This document summarizes anti-tuberculosis therapy (ATT). It describes the typical and atypical mycobacteria treated by ATT. The first and second line drugs used are outlined, including their mechanisms of action, pharmacokinetics, clinical uses, and adverse effects. DOTS (Directly Observed Treatment Short-course) is also summarized, which follows the WHO recommended approach of direct observation to ensure patient adherence to the drug regimen. Drug-resistant forms of tuberculosis including MDR-TB and XDR-TB are defined.

1. Anti tuberculosis
therapy ( ATT)

2. Typical mycobacteria: Mycobacterium tuberculosis
Non tuberbulous/atypical mycobacteria: M. kansasii, M. marinum, M.
avium, M. avium complex, M. scrofulaceum

3. Classification
First line Second line
Isoniazid ( INH/H)
Rifampin ( R)
Pyrazinamide ( Z)
Ethambutol ( E)
inj. Streptomycin ( S)
Oral Injectable
Fluoroquinolones
( ofloxacin,
levofloxacin,
moxifloxacin)
Ethionamide
Cycloserine
Para-aminosalicyclic
acid ( PAS)
Rifabutin/rifapentine
Amikacin
Kanamycin
Capreomycin
New drugs
Linezolid, bidaquiline

4. ISONIAZID ( inh/h)
MOST ACTIVE drug for treatment of TB. For rapidly multiplying
mycobacterium
Mechanism of action
Isoniazid ( prodrug)
Active form
Blocks Mycolic acid
synthesis
Cell wall is not formed
KatG ( catalase
peroxidase of MTB)
Mutation in KatG
causes resistance

5. Mechanism of resistance:
1. Mutation in KatG
2. Mutation of InhA
 Pharmacokinetics:
1. Absorption: Readily absorbed through GIT.
2. Distribution: in all body fluids and tissues
including CSF
3. Metabolism: Acetylation in liver
4. Excretion : renal route

6. Clinical use:
1. Adult dose: 300mg OD
2. used in combination of other antitubercular agents
3. Also used as single agent in treatment of latent TB
Adverse Effects:
1. Fever, skin rash
2. Isoniazid induced hepatitis : jaundice, loss of apatite,
nausea, vomiting, pain stop isoniazid
3. Peripheral neuropathy due to pyridoxine deficiency 
administer pyridoxine 10mg/day
4. Less common: CNS toxicity ( memory loss, seizures etc),
GIT discomfort, anemia

7. RIFAMPIN
 Active against: slowly growing / Spurters; both intracellular
and extracellular; bactericidal
Mechanism of action:

8. Pharmacokinetics
1. Absorption: well absorbed from GIT
2. Distribution : all tissues, tubercular cavities, placenta, CSF
3. Metabolism: liver
4. Excretion: through liver into bile
Clinical Use
1. Adult Dosage: 600mg/day
2. MTB, atypical mycobacterium
3. Leprosy ( + dapsone)
4. Prophylaxis of maningiococcal ( Neisseria meningitidis)
5. Prophylaxis of haemophilus influenzae B
6. Staphylococcal infections: osteomyelitis, endocarditis

9. Adverse Effects:
1. Hepatitis
2. Orange discoloration of urine, sweat, tears
3. Flu like symptoms: fever, chills, myalgia
4. Occasionally: rashes, GI disturbances, nephritis.
Drug-Drug interactions:
1. Potent enzyme inducer ( cytochrome p450)
2. Increases elimination of : anticonvulsants, anticoagulants,
OCPs, anti- HIV drugs replace with refabutin

10. Pyrazinamide
Active against bacteria in acidic environment of
macrophages ( intracellular )
Mechanism of action :
pyrazinamide
active
inhibits Cell membrane
metabolism and transport
Pyrazinamidase

11. Pharmacokinetics:
1. Absorption: well absorbed GIT
2. Distribution: all body tissues
3. Metabolism: liver
4. Excretion: renal
Clinical use
1. Bactericidal to MTB
2. Adult Dosage: 1600mg/day
Adverse effects
1. Hepatotoxicity
2. Hyperuricemia  acute episodes of gout stop if symptomatic
3. Nausea, vomiting, photosensitivity

12. Ethambutol
Arabinosyl transferase
Polymerization of
arabinoglycan
mycobacterial Cell wall
Ethambutol
inhibition
Mechanism of action

13. Pharmacokinetics:
1. Absorption: well absorbed GIT
2. Distribution: all body tissues
3. Metabolism: liver
4. Excretion: renal ( 80%) reduce dose in renal failure, feces ( 20%)
Clinical use
1. Bacteriostatic to MTB
2. MTB, atypical mycobacterium
3. Adult Dosage: 1100 mg/day
Adverse effects
1. Retrobulbar neuritis  impairment of visual aquity, red-green
colorblindness
2. Hyperuricemia  acute episodes of gout stop if symptomatic
3. Nausea, vomiting, rash, fever.

14. Streptomycin
Aminoglycoside
Against extracellular tubercular bacteria
Injectable
 mechanism of action : binds to 30s ribosome prevents
formation of initiation complex
Adverse effects:
1. Ototoxicity- vertigo, hearing loss
2. Nephrotoxicity- adjust dose

15. DOTS
 DOTS: Directly Observed Treatment Short-course
RNTCP follows WHO-DOTS
Under direct supervision of health care professional , patient takes the
drug.
New case: microbiologically confirmed / clinically diagnosed TB case
never have been treated earlier
Previously treated case:
o recurrent TB
o Failure
o lost to followup
o outcome unknown of previous treatment

18. Multi-drug resistant ( MDR) : resistant to H and R
Extensive Drug Resistant ( XDR) : MDR-Tb case also
resistant to
A Fluroquinolone ( Ofloxacin, moxifloxacin, levofloxacin)
A second line injectable ( amikacin, kanamycin,
capreomycin)

19. Fluoroquinolones
Intracellular mycobacterium
Orally
Against MDR-TB, Mycobacterium avium complex ( MAC) in HIV
Example: ciprofloxacin, ofloxacin, moxifloxacin, levofloxacin

20. ethionamide
Isoniazid like, blocks mycolic acid
Bacteriostatic
Rarely used
ADR: intense gastric irritation , CNS toxicity , hepatitoxic

21. Para-aminosalicylic Acid ( PAS)
Bacteriostatic
Rarely used
ADR: GI irritation , hypersensitivity reaction

22. Cycloserine
Inhibit bacterial cell wall
Bacteriostatic
Excreated unchanged through renal route : used in renal TB
ADR: CNS toxicity( dizziness, psychotic behaviour, peripheral
neuropathy

23. Rifabutin
Same mechanism of action as rifampin
ADR: skin rash, GIT intolerance , red-orange discoloration of urine
Rifampin Rifabutin
More enzyme inducer Less enzyme inducer
More interaction with ART Less interaction with ART
Lesser activity against MAC More activity against MAC
Shorter plasma half life Longer plasma half life

24. Kanamycin, amikacin
Aminoglycoside injectables
Used: MDR-TB, MAC in AIDS( amikacin)
ADR: ototoxicity, nephrotoxicity
Uses: MTB, M. kansasii, M. avium
ADR: ototoxicity, nephrotoxicty
Capreomycin