Anti-TB drugs

Tuesday 7
th
Oct
1-3 pm
Learning objectives
At the end of the session students will be able to:
List first line and second line drugs used in the treatment
of TB.
Enumerate the mechanism of action, side effects and
drug interactions with first line anti-TB drugs.



Anti-TB drugs
1
st
Line drugs: Isoniazid (INH) (H), Rifampicin
(R), Ethambutol (E), Pyrazinamide (Z),
Streptomycin (S)
Combine maximum efficacy and least side-
effects
Should always be used unless contraindicated or
organisms are resistant
All the first line drugs are active against
intracellular and extracellular bacilli, can
penetrate cavities and can cross BBB except
pyrazinamide which is effective only against
intracellular and streptomycin only effective
against extracellular organisms.

2
nd
Line Drugs: Comprise many different
groups like ciprofloxacin, Ofloxacin,
Cycloserine, PAS. Used when first-line drugs are
contraindicated or organisms are resistant
All anti-TB drugs are hepato-toxic,
Pyrazinamide causes most serious hepatotoxicty.

Long duration of treatment


Patient compliance
Isonicotinic hydrazide(INH)
Inhibits synthesis of Mycolic acid present
in the cell wall of mycobacterium.
Well absorbed orally
Undergoes metabolism by acetylation
followed by hydrolysis
Slow & Fast acetylators, Microsomal
enzyme inhibitor
Adverse effects

Hepatotoxicity
Peripheral neuropathy : due to deficiency of
Vit B6
CNS adverse effects
Safe in pregnancy
Pyridoxine used in treatment of overdose
Rifampin
Effective against mycobacterium & E.coli,
Pseudomonas, Klebsiella, S. aureus, N.meningitidis,
H.infuenzae.

Mechanism: Inhibits DNA dependent RNA
polymerase enzyme in bacteria: beta subunit
Cidal, effective against intracellular &
extracellular organisms, penetrates cavities
Well absorbed orally, Large Vd, crosses BBB
Gives harmless orange red color to body fluids
Adverse effects
Hepatotoxicity
**Flu-like syndromes
CNS adverse effects
Avoided in pregnancy
**Orange red discoloration of body
fluids like urine, tears, saliva
**It is microsomal enzyme inducer

Uses of Rifampin: Treatment of TB and
other infections, Prophylaxis of
meningococcal disease & H. influenzae
meningitis

Rifabutin is a rifampin derivative used in
TB in HIV patients as it is a less potent
inducer of CYP
Rifapentine is intermediate potency in
inducing CYP (max is rifampin, least is
rifabutin) and is longest acting, can be
given once daily
Ethambutol
Inhibits Arabinosyl transferase enzyme
involved in synthesis of arabinogalactan,
a cell wall component, STATIC

A/E: EYE: OPTIC NEURITIS:
decreased visual acuity & loss of red
green discrimination; not recommended
in children less than 5 years.
Hyperuricemia: can ppt gout

Pyrazinamide
Unknown mechanism, cidal
Only effective against intracellular
mycobacteria, crosses BBB
Hepatotoxicity common & serious
Hyperuricemia can result
DOTS

Drug resistance

MDR-TB

XDR- TB
Try To Remember
INH inhibits mycolic acid synthesis, cidal, causes peripheral
neuritis in slow acetylators, hemolysis in G6PD deficiency

Rifampin inhibits DNA dependent RNA polymerase, causes
orange discoloration of body fluids and flu like syndromes and
potent enzyme inducer

Ethambutol inhibits synthesis of arbinogalactan, causes
retrobulbar neuritis (manifested by diminished acuity of vision
and failure to discriminate between red and green color) and
hyperuricemia.

Pyrazinamide can cause hyperuricemia and ppt gout, highly
hepatotoxic
Summary of anti-TB drugs