antimycobacterial drugs Flashcards
1st line for TB
isoniazid rifampin rifabutin (1st line in HIV) ethambutol pyrazinamide
1st line TB tx in HIV
rifabutin
2nd line for TB
streptomycin
ethionamide
levofloxacin
amikacin
TB tx goals
1) kill bacilli
2) prevent emergence of resistance
3) eliminate persistence bacilli to prevent relapse
needs multiple drugs and long duration of tx
Directly Observed Treatment
recommended in noncompliant pt or in resistant strains
Isoniazid
1st line
most potent anti-TB drug
used in combo tx
Isoniazid MOA
pro-drug: activated by mycobacterial catalase peroxidase - KatG
targets: enoyl acyl carrier protein reductase (InhA) AND beta-ketoacyl-ACP synthase (KasA)
- similar as cell wall synthesis inhibitor
bacteriostatic and cidal
why should isoniazid not be given alone
resistance emerges rapidly
Isoniazid resistance
NO cross resistance with other anti-tb drugs
mutations in: deletion of KatG, acyl carrier protein mutations, inhA overexpression
ioniazid AE
**peripheral neuritis (d/t pyridoxine deficiency) - 1st AE to be seen; easily corrected with B6
hepatotoxic
p450 inhibitor
Lupus like syndrome
if pregnant, HIGH risk of hepatitis (dec risk with B6 supplement)
Rifamycins
rifampin, rifabutin
rifampin
cidal, given in combo
1st line
P450 INDUCER
rifampin MOA
block transcription by binding to beta subunit of bacterial RNA pol = inhibit RNA synth
rifampin use
intra AND extracellular mycobacteria = m. tuberculosis AND m. kansasii
Gram - and +
can also tx MRSA (its an OPTION - not necessarily a 1st/2nd/3rd)
rifampin resistance
mutations to rpoB
gene for B subunit of RNA pol = dec affinity of RNA pol
dec permeability
rifampin clinical app
RB
latent tb in INH intolerant
leprosy
prophylaxis in those w/ meningitis exposure
rifampin AE
proteinuria
GI distress
thrombocytopenia, rashes, nephritis, liver dysfunction
orange color to body fluids
P450 inducer
(safe in pregnancy)
isoniazid vs rifampin: P450 inducer/inhibitor
isoniazid: P450 inhibitor
rifampin: P450 inducer
If given together, inducer effect wins
rifabutin
used in HIV pt - b/c of dec effect on CYP
substitute for rifampin if intolerable
ethambutol
1st line
COMBO tx
for m. tuberculosis, m. kansasii
ethambutol MOA
inhibits arabinosyl transferases
ethambutol use
in combo with pyrazinamide, izoniazid, rifampin
resistance happens if used alone
ethambutol AE
*****dose dependent visual disturbances (red/green color blindness) - cannot be used in children too young to recieve sight tests –> can become permanent
confusion
hyperuricemia
peripheral neuritis
pyrazinamide
1st line
hydrolyzed to active pyrazinoic acid
pyrazinamide use
in combo with isoniazid, rifampin, ethambutol
pyrazinamide AE/contraindications
renal/hepatic insufficiency = lower doses
**nongouty polyarthralgia
hyperuricemia
heptaotoxicity
photosensitivity
only use in pregnancy when benefits outweigh risk
streptomycin
in drug resistant strains
streptomycin use
TB disease of meningitis, miliary, severe organ TB
**more severe AE and inc risk of resistance = limited use
amikacin
2nd line
streptomycin or multi drug resistant strains
teratogenic
similar AE to streptomycin
levofloxacin
if TB is resistant against 1st lines
always use in combo tx
teratogenic
ethionamide
no cross resistance with INH. “congener of INH”
SEVERE neuro effects
teratogenic
duration of isoniazid tx in latent TB
6-9 months
duration of rimfapin tx in latent TB
4 months
Empirical tx options - INITAL PHASE and duration
isoniazid + rifampin + pyrazinamide + ethambutol = 8 weeks - THEN isoniazid + rifampin = 18 weeks
OR just izoniazid + rifampin + ethambutol THEN isoniazid and rifampin = 31 weeks
Leprosy combo drugs
dapsone
clofazimine
rifampin
dapsone
bacteriostatic
also used in PCP tx in HIV pt
dapsone MOA
inhibits folate synthesis
repository form of dapsone
acedapsone
dapsone AE
hemolysis
erythema nodosum leprosum
p450 inhibitor
fever/hepatitis/methemoglobinemia
clofazimine
phenazine dye (can dye skin)
bactericidal
clofazimine MOA
binds DNA - inhibits replication
generate oxygen radicals
clofazimine AE
red brown discoloration of skin
eosinophilic enteritis
(NO erythema nodosum)
WHO Leprosy tx
1-5 skin lesions: rifampin + dapsone ( 6 months)
> 5: rifampin + clofazimine + dapsone (12 months)
m. kansaii tx
isoniazid + rifamin + ethambutol
resembles TB
m. marinum tx
2 drug combo: rifampin, ethambutol, clarithromycin, minocycline, doxycycline, sulfonamide
resembles granulomatous cutaneous disease
m. avium tx
clarithromycin + ethambutol +– rifabutin
m. chelonae tx
clarithromycin (monotherapy is adequate)
m. fortuitum tx
amikacin, cefoxitin, levofloxacin, sulfonamides, imipenem
