E5 Lacount mcmp

Question 1

is mycobacterium TB GN or GP

Answer 1

neither its acid fast

Question 2

Mycobacterium TB can be _______ and form ________

Answer 2

dormant
granulomas

Question 3

what does acid fast mean?

Answer 3

these bacteria retain a dye stain even after a strong acid wash

Question 4

acid fast bacteria retain a dye stain, why is this?

Answer 4

lipid-rich cell wall that contains mycolic acids

Question 5

what is significantly different in mycobacteria cell walls vs GP and GN?

Answer 5

more complex and lipid-heavy than either of those, also resistant to a ton of antibiotics due to impermeability

Question 6

most common tx of active TB infection (4)

Answer 6

combo of rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE)

Question 7

alternative tx of active TB infection

Answer 7

rifapentine, isoniazid, pyrazinamide, moxi

Question 8

why do we use a combo of drugs when treating active TB

Answer 8

different drugs are needed to combat dividing and dormant forms

Question 9

isoniazid activation

Answer 9

prodrug activated by KatG (a catalase-peroxidase in M. tb)

Question 10

isoniazid MOA:

Answer 10

• forms NAD+ and NADP+ adducts that inhibit InhA and KasA (enzymes involved in mycolic acid synthesis
• inhibits FAS-II system -> halts cell wall formation

Question 11

isoniazid resistance mechs (2)

Answer 11

• mutation or overexpression of InhA
• mutations that affect KatG activation

Question 12

contribution Isoniazid makes to an effective anti-
tuberculosis treatment (cidal/static + other shit)

Answer 12

• cidal
• active against actively dividing mycobacterium TB

Question 13

activation of rifampin

Answer 13

not a prodrug, not activated

Question 14

MOA of rifampin (2)

Answer 14

• binds to rna polymerase in DNA/RNA channel
• blocks the path of elongating RNA

Question 15

contribution rifampin makes to an effective anti-
tuberculosis treatment (cidal/static + other shit) (5)

Answer 15

• cidal
• most effective 1st line agent
• works on growing AND stationary cells
• high sterilizing activity
• shortens duration of therapy

Question 16

when is rifampin most effective?

Answer 16

when cell division is occuring

Question 17

ethambutol activation

Answer 17

not a prodrug

Question 18

ethambutol MOA

Answer 18

inhibits mycobacterial arabinosyl transferases -> blocking arabinogalactan and LAM synthesis in cell wall

Question 19

ethambutol resistance

Answer 19

overexpression/mutations in arabinosyl transferase

Question 20

niche AE of rifampin

Answer 20

colors urine, tears, and sweat orange

Question 21

what is ethambutol synergistic with and why?

Answer 21

rifampin -> increase penetration into cell

Question 22

one important toxicity of ethambutol

Answer 22

optic neuritis

Question 23

ethambutol cidal or static

Answer 23

static

Question 24

activation of pyrazinamide

Answer 24

prodrug activated to pyrazinoic acid by pncA (nicotinamidase)
requires acidic pH <5.5 for activity

Question 25

Pyrazinamide mechanism (best evidence)

Answer 25

- inhibition of panD leading to inhibition of Coenzyme A synthesis (this is very confusing so hopefully there's not a question about it)

Question 26

eh pyrazinamide mechanism continued: - panD binding affinity is (low/high) - POA (does/does not) inhibit panD efficiently - Binding leads to _______ of panD - Accumulation in ______ offsets low binding affinity

Answer 26

-low - does not - degradation - granuloma

Question 27

pyrazinamide resistance: primarily (1) can also be (3)

Answer 27

- primarily due to mutations in pncA - can also be panD, RpsA, ClpC1

Question 28

most common side effect pyrazinamide then most dangerous

Answer 28

joint pain (arthralgia) hepatitis

Question 29

contribution of pyrazinamide to TB tx (2)

Answer 29

- sterilizing agent against intracellular M. TB - shortens treatment to 6 months

Question 30

what is the main FQ we will use in tx of TB

Answer 30

moxi

Question 31

mechanism of moxi (3)

Answer 31

- traps gyrase on DNA ternary complex - prevents resolution of supercoiled DNA - disrupts DNA replication

Question 32

moxi cidal or static

Answer 32

cidal

Question 33

contribution of moxi in tx of TB (2)

Answer 33

- can replace ethambutol in certain regimens - superior tissue penetration and lesion killing than the other FQs

Question 34

does not cause hepatitis: A. isoniazid B. moxifloxacin C. pyrazinamide D. rifampin

Answer 34

B

Question 35

which of the following causes eye damage? A. isoniazid B. moxifloxacin C. Ethambutol D. rifampin

Answer 35

C

Question 36

what are the 3 drugs in the BPaL regimen?

Answer 36

bedaquiline pretomanid linezolid

Question 37

when is BPaL considered?

Answer 37

extensively drug-resistant TB or treatment-intolerant or non-responsive multidrug-resistant TB

Question 38

activation of bedaquiline

Answer 38

not a prodrug dont worry

Question 39

how is bedaquiline adminstered

Answer 39

oral

Question 40

bedaquiline cidal or static

Answer 40

cidal

Question 41

T or F: bedaquiline kills actively growing and dormant bacilli

Answer 41

true

Question 42

MOA of bedaquiline

Answer 42

inhibits ATP synthase -> disrupts energy production in active and dormant bacilli

Question 43

resistance of bedaquiline

Answer 43

mutations in atpE

Question 44

what class is pretomanid in

Answer 44

nitroimidazoles

Question 45

activation of pretomanid

Answer 45

activated by M. tb deazaflavin-dependent nitroreductase

Question 46

MOA of pretomanid: aerobic: anaerobic/dormant:

Answer 46

- forms a reactive intermediate that inhibits mycolic acid synthesis - generates reactive nitrogen species -> poisons respiratory complex + depletes ATP

Question 47

Pretomanid contributions to tx of TB (2)

Answer 47

-kills both replicating and persistent bacilli - enhances immune-mediated killing

Question 48

second line agents fall under what general category for tx of TB?

Answer 48

anti-tubercular agents*

Question 49

4 times second line agents are usually considered

Answer 49

- resistance to first line agent - failure of clinical response to first line agents - intolerance to first line agents - expert guidance available to deal with toxic side effects

Question 50

what are the 5 second line agents used in tx of TB

Answer 50

- streptomycin - ethionamide - para-aminosalicylic acid - cycloserine - capreomycin