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Flashcards in TB therapeutics Deck (28)
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1

What are the 3 main principles of TB treatment?

1) multi drug therapy

2) focus on increasing adherence

3) adequate duration of therapy

2

What is the first line drug for active pulmonary TB?

isoniazid HCl (INH)

(but not used as a single drug - used in combination)

3

What is the MOA of INH?

prodrug activated by catalase peroxidase (the TB katG gene) then targets the inhA gene product

it is CIDAL for replicating orgs and STATIC for resting orgs

4

Name two mechanisms for INH resistance?

1) mutations in katG gene (cannot activate INH)
2) mutations in inhA gene (cannot impair cell wall synthesis)

5

How is INH metabolized?

acetylated in liver (degree of acetylation varies with one's genetics)

non acetylated drug is excreted in urine

6

true or false: INH distributes to the CNS

TRUE

7

What are 3 toxicities of INH?

1) hepatotoxicity (especially bad with rifampin)

2) neurotoxicity

3) hypersensitivity rxns

8

What can rifampin NOT be used alone?

rapid development of resistance

9

What are the main mechanisms of resistance for rifampin?

rpoB mutations

rpoB encodes RNA polymerase

10

What are 3 common toxicities of rifampin?

1) red discoloration of body fluids

2) influenza syndrome

3) thrombocytopenia

11

What is a huge pitfall of rifampin?

drug interactions!! accelerates clearance and reduces effective conc of many drugs

12

What is the MOA of ethambutol?

inhibits TB arabinosyl transferase encoded by embB gene (affects cell wall synthesis)

13

What are the 2 big toxicities?

1) optic neuritis
2) peripheral neuropathy

14

What TB drug has known optic toxicity?

ethambutol

15

What is the P in RIPE TB therapy?

pyrazinamide (PZA)

16

When do you use PZA?

the first two months of therapy

17

What is the MOA of PZA?

it is a prodrug activated by TB pyrazinamidase encoded by pncA

(resistance comes in the form of pncA mutations)

18

Which TB drug is only used in the initial stages of TB?

PZA

19

What is a big toxicity of PZA?

hepatitis

20

What is the second line TB drug?

streptomycin

21

What are the two types of TB resistance?

primary (acquired at infection by getting a drug resistant bug)

secondary (developed during therapy due to ineffective therapy design or adherence)

22

What is the rationale for treatment with multiple drugs for TB

decrease the odds of evolution of resistance

23

How do you calculate the risk f evolution of resistance to two drugs?

the product of the risk of development of resistance to each drug

24

Define multi drug resistant TB

resistance to BOTH INH and rifampin

25

Why is rifampin resistance so concerning?

eliminates the option of short course (6 month) therapy and instead requires 18-24 month therapy

26

Define extensively drug resistant TB

resistance to ALL of the following
- INH and rifampin
- fluoroquinolones
- one of three injectable antibiotics

27

The initial phase of TB treatment is ______ while the continuation phase is ___

RIPE

RI

28

True or False: intermittent therapy (2-3x week) is ONLY with daily observance

True

6 month therapy can be successful on if adherence is high, sputum cultures convert by 2 months and there is no major cavitary lung problems