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
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
16.
17.
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)
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