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

• 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.

Isoniazid

CLASSIFICATION OF DRUGS USED IN ANTI-TUBERCULOSIS TREATMENT

• ISONIAZIDE

• RIFAMPIN

• PYRAZINAMIDE

• ETHAMBUTOL

• STREPTOMYCIN

• AMIKACIN

• AMINOSALICYCLIC ACID

• CAPREOMYCIN

• CIPROFLOXACIN

• CLOFAZIMINE

• CYCLOSERINE

• ETHIONAMIDE

• LEVOFLOXACIN

• RIFABUTIN

• RIFAPENTINE

FIRST LINE DRUGS SECOND LINE DRUGS

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