Exam 5: LaCount TB

Question 1

organism that causes TB

Answer 1

mycobacterium TB

Question 2

what type of bacteria is TB

Answer 2

acid fast bacteria (AFB)

obligate aerobe

Question 3

What is AFB

Answer 3

After staining with a dye, cannot be decolorized acid wash

Question 4

why is TB cause drug resistance

Answer 4

Lipid rich cell wall contains mycolic acids and is impermeable to many drugs

Question 5

what makes up TB cell wall

Answer 5

mycolic acid
arabinoglactan
peptidoglycan
lipid bilayer

Question 6

TB transmission

Answer 6

only people with active TB infections transmit disease via aerosol droplets, which can remain airborne for hours

Question 7

TB pathology

Answer 7

1. bacteria is phagocytosed by alveolar macrophages in the lung to induce proinflammatory response
2. recruited cells form granuloma
3. granuloma develops a fibrous sheath with fewer penetrating blood vessels in the later stages
4. granuloma decays, ruptures and spills thousands of viable, infectious bacilli into airways

Question 8

Gold standard treatment for active Tb

Answer 8

RIPE

rifampin, isoniazid, pyrazinamide, ethambutol

Question 9

isoniazid: static or cidal

Answer 9

cidal

Question 10

isoniazid: prodrug or no

Answer 10

Yes: activated by M. tb KatG protein to nicotinoyl-NAD

Question 11

isoniazid MOA

Answer 11

inhibits InhA to prevent FAS II from making mycolic acid, thus creating a defective cell wall

Question 12

isoniazid resistance mechanisms

Answer 12

KatG resistance enzyme

Over-expression of InhA

Question 13

Isoniazid metabolism

Answer 13

acetylation by liver N-acetyltransferase, but rate is determined genetically as slow or fast

Question 14

what vitamin needs to be given with isoniazid and why

Answer 14

Vit B6 b/c isoniazid inhibits metabolism of pyridoxine to pyridoxal phosphate because of structural similarities

Question 15

Isoniazid toxicity

Answer 15

Acetylisoniazid can be converted to acetylhydrazine, which leads to hepatic metabolites

This creates problems when pt is slow metabolizer

Question 16

is pyrazinamide a prodrug?

Answer 16

Yes: converted to pyrazinoic acid by pncA

Question 17

pyrazinamide activity

Answer 17

based on pH: activated by low pH

Question 18

potential MOA of pyrazinamide

Answer 18

inhibition of CoA synthesis by inhibiting panD

Question 19

resistance mechanisms of pyrazinamide

Answer 19

primarily due to mutations in pncA

Question 20

pyrazinamide toxicity

Answer 20

hepatitis

Question 21

ethambutol: static or cidal

Answer 21

static inhibitor of M. tb

Question 22

ethambutol MOA

Answer 22

inhibits mycobacterial arabinosyl transferases, which is involved in the polymerization of arabinogalactan

inhibits formation of arabinogalactan and lipoarabinomannan

Question 23

ethambutol co-administration

Answer 23

synergistic with rifampin to increase penetration into cell wall

Question 24

ethambutol toxicity

Answer 24

optic neuritis

Question 25

ethambutol resistance

Answer 25

resistance due to over-expression of mutations in arabinosyl transferase

Question 26

rifampin: cidal or static

Answer 26

cidal- most effective when cell division is occurring

Question 27

most effective first line agent for TB

Answer 27

rifampin

Question 28

rifampin MOA

Answer 28

binds to RNA polymerase deep within the DNA/RNA channel to block the path of elongating RNA

Question 29

rifampin AE

Answer 29

1. colors urine, tears, and sweat orange | 2. Cyp450 inducer

Question 30

streptomycin MOA

Answer 30

protein synthesis inhibitor

Question 31

streptomycin issue in Tb

Answer 31

penetrates poorly into cells, only used in severe TB

Question 32

bedaquiline MOA

Answer 32

bactericidal against actively growing and dormant bacilli by inhibiting ATP synthase

Question 33

bedaquiline resistance

Answer 33

mutations in atpE

Question 34

pretomanid MOA

Answer 34

prodrug activated by Ddn that forms reactive intermediate metabolite that inhibits mycolic acid production