2. Antituberculosis
• Treatment of tuberculosis assumes the
principle of combination therapy for two
main reasons:
– To prevent emergence of resistance.
– To reduce the rate of spread by reducing the
bacterial population rapidly.
• For this reason the available tablets contain
multiple drugs in Fixed Dose Combinations
(FDC).
3. Antituberculosis
• Anti TB agents are divided into first-line and
second-line.
• The first-line drugs include isoniazid,
rifampin/rifampicin, rifabutin, ethambutol,
pyrazinamide.
• While the second line drugs include
capreomycin,cycloserine, streptomycin,
clarithromycin and ciprofloxacin.
4. Antituberculosis
• The treatment of TB take two phases.
• The first initial phase: takes two months and
three drugs are used concomitantly.
• These include isoniazid, rifampicin,
pyrazinamide (plus ethambutol or
streptomycin if resistant organisms is
suspected).
• The combination reduces bacterial population
rapidly.
5. Antituberculosis
• Continuation phase takes four months and
two drugs are used.
• These are isoniazid and rifampicin.
• Sometimes ethambutol may be used instead
of rifampicin in which case the treatment
proceeds for 6 months instead of 4 months.
• Long term treatments are required for TB
meningitis, bone/joint involvement or
resistance is involved.
6. Isoniazid
• Pharmacodynamics of isoniazid is not clear
but postulated to inhibit synthesis of mycobic
acid, important constituent of cell wall and
peculiar to mycobacterium.
• Isoniazid is bacteriostatic against resting
organism but can also kill dividing bacteria.
• Resistance is due to reduced penetration in
the mycobacterial cell.
7. Isoniazid
• It has good gut absorption and wide
distribution.
• Metabolism is usually through acetylation.
• It is excreted in urine partly unchanged and
partly acetlylated form.
• Adverse effects are dose dependent and occur
in 5% of patients.
• Allergy skin eruptions are the commonest side
effects.
8. Isoniazid
• Other adverse effects include fever,
hepatotoxicity, hematological changes,
arthritic symptoms and vasculitis.
• Drug interactions: inhibits metabolism of
antiepileptic agents like phonation,
ethosuximide, carbamazipe which lead to
increased plasma concentration and potential
toxicity of these drugs.
9. Rifampicin
• It is active against gram positive and negative
bacteria.
• It enters phagocytic cells and kills intracellular
microorganism.
• It acts by inhibiting DNA dependent RNA
polymerase in eukaryotic cells.
