TB Drugs

Question 1

what are the two phases of TB drug treatment?

Answer 1

intensive and continuation phases

Question 2

what drugs are used during intensive phase? how long is it for drug susceptible and drug resistant?

Answer 2

all four first line…isoniazid, ethambutol, rifampin, pyrazinamide

lasts 8 weeks
lasts 6 months

Question 3

what drugs are used during continuation phase? how long is it for drug susceptible and drug resistant?

Answer 3

isoniazid and rifampin
18 weeks
18 months

Question 4

what is the common toxicity with isoniazid?

Answer 4

hepatotoxicity

Question 5

rate the types of drug resistant TB from best to worst to have

Answer 5

MDR…XDR…TDR

Question 6

what drugs are you resistant to with MDR?

Answer 6

rifampin and isoniazid

Question 7

what drugs are you resistant to with XDR?

Answer 7

rifampin isoniazid and 2 2nd class drugs

Question 8

what drugs are you resistant to with TDR?

Answer 8

rifampin isoniazid, 2 2nd class, and others

Question 9

do most TB drugs kill latent or proliferating bacteria?

Answer 9

proliferating

Question 10

what is the mechanism of isoniazid and delamanid?

Answer 10

they block the synthesis of mycolic acid by inhibiting InhA

Question 11

what are the two TB drugs that are mycolic acid synthesis inhibitors?

Answer 11

isoniazid and delamanid

Question 12

what is unique about isoniazid and delamanid? what protein takes care of this?

Answer 12

they are pro drugs…converted by KatG in the TB

Question 13

what two enzymes can pick up mutations to yield resistance to isoniazid and delamanid?

Answer 13

KatG and InhA

Question 14

explain how isoniazid causes hepatotoxicity

Answer 14

there are two metabolic pathways…one a fast and one a slow acetylation…the slow leads to a toxic metabolite to the liver

Question 15

what chemical induces the slow pathway for isoniazid metabolism?

Answer 15

ethanol

Question 16

what is the mechanism of ethambutol and cycloserine?

Answer 16

they are cell wall inhibitors

Question 17

what two TB drugs are cell wall inhibitors?

Answer 17

ethambutol and cycloserine

Question 18

what is a toxicity of ethambutol?

Answer 18

optic neuritis…red/green color blindness

Question 19

which of ethambutol and cycloserine is first and second line?

Answer 19

ethambutol is first and cycloserine is second

Question 20

what two TB drugs are RNA polymerase inhibitors?

Answer 20

rifampin and rifabutin

Question 21

what is a weird toxicity of rifabutin?

Answer 21

orange colorationof skin, urine, feces, saliva, tears

Question 22

what is a common toxicity of rifampin and rifabutin related to their clearance?

Answer 22

nephrotoxicity

Question 23

rifampin and rifabutin are inducers of what class of molecules that can lead to serious drug interactions?

Answer 23

CYPs

Question 24

what class of drugs must you be careful with when giving rifampin or rifabutin because of the CYP induction?

Answer 24

HIV drugs…induces the CYPs that clear the HIV drugs…so they are gone quick

Question 25

what TB drug is cleared by the CYPs that rifampin and rifabutin induce?

Answer 25

bedaquline

Question 26

what is the mechanism of pyrazinamide?

Answer 26

it is unclear but it does get trapped in the myco TB cell and is effective there

Question 27

what enzyme converts pyrazinamide into its active state in the TB cells?

Answer 27

PZase...mutations here yield resistance

Question 28

what is the common toxicity with pyrazinamide?

Answer 28

hepatotoxicity

Question 29

what is the mechanism of bedaquiline?

Answer 29

ATP synthase inhibition

Question 30

what TB drug is an ATP synthase inhibitor?

Answer 30

bedaquiline