Antitubercular drugs: Introduction, classification and mode of action


  • Tuberculosis (TB) is a chronic infectious disease caused by M. tuberculosis, an acid-fast bacillus (AFB).
  • Mycobacterial infections require prolonged treatment. Since TB is a chronic infection, it consists of excessive fibrous tissue with central necrosis. So vascularity of the lesion is poor; hence, the penetration of the drug into the lesion is decreased.

Classification of drug

1. First-line antitubercular drugs (standard drugs)

Isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), streptomycin (S).

2. Second-line antitubercular drugs (reserve drugs)

Para-aminosalicylic acid, thiacetazone, cycloserine, ethionamide, kanamycin, capreomycin, amikacin.

3. Others: Ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, clarithromycin, rifabutin, rifapentine.

First-line drugs

1. Isoniazid

Highly effective and the most widely used anti-tubercular agent.

It is active against both intracellular and extracellular bacilli.


  • Administration: Oral
  • Absorption: Readily absorbed from the gut,
  • Distribution: Distributed well all over the body, tubercular cavities and body fluids like CSF; it also crosses placental barrier.
  • Metabolism: Metabolized by acetylation
  • Excretion: metabolites are excreted in urine.

Mechanism of action

Mode of action of Isoniazid against tuberculosis
Mode of action of Isoniazid

Adverse reactions

  • Hepatotoxicity: Patients receiving INH should be monitored for symptoms like anorexia, nausea, vomiting, jaundice, etc.
  • Peripheral neuritis: It is a dose-related toxicity. INH is structurally similar to pyridoxine; hence, INH

competitively interferes with utilization of pyridoxine. It also promotes the excretion of pyridoxine.

Pyridoxine 10 mg/day is routinely given along with INH to reduce the risk of peripheral neuritis. It is also used for the treatment of INH induced peripheral neuritis.

  • Other side effects are fever, skin rashes, arthralgia, anaemia, GI disturbances, psychosis and rarely


  • Isoniazid inhibits the metabolism of phenytoin, carbamazepine, warfarin, etc. increases the

plasma levels of these drugs  may result in toxicity.

2.  Rifampin (Ripampicin)

  • Derivative of rifamycin.
  • kills intracellular and extracellular bacilli including spurters (those residing in caseous lesion). It is the only agent that can act on all types of bacillary subpopulations; hence rifampin is called sterilizing agent.


  • Administration: Oral
  • Absorption: Rapidly absorbed from the GI tract, but presence of food reduces its absorption.
  • Distribution: Distributed widely throughout the body.
  • Metabolism: In liver by deacetylation.
  • Excretion: Active deacetylated form is excreted in bile and undergoes enterohepatic recycling. The rest of the drug is excreted in urine.

Mechanism of action

Mode of action of Rifampin against tuberculosis
Mode of action of Rifampin

Therapeutic uses

Prophylaxis of meningococcal and H. influenzae meningitis

Rifampin in combination with -lactam antibiotics may be useful in staphylococcal infections suchas endocarditis, osteomyelitis, etc.

Rifampin is used with doxycycline for the treatment of brucellosis.

Adverse effects

1. Leprosy

 2. Hepatitis

3. Flu-like syndrome with fever, chills, headache, muscle and joint pain.

4. GI disturbances such as nausea, vomiting and abdominal discomfort.

5. Skin rashes, itching and flushing.

3. Pyrazinamide

  • Pyrazinamide is a synthetic analogue of nicotinamide. It is active in acidic pH—effective against intracellular bacilli (has sterilizing activity). It has tuberculocidal activity. Like INH, pyrazinamide inhibits mycobacterial mycolic acid biosynthesis but by a different mechanism.
    • Administration: It is given orally,
    • Absorption: Absorbed well from GI tract and is
    • Distribution: Distributed widely throughout the body including the CSF.
    • Metabolism: It is metabolized in liver and
    • Excretion: Excreted in urine.
  • The most important adverse effect of pyrazinamide is dose-dependent hepatotoxicity. It impairs the excretion of urates resulting in hyperuricaemia and may also precipitate acute attacks of gout in susceptible individuals. The other side effects are anorexia, nausea, vomiting, fever and skin rashes.

4. Ethambutol

  • It inhibits arabinosyl transferases that are involved in mycobacterial cell wall synthesis. It is a bacteriostatic drug. It is used in combination with other antitubercular drugs to prevent emergence of resistance and for faster sputum conversion.
  • There is no cross-resistance with other antitubercular drugs.
    • Absorption: well absorbed after oral administration
    • Distribution: distributed widely in the body, crosses BBB in meningitis
    • Metabolism: metabolized in liver
    • Excretion: excreted in urine
  • Optic neuritis is the main adverse effect seen with ethambutol, which is characterized by decreased visual acuity and colour-vision defects (red–green).
  • Hyperuricaemia is due to the decreased clearance of urates.
  • Other side effects are nausea, vomiting, abdominal pain, skin rashes, itching and joint pain.

Second-line drugs

Para-aminosalicylic Acid (PAS)

  • It is structurally similar to sulphonamides. Like sulphonamides, PAS also competitively inhibits folate synthetase enzyme and produces tuberculostatic effect. At present, PAS is a reserve drug for the management of MDR-tuberculosis. The common adverse effects are GI disturbances, anorexia, nausea, vomiting and abdominal discomfort.


  • It is structurally similar to INH but is less efficacious. It inhibits synthesis of mycolic acids. It is a bacteriostatic drug. The adverse effects are nausea, vomiting and epigastric pain. Other side effects are hepatitis, headache, blurred vision and paraesthesia.


  • It has bacteriostatic activity. It inhibits bacterial cell wall synthesis. The common side effects are on CNS and include headache, tremor, psychosis and convulsions.

Other agents

  • Fluoroquinolones: Ciprofl oxacin, moxifl oxacin and levofl oxacin—bactericidal agents, given orally.
  • Aminoglycosides: Amikacin and kanamycin—bactericidal agents, administered parenterally.
  • Capreomycin (i.m.): May cause nephrotoxicity and ototoxicity.
  • Macrolides: Azithromycin and clarithromycin, given orally.
  • Rifamycins: Rifapentine and rifabutin—bactericidal agents, given orally.
  • Rifabutin: It is a derivative of rifampin. Rifabutin is preferred to rifampin for the treatment of tuberculosis in HIV-infected patients on protease inhibitors (PIs) as rifabutin is a less potent enzyme inducer. Rifabutin is also used for the treatment of MAC infection in combination with clarithromycin and ethambutol.
  • Rifapentine: analogue of rifampin, is also a potent enzyme inducer.