Drugs/Infos
Isoniazid (INH)
Adsorption
1. Well absorbed orally
Distribution
1. Readily distributed in all
body fluid
2. Easily reaches Tx level
in CSF
Metabolism
1. Undergoes 2nd phase
of metabolism
(Conjugation phase )
2. Being acetylated by
Acetyltransferase in
liver.
3. Acetyltransferase
expression is highly
genetic polymorphism*
Excretion
1. Metabolites and
unchanged form
excreted via urine
Tuberculocidal
Mechanism of Action
Clinical Uses
INH is a mycolic acid
synthesis inhibitor
1. Activated by
Mycobacterial
Catalase Peroxidase
2. The activated INH
binds covalently with
a. Acyl carrier protein
b. Beta-ketoacyl
carrier protein
synthetase
1. One of the two most potent anti-TB
drugs
Anti-TB Regimens
1. I+R = 9months of Tx
2. I+R+Z (for the first 2 months) =
6months of Tx
3. COMMON PRACTICE (6months of Tx)
a. Initial phase (1st 2months)
i. I+R+Z+E/S
1. Eradication of
mycobacterium
2. Conversion of +ve sputum to
Spectrum of Activities
–ve sputum
b.
Continuation
phase (the last
1. Tuberculocidal for
4months)
rapid growers
i. I+R
(extracellular)
1. Prevention of relapse
2. Tuberculostatic for
2. Complete mycobacterial
slow growers
eradication
(intracellular)
Prophylaxis (Preventive) Regimen
1. Daily dose of INH for 6 to12 months
2. Daily I+R doses for 6 months
3. If cant use INH
a. Rifampicin 4months
b. R+Z 2 months
Side Effects
1. Peripheral
Neuropathy
a. INH promotes
Pyridoxine (Vit
B6) elimination
b. Counter by VitB6
supplementation
2. Hepatotoxicity
*Genetic
polymorphism
1. Slow acetylator
leads to ↑
susceptibility to
toxicity
Drug drug interaction
1. Potent CYP450
inhibitor
Drugs/Infos
Rifampicin
Adsorption
1. Well absorbed orally
Distribution
1. Readily distributed in all
body fluid
2. Undergoes
enterohepatic
recycling
3. Easily reaches Tx level
in CSF only during
meningeal
inflammation
4. Extensively bind to
plasma protein
Metabolism
1. Undergoes CYP450
metabolism
Excretion
1. Urine
2. Bile
Mechanism of Action
1. Binds to B subunit of
bacterial DNAdependent RNA
polymerase
2. Therefore inhibiting
mRNA synthesis
Spectrum of
Activities
1. Bactericidal for
a. Rapid growers
b. Slow growers
c. Spurters
Side Effects
1. Common
a. Rash
b. Fever
c. Arthralgia
d. Nausea
2. Orange discoloration of
a. Tears
i. Permanently stained contact
lens
b. Sweats
c. Urine
3. Hepatitis (rare)
4. High dose will lead to flu like
syndrome
Drug drug interaction
1. Potent CYP450 inducer
2. Should be replaced by less potent
CYP450 inducer; Rifabutin in HIV
patients undergoing HAART
especially
a. Protease inhibitor (Ritonavir)
b. NNRTI (Efavirenz)
Drugs/Infos
Pyrazinamide
Adsorption
1. Well absorbed orally
Distribution
1. Readily distributed in all body
fluid
2. Easily reaches Tx level in CSF
only during meningeal
inflammation
Metabolism
1. Undergoes CYP450
metabolism
Excretion
1. Urine
Streptomycin
Adsorption
1. Poorly absorbed orally
2. Given only parenterally
Distribution
1. Poorly penetrates cellular
membrane
2. Easily reaches Tx level in CSF
only during meningeal
inflammation
Excretion
1. Urine in unchanged form
Mechanism of Action
Spectrum of Activities
Side Effects
1. Active in acidic pH
1. Weak tuberculocidal to
2. Kill mycobacterium inside
a. Intracellular
the acidic lysosome
mycobacterium
3. Converted to Pyrazinoic
acid by Mycobacterial
Pyrazinamidase
4. It is believed that it acts by
inhibiting Fatty Acid
Synthase at the
Mitochondria and Cell
membrane
a. But still yet to be
proven
1. Common
a. Rash
b. Fever
c. Arthralgia
d. Nausea
2. Hyperuriceamia
a. May cause
acute gouty
attack
3. Hepatitis
1. It binds to the small 16S
1. Tuberculocidal only to
rRNA of the 30S subunit of
extracellular
the bacterial ribosome
mycobacterium
2. Interfering with the binding
of formyl-methionyl-tRNA
to the 30S subunit
3. Leading to codon
misreading
1. Ototoxicity
a. Hearing loss
b. Vertigo
2. Nephrotoxicity
Drugs/Infos
Ethambutol
Tuberculostatic
Mechanism of Action
Spectrum of Activities
Ethambutol is an
Arabinogalactan synthesis
Adsorption
inhibitor
1. Well absorbed orally
1. Inhibits the
Distribution
Mycobacterial
1. Poorly penetrates cellular
Arabinosyl Transferase
membrane
2. Therefore inhibiting the
2. Easily reaches Tx level in
polymerization of
CSF only during
Arabinoglycan in cell
meningeal inflammation
wall synthesis
Excretion
1. Urine in unchanged form
1. Tuberculostatic against
rapid growers
2. Suppresses growth of
most INH and
streptomycin-resistant
tubercle bacilli
3. Prevent emergence of
resistance
Side Effects
1. Optic neuritis
a. Contraindicated in
very small children to
permit assessment of
visual acuity and redgreen color
discrimination