Antimycobacterial

Question 1

What is the mechanism of action of isoniazid

Answer 1

inhibits synthesis of mycolic acid

Question 2

How is isoniazid metabolized

Answer 2

prodrug activated in the mycobacteria by KatG to enzyme inhibitor
Metabolized by NAT2 in the liver (fast and slow acetylators)

Question 3

Is isoniazid bacteriostatic or bacteriaicidal?

Answer 3

static in quiescent bacilli and cidal in active bacilli

Question 4

What is the half-life of izoniazid

Answer 4

1 hr in rapid acetylators, 3 hrs in slow acetylators

Question 5

Adverse effects of izoniazid

Answer 5

20% peripheral neuropathy, can be reduced by vitamin B6

8% in patients over 65 hepatotoxicity

Question 6

What is the most common TB drug

Answer 6

Rifamycins-rifampin (also used for other bacterial infections)

Question 7

What is the MOA of rifampin

Answer 7

inhibitor of RNA polymerase

Question 8

Is rifampin static or cidal

Answer 8

cidal

Question 9

Therapeutic uses of rifampin (3)

Answer 9

1) in combo with isoniazid for TB
2) Leprosy
3) broad spectrum antibiotic

Question 10

Adverse reactions to rifampin

Answer 10

1) cholestatic jaundice and hepatitis (rare)
2) discoloration of body fluids- red-orange color
3) inducer of CYP isoforms

Question 11

What is the MOA of ethambutol

Answer 11

inhibits arabinosyl transferase III, bacteriostatic

Question 12

Therapeutic use of ethambutol

Answer 12

in combo for TB only

Question 13

Adverse effect of thembutol

Answer 13

optic neuritis

Question 14

Pyrazinamide MOA

Answer 14

prodrug converted to pyrazinoic acid (POA) by mycobacterial pyrazinamidase, bactericidal, target unknown

Question 15

Therapeutic use of pyrazinamide

Answer 15

Sterilizing agent

Question 16

Adverse effects of pyrazinamide

Answer 16

Hepatotoxicity

Hyperuricemia (gout)

Question 17

Which TB drug is associated with the worst hepatotoxicity

Answer 17

isoniazid, has actually been fatal

Question 18

What is prophylactic therapy for TB

Answer 18

one drug- isoniazid, rifampin

Question 19

Treatment of active infection

Answer 19

guided by drug sensitivity screen

Question 20

What are the phases of therapy for active TB

Answer 20

1) induction phase- eliminates active mycobacteria and renders non-infection
2) Continuation phase- eliminates intracellular “persisters”

Question 21

What are drugs used in induction phase

Answer 21

INH, rifampin, and pyrazinamide then INH and rifampin for 4 months
Ethambutanol or streptomycin for resistance to INH

Question 22

Which drugs are used in the continuation phase

Answer 22

intermittent therapy with INH and rifampin

Directly observed therapy is the standard of care