Tuberculosis and Antituberculosis
(Anti-TB) drugs
Tuberculosis or pulmonary tuberculosis is caused by
Mycobacterium Tuberculosis( MTB)
CLASSIFICATION OF DRUGS
: base on their efficacies and toxicities
First-line drugs: Good efficacy, cheap, less
toxicity and being well tolerated to patients
(PRIEST) P-pyrazinamide,R-Rifampicin, I-
Isoniazide,E-ethambutol,S-Streptomycin
. Second-line drugs:less efficacy,More
toxicity,veryexpensive, Difficult for patient to tolerate
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P-PAS ( P-aminosalicylicacid) ,T-thioacetazone,A-
Amikacin,K-Kanamycin,E-ethionamide, C-
Cyclserine, C-Capreomycin
Antibiotics used In TB
a) Aminoglycosides—
Streptomycin,Kanamycin,Amikacin
b) Macrolides-RACE
C) Natural derivative- Rifampicin
D) Fluroquinolones( FQ)-Ciprofloxacin
Based on mechanism of action
[Link] Cell wall synthesis blockers
Mycolic acid synthesis blocker-Isoniazide,Pyrazinamide
Arabinogalan synthesis blocker-Ethambutol
Peptidoglycan synthesis blocker- Cycloserine
[Link] inhibiting protein synthesis
a) By blocking 30 s ribsome- Aminoglycosides
b) By blocking 50 s ribosome- Macrolides
[Link] inhibiting Nucleic acid synthesis
a)Inhibiting RNA synthesis- Rifampicin
b)Inhibiting DNA Synthesis-Fluroquinolones
[Link] Inhibiting folic acid synthesis- PAS
[Link] wall synthesis blockers
a) Drugs inhibiting fatty acid ( mycolic acid) layer
of cell wall
Example - Isoniazide (INH) , Pyrazinamide
Isoniazide( INH) - Isonicotinyl hydrazide
Mechanisam:
INH inhibits synthesis of mycolic acid ( fatty
acid layer) in the mycobacterial cell wall- cell wall
loses its rigidity - acts as bactericidal
Adverse effects-nephrotoxicity,Hepatotoxicity
so reduce toxicity it is coadminstrated with
vitamin B6
6
b) Drugs inhibiting arabino galactan layer of cell
wall Example- Ethambutol( eye toxicity)
Mechanisam
Ethambutol inhibits Arabinosyl transferase (AT) enzyme
there by prevent synthesis of arabinogalactan layer in the
in the mycobacterial cell wall- (act as Bactrostatic)
Arabinose + Galactan ( galactose polymer)
Ethambutol Arabinosyl transferase ( AT)
Arabino galactan (AG)
Required for cell wall re rigidity
c) . Drugs inhibiting peptidoglycan layer of cell
wall Example- Cycloserine
Cycloserine inhibits L-alanine racemase
and D-alanine lygase there by prevent
synthesis of dipeptide –D-alanyl D-alanine
L-alanine
L-alanine racemase
D-alanine
Cycloserine
D-alanine lygase
D-alanyl-D-alanine
[Link] inhibiting protein synthesis
A) AMINOGLYCOSIDES- STREPTOMYCIN
Aminoglycoside - Inhibits protein synthesis by
blocking to 30 S ribosome subunit
Bactericidal 5 NOS- 1) No To pregnacy woman
2) No protein synthesis
3) Not orally( IM)
Effective against Aerobic 4) NO- negative-organisaM
5) NO-
nephrotoxicty ,Ototoxicity
[Link] inhibiting protein synthesis
B)MACROLIDES-RACE
Macrolides - Inhibits protein synthesis by blocking
to 50 S ribsome subunit
Bactreostatic
RACE- Roxithromycin, Azithromycin,
Clarithromycin,Erythromycin
[Link] inhibiting Nucleic acid synthesis
a) Rifampicin ( m RNA synthesis blocker)
Broad-spectrum
It is bactericidal for mycobacteria.
Mechanism
RFP inhibits DNA depended RNA polymerase
(DDRP)and thereby inhibits m RNA synthesis. so
RFP inhibits transcription process
Transcription DDRP
DNA RNA
Uses – Anti leprotic
b) Flouroquinolones ( DNA synthesis blocker)
Broad-spectrum
It is bactericidal for mycobacteria.
Mechanism
Fluroquinolines inhibits DNA Gyragse
(Topoisomerase-II )and thereby inhibits RNA
synthesis.
4. Drug inhibiting Folic acid synthesis
PAS-(p-amino salicylic acid)
It act as second line anti TB drug-
Act as Bactriostaic
Mechanism
PAS inhibits DHFR ( dihydrofolate reductase )
there by inhibits synthesis of folic acid
4. P-aminosalicylic acid- DHFR blocker
PAS
Fansidar- sulfadoxine+ pyrimethamine
Clotimaxozle- sulfamethoxazole+
trimethoprim
14
PULMONARY TB
Initial phase –
INAH+Pyridoxine
Rifampicin
2 months
Ethambutol
Pyrazinamide
Continuation phase –
INAH+Pyridoxine
Rifampicin 4 months
