anti-tubercular

1. ANTI- TUBERCULAR DRUGS

2. Classification Of ATT Drugs
FIRST line drugs[HRZSE]
• Isoniazid (INH) [H]
• Rifampicin [R]
• Pyrazinamide [Z]
• Streptomycin [S]
• Ethambutol [E]

3. SECOND line drugs
• Salicylates like Para-amino salicylate
• Ethionamide
• Cycloserine
• Thiacetazone
Newer Drugs:
Quinolones e.g. Ciprofloxacin, Levofloxacin,
Moxifloxacin
Macrolides e.g. Clarithromycin,Azithromycin
Drugs rarely used: Aminoglycosides e.g.
Capreomycin, Kanamycin,Amikacin

4. MECHANISM
It inhibit the synthesis of mycolic acid which is
important component of mycobacterial cell wall
resulting in cell wall disruption.
Dose and Route: 300-400 mg oral
1. ISONIAZID

5. Contraindications
⚫Previous INH hepatic injury or reaction
⚫Acute liver damage
⚫Hypersensitivity

6. Adverse Effects
⚫Peripheral neuropathy (numbness and
weakness in hands and feets)
⚫Loss of appetite,
⚫Nausea, Vomiting,
⚫Stomach pain,
⚫Dizziness, Slurred speech
⚫Seizures
⚫Hepatitis

7. DRUG INTERACTIONS:
⚫INH and ethionamide may cause a temporary
increase in serum concentrations of INH.
⚫Aluminum salts, decrease the absorption of INH
by a reducing gastric emptying. Administration
of INH 1 hour before antacids is recommended.
⚫INH may inhibit valproic acid hepatic
metabolism. Elevated valproic acid
concentrations and hepatotoxicity.

8. 2. RIFAMPICIN
•Rifampicin has broader antimicrobial activity than
isoniazid and can be used as part of treatment for
several different bacterial infections.
•Effective against TB and Leprosy.
Mechanism
Rifampin acts via the inhibition of DNA-dependent
RNA polymerase, leading to a suppression of RNA
synthesis and cell death.

9. Contraindications
⚫Hypersensitivity to rifamycins
⚫Concomitant administration of live bacterial
vaccines.
Precautions
⚫Maydecrease the effectiveness of
oral contraceptive pills (OCPs)
⚫Use with caution in patients with history of
alcoholism and patients receiving additional
medications that may cause hepatotoxicity.

10. Adverse Effects:
⚫Hepatitis and hepatotoxicity
⚫Thrombocytopenia
⚫Hemolytic anemia
⚫Renal failure
⚫Nephritis
⚫Nausea, vomiting
⚫Orange red staining of all body fluids
⚫Flu like symptoms

11. Drug Interactions:
Reduce the plasma concentrations and efficacy
of phenobarbital, chloramphenicol and
sulfonylureas.

12. 3. Pyrazinamide
Mechanism of Action
• Pyrazinamide's exact mechanism of action is not known.
• Prodrug release pyrazinamidase, which converts PZA to
pyrazinoic acid (POA). POA decreases the pH below that
which retards the growth of M. tuberculosis and
inhibiting the fatty acid synthesis which is required for
bacterial growth.

13. Contraindications
⚫Hypersensitivity
⚫Severe liver damage
⚫Acute gout
Adverse Effects
⚫Malaise,
⚫Nausea, V
omiting ,
⚫Anorexia,
⚫Arthralgia, Myalgia
⚫Gout,
⚫Dysuria,
⚫Thrombocytopenia, Hepatotoxicity.

14. Drug Interactions
⚫PZA can increase serum uric acid levels and
precipitate gout attacks. The dosages of antigout
agents, including allopurinol and sulfinpyrazone may
need to be adjusted.
⚫Daily use of ethanol while receiving pyrazinamide
increases the risk of drug-induced hepatitis.

15. 4. Ethambutol
Mechanism
It inhibits synthesis of Mycolic acid which is an
essential component of mycobacterial cell wall.

16. Contraindications
⚫Optic neuritis
⚫Hypersensitivity
Adverse Effects
⚫Acute gout or hyperuricemia,
⚫Abdominal pain,
⚫Anaphylaxis,
⚫Optic neuritis; symptoms may include decreased
acuity, color blindness or visual defects
⚫Peripheral neuritis
⚫Rash

17. Drug Interactions
⚫Aluminum hydroxide can reduce the rate of
ethambutol absorption. At least 4 hours
should elapse between doses of aluminum
hydroxide-containing antacids and
ethambutol.
⚫Ethambutol may interfere with the development
of an immune response following Bacillus
Calmette-Guerin vaccine (BCG).

18. 5. Streptomycin
Streptomycin is the first discovered
aminoglycoside antibiotic, originally isolated from
the bacteria Streptomyces griseus.
Mechanism of action:
It inhibits the protein synthesis of mycobacteria in
the ribosome and results in bacterial cell death.

19. Contraindications
•Hypersensityvity to streptomycin
•Concomitant live bacterial vaccines
Adverse Effects
•Hypotension,
•Neurotoxicity,
•Drowsiness,
•Nausea, Vomiting,
•Arthralgia,
•Ototoxicity (auditory, vestibular),
•Nephrotoxicity

20. Drug Interactions
⚫Streptomycin may interfere with the development of an
immune response following administration of BCG
vaccine.
⚫ Loop diuretics may cause volume depletion and allow
for the concentration of aminoglycosides within the
nephron; concurrent therapy has been considered a
risk-factor for aminoglycoside- induced nephrotoxicity.

21. SECOND LINE ANTI-TUBERCULAR
DRUGS
Second line drugs are more toxic and less
efficacious as compared to first line anti
tubercular drugs.
These are used when the tubercular bacilli
shows resistance to the first line drugs or when
first line drugs are not tolerated or contraindicated.

22. 1. Para-amino salicylic acid
•These drugs act by the same mechanism as
sulfonamides.
•It is tuberculostatic and one of the least active
drug.
•Dose: 200-300 mg/kg/day
•Contraindicated in hypersensitivity and ESRD.
•Adverse effects are anorexia, nausea, epigastric
pain, rashes, fever, malaise, hypokalemia, goitre
and liver dysfunction

23. 2. ETHIONAMIDE
•This is sulfur containing structural analog of
isoniazid that also distrupts mycolic acid synthesis.
•Dose: 10-20 mg/kg/day oral
•Contraindicated for patients with severe hepatic or
renal dysfunction
Adverse Effects:
•Anorexia, Nausea, Vomiting, Hepatotoxicity,
Peripheral neuritis

24. 3. Cycloserine
•It is an orally effective structural analogue of
isoniazid that also distrupts mycolic acid synthesis.
•Dose: 10-20 mg/kg/day oral
•Adverse effects are CNS disturbances like
lethargy, anxiety and suicidal tendencies.
•Therefore in patients with history of seizures and
other mental illness, it is contraindicated.

25. 4. Thiacetazone
It continues to be used as a convenient low cost
drug to prevent emergence of isoniazid resistance,
streptomycin & ethambutol.
Dose:150 mg OD oral.
Adverse Effects: Abdominal discomfort, diarrhea,
rashes, mild anemia, anorexia, hepatitis

26. 5. Flouroquinolones
•The drugs are potent oral bactericidal drugs for
T.B. The preferred ones are moxifloxacin and
levofloxacin.
•The antitubercular doses are:
•Moxifloxacin-400mg OD, oral
•Levofloxacin-750 mg OD, oral
•Ofloxacin-800 mg OD. Oral
Adverse Effects: Nausea, vomiting, diarrhoea,
Headache, dizziness, insomnia, skin rash,
photosensitivity.

27. 6. Clarithromycin
It is a semisynthetic macrolide antibiotic that inhibit RNA-
dependent protein synthesis thereby inhibiting bacterial
growth (bacteriostatic).
Dose: 500 mg PO 12 hourly
Adverse Effects: Abnormal taste, Diarrhea, Nausea,
Vomiting, Elevated BUN, Abdominal pain, Rash,
Dyspepsia, Headache
Contraindications: Cholestatic jaundice or hepatic
dysfunction

28. 7. KANAMYCIN(Km) /AMIKACIN(Am)
•These are tuberculocidal aminoglycosides and
very much similar to streptomycin in antitubercular
activity and adverse effects.
•During the intensive phase of MDR-TB treatment,
one of these drugs is mostly included in the
regimen.
•Dose: 10-15 mg/kg/day. IM, OD

29. 8. CAPREOMYCIN (Cm)
•It has similar bactericidal activity against
Mycobacterium as aminoglycosides.
•It is used only as an alternative to Streptomycin
and Amikacin resistant M. Tuberculosis.
•Dose: 10-15 mg/kg/day. IM, OD