Isoniazid

Isoniazid (often abbreviated as INH) is an antibiotic primarily used for the treatment and prevention of tuberculosis (TB). Since its discovery in the early 1950s, it has become a cornerstone drug in first-line anti-tuberculosis regimens worldwide. Its mechanism of action involves inhibiting the synthesis of mycolic acids, which are essential components of the bacterial cell wall of Mycobacterium tuberculosis.

Isoniazid skeletal

Overview

Isoniazid is an essential medicine on the World Health Organization's List of Essential Medicines, emphasizing its significance in global health. It is often prescribed in combination with other anti-tuberculosis drugs to enhance efficacy and prevent the emergence of drug-resistant TB strains.

Pharmacology

1. Mechanism of Action: Isoniazid is a prodrug and, once activated by the bacterial catalase enzyme KatG, inhibits the synthesis of mycolic acids in Mycobacterium tuberculosis. This leads to impaired cell wall synthesis and bacterial cell death.
2. Metabolism: It is primarily metabolized in the liver via acetylation. Genetic factors determine the rate of acetylation, with individuals being classified as slow or fast acetylators.
3. Excretion: The drug is primarily excreted in urine.

Indications

• Treatment of active tuberculosis, often in combination with other drugs like rifampicin, pyrazinamide, and ethambutol.
• Prophylactic treatment in individuals who have been exposed to active TB cases, especially in close contacts.
• Latent TB infections.

Contraindications

Isoniazid is contraindicated in individuals:

• With acute liver disease or a history of drug-induced hepatitis.
• With severe hypersensitivity reactions to the drug.

Side Effects

Like all drugs, isoniazid is associated with a range of side effects:

• Hepatotoxicity: It can cause drug-induced liver injury, ranging from asymptomatic increases in liver enzymes to acute liver failure.
• Peripheral neuropathy: This may manifest as tingling or numbness in the extremities.
• Gastrointestinal symptoms: Including nausea, vomiting, and abdominal discomfort.
• Rash.
• Fever.
• Hematological disorders: Such as anemia, thrombocytopenia, or leukopenia.
• CNS effects: Including seizures, psychosis, or dizziness.

Drug Interactions

• Isoniazid may increase blood levels of phenytoin, leading to phenytoin toxicity.
• Concurrent use with alcohol increases the risk of hepatotoxicity.
• Antacids can reduce the absorption of isoniazid if taken simultaneously.

Prophylaxis and Management

To reduce the risk of peripheral neuropathy, pyridoxine (vitamin B6) supplementation is recommended, especially in pregnant women, breastfeeding mothers, malnourished individuals, and those with diabetes or HIV.

Resistance

Resistance to isoniazid is a growing concern, especially in regions with high TB burden. It is usually due to mutations in the katG gene or inhA promoter of the bacterium.

See Also

• Tuberculosis
• Mycobacterium tuberculosis
• Antibiotics
• World Health Organization

• Dailymed label info on Isoniazid
• FDA Isoniazid