Anti-TB

Question 1

innate resistance TB

Answer 1

• highly complex
• impermeable mycobacterium wall
• efflux transporters
• intracellular location of infection
• slow proliferation, dormancy

Question 2

Acquired resistance TB

Answer 2

• spontaneous mutations (therapy long term)

- each mutation confers resistance to one drug

Question 3

mutation frequency in TB

Answer 3

1 in 10^6

Question 4

The chance of one bacterium developing resistance to 2 drugs is

Answer 4

1 in 10^12

Question 5

What reduces incidence of relapse in TB?

Answer 5

multi drug therapy

- some drugs are effective against active bacilli other against dormant

Question 6

Why dose multi drug anti-TB therapy not lead to superinfection?

Answer 6

• standard drugs highly selective for TB

Question 7

MDR to TB due to what? and what drugs?

Answer 7

Isoniazid + rifampin

• inadequate drug therapy
• lack of compliance

Question 8

Extensive drug resistance (XDR)

Answer 8

MDR + fluoroquinolone and aminoglycosides

Question 9

INH MOA

Answer 9

• inhibit synthesis of mycolic acid

- prodrug activated by KatG

Question 10

INH bactericidal or bacteriostatic?

Answer 10

bactericidal –> active

bacteriostatic –> quiescent

Question 11

INH active against extracellular or intracellular?

Answer 11

both!

Question 12

INH resistance

Answer 12

mutation or deletion of katG gene

Question 13

INH in host liver

Answer 13

NAT2 –> inactive

Question 14

INH in bacillus

Answer 14

KatG –> INH radical –> active form

Question 15

INH metabolism

Answer 15

• inactivated by liver by acetylation

- N-acetyl-INH excreted by kidneys

Question 16

Which drug has slow or rapid acetylators?

Answer 16

INH

Question 17

T/F acetylator status effects dosing and therapeutic outcomes?

Answer 17

false!

dose not

Question 18

INH use

Answer 18

Latent: alone
Active: combo

Question 19

Adverse reaction INH

Answer 19

• peripheral neuropathy
• hepatotoxicity
• hepatitis

Question 20

peripheral neuropathy in INH

Answer 20

• caused by drug induced deficiency in pyridoxine

Question 21

peripheral neuropathy in INH can be reduced by

Answer 21

taking B6

Question 22

BBW INH

Answer 22

hepatitis: fatal hepatic necrosis

Question 23

Rifampin MOA

Answer 23

inhibit DNA dependent RNA polymerase

Question 24

Rifampin bacteriostatic or bactericidal?

Answer 24

bactericidal

Question 25

Rifampin for intracellular or extracellular organisms?

Answer 25

intracellular

Question 26

Rifampin resistance

Answer 26

- mutation in rpoB gene for B subunit | - not used for mono therapy!

Question 27

Rifampin use

Answer 27

active: combo with INH MAC: combo with macrolide serious deep seated staph infection: combo with other antibiotics

Question 28

Rifampin adverse reactions

Answer 28

- hepatotoxicity: cholestatic jaundice - discoloration of body fluids (red/orange) - strong induction of CYP

Question 29

Which drug can increase elimination of contraceptives, warfarin and hIV drugs?

Answer 29

rifampin

Question 30

Ethambutol MOA

Answer 30

inhibit mycobacterial arabinosyl transferase

Question 31

Ethambutol bacteriostatic or bactericidal

Answer 31

bacteriostatic

Question 32

Ethambutol intracellular or extracellular organisms

Answer 32

both!!!

Question 33

ethambutol resistance

Answer 33

mutation of embAB

Question 34

Ethambutol use

Answer 34

active: combo | MAC

Question 35

ethambutol adverse effect

Answer 35

optic neuritis (loss of visual acuity, red/green blindness)

Question 36

Pyrazinamide MOA

Answer 36

- prodrug converted to POA (active in acidic conditions) | - molecular target unknown

Question 37

Pyrazinamide bacteriostatic or bactericidal

Answer 37

bactericidal

Question 38

pyrazinamide intracellular or extracellular oganisms

Answer 38

intracellular organisms

Question 39

Pyrazinamide use

Answer 39

combo

Question 40

Pyrazinamide adverse effects

Answer 40

- hepatotoxicity | - hyperuricemia

Question 41

2nd line antimycobacterial agents

Answer 41

streptomycin

Question 42

Streptomycin use

Answer 42

severe life threatening TB

Question 43

streptomycin intracellular or extracellular organisms

Answer 43

extracellular

Question 44

TB prophylaxis use

Answer 44

- high risk patients with latent infections to prevent emergence of active

Question 45

TB prophylaxis therapy

Answer 45

- daily mono therapy 9 months: INH | - daily mono therapy 4months: rifampin alternative

Question 46

TB combination therapy use

Answer 46

confirmed active infection

Question 47

2 phases of TB combo therapy

Answer 47

``` induction phase (first 2 months) continuation phase (next 4 months) ```

Question 48

Induction phase TB

Answer 48

Rifampin, INH, pyrazinamide, ethambutol

Question 49

Goal of induction phase TB

Answer 49

- eliminate actively dividing extracellular organisms - render non-infectious - prevent development of resistance

Question 50

Most common cause of treatment failure in induction phase TB

Answer 50

non-adherence | - Directly observed therapy (DOT) is standard of care

Question 51

Continuation phase TB

Answer 51

``` intermittent therapy (2 weekly): INH + rifampin - may prolong to 7 months if more severe ```

Question 52

In continuation phase TP what should you monitor for?

Answer 52

hepatotoxicity