Flashcards in antimycobacterial drugs Deck (48):
1
1st line for TB
isoniazid
rifampin
rifabutin (1st line in HIV)
ethambutol
pyrazinamide
2
1st line TB tx in HIV
rifabutin
3
2nd line for TB
streptomycin
ethionamide
levofloxacin
amikacin
4
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
5
Directly Observed Treatment
recommended in noncompliant pt or in resistant strains
6
Isoniazid
1st line
most potent anti-TB drug
used in combo tx
7
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
8
why should isoniazid not be given alone
resistance emerges rapidly
9
Isoniazid resistance
NO cross resistance with other anti-tb drugs
mutations in: deletion of KatG, acyl carrier protein mutations, inhA overexpression
10
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)
11
Rifamycins
rifampin, rifabutin
12
rifampin
cidal, given in combo
1st line
P450 INDUCER
13
rifampin MOA
block transcription by binding to beta subunit of bacterial RNA pol = inhibit RNA synth
14
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)
15
rifampin resistance
mutations to rpoB
gene for B subunit of RNA pol = dec affinity of RNA pol
dec permeability
16
rifampin clinical app
RB
latent tb in INH intolerant
leprosy
prophylaxis in those w/ meningitis exposure
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rifampin AE
proteinuria
GI distress
thrombocytopenia, rashes, nephritis, liver dysfunction
orange color to body fluids
P450 inducer
(safe in pregnancy)
18
isoniazid vs rifampin: P450 inducer/inhibitor
isoniazid: P450 inhibitor
rifampin: P450 inducer
If given together, inducer effect wins
19
rifabutin
used in HIV pt - b/c of dec effect on CYP
substitute for rifampin if intolerable
20
ethambutol
1st line
COMBO tx
for m. tuberculosis, m. kansasii
21
ethambutol MOA
inhibits arabinosyl transferases
22
ethambutol use
in combo with pyrazinamide, izoniazid, rifampin
resistance happens if used alone
23
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
24
pyrazinamide
1st line
hydrolyzed to active pyrazinoic acid
25
pyrazinamide use
in combo with isoniazid, rifampin, ethambutol
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pyrazinamide AE/contraindications
renal/hepatic insufficiency = lower doses
**nongouty polyarthralgia
hyperuricemia
heptaotoxicity
photosensitivity
only use in pregnancy when benefits outweigh risk
27
streptomycin
in drug resistant strains
28
streptomycin use
TB disease of meningitis, miliary, severe organ TB
**more severe AE and inc risk of resistance = limited use
29
amikacin
2nd line
streptomycin or multi drug resistant strains
teratogenic
similar AE to streptomycin
30
levofloxacin
if TB is resistant against 1st lines
always use in combo tx
teratogenic
31
ethionamide
no cross resistance with INH. "congener of INH"
SEVERE neuro effects
teratogenic
32
duration of isoniazid tx in latent TB
6-9 months
33
duration of rimfapin tx in latent TB
4 months
34
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
35
Leprosy combo drugs
dapsone
clofazimine
rifampin
36
dapsone
bacteriostatic
also used in PCP tx in HIV pt
37
dapsone MOA
inhibits folate synthesis
38
repository form of dapsone
acedapsone
39
dapsone AE
hemolysis
erythema nodosum leprosum
p450 inhibitor
fever/hepatitis/methemoglobinemia
40
clofazimine
phenazine dye (can dye skin)
bactericidal
41
clofazimine MOA
binds DNA - inhibits replication
generate oxygen radicals
42
clofazimine AE
red brown discoloration of skin
eosinophilic enteritis
(NO erythema nodosum)
43
WHO Leprosy tx
1-5 skin lesions: rifampin + dapsone ( 6 months)
>5: rifampin + clofazimine + dapsone (12 months)
44
m. kansaii tx
isoniazid + rifamin + ethambutol
resembles TB
45
m. marinum tx
2 drug combo: rifampin, ethambutol, clarithromycin, minocycline, doxycycline, sulfonamide
resembles granulomatous cutaneous disease
46
m. avium tx
clarithromycin + ethambutol +-- rifabutin
47
m. chelonae tx
clarithromycin (monotherapy is adequate)
48