages to avoid toxicity. The
    recommended dose for children is 8 to 12 mg/kg/day.[8]
    Side effects

    Adverse reactions include rash, abnormal liver function tests, hepatitis,


    sideroblastic anemia, high anion gap metabolic acidosis, peripheral neuropathy,
    mild central nervous system (CNS) effects, drug interactions resulting in
    increased phenytoin (Dilantin) or disulfiram (Antabuse) levels and intractable
    seizures (status epilepticus).

    Peripheral neuropathy and 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.

    Hepatotoxicity can be avoided with close clinical monitoring of the patient,


    specifically nausea, vomiting, abdominal pain and appetite. Isoniazid is
    metabolized by the liver mainly by acetylation and dehydrazination. The N-
    acetylhydrazine metabolite is believed to be responsible for the hepatotoxic
    effects seen in patients treated with isoniazid. The rate of acetylation is
    genetically determined. Approximately 50% of blacks and Caucasians are slow
    inactivators; the majority of Inuit and Asians are rapid inactivators. The half-life
    in fast acetylators is 1 to 2 hours while in slow acetylators it is 2 to 5 hours.
    Elimination is largely independent of renal function, however the half-life may be
    prolonged in liver disease. The rate of acetylation has not been shown to
    significantly alter the effectiveness of isoniazid. However, slow acetylation may
    lead to higher blood concentrations with chronic administration of the drug, with
    an increased risk of toxicity. Isoniazid and its metabolites are excreted in the
    urine with 75 to 95% of the dose excreted in 24 hours. Small amounts are also
    excreted in saliva, sputum and feces. Isoniazid is removed by hemodialysis and
    peritoneal dialysis.[9]

    Headache, poor concentration, weight-gain, poor memory and depression have


    all been associated with isoniazid use. All patients and health-care workers
    should be aware of these serious adverse effects, especially if suicidal thinking or
    behavior are suspected.[10][11][12]

    INH therapy will decrease the efficacy of hormonal birth control when combined
    with Rifampin.

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