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PHARM 2 > antimycobacterial drugs > Flashcards

antimycobacterial drugs Flashcards

1
Q

1st line for TB

A 
isoniazid
rifampin
rifabutin (1st line in HIV)
ethambutol
pyrazinamide
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2
Q

1st line TB tx in HIV

A

rifabutin

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3
Q

2nd line for TB

A

streptomycin
ethionamide
levofloxacin
amikacin

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4
Q

TB tx goals

A

1) kill bacilli
2) prevent emergence of resistance
3) eliminate persistence bacilli to prevent relapse

needs multiple drugs and long duration of tx

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5
Q

Directly Observed Treatment

A

recommended in noncompliant pt or in resistant strains

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6
Q

Isoniazid

A

1st line
most potent anti-TB drug

used in combo tx

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7
Q

Isoniazid MOA

A

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

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8
Q

why should isoniazid not be given alone

A

resistance emerges rapidly

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9
Q

Isoniazid resistance

A

NO cross resistance with other anti-tb drugs

mutations in: deletion of KatG, acyl carrier protein mutations, inhA overexpression

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10
Q

ioniazid AE

A

**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)

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11
Q

Rifamycins

A

rifampin, rifabutin

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12
Q

rifampin

A

cidal, given in combo
1st line

P450 INDUCER

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13
Q

rifampin MOA

A

block transcription by binding to beta subunit of bacterial RNA pol = inhibit RNA synth

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14
Q

rifampin use

A

intra AND extracellular mycobacteria = m. tuberculosis AND m. kansasii

Gram - and +

can also tx MRSA (its an OPTION - not necessarily a 1st/2nd/3rd)

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15
Q

rifampin resistance

A

mutations to rpoB

gene for B subunit of RNA pol = dec affinity of RNA pol

dec permeability

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16
Q

rifampin clinical app

A

RB

latent tb in INH intolerant

leprosy

prophylaxis in those w/ meningitis exposure

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17
Q

rifampin AE

A

proteinuria

GI distress

thrombocytopenia, rashes, nephritis, liver dysfunction

orange color to body fluids

P450 inducer

(safe in pregnancy)

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18
Q

isoniazid vs rifampin: P450 inducer/inhibitor

A

isoniazid: P450 inhibitor
rifampin: P450 inducer

If given together, inducer effect wins

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19
Q

rifabutin

A

used in HIV pt - b/c of dec effect on CYP

substitute for rifampin if intolerable

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20
Q

ethambutol

A

1st line
COMBO tx

for m. tuberculosis, m. kansasii

21
Q

ethambutol MOA

A

inhibits arabinosyl transferases

22
Q

ethambutol use

A

in combo with pyrazinamide, izoniazid, rifampin

resistance happens if used alone

23
Q

ethambutol AE

A

*****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
Q

pyrazinamide

A

1st line

hydrolyzed to active pyrazinoic acid

25
Q

pyrazinamide use

A

in combo with isoniazid, rifampin, ethambutol

26
Q

pyrazinamide AE/contraindications

A

renal/hepatic insufficiency = lower doses

**nongouty polyarthralgia

hyperuricemia
heptaotoxicity
photosensitivity

only use in pregnancy when benefits outweigh risk

27
Q

streptomycin

A

in drug resistant strains

28
Q

streptomycin use

A

TB disease of meningitis, miliary, severe organ TB

**more severe AE and inc risk of resistance = limited use

29
Q

amikacin

A

2nd line
streptomycin or multi drug resistant strains

teratogenic
similar AE to streptomycin

30
Q

levofloxacin

A

if TB is resistant against 1st lines

always use in combo tx

teratogenic

31
Q

ethionamide

A

no cross resistance with INH. “congener of INH”

SEVERE neuro effects
teratogenic

32
Q

duration of isoniazid tx in latent TB

A

6-9 months

33
Q

duration of rimfapin tx in latent TB

A

4 months

34
Q

Empirical tx options - INITAL PHASE and duration

A

isoniazid + rifampin + pyrazinamide + ethambutol = 8 weeks - THEN isoniazid + rifampin = 18 weeks

OR just izoniazid + rifampin + ethambutol THEN isoniazid and rifampin = 31 weeks

35
Q

Leprosy combo drugs

A

dapsone
clofazimine
rifampin

36
Q

dapsone

A

bacteriostatic

also used in PCP tx in HIV pt

37
Q

dapsone MOA

A

inhibits folate synthesis

38
Q

repository form of dapsone

A

acedapsone

39
Q

dapsone AE

A

hemolysis

erythema nodosum leprosum

p450 inhibitor

fever/hepatitis/methemoglobinemia

40
Q

clofazimine

A

phenazine dye (can dye skin)

bactericidal

41
Q

clofazimine MOA

A

binds DNA - inhibits replication

generate oxygen radicals

42
Q

clofazimine AE

A

red brown discoloration of skin

eosinophilic enteritis

(NO erythema nodosum)

43
Q

WHO Leprosy tx

A

1-5 skin lesions: rifampin + dapsone ( 6 months)

> 5: rifampin + clofazimine + dapsone (12 months)

44
Q

m. kansaii tx

A

isoniazid + rifamin + ethambutol

resembles TB

45
Q

m. marinum tx

A

2 drug combo: rifampin, ethambutol, clarithromycin, minocycline, doxycycline, sulfonamide

resembles granulomatous cutaneous disease

46
Q

m. avium tx

A

clarithromycin + ethambutol +– rifabutin

47
Q

m. chelonae tx

A

clarithromycin (monotherapy is adequate)

48
Q

m. fortuitum tx

A

amikacin, cefoxitin, levofloxacin, sulfonamides, imipenem

PHARM 2 (18 decks)

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