•Tuberculosis is a chronic infectious disease

caused by Mycobacterium tuberculosis.

•Tuberculosis is the world’s second
commonest cause of death from infectious
disease, after AIDS.
•The mode of infection is mainly through
inhalation of droplets of infected
secretions.
•Tuberculosis is a difficult disease to treat.
•A single drug should be never used in
Tuberculosis.
 Isoniazid ( H )
 Rifampicin ( R )
 Pyrazinamide ( Z )
 Ethambutol ( E )
 Streptomycin ( S )
 Thiacetazone
 Paraaminosalicylic acid
 Ethionamide
 Cycloserine
 Kanamycin
 Amikacin
 Capreomycin
 Ciprofloxacin
 Ofloxacin
 Clarithromycin
 Azithromycin
 Rifabutin
 It is bactericidal and acts well
against rapidly multiplying organisms.
 Acts on both extracellular and
intracellular organisms.
Mechanism of action:
 INH is a prodrug.
 In the bacilli it gets converted to
active metabolite by the enzyme
Catalase peroxidase-which inhibits
the synthesis of Mycolic acid.
 Mutation of Gene responsible for the
production of catalase peroxidase.
 Mutation on the target Gene – inh A.
 Bacilli lose INH concentrating process.

PHARMACOKINETICS:
 INH is well absorbed orally and widely
distributed.
 It is mainly metabolized in the liver by
acetylation.
 Rate of acetylation shows Genetic
variation.
• Rapid acetylators → 30 to 40% of Indians
t ½ - 1 hour
4mg per kg, after 6 hours plasma level
is 0.2 mcg per ml or less.

• Slow acetylators → 60 to 70% of Indians

t ½ - 3 hours
4mg per kg, after 6 hours plasma level
is 0.8 mcg per ml or more.
 Peripheral neuritis and neurological
manifestations.
For prophylaxis and treatment →
Pyridoxine.
 Hepatitis
 Rashes, fever and arthralgia.

DOSE:– 300mg/day or
5 mg/kg/day-in single dose.
 Aluminium hydroxide inhibits
INH absorption.

 INH inhibits metabolism

phenytoin, carbamazepine and
diazepam.

 PAS inhibits INH metabolism.

 Rifampicin is a semisynthetic
derivative of rifamycin B, isolated
from Streptomyces mediteranei.
 It is bactericidal and acts on both
intracellular and extracellular bacilli.
 It is the only drug acting against
persisters.

Mechanism of action:
 It binds to ß – subunit of DNA
dependent RNA polymerase and
inhibits RNA synthesis of bacteria.
Resistance:Rifampicin
•Mutation in the rpo gene on RNA
polymerase, thereby preventing the binding
of the drug to RNA polymerase.
Pharmacokinetics:
•Well absorbed orally and widely
distributed.
•Metabolized in liver to an active
deacetylated metabolite.
•Rifampicin and metabolite undergo
enterohepatic circulation.
•T ½ - 2-5 hours.
 Hepatitis
 Respiratory syndrome
 Haemolysis, shock and failure
 Cutaneous syndrome
 Flu syndrome
 Abdominal syndrome
 Orange – red discoloration of
urine & secretions.
Enzyme inducer.
It enhances the metabolism of
itself, warfarin,oral
contraceptives,
corticosteroids,Protease
inhibitors,digitoxin,etc

Dose:600 mg/day ( 10 mg/kg/day)

in a single dose before breakfast.
 Leprosy
 Prophylaxis of
Meningococcal and
H.influenzae meningitis and
carrier state.
 MRSA
 Legionella
 Brucellosis
 It is tuberculostatic
and also effective
against atypical
mycobacteria.
 Good action against
rapidly multiplying
bacilli.
Mechanism of action:
Inhibits the enzyme
Arabinosyl transferase and
this prevents polymerization
of Arabinoglycans, an
essential component of
mycobacterial cell wall.
( E ): Resistance:
Mutations take place in the emb B gene that
encodes the arabinosyl transferase enzyme.
Pharmacokinetics:
•Well absorbed from the gut and widely
distributed.
•Penetrates meninges incompletely.
•Stored temporarily in Erythrocytes.
•About 50% of the drug is eliminated
unchanged in the urine.
•Plasma t ½ - 4 hours.
 Impairment of visual acuity and
colour vision due to retrobulbar
neuritis.
 May precipitate gouty arthritis.
 Nausea, rashes &fever.

 Dose: 800 – 1000 mg/day (15

mg/kg/day)
 It is a weak tuberculocidal.
 It is highly effective against
- Intracellular bacilli.
-Bacilli at inflammatory sites.
[pH is acidic at these sites]
Mechanism of action:
 In the bacilli it is converted
into Pyrazinoic acid by
Pyrazinamidase enzyme
It inhibits mycobacterial
fatty acid synthase –I enzyme
Disrupts mycolic acid
synthesis needed for cell wall
synthesis.
Pharmacokinetics:
•Well absorbed orally and widely
distributed.
•Good penetration in CSF.
•Metabolized in liver and excreted
by kidneys.
•Plasma t ½ - 6 to 10 hours.
Resistance:
•Mutation in gene pcn A that
encodes pyrazinamidase enzyme.
Dose:
•1500mg/day single or
•2 divided doses (25 mg/kg/day)
 Hepatotoxicity
 Hyperuricemia
 Nausea,Vomiting,Anore
xia,Arthralgia,loss of
diabetes control.
 It is bactericidal and effective
against extracellular bacilli only.
 Does not cross to the CSF and poor
action in acidic medium.
 Not very popular due to need to be
given I.M.,ototoxicity and
nephrotoxicity.
Dose:
1000mg I.M.(15mg/kg/day),In elderly
and renal disorders 500 – 750
mg/day.