antimycobacterial drugs Flashcards Preview

PHARM 2 > antimycobacterial drugs > Flashcards

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

17

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

26

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

m. fortuitum tx

amikacin, cefoxitin, levofloxacin, sulfonamides, imipenem