Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and commonly affects the lungs. It can be transmitted through airborne droplets when an infected person coughs or sneezes. TB is diagnosed through chest x-rays, sputum examination, tuberculin tests, and PCR analysis. The first-line drugs isoniazid, rifampin, pyrazinamide, and ethambutol are used to treat TB according to standard 6-month regimens recommended by the WHO. These drugs work by inhibiting cell wall synthesis and other critical bacterial processes. While generally safe, they can cause adverse effects like hepatitis, rashes, and neuropathy, requiring monitoring during treatment.

1. TB (TUBERCULOSIS)
Discovered by Dr. Robert Koch in 1882.
One of leading cause of death in the
world.
Causative Agent:
Mycobacterium tuberculosis
Characterstics:
Acid fast Gram Positive
bacteria
Rod-shaped, slow-growing,
aerobic bacteria
Can live only in people
Usually attack lungs, kidney,
spine, and brain.

2. Diagnosis:
1.Chest X-Ray
2.Sputum examination
3.Mantoux Tuberculin Test
4.Polymerase Chain Reaction

3. • Tuberculosis is a chronic granulomatous disease
caused by Mycobacterium tuberculosis that
affects lungs and also invades other parts of the
body.
• TB is a communicable disease and is transmitted
through air when affected person coughs,
sneezes or talks.

4. ANTITUBERCULAR DRUGS
First line: These drugs have high anti-tubercular efficacy as
well as low toxicity and are used routinely.
1. Isoniazid (H)
2. Rifampin (R)
3. Pyrazinamide (Z)
4. Ethambutol (E)
5. Streptomycin (S)

5. Second Line: These drugs have either low antitubercular
efficacy or higher toxicity and are used as reserve drugs.
•Ethionamide (Eto)
•Prothionamide (Pto)
•Cycloserine (Cs)
•Terizidone (Trd)
•Para-aminosalicylic acid (PAS)
•Rifabutin
•Thiacetazone (Thz)
Fluoroquinolones
•Ofloxacin (Ofx)
•Levofloxacin (Lvx/Lfx)
•Moxifloxacin (Mfx)
•Ciprofloxacin (Cfx)
Injectable drugs
•Kanamycin (Km)
•Amikacin (Am)
•Capreomycin (Cm)

7. ISONIAZID/ISONICOTINIC ACID HYDRAZIDE (H)
MOA: INH inhibits the synthesis of mycolic acids which are
unique fatty acid components of mycobacterial cell wall.
INH enters sensitive mycobacteria which is converted into
reactive metabolite by a catalase-peroxidase (KatG)
enzyme.
The reactive metabolite forms adduct with NAD and NADP
which inhibits mycobacterial DHFRase resulting in
interruption of DNA synthesis.
Indication: 1st
line drug against tuberculosis
Adverse effects: Peripheral neuritis, paresthesias,
numbness, mental disturbances, rarely convulsions,
hepatitis
Contraindication: Hepatitis
Pyridoxine (10-50 mg/day) should be administered with

9. RIFAMPICIN (R)
• MOA: Rifampicin interrupts RNA synthesis by
binding to β subunit of mycobacterial DNA-
dependent RNA polymerase and blocking its
polymerizing function.
• Rifampicin is bactericidal.
• Indication: TB, Leprosy & other gram positive &
gram negative bacterial infections.
• Adverse effects: Hepatitis, Jaundice, Rash, Flu
syndrome
• Orange discolouration of urine & body secretions!
• Contraindications: Patients with Hepatic Failure
(Jaundice may occur) & renal disease.

11. PYRAZINAMIDE (Z)
MOA: Pyrazinamide inhibits fatty acid synthase I gene
involved in mycolic acid synthesis.
Pyrazinamide is converted into an active metabolite
pyrazinoic acid by an enzyme pyrazinamidase inside the
mycobacterial cell. This metabolite gets accumulated in
acidic medium and inhibits mycolic acid synthesis.
Pyrazinoic acid also disrupts mycobacterial cell membrane
and its transport function.
Indication: 1st
line drug against tuberculosis. It has good CSF
penetration so, it is highly useful in meningeal TB.
Adverse effects: hepatotoxicity, hyperuricaemia, Gout,
arthralgia, rashes, etc.
Contraindications: Liver diseases, Caution in diabetes!

13. ETHAMBUTOL (E)
MOA: Ethambutol inhibits enzyme arabinosyl
transferases involved in synthesis of arabinogalactan
and interferes with mycolic acid synthesis in
mycobacterial cell wall.
Ethambutol is added to the triple drug regimen of
RHZ to hasten the rate of sputum conversion and to
prevent development of resistance.
Indications: Pulmonary Tuberculosis
Adverse effects: Optical neuritis, Peripheral neuritis,
Rashes, Hyperuricaemia, Fever, Nausea, etc.
Contraindications: Optic neuritis, Renal disease,
Children under 5 years of age!

14. MOA of 1MOA of 1stst
line drugsline drugs
Mycolic Acid
Arabinogalactan
Peptidoglycan
Cell membrane
DNA RNA
polymerase
mRNA R
I
B
O
S
O
M
e
Protein
Isoniazid
-
Pyrazinamide
- Mitochondria
(ATP)
- Rifampin
-
Ethambutol
-
Streptomycin
- Cytoplasm

15. TREATMENT REGIMEN FOR TUBERCULOSIS
The conventional 12-18 month treatment has been
replaced by more effective and less toxic 6 month
treatment (DOTS).
Isoniazid and Rifampicin are the most efficacious drugs.
Their combination shows synergistic effects and duration
of treatment is shortened to 9 months, further
combination of Pyrazinamide & Ethambutol shortened
the duration of therapy to 6 month.
Drug Daily Dosing Weekly Dosing (3 times a week)
Isoniazid(H) 5mg/kg 300mg 10mg/kg 600mg
Rifampicin (R) 10mg/kg 600mg 10mg/kg 600mg
Pyrazinamide (Z) 25mg/kg 1500mg 35mg/kg 2000mg
Ethambutol (E) 15mg/kg 1000mg 30mg/kg 1600mg
Pyridoxine (10mg/day) should be administered with antitubercular drug regimen.

16. TREATMENT REGIMEN OF TUBERCULOSIS BY WHO UIDELINES 2010
H-ISONIAZID R-RIFAMPICIN Z-PYRAZINAMIDE E-ETHAMBUTOL S-STREPTOMYCIN
Number indicated months of treatment DST-Drug Sensitivity Testing

19. TUBERCULOSIS IN PREGNANT WOMEN
• The WHO and British Thoracic Society consider H, R, Z &
E to be safe to the foetus and recommend the standard
6 month (2HRZE + 4HR) regimen for pregnant women
with TB.
• S is contraindicated because it is ototoxic to the foetus.
However, Z is not recommended in the USA (due to lack
of adequate teratogenicity data). All pregnant women
being treated with INH should receive pyridoxine 10–25
mg/day.
• All anti-TB drugs are compatible with breastfeeding. The
infant should receive BCG vaccination and 6 month
isoniazid preventive treatment.