Isoniazid

Prepared by:
Nahry Omer Muhammad
 Contents
• Introduction
• Mechanism of action
• Pharmacokinetics
• Dosage and Administration
• Contraindications
• Drug Interactions
• Adverse Reactions/Side effects
• Precautions
• Overdosage
• Patient Information
Synonyms and Abbreviations

• Isonicotinyl hydrazine
• Isonicotinic acid hydrazide
• INH
• H (for "hydrazide", and also
the WHO standard abbreviation)
 Trade Name
• Nydrazid:
-Injection: 100mg/ml
• Isoniazid
- Tablets 100 mg
- Tablets 300 mg
- Tablets 500 mg
- Syrup 50 mg/5 mL
• Isotamine
• Laniazid
 Isoniazid
• first-line medication in prevention and treatment of
Tuberculosis.
• Synthesized in the early 20th century.
• Isoniazid is available in tablet, syrup, and injectable
forms (given intramuscularly or intravenously).
• Isoniazid is manufactured from isonicotinic acid,
which is produced from 4-methylpyridine.
 CLASSIFICATION OF DRUGS USED IN ANTI-
TUBERCULOSIS TREATMENT
FIRST LINE DRUGS SECOND LINE DRUGS
• ISONIAZIDE • AMIKACIN
• RIFAMPIN • AMINOSALICYCLIC ACID
• PYRAZINAMIDE • CAPREOMYCIN
• ETHAMBUTOL • CIPROFLOXACIN
• STREPTOMYCIN • CLOFAZIMINE
• CYCLOSERINE
• ETHIONAMIDE
• LEVOFLOXACIN
• RIFABUTIN
• RIFAPENTINE
 MECHANISM OF ACTION
• Inhibit synthesis of Mycolic acid.
• It’s a pro drug activated by KatG.
• Resistance to INH is associated with overexpression
of inhA.
• Overproducers of inhA express low level INH
resistance & cross resistance to ethionamide.
• KatG mutants express high level of INH resistance &
usually no cross resistance to ethionamide.
 Pharmacokinetics
• Absorption: T max is 1 to 2 h.
• Distribution: Diffuses readily into cerebrospinal, pleural,
and ascitic fluids, tissues, organs, saliva, sputum, feces,
placental barrier, and in breast milk.
• Metabolism: Primarily by acetylation and
dehydrazination.
• Elimination: 50% to 70% excreted in the urine in 24 h.
 Dosage and Administration
• Tuberculosis:
Adults
• PO / IM 5 mg/kg/day as single daily dose (max,
300 mg/day) or 15 mg/kg 2 to 3 times/wk (max, 900 mg).
• Infants and Children
• PO / IM 10 to 20 mg/kg/day in single daily dose (max,
300 mg/day) or 20 to 40 mg/kg 2 or 3 times/week (max,
400 mg).
 Contraindications
• Previous isoniazid-associated hepatic injury
• Drug fever
• Chills
• Arthritis
• Acute liver disease.
• Pregnant women.
• Breast feeding women
 Drug Interactions
• Aluminum salts
• Carbamazepine
• Disulfiram
• Enflurane
• Hydantoins
• Rifampin
 Adverse Reactions
• CNS: Peripheral neuropathy; convulsions; toxic encephalopathy; optic
neuritis and atrophy; memory impairment; toxic psychosis.
• Dermatologic: Morbilliform, maculopapular, purpuric, or exfoliative skin
eruptions.
• GIT: Nausea; vomiting; epigastric distress.
• Hematologic: Agranulocytosis; hemolytic, sideroblastic, or aplastic
anemia; thrombocytopenia; eosinophilia.
• Hepatic: Hepatotoxicity, including elevated serum transaminase levels,
bilirubinemia, bilirubinuria, jaundice, severe and sometimes fatal hepatitis.
• Metabolic: Pyridoxine deficiency; pellagra; hyperglycemia; metabolic
acidosis; hypocalcemia; hypophosphatemia.
• Miscellaneous: Gynecomastia; rheumatic syndrome; systemic lupus
erythematosus-like syndrome; local irritation at IM injection site.
 Precautions
• Pregnancy
• Lactation
• Hypersensitivity
• Renal Function
• Hepatic Function
• Pyridoxine administration
 Overdosage
Symptoms:
Nausea, vomiting.
dizziness, slurring of speech.
blurring of vision, visual hallucinations.
respiratory distress, CNS depression.
stupor, coma.
severe seizures (Diazepam (Valium), 5 to 10 mg).
 Patient Information
• Advise patient to minimize daily alcohol consumption while
taking isoniazid because of the increased risk of hepatitis.
• Instruct patient to report the following symptoms to health
care provider: weakness; fatigue; loss of appetite; nausea and
vomiting; yellowing of skin or eyes; darkening of urine;
numbness or tingling in hands or feet.
• Emphasize to patient that treatment will be lengthy and that
patient must complete entire course of therapy. Relapse of
tuberculosis is higher if chemotherapy is discontinued
prematurely.
• Advise patient to return for laboratory follow-up.
• Caution patient not to perform activities that require mental
alertness if adverse CNS symptoms occur.
 Referneces:
• Katzung & Trevor’s Pharmacology/Examination &
Board Review/Sixth edition 2002
• www.drugs.com
• www.wikipedia.org
• www.dictionary.reference.com
• www.webmd.com
• www.fda.gov
• www.floridarehab.com
Thank You