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Antituberculosis
Chemotherapy
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Older “Standard”
Chemotherapy
(Streptomycin, INH, PAS x 18-24 months)
- Inconveniently
long regimen
- Poor compliance
- Low overall success (estimated to be 8% in Indian conditions)
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In India, it is
estimated that only 30% of cases in the community are diagnosed to
start with, and of this, only 35% remain under treatment for an adequate
period of time. Further, only 75% of these patients who complete the
treatment are finally cured. This means that out of every 100 cases
in the community, the overall level of success is only 8%.
- Fox W., Lung
India, 1984, II, 161-174
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Newer
Short Course Chemotherapy
- Based on
improving compliance to achieve better overall success
- Drugs must inhibit actively multiplying organisms as well as persisters
- Main drugs include rifampicin, INH and pyrazinamide, each having
actions against particular populations of Mycobacterium tuberculosis
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|
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Cavitary
lesions |
Caseous
lesions |
Macrophages |
| 1.
Location of bacilli |
Extracellular |
Extracellular |
Intracellular |
| 2.
Population of bacilli |
+++ |
++
|
++ |
| 3.
Oxygen tension |
high |
low
|
low
|
| 4.
Medium |
Neutral
/Alkaline |
Neutral
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Acidic
|
| 5.
Resistant mutants |
Common |
Uncommon |
Uncommon
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Usual Anti
TB Regimen
6
months regimen:
First 2 months
(Intensive phase) : EHRZ
Next 4 months (Continuation phase) : HR
(H = Isoniazid; R = Rifampicin; Z = Pyrazinamide
E = Ethambutol)
* Ethambutol
is optional; another drug may be used in its place
* Regimens of longer duration and/or with 3 or 5 drugs in intensive
phase may be used
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Cardinal
Anti TB drugs- Important features
Rifampicin
-
Active against various mycobacterial populations, hence mainstay of
treatment
- Very rapid bactericidal action Isoniazid
- Active against various mycobacterial populations, hence mainstay
of treatment
- Bactericidal
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Anti TB drugs
- Important features (contd.)
Pyrazinamide
- Active against intracellular organisms in acidic pH
- Bactericidal
Ethambutol
- Bacteriostatic drug, added to regimen to take care of resistance
Other drugs
- May need to be added to regimen especially in cases of relapse,
because of multi drug resistance (MDR)
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Daily
Dosages
| |
Adults
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Children
|
|
Rifampicin
|
400-600
mg
|
10-20
mg/kg
|
|
Isoniazid
|
300
mg
|
5-20
mg/kg
|
|
Pyrazinamide
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1.5
- 2 g
|
20-35
mg/kg
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Ethambutol
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15-25
mg/kg
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15-25
mg/kg
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Some Adverse
Effects of the Main Anti TB drugs
Rifampicin
: brownish discolouration of urine, hepatoxicity Isoniazid : hepatotoxicity,
peripheral neuropathy Pyrazinamide : hepatotoxicity, hyperuricaemia
Ethambutol : optic neuritis
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Some Other
Anti TB drugs
Capreomycin
Dosage : 1 g daily (15-20 mg/kg/day) given IM for 60-120 days; then
2-3 times weekly upto 18-24 months
Cycloserine
Dosage : 250 mg 12 hourly for 2 weeks, increased to 500 mg 12 hourly.
Children 10 mg/kg/day
Ethionamide
Dosage : 15-20 mg/kg o.d. (max 1 g daily)
Prothionamide
Dosage :15-20 mg/kg/day (max 1 g daily)
Streptomycin
Dosage : Adults 0.75-1 g daily. Children 15-20 mg/kg/day. Daily for
1st 2 months; thrice weekly for next 2-6 months
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