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Flashcards in Lecture 2: Pharm of TB Deck (43)
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1

What 4 drugs are the standard first-line agents for tx of TB?

- Rifampin

- Isoniazid

- Pyrazinamide

- Ethambutol

*RIPE*

2

Which 3 first-line agents for TB can cause liver damage as an AE?

- Isoniazid

- Rifampin

- Pyrazinamide

3

What is the MOA of isoniazid?

Inhibits mycolid acid synthesis

4

What are 3 ways of developing resistance to isoniazid?

- Overexpression of inhA or kasA

- Mutation/deleltion of katG

5

Which second-line TB drug has same pharmacokinetics as isoniazid, but can be used in its place when resistance to isoniazid develops?

Ethionamide

6

What is the strategy for treating PPD reactors w/ active TB rules out (aka latent TB)?

- Isoniazid for 9 months

- Rifampin for 4 months or combo of 1x/week isoniazid + rifapetine for 3 months

7

What is the MOA of Rifampin?

Binds β subunit of bacterial DNA-dependent RNA polymerase --> inhibits RNA synthesis

8

Which first-line TB agent readily penetrates most tissues and phagoytic cells, allowing for bactericidal action in abscesses and lung cavities?

Rifampin

9

Resistance to rifampin may devlop by mutation in what gene?

rpoB

10

After oral administration where is majority of rifampin excreted and enters into where?

Mainly via liver --> bile and undergoes enterohepatic circulation

11

What are 2 major AE's associated with Isoniazid?

- Hepatotoxicity

- Peripheral neuropathy can be ↓ w/ pyridoxine (B6)

12

What are the major AE's associated with Rifampin?

- Orange/red color to urine, sweat, and tears

- Rashes, thrombocytopenia and nephritis

- Hepatitis and cholestatic jaundice

13

What is the MOA of Ethambutol?

Inhibits mycobacterial arabinosyl transferases, needed for polymerization of arabinoglycan essential for cell wall

14

Overexpression/mutuation of which gene may cause resistance to Ethambutol?

emb CAB

15

Higher does of ethambutol may be used to tx tuberculosis infections where?

Tuberculosis meningitis; crosses the BBB at high doses

16

Most common AE associated with Ethambutol and should not be given to whom?

- Retrobulbar neuritis --> ↓ visual acuity and red-green color blindness

- Don't give to children too young to permit assessment of visual acuity and color discrimination!

17

What is the MOA of Pyrazinamide and where does it exert its effects?

- Converted to pyrazinoid acid (active form) inside lysosome by mycobacterial pyrazinamidase

- Disrupts mycobacterial cell wall membrane metabolism and transport functions

18

What are 2 ways in which resistance to Pyrazinamide may occur?

- Impaired uptake of pyrazinamide into lysosome

- Mutations in pncA which encodes enzyme necessary for conversion to active form PZA

19

Which 1st line agent for TB is the "sterilizing agent" and what does adding this agent to the regimen do?

- Pyrazinamide

- Shortens regimen from 9 months --> 6 months!!!

20

Major AE's of Pyrazinamide?

- Hepatotoxicity

- Hyperuricemia may precipitate gout

21

Which first-line TB agent diffuses readily into ALL tissues and body fluid, including the CNS?

Isoniazid

22

How does the 6 month regimen of first-line agents for active TB work (i.e., which drugs given and when)?

- 2 months INTENSIVE phase w/ RIPE

- Then 4 months of isoniazid and rifampin

*Remember 4 for 2; then 2 for 4

23

Which class does Streptomycin belong to and its MOA?

When would it be used for TB?

- Aminoglycoside --> protein synthesis inhibitor

- Used when IV or IM route is desired and in cases where there is resistance

24

Ethionamide has the same MOA, resistance, and AE's as what other TB agent?

Isoniazid

25

What is the MOA of Capreomycin?

Protein synthesis inhibitor

26

Which 2nd-line TB agents can be used for streptomycin-resistant strains?

Which is specifically used if an IV or IM route is desired?

- Capreomycin --> can be given IV or IM

- Kanamycin and Amikacin --> only amikacin used in US!

27

What is the MOA of Cycloserine?

Structural analog of D-alanine inhibits alanine racemase and D-alanyl-D-alanine ligase --> cell wall synthesis inhibitor

28

Cycloserine is given via which route and is cleared by which organ?

Oral dose and is cleared renally

29

What are the most serious AE's associated w/ Cycloserine?

- CNS dysfunction

- Peripheral neuropathy --> can be ↓ w/ pyridoxine (B6)

30

What is the MOA of Aminosalicylic Acid as 2nd-line against TB?

Structural analog of PABA = folate synthesis inhibitor