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Overview
INH (H)
Ethambutol (E)
Pyrazinamide (Z)
Rifampicin (R)
Dapsone (D) Clofazimine (C)
For TBC
For Leprosy
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Overview
TB is a chronic infection due to M.tuberculosis
- (acid fast bacilli)mycolic acid
- slow growth resistant to most AM and need long
therapy
Monotherapy leads to resistance
need combination therapy (> 2 drugs)
Long therapy : 6-m 2-y
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Overview
Long therapycost
Multiple drugs AEs
Thats why morbidity & mortality are still high
Indonesia : the 3rd in the world
HIV (+) and poor increase the occurrence of TB
compliance
treatment failure
drug resistance
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Overview
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Overview
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Overview
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M.O.A and spectrum: inhibit DNA replication byinhibiting DNA polymerase specific
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bactericidal for intra- & extracellular mycobacteria
the most active anti TB drug
also active for gram (-) sp.
TBC, Leprosy, severe gram (-) infection
Resistance: changes the affinity of the enzyme
decreased permeability of the mycobacteria
RIFAMPICIN
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GI upset (but not to give with dairy product or antacid!)
Coloration of urine, saliva, etc
Rash, fever, arthralgia ( uric acid),
Hepatitis
Check for LFT and uric acid regularly
Becareful in elderly, alcoholism
Drug Interaction!
RIFAMPICIN
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ISONIAZID
The hydrazide of isonicotinic acid, a synthetic analogue
of pyridoxine (B6)
MOA ? Unclear inhibit synthesis of mycolic acid
Spectra? limited to mycobacteria
Bacteriostatic (for dormant) but cidal (for growing)
Resistance: reduced penetration of the drug
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A : orally, impaired abs if taken with food and antacid
D: Widely distributed (include in caseous material), CSF
M: liver acetylation (slow and fast) related to AEs
and drugs concentrations; involved by genetics
E: kidney
ISONIAZID
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Peripheral neuritis (numbness) B6
Hepatitis (together with R and Z)
Skin reaction
G-6 PD hemolytic anemia
DI: inhibitor CYP
ISONIAZID
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Only for mycobacterium
MOA is ??
Bacteristatic
Oral kidney
AEs : optic neuritis visual acquity and red/green
blindness
CI for children
Only for the first 2-m of TB treatment
ETHAMBUTOL
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2nd ANTI TB
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2nd ANTI TB
inhibit cell wall synthesis (involving D-alanin)
liver metabolism, renal excreted
AEs: CNS disturbance, epileptic seizure, peripheral
neuropathy
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Overview
Leprosy (Hansens disease) is caused by M.leprae
Bacilli from skin or nasal discharge
2 extreme conditions:
skin macules: cell mediated imm is OK
disseminated lepromatous:
cell mediated imm is impaired
all destruction happen
WHO: triple drug regimen: R + D + CL
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WHO recommendation
for tuberculoid leprosy: D + R
for lepromatous leprosy: D + R + CL (2 - 5years)
100 mg D + 50 mg C daily (unsupervised at home)
+
600 mg R + 300 mg CL monthly (supervised)
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A phenazine dye binds to DNA block the
template function
Bactericid for m.leprae
Oral well distributed accumulated in the tissue
Effect is delayed after 6-7 weeks
Very very long half-life (8-weeks)
AEs: red-brown discolorization
CLOFAZIMINE
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