Anti-TB Agents Flashcards
first line TB agents
isoniazid, rifampin, pyrazinamide, ethamobutol, streptomycin
most active drug against TB
isoniazid
isoniazid MOA
inhibits synthesis of mycolic acids (mycobacterial cell wall)
covalent complex with AcpM and KasA
resistance with isoniazid
overexpress inhA
mutation of katG
overexpress ahpC
mutation kasA
adverse with INH
hepatitis - major toxic effect
peripheral neuropathy - B6 deficiency
vit B6 deficiency
pyridoxine
with isoniazid tx
peripheral INH
rifampin MOA
binds to beta-subunit of bacterial DNA-dependent RNA polymerase and inhibits RNA synthesis
bacteriacidal for mycobacterium
resistance in rifampin
mutation of rpoB
P450 inducer
rifampin
-may alter HIV NNRTI treatment
red/orange urine color
rifampin
pyrazinamide
MOA unknown
-active at pH 5.5
converted to pyrazinoic acid in macrophages
pyrazinamide resistance
mutation of pncA
most hepatotoxic first line agent
pyrazinamide
ethambutol MOA
inhibit mycobacterial arabinosyl transferase - encoded by embCAB operon
involved in polymerization rxn of arabinoglycan - component of mycobacterial cell wall
arabinoglycan
ethambutol inhibits this
ethambutol resistance
overexpress emb gene
mutation of embB gene
streptomycin
aminoglycoside
IM/IV administer
streptomycin MOA
irreversible inhibitor of protein synthesis
binds S12 of 30S subunit
streptomycin resistance
mutations in rspL gene or rrs gene
streptomycin scope
mycobacterium tuberculosis
mycobacterium avium complex
mycobacterium kansasii
vertical nystagmus
ethambutol
vertigo and hearing loss
streptomycin
severe/life-threatening TB
streptomycin
administered IV
ethionamide
isoniazid second-line
rifabutin
rifapentine
rifampin second-line
amikacin
capremoycin
kanamycin
streptomycin second line
leprosy drugs
clofazimine
dapsone
four drug regimen
administered until susceptibility is determined
done bc drug resistant mutants are very frequent in population
hepatotoxic drugs
INH, rifampin, pyrazinamide
pyrazinamide is most hepatotoxic
should be stopped - serum aminotransferase reaches 5x upper limit
N-acetyltransferase
polymorphism at NAT2 cause variation in rate of acetylation
slow vs. fast acetylators
isoniazid biotransformation