Mycobacterial Drugs

Question 1

Treatment combination for M. tuberculosis

Answer 1

rifampin, isoniazid, pyrazinamide, ethambutol (RIPE)

Question 2

Prophylaxis for M. tuberculosis

Answer 2

isoniazid

Question 3

Treatment for M. avium-intracellulare

Answer 3

azithromycin or clarithryomycin + ethambutol

can add rifabutin or ciprofloxacin

Question 4

Prophylaxis for M. avium-intracellular

Answer 4

azithromycin, rifabutin

Question 5

Treatment for M. leprae

Answer 5

rifampin and dapsone (6 months)

add clofazimine for lepromatous form (2-5 years)

Question 6

Name the rifamycins

Answer 6

rifampin, rifabutin

Question 7

Mechanism of rifamycins

Answer 7

inhibit DNA-dependent RNA polymerase (impacts bacterial protein synthesis

Question 8

Use of rifamycins

Answer 8

M. tuberculosis

Question 9

What do rifamycins do when used with dapsone?

Answer 9

delay resistance to dapsone when using to treat leprosy

Question 10

What bugs use rifampin for prophylaxis?

Answer 10

Neisseria

Haemophilus influenza B

Question 11

Toxicity of rifamycins

Answer 11

minor hepatotoxicity and drug interactions (INDUCE cytochrome p450)
rifabutin favored in patients with HIV due to less induction of cyt p450

Question 12

Mechanism of resistance to rifamycins

Answer 12

mutations reduce drug binding to RNA polymerase

monotherapy rapidly leads to resistance

Question 13

The four Rs of rifampin

Answer 13

RNA polymerase inhibitor
RAMP up cyt p450
Red/orange body fluids
Rapid resistance if used alone

Question 14

Mechanism of isoniazid

Answer 14

decreases synthesis of mycolic acids

bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite

Question 15

Use of isoniazid

Answer 15

M. tuberculosis

solo prophylaxis against M. tuberculosis also

Question 16

Metabolism of isoniazid

Answer 16

different INH half-lives in fast vs. slow acetylators

Question 17

Toxicity of isoniazid

Answer 17

neurotoxicity, hepatotoxicity

pyridoxine (vitamin B6) can prevent neurotoxicity

Question 18

What vitamin can give with isoniazid?

Answer 18

B6 - pyridoxine to prevent neurotoxicity

Question 19

Mechanism of resistance of isoniazid

Answer 19

mutations leading to underexpression of KatG so no catalase-peroxidase to activate the drug

Question 20

Mechanism of pyrazinamide

Answer 20

uncertain

prodrug converted to active compound pyrazinoic acid

Question 21

Use of pyrazinamide

Answer 21

M. tuberculosis

Question 22

Toxicity of pyrazinamide

Answer 22

hyperuricemia, hepatotoxicity

Question 23

Mechanism of ethambutol

Answer 23

decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase

Question 24

Use of ethambutol

Answer 24

M. tuberculosis

Question 25

Toxicity of ethambutol

Answer 25

OPTIC neuropathy (red-green color blindness)

EYEthambutol

Question 26

Is ethambutol optic neuropathy reversible?

Answer 26

yes usually when discontinue the drug!