TB Drugs

Question 1

which drugs are mycolic acid synthesis inhibitors (what line are they)

Answer 1

• isoniazid (first line)
• dalamanid (second line)
• pretomanid (second line)

Question 2

what drugs are cell wall synthesis inhibitors (what line are they)

Answer 2

• ethambutol (first line)

- cycloserine (second line)

Question 3

what drugs are RNA polymerase inhibitors (what line)

Answer 3

• rifampin (first line)

- rifabutin (first line)

Question 4

what drugs are protein synthesis inhibitors (what line)

Answer 4

aminoglycosides

• streptomycin (second line)
• amikacin (second line)
• kanamycin (second line)

Question 5

what drugs are DNA synthesis inhibitors (what line)

Answer 5

• levofloxacin (second line)

- moxifloxacin (second line)

Question 6

what drugs are ATP synthase inhibits (what line)

Answer 6

• bedaquiline (second line)

Question 7

intensive phase uses which drugs

how long is intensive phase

Answer 7

• all 4 front line drugs
• H+R+Z+E
• 8 weeks

Question 8

continuation phase uses which drugs

how long is continuation phase

Answer 8

• H+R

- 18 weeks

Question 9

what drugs are effective against latent TB

Answer 9

• rifampin (also effective against active)
• rifabutin (also effective against active)
• pyrazinamide

Question 10

isoniazid bacterial enzymes needed to convert it to active form

Answer 10

• KatG

Question 11

what bacterial enzyme does isoniazid inhibit

result

Answer 11

• InhA

- prevents mycolic acid precursor from turning into mycolic acid

Question 12

mutations in ______ and ______ confer resistance to isoniazid

Answer 12

• KatG

- InhA

Question 13

isoniazid toxicities

Answer 13

• hepatotoxicity
• peripheral neuropathy

INH - INJURY TO NERVES AND HEPATOCYTES

Question 14

how does isoniazid cause toxicities

Answer 14

• intermediate compounds produce toxic reactive metabolites which cause liver damage

Question 15

which acetylators of isoniazid are less prone to toxicity

Answer 15

• fast acetylation

Question 16

why are slow acetylators of isoniazid more prone to toxciity

Answer 16

• accumulate toxic metabolite

Question 17

what is the polymorphism in isoniazid that can cause more toxicities

Answer 17

• NAT2

Question 18

inductors of ______ also promote damage in isoniazid toxicities

how

example

Answer 18

• CYP2E1
• convert to toxic reactive metabolite faster
• alcohol

Question 19

toxicities of delamanid

Answer 19

• no significant CYP-associated drug interactions

Question 20

ethambutol MOA

Answer 20

• inhibits arabinosyltransferase

- inhibits synthesis of galactan portion of cell wall

Question 21

cycloserine MOA

Answer 21

• inhibits cytoplasmic enzymes

Question 22

mutations in _________ confer resistance to ethambutol

Answer 22

• arabinosyltransferase

Question 23

ethambutol toxicities

is this reversible?

Answer 23

• optic neuritis (color blindness)

- reversible with removal of drug

Question 24

cycloserine toxicities

Answer 24

• various neurologic symptoms

Question 25

mutations in ____ confer resistance to rifampin and rifabutin

Answer 25

- RNA polymerase

Question 26

interesting toxicity of rifabutin

Answer 26

- orange coloration of skin, urine, feces, saliva, tears

Question 27

rifampin and rifabutin toxicities

Answer 27

- nephrotoxicity/interstitial nephritis | - drug interactions

Question 28

how do rifampin and rifabutin interact with other drugs which drugs

Answer 28

- induces important cytochromes that speed up metabolism of clinically relevant drugs - reduces their effectiveness - HIV protease/RT inhibitors - Bedaquiline RIFAMPIN REVS UP DRUG METABOLISM

Question 29

how Pyrazinamide works

Answer 29

- enters bacterium and gets converted to charged form (negative form) - trapped by higher pH and disrupts cell energetics

Question 30

mutations in _______ confer resistance to Pyrazinamide normal role

Answer 30

- PZase | - converts Pyrazinamide to charged negative form to keep it trapped in cell

Question 31

Pyrazinamide toxicities Pyrazinamide toxicities more common when

Answer 31

- hepatoxicity -> drug induced hepatitis | - drug dose used was higher

Question 32

MOA of Bedequiline

Answer 32

- disrupts production of ATP within bacterial cells

Question 33

Bedaquiline coadministration with _____ reduces its effectiveness

Answer 33

- rifampin

Question 34

which drugs are only effective against active TB

Answer 34

- cell wall synthesis inhibitors | - ATP synthase inhibitor

Question 35

which drugs are only effective against latent TB

Answer 35

- pyrazinamide