This document discusses drugs used to treat tuberculosis. It begins by describing tuberculosis as an infectious disease caused by the bacterium Mycobacterium tuberculosis that commonly affects the lungs. It then lists first and second line drugs used to treat tuberculosis, including isoniazid, rifampicin, ethambutol, pyrazinamide, and para-amino salicylic acid. The document goes on to discuss the classification, mechanism of action, synthesis, dosing, and side effects of several key anti-tubercular drugs like isoniazid, rifampicin, ethambutol, pyrazinamide, and para-amino salicylic acid in more detail.

1. Presented by
Ms. Mitesh Sachdeva
Assistant Professor, miteshsachdeva@moderninstitutes.in
MIPS, Alwasa, Indore.
VI SEMESTER, UNIT - III, BP 601T, CHAPTER - 1, SYNTHETIC ANTI-TUBERCULAR
AGENTS

2. ANTI-TUBERCULAR DRUGS
(Intro, synthesis, sar…)

3. TUBERCULOSIS
 An infectious disease caused by the bacterium Mycobacterium tuberculosis.
 Commonly affect the lungs but can also affect other parts of the body.
 Symptoms include:
Chronic cough
Hemoptysis
Fever
Night sweats
Weight loss
 It is spread through air via cough, sneeze, speak or spit.

4. DRUGS
 1st line:
Isoniazid
Rifampicin
Ethambutol
Pyrazinamide
Streptomycin
 2nd line:
Para amino salicylic acid
Capreomycin
Ciprofloxacin
Cycloserine
Ethionamide
Amikacin
Rifabutin

5. Drugs used in the treatment of tuberculosis

6. CLASSIFICATION ON THE BASIS OF
CHEMICAL MOEITY
1. PYRIDINE DERIVATIVES - ISONIAZID*, ETHIONAMIDE
2. ETHYLENEDIAMINOBUTANOL DERIVATIVES - ETHAMBUTOL
3. PYRAZINE DERIVATIVES - PYRAZINAMIDE
4. SALICYLIC ACID DERIVATIVES - PARA AMINO SALICYLIC ACID* [PAS]

7. TUBERCULOSIS
Recommended treatment of pulmonary T.B is 6 months of combination of drugs.
 Intensive phase (2 months):
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
 Continuation phase (4 months):
Isoniazid
Rifampin
Ethambutol (Optional)

8. ISONIAZID
 Also known as isonicotinylhydrazide, 4-
Pyridinecarboxylic acid hydrazide.
 Isoniazid was first made in the early 20th
century but its activity against
tuberculosis was first reported in the early
1950s and was marketed in 1952.
 It is on the World Health Organization's List
of Essential Medicines, a list of medicines
that constitute the bare minimum for a
basic health system.

9. BRANDS
 NYDRAZIDE (Wilshire)
 ISONIAZID (Unexo)
 FAIRZIDE (Ferro)

10. MECHANISM OF ACTION
 Inhibits synthesis of mycolic acid which
is an essential components of
mycobacterial cell wall
 Isoniazid is a prodrug that is activated
by KatG, the mycobacterial catalase-
peroxidase.
 The enzyme inhA, is an NADH-
dependent, enoyl (acyl carrier protein)
reductase protein thought to be involved
in double-bond reduction during fatty
acid elongation.
 Isoniazid has bactericidal effect.

11. SYNTHESIS
 Step 1:
 4-methyl pyridine is oxidized to obtain Iso-nicotinic acid.

12. SYNTHESIS
 Step 2:
 Iso-nicotinic acid upon heating with anhydrous hydrazine form Isoniazid

13. S.A.R
 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 but exhibit psychomotor
stimulant activity, while acetyl isoniazid
is inactive.
 Any substitution (Alkyl) at R-3 results in
loss of activity
 INH is most active derivative.

14. SIDE EFFECT
The most frequent reactions are those affecting the nervous system and the liver.
 Peripheral neuropathy (Dose related)
Prophylaxis Pyridoxine:
Adult: 100-200mg/day orally for 3 weeks or 25 to 100 mg/day for prophylaxis.
 Elevated LFT’s
 Fatal hepatitis
 Aplastic anemia.
 Hypersensitivity reaction
 Dark urine

15. DOSING
 Active tuberculosis:
Oral
Adult: 5 mg/kg/day in combination with other drugs.
Children: 10-30mg/kg/day in 2 divided doses
 Prophylaxis:
Oral
Adult: 300mg once daily
Children: 10mg/kg/day
 SIDE EFFECT:
Peripheral neuritis (Pyridoxine):
Adult: 100-200mg/day orally for 3 weeks or 25 to 100 mg/day for prophylaxis.

16. ETHIONAMIDE
nicotinamide
Ethionamide

18. PYRAZINAMIDE
 It is a close analog of isoniazid
 It is a pro-drug (Pyrazinoic acid).
 The drug is largely bacteriostatic, but
can be bactericidal on actively
replicating tuberculosis bacteria.
 It is on the World Health Organization's
List of Essential Medicines.

19. BRANDS
 PYRAZINAMIDE (Pfizer)
 PZA CIBA500 (Novartis)
 PYRAZID (Schazoo zaka)

20. MECHANISM OF ACTION
 Susceptible organisms produce pyrazinamidase, which is responsible for conversion
of pyrazinamide (Prodrug) to Pyrazinoic acid (Active) intracellularly.
 The protonated Pyrazinoic acid can permeate the mycobacterial membrane to lower
the pH of the cytoplasm, hence disrupting basic chemical processes especially energy
production.

21. DOSING
 Active Tuberculosis:
Oral:
15 to 30 mg/kg (Max 2g/day) OD in combination with other drugs.
 Latent Tuberculosis:
Oral:
15 to 20 mg/kg (Max 2g/day) OD for 2 months

23. ETHAMBUTOL
 Ethambutol was discovered in 1961.
 It possesses bacteriostatic action against
Mycobacterium tuberculosis.
 Its (+) enantiomer is used as it is more
effective.
 It is on the World Health Organization's
List of Essential Medicines.

25. BRANDS
 MYAMBUTOL(Pfizer)
 TUBERCURE (Lowitt)
 ABBUTOL(Abbott)

26. MECHANISM OF ACTION
 Ethambutol is bacteriostatic against actively growing TB bacilli.
 It disrupts arabinogalactan (Polymer) synthesis by inhibiting the enzyme arabinosyl
transferase leads to increased permeability of the cell wall.

27. DOSING
 Active Tuberculosis:
Oral:
15 mg/kg OD for 2 months in combination with other drugs.

28. PARA AMINO
SALYCILIC ACID

33. SYNTHESI OF PAS

35. BRANDS (Multi ingredient)
 MYRIN (Pfizer):
 Isoniazid, Rifampicin, Ethambutol
 MYRIN-P(Pfizer):
 Isoniazid, Rifampicin, Ethambutol, Pyrazinamide
 RIMACTAL-INH (Novartis):
 Isoniazid, Rifampicin
 RIFAPIN-H (Schazoo zaka):
 Isoniazid, Rifampicin

36. THANK YOU!