CHEMOTHERAPY OF TB

• TB – a chronic , granulomatous infectious disease –

AFB- Mycobacterium tuberculae.

• Primarily affecting the LUNGS (PULMONARY) – Left untreated

spreads to BONE & BRAIN also
( EXTRA PULMONARY) .

• With the increase in the incidence of AIDS >>>> Increase in the TB

infections.
• Only MULTIPLE DRUG THERAPY .

• DRTB – Common

• NOW TDR-TB REPORTED ( FROM INDIA).

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 OBJECTIVES IN THE CHEMOTHERAPY OF
TB
TO KILL DIVIDING CELLS – The initial intensive therapy.
 Possible with the use of BACTERICIDAL anti TB drug like ISONIAZID &
RIFAMPIN.
 Helps to reduce bacterial load / to achieve negative for pathogen in the
sputum.
 Helps to achieve quick symptomatic relief.

TO KILL PERSISTANT PATHOGENS – The continuation

therapy.
 To cure and prevent relapse.
 Sterilizing the affected organ.
 Drug – PYRIZINAMIDE.

TO PREVENT EMERGENCE OF RESISTANCE

 So that the pathogens will remain sensitive to the influence of the
drug.
 ETHAMBUTOL.
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 OBJECTIVES IN THE CHEMOTHERAPY OF
TB
 MULTIPLE DRUGS ARE USED TO ACHIEVE THIS
OBJECTIVE.

Anti- TB drugs

FIRST LINE DRUGS : ISONIAZID, RIFAMPIN, PYRAZINAMIDE ,

ETHAMBUTOL & STREPTOMYCIN.
 3+ ANTIBACTERIAL ACTIVITY, LOW TOXICITY and ROUTEINLY USED.

SECOND LINE DRUGS : THIOACETAZONE , PARA AMINOSALICYCLIC ACID,

ETHIONAMIDE, CYCLOSERINE , KANAMYCIN, AMIKACIN & CAPREOMYCIN.

 RELATIVELY POOR ANTIBACTERIAL ACTIVITY, HIGHLY TOXIC and RESERVED IN

CASE
OF RESISTANCE EMERGES.

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 DRUGS FOR CHEMOTHERAPY OF
TB

 ISONIAZID & RIFAMPIN – Most potent bactericidal

activity against TB.
 PYRAZINAMIDE – Good sterilizing activity- effective at
intracellular bacilli and at inflamed sites.
 STREPTOMYCIN – active only against FAST
MULTIPLYING pathogens. – Not a preferred – resistance.
 ETHAMBUTOL – Is bacteriostatic – helps prevent the
development of resistance.
 Drug combinations are made to maximize the objective
attainment.

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 MULTI DRUGS FOR CHEMOTHERAPY OF
TB

Why MULTIDRUGS?
 Single drug exposure >>> development of resistance at faster
rate & Chances of relapse.
 Combinations produce synergistic effect.
 Reduces the duration of chemotherapy (9-12 months).
 Faster response ( within few weeks of initiating the therapy)
and symptomatic relief evident within 2-4 weeks.
 However, improvement slowly declines as slow multiplying
pathogens respond gradually / slowly.

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 REGIMENS IN THE CHEMOTHERAPY OF
TB

1.CONVENTIONAL THERAPY

 FOR A PERIOD OF 12-18 MONTHS.

 Combination of ISONIAZID + THIOACETAZONE
/ ETHAMBUTOL ± STREPTOMYCIN.
 Higher failure rate, Poor compliance .
 Not a preferred / recommended.

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 REGIMENS IN THE CHEMOTHERAPY OF
TB

2. SHORT TERM THERAPY

 FOR A PERIOD OF 6-9 MONTHS.
 Consists of TWO phases
1. INITIAL INTENSIVE THERAPY – Lasting for 2-3
months- aim is to rapidly kill TB bacilli and produce
symptomatic relief.
2. CONTINUATION PHASE – Lasting for 4-6 months –
aim is to prevent emergence of resistance and relapse.
 Treatment is based on site of disease (Pulmonary / extra
pulmonary), Severity , bacterial load, presence/ absence
of bacilli in the sputum and history of previous treatment.

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 DRUGS USED IN THE CHEMOTHERAPY OF TB

FOR INITIAL PHASE ( THAT LASTS FOR 2-3 MONTHS)

• ISONIAZID + RIFAMPICIN + PYRAZINAMIDE + ETHAMBUTOL /

STREPTOMYCIN - daily / thrice weekly for 2 months.
• If sputum positive for Bacilli –even after 2 months of intense therapy ,
extended for another month.
• Shift to CONTINOUS PHASE, irrespective of sputum status after
3 months.

FOR CONTINOUS PHASE ( THAT LASTS FOR 4 – 6/7 MONTHS)

 ISONIAZID + RIFAMPIN for 4 months /

 ISONIAZID + ETHAMBUTOL FOR 6 months
 Thrice weekly.
 Extended for another one month – if extra pulmonary.

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 DRUGS USED IN THE CHEMOTHERAPY OF TB

FOR CHRONIC CONDITIONS

 When smear is positive even after completing above
mentioned intense therapy.
 Possibility of MULTIDRUG RESISTANT TB.
 DIFFICULT to treat
 Even II line drugs are likely to less effective.
 Cost of treatment is expensive.
 PRE-EXSISTING conditions- AIDS, Leukemia, silicosis,
Diabetes mellitus are considered before selecting
combination of drugs for such chronic conditions.

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CHOICE OF DRUGS USED IN THE CHEMOTHERAPY OF RESISTANT TB

 If pathogen is resistant to ISONIAZID

RIFAMPICIN + PYRIZINAMIDE + ETHAMBUTOL for a period
of 12 months.

 If pathogen is resistant to ISONIAZID and RIFAMPICIN

PYRIZINAMIDE + ETAMBUTOL + STREPYTOMYCIN
OR
ETHAMBUTOL + CIPROFLOXACIN / OFLOXACIN till
improvement in clinical signs.
Believed to produce Higher cure rate.

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 CHEMOTHERAPY OF TB IN SPECIAL SITUATIONS

 DURING PREGANANCY
2 MONTHS of ISONIAZID+ RIFAMPIN+ PYRIZINAMIDE
followed by
4 MONTHS of ISONAIZID + RIFAMPICIN
 FOR BREAST FEEDING MOTHER
SAME AS ABOVE ( MOTHER) + Child immunized with BCG
and isoniazid Prophylaxsis.
 IF SENSITIVE/ ALLERGIC
If minor – symptomatic relief- if serious stop the drugs.
Can be restarted with after small challenging dose.
in case of hepatitis ( commonly occurs) – stop – can be
continued later – better to avoid Pyrizinamide.
Fluoroquinolone is a choice over strepto/ ciprofloxacin.
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 CHEMOPROPHYLAXSIS OF TB

 When ?
 Frequently coming in contact with actual TB patients.
 if tested positive for bacilli ( sputum).
 TB patient in the family.
 Neonate of TB affected mother.
 Patients on steroid therapy, diabetic , HIV , Silicosis and leukemic
patient (since prone for opportunistic infections).
 Disease inactive - but had received INADEQUATE therapy.
 DRUGS used ?
 ISONIAZID 300 mg daily for 6-12 months /
 ISONIAZID 350mg + RIFAMPIN 700 mg for 6 months.

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 PHARMACOLOGY OF SELECTED ANTI-TB DRUGS

1. ISONIAZID
 EXCELLENT ANTI- TB DRUG and is a part of MDT of TB.
 TUBERCULOCIDAL
 Kills fast multiplying organism ( cidal) and inhibits the growth of
slowly multiplying pathogens ( static).
 MOA: Inhibits the synthesis of MYCOLIC ACID – a unique fatty
acid component of cell wall of TB pathogen. – selectively
acting on that – and not on other gram negative pathogen.
 Adverse effects : Dose dependent CNS and hepatotoxicity.

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 PHARMACOLOGY OF SELECTED ANTI-TB DRUGS
2. RIFAMPIN / RIFAMPICIN
 Semi synthetic derivative of Rifamycin B.
 Tuberculocidal ( bactericidal) and is as effective as INH>>>
by inhibiting DNA dependent RNA synthesis.
 Exerts bactericidal effect on slowly multiplying pathogens
and affecting both intracellular and extracellular
organisms.
 Only disadvantage: rapid development of resistance.

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 PHARMACOLOGY OF SELECTED ANTI-TB DRUGS

3. PYRAZINAMIDE
 Chemically similar to INH.
 Weak Tuberculocidal action ( bactericidal) and effective
only in acidic PH.
 Highly lethal against intracellularly located pathogen and
in inflammatory sites .
 Employed in the intensive therapy part of MDT of TB – the
early part ( 2-3 months) – reduces the duration of therapy
and prevents relapse .
 MOA: Similar to INH- Inhibition of Mycolic acid synthesis.
 Slowly developing resistance ( since used in combination).

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 PHARMACOLOGY OF SELECTED ANTI-TB DRUGS

4. ETHAMBUTOL
 Selectively tuberculostatic, as effective as streptomycin.
 Always as part of MDT of TB.
 Helps prevent development of resistance.
 MOA: Inhibits ARABINOGALACTAN synthesis and
interferes with the incorporation of Mycolic acid
incorporation into the cell wall of pathogen.
 Slowly developing resistance.

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 PHARMACOLOGY OF SELECTED ANTI-TB DRUGS

5. STREPTOMYCIN
 Earliest anti- TB drug to be used.
 Tuberculocidal
 Used alone – resistance and always as a part of MDT.
 Effective against extracellular and rapidly dividing
pathogen.
 No more a part of MDT and is substituted with Rifampicin /
Ciprofloxacin.
6. THIOACETAZONE
 Relatively weaker
 Earlier a part of MDT.
 ONLY used as a cost effective
 TUBERCULOSTATIC and helps prevent development of
resistance.

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 PHARMACOLOGY OF SELECTED ANTI-TB DRUGS

6. ETHIONAMIDE
 Tuberculostatic.
 Moderately effective with short duration of action.( t1/2 =
2-3 hrs).
 Resistance develops >>> hardly used now.
7. CYCLOSPORINE
 TUBERCULOSTATIC.
 Inhibits bacterial wall synthesis by inactivating enzyme
which racemizses L- Alanine and link 2 alanine residues.
 Slowly developing resistance.
 Part of reserve drug in the MDT of TB.

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