Anti Tuberculosis Drug - Pharmacology

 Anti tuberculosis Drug 

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Introduction:

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The treatment of TB involves a combination of drugs over an extended period, typically ranging from 6 months to 2 years, depending on the disease's nature (drug-sensitive or drug-resistant). The primary goal of anti-TB therapy is to eradicate the infection, prevent transmission, and avoid the development of drug-resistant TB.

Classification of Anti-TB Drugs:

1. First-Line Drugs: These are the most effective with the least toxicity.

•Isoniazid (INH)

•Rifampicin (RIF)

•Pyrazinamide (PZA)

•Ethambutol (EMB)

•Streptomycin (SM)

2. Second-Line Drugs: Used in cases of drug-resistant TB.

•Fluoroquinolones (e.g., Levofloxacin, Moxifloxacin)

•Aminoglycosides (e.g., Amikacin, Kanamycin)

•Ethionamide

•Cycloserine

•Capreomycin

•Linezolid

•Bedaquiline

•Delamanid

•Para-aminosalicylic acid (PAS)

3. Third-Line Drugs: Less effective and more toxic, used only in extensively drug-resistant TB (XDR-TB).

•Clofazimine

•Imipenem-cilastatin

•Meropenem

Detailed Overview of Common Anti TB Drugs:

1. Isoniazid (INH)

Dose: 5 mg/kg daily (usually 300 mg once daily for adults).

Indication: Active TB (in combination), latent TB.

Contraindications: Severe hepatic dysfunction, hypersensitivity.

Adverse Effects: Hepatotoxicity, peripheral neuropathy (preventable by pyridoxine), rash.

2. Rifampicin (RIF)

Dose: 10 mg/kg daily (600 mg once daily for adults).

Indication: Active TB, latent TB, leprosy, MRSA infections.

Contraindications: Liver disease, hypersensitivity, HIV patients on protease inhibitors.

Adverse Effects: Hepatotoxicity, red-orange discoloration of body fluids, flu-like symptoms, drug interactions (induces cytochrome P450 enzymes).

3. Pyrazinamide (PZA)

Dose: 25-30 mg/kg daily (typically 1.5-2 g daily for adults).

Indication: Active TB (shortens treatment duration).

Contraindications: Severe liver disease, gout.

Adverse Effects: Hepatotoxicity, hyperuricemia (leading to gout), arthralgia.

4. Ethambutol (EMB)

Dose: 15-25 mg/kg daily (typically 800 mg-1.2 g daily for adults).

Indication: Active TB (used to prevent resistance).

Contraindications: Optic neuritis, children <5 years.

Adverse Effects: Optic neuritis (dose-related), color blindness, peripheral neuropathy.

5. Streptomycin (SM)

Dose: 15 mg/kg IM/IV daily (max 1 g daily for adults).

Indication: Drug-resistant TB, severe forms of TB (e.g., TB meningitis).

Contraindications: Pregnancy, renal impairment, hypersensitivity.

Adverse Effects: Ototoxicity (hearing loss), nephrotoxicity.

Second-Line Drugs:

1. Fluoroquinolones (Levofloxacin, Moxifloxacin)

Dose: Levofloxacin: 750-1000 mg daily; Moxifloxacin: 400 mg daily.

Indication: Multi-drug resistant TB (MDR-TB).

Contraindications: QT prolongation, hypersensitivity.

Adverse Effects: Tendonitis, QT prolongation, gastrointestinal upset.

2. Ethionamide

Dose: 500-750 mg daily.

Indication: MDR-TB.

Contraindications: Severe liver disease, psychiatric illness.

Adverse Effects: GI upset, hepatotoxicity, hypothyroidism.

3. Cycloserine

Dose: 500-750 mg daily in divided doses.

Indication: MDR-TB.

Contraindications: Epilepsy, severe depression, alcohol use.

Adverse Effects: CNS toxicity (seizures, depression), peripheral neuropathy.

4. Capreomycin

Dose: 15-20 mg/kg IM/IV daily (1 g daily for adults).

Indication: MDR-TB.

Contraindications: Renal dysfunction, hearing loss.

Adverse Effects: Nephrotoxicity, ototoxicity.

5. Bedaquiline

Dose: 400 mg daily for 2 weeks, followed by 200 mg three times per week.

Indication: MDR-TB.

Contraindications: QT prolongation, severe liver disease.

Adverse Effects: QT prolongation, hepatotoxicity, nausea.

6. Delamanid

Dose: 100 mg twice daily.

Indication: MDR-TB.

Contraindications: QT prolongation.

Adverse Effects: QT prolongation, hypokalemia, GI upset.

Indications of Anti-TB Drugs:

Active TB: Always treated with a combination of drugs (e.g., Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol for 2 months followed by Isoniazid and Rifampicin for 4 months).

Latent TB: Isoniazid or Rifampicin alone, or a combination for shorter courses.

Contraindications:

Hepatotoxicity: Avoid or closely monitor drugs like Isoniazid, Rifampicin, and Pyrazinamide in patients with liver disease.

Renal Dysfunction: Dose adjustment may be necessary for drugs like Streptomycin, Ethambutol, and Capreomycin.

Pregnancy: Some drugs (e.g., Streptomycin, Ethionamide) are contraindicated.

Adverse Effects:

Hepatotoxicity: Common with Isoniazid, Rifampicin, and Pyrazinamide.

Neurotoxicity: Peripheral neuropathy with Isoniazid and Cycloserine.

Ototoxicity and Nephrotoxicity: Common with Streptomycin and Capreomycin.

Gastrointestinal Disturbances: Common with second-line drugs like Ethionamide and Cycloserine.

Visual Changes: Ethambutol can cause optic neuritis.