The document discusses various anti-tubercular agents used to treat tuberculosis. It describes first-line drugs like isoniazid, rifampicin, pyrazinamide, and ethambutol. It also covers second-line drugs such as ethionamide, para-amino salicylic acid, cycloserine, and streptomycin. For each drug, it provides information on structure, mechanism of action, uses, and common adverse effects.

1. Anti-tubercular Agents
By- Md Haider
Assistant professor
RVIP, Bijnor

2. Tuberculosis
 The chronic disease tuberculosis and leprosy are due to infections
by Mycobacterium species. Tuberculosis is caused by
Mycobacterium tuberculosis or sometimes M. bovis. M. africanum is
also occasionally a cause of human tuberculosis.
 It may affect the almost any tissue or organ of the body but most
commonly affected to the lungs
 Antitubercular drugs are the agents which are used in the
treatment of tuberculosis.

3. Classification
First line drug- e.g., Isoniazid, Rifampicin, Pyrazinamide,
Ethambutol, Streptomycin

4. Second line drugs- Thioacetazone, Para-amino salicylic acid,
Ethionamide, Cycloserine, Kanamycin, Amikacin, Capreomycin

5. Newer drugs- Ciprofloxacin, Ofloxacin, Clarithromycin,
Azithromycin, Rifabutin

6. Synthetic Anti-tubercular Agents
Isoniazid
Isoniazid is an antibacterial drug that is primarily used in the treatment
of tuberculosis (TB). It is a first-line drug that is typically used in
combination with other TB drugs, such as rifampicin, pyrazinamide, and
ethambutol, to form a multidrug regimen that is effective against TB.
Structure-

7. MOA
 Isoniazid works by inhibiting
the synthesis of mycolic acids,
which are important
components of the bacterial cell
wall of Mycobacterium
tuberculosis, the bacterium that
causes TB.
 This inhibition weakens the cell
wall, making it easier for other
TB drugs to penetrate the
bacterium and kill it.

8. Synthesis

9. SAR
 Pyridine ring is essential for
activity.
 Substitution of R-1, R-2 at N-2
leads to variable activity.
 Addition of isopropyl group at
position R-2 results in loss of
anti-tubercular activity.
 Any substitution (alkyl) at R-3
results in loss of activity
 INH is most active derivative.

10. Uses
 Isoniazid is an antimycobacterial drug that is primarily used in the
treatment of tuberculosis (TB).
 It is often used in combination with other drugs to form the standard
TB treatment regimen known as directly observed therapy short
course (DOTS).
 Isoniazid can also be used in the treatment of other mycobacterial
infections, such as Mycobacterium avium complex (MAC) and
Mycobacterium kansasii.
 Isoniazid can be used to prevent the development of active TB in
people who have been exposed to the bacterium but do not have
active disease.

11. Adverse effect
 Hepatotoxicity
 Ototoxicity
 Allergic reactions
 Nausea
 Vomiting
 Abdominal pain
 Hypersensitivity reactions

12. Ethionamide
 Ethionamide is an antimycobacterial drug that is used in the treatment
of tuberculosis (TB).
 It is a second-line drug that is used when the first-line drugs, such as
isoniazid and rifampicin, are not effective or cannot be used due to
drug resistance or intolerance.
Structure-

13. MOA
 Ethionamide works by inhibiting the synthesis of mycolic acids,
which are essential components of the cell wall of Mycobacterium
tuberculosis, the bacterium that causes TB.
 The drug is activated by an enzyme called EthA, which is present in
the bacteria. Once activated, ethionamide enters the bacterial cell and
binds to the enzyme InhA, which is involved in the synthesis of
mycolic acids.
 This binding inhibits the activity of InhA, which leads to the
disruption of the cell wall and the eventual death of the bacterium.

14. Uses
 Ethionamide is primarily used in the treatment of tuberculosis
(TB).
 Ethionamide is typically used in combination with other TB drugs,
such as pyrazinamide, to form a multidrug regimen that is
effective against TB.
 Ethionamide is also sometimes used in the treatment of leprosy, a
chronic bacterial infection caused by Mycobacterium leprae.

15. Adverse effects
 Gastrointestinal disturbances
 Neurological symptoms
 Liver damage
 Nausea
 Vomiting
 Dizziness
 Headache

16. Ethambutol
 Ethambutol is an antimycobacterial drug that is used in the
treatment of tuberculosis (TB). It is a first-line drug that is typically
used in combination with other TB drugs, such as isoniazid,
rifampicin, and pyrazinamide, to form a multidrug regimen that is
effective against TB.
Structure-

18. MOA
 Ethambutol works by inhibiting the synthesis of the cell wall of
Mycobacterium tuberculosis, the bacterium that causes TB.
 Specifically, it inhibits the synthesis of arabinogalactan, a
component of the bacterial cell wall.
 This inhibition weakens the cell wall, making it easier for other TB
drugs to penetrate the bacterium and kill it.

19. Uses
 Ethambutol is primarily used in the treatment of tuberculosis
(TB).
 It is an effective first-line drug that is used in combination with
other drugs to form a multidrug regimen that is effective against
TB.
 Ethambutol is also sometimes used in the treatment of other
mycobacterial infections, such as Mycobacterium avium complex
(MAC) and Mycobacterium kansasii.

20. Adverse effects
 Visual disturbances
 Gastrointestinal disturbances
 Allergic reactions
 Hyperuricemia
 Nausea
 Dizziness

21. Pyrazinamide
Pyrazinamide is an antimycobacterial drug that is used in the treatment
of tuberculosis (TB). It is a first-line drug that is typically used in
combination with other TB drugs, such as isoniazid, rifampicin, and
ethambutol, to form a multidrug regimen that is effective against TB.
Structure-

22. MOA
 Pyrazinamide works by disrupting the metabolism of
Mycobacterium tuberculosis, the bacterium that causes TB.
 Specifically, it inhibits the synthesis of fatty acids in the
bacterium, which leads to the accumulation of toxic intermediates
and ultimately results in the death of the bacterium.

23. Uses
 Same as ethambutol

24. Adverse effects
 Gastrointestinal disturbances
 Liver damage
 Hypersensitivity reactions
 Jaundice

25. Para-amino salicylic acid (PAS)
 Para-amino salicylic acid (PAS) is an antibacterial drug that is used in
the treatment of tuberculosis (TB). It is a second-line drug that is
typically used when first-line TB drugs, such as isoniazid, rifampicin,
pyrazinamide, and ethambutol, are not effective or are
contraindicated.
Structure-

26. Synthesis

27. SAR
For maximum activity –
COOH and –NH2 groups
should be at para-position to
each other.
-OH group should be at
ortho or meta position, but
the maximum activity when
at ortho.
-NH2 group if replaced with
Cl or alkyl activity will
reduced.
-COOH if converted into
amide or ester compound
became less active.

28. MOA
 PAS works by inhibiting the synthesis of folic acid, which is an
important component of the bacterial cell.
 This inhibition weakens the cell wall, making it easier for other
TB drugs to penetrate the bacterium and kill it.

29. Uses
 Para-amino salicylic acid (PAS) is primarily used in the treatment
of tuberculosis (TB).
 It is a second-line drug that is typically used when first-line TB
drugs, such as isoniazid, rifampicin, pyrazinamide, and
ethambutol, are not effective or are contraindicated.
 PAS has been used in the treatment of other bacterial infections,
such as infections caused by Streptococcus pyogenes and
Staphylococcus aureus.

30. Adverse effects
 Gastrointestinal disturbances
 Liver damage
 Hypersensitivity reactions
 Joints pain
 Hypokalemia

31. Anti-tubercular Antibiotics
Rifampicin
Rifampicin is an antibiotic used to treat several types of mycobacterial
infections including Mycobacterium avium complex, leprosy, and in
combination with other anti-bacterials to treat latent or active
tuberculosis. It is also known as rifampin.
Structure-

32. MOA
 Rifampicin works by inhibiting the bacterial RNA polymerase
enzyme, which is responsible for the synthesis of RNA in the
bacterial cell.
 This inhibition prevents the bacterium from synthesizing RNA,
which is essential for its survival, and eventually leads to its death.

34. Uses
It is used in the treatment of tuberculosis (TB).
 Rifampicin is also used in the treatment of other bacterial
infections, such as
 Leprosy
 Meningococcal meningitis
 Staphylococcal infections

35. Adverse effects
 Diarrhea
 Stomach upset
 Jaundice
 Nausea
 Hepatotoxicity
 Vomiting
 Headache
 Skin rash

36. Rifabutin
Rifabutin is an antibacterial drug that belongs to the same class of
antibiotics as rifampicin. It is primarily used in the treatment of
tuberculosis (TB) and also in the treatment and prevention of
Mycobacterium avium complex (MAC) infections in people with
HIV/AIDS.
Structure-

37. MOA
 Rifabutin works by inhibiting the bacterial RNA polymerase
enzyme, similar to rifampicin, which is responsible for the
synthesis of RNA in the bacterial cell.
 This inhibition prevents the bacterium from synthesizing RNA,
which is essential for its survival, and eventually leads to its death.

38. Uses
 It is used in TB and MAC infections.
 Rifabutin has also been used in the treatment of other bacterial
infections, such as Helicobacter pylori infections and
staphylococcal infections.
 It has also been used in the prevention of opportunistic infections
in people with HIV/AIDS.

39. Adverse effects
 Diarrhea
 Stomach upset
 Jaundice
 Nausea
 Hepatotoxicity
 Vomiting
 Headache
 Skin rash

40. Cycloserine
Cycloserine is an antibiotic drug that is primarily used in the
treatment of tuberculosis (TB). It is a second-line drug that is
typically used when first-line TB drugs, such as isoniazid and
rifampicin, are not effective or are contraindicated.
Structure-

41. MOA
 Cycloserine works by inhibiting the synthesis of cell wall
components in the bacterial cell, which weakens the cell wall and
makes it easier for other TB drugs to penetrate the bacterium and
kill it.

42. Uses
 It is use in TB treatment, cycloserine has also been used in the
treatment of other bacterial infections, such as urinary tract
infections caused by drug-resistant strains of bacteria.

43. Adverse effects
 Central nervous system (CNS) disturbances, such as
 Dizziness
 Headache
 Confusion
 Seizures
 Anxiety

44. Streptomycin
Streptomycin is an antibiotic drug that was the first effective
treatment for tuberculosis (TB). It is a first-line TB drug that is still
used today in combination with other TB drugs, such as isoniazid,
rifampicin, pyrazinamide, and ethambutol, to form a multidrug
regimen that is effective against TB.
Structure-

45. MOA
 Streptomycin works by inhibiting protein synthesis in the bacterial
cell, which prevents the bacterium from growing and dividing.
 This eventually leads to its death.
 Streptomycin is particularly effective against the rapidly growing
bacteria that cause TB.

46. Uses
 It is used in the treatment of tuberculosis.
 Streptomycin has also been used in the treatment of other bacterial
infections, such as brucellosis and plague.

47. Adverse effects
Kidney damage
Hearing loss
Loss of appetite
Nausea
Vomiting
Stomach pain
Rashes
Hives
Fever

48. Capreomycin sulphate
Capreomycin sulfate is an injectable antibiotic drug that is primarily
used in the treatment of multidrug-resistant tuberculosis (MDR-TB). It
is a second-line TB drug that is typically used when first-line TB drugs,
such as isoniazid and rifampicin, are not effective or are
contraindicated.
Structure-

49. MOA
 Capreomycin works by inhibiting protein synthesis in the bacterial
cell, which prevents the bacterium from growing and dividing.
This eventually leads to its death.
 Capreomycin is particularly effective against the mycobacterium
tuberculosis bacteria that cause TB.

50. Uses
 It is used in MDR-TB treatment.
 capreomycin has also been used in the treatment of other bacterial
infections, such as urinary tract infections caused by drug-resistant
strains of bacteria.

51. Adverse effects
 Black stools
 Blood in urine
 Chest pain
 Nausea
 Vomiting
 Chills
 Dizziness
 Drowsiness
 Difficulty in breathing

52. Thank you