Antimycobacterial Drugs

Question 1

Exmaples of mycobacterium

Answer 1

M. tuberculosis
M. leprae
M. avium-intracellulare

Question 2

Primary or “First-line” for TB Therapy

Answer 2

Isoniazid*

Question 3

Is Isoniazid* bactericidal or bacteriostatic?

Answer 3

Bactericidal for actively growing bacilli

Bacteriostatic for “resting cells”

Question 4

MOA of Isoniazid*

Answer 4

Inhibits synthesis of mycolic acids (branched hydroxy fatty acids of mycobacterial cell walls)

Question 5

Is Isoniazid* a prodrug or a drug?

Answer 5

prodrug

Question 6

How is my colic acid inhibited by Isoniazid*?

Answer 6

Isoniazid* is activated by a catalase-peroxidase (KatG protein) of the tubercle bacillus; the activated drug’s target is the enoyl-acyl carrier protein reducatase (InhA protein)

Question 7

Where do resistant strains of Isoniazid come from?

Answer 7

mutations in KatG or InhA

Question 8

Side effects of Isoniazid*

Answer 8

1. Neurotoxicity, esp. peripheral neuritis, but improved with B6 administration
2. Hepatotoxicity

Question 9

MOA of Rifampin*

Answer 9

Inhibits bacterial DNA-dependent RNA polymerase, which suppresses RNA synthesis; bactericidal

Question 10

Side effects of Rifampin*

Answer 10

1. Hepatotoxicity
2. Potent inducer of multiple CYPs, increasing metabolism of other drugs
3. Orange-red color to urine, feces, etc.

Question 11

MOA of Ethambutol*

Answer 11

Interferes with arabinosyl transferase, blocks cell wall synthesis; Tuberculostatic

Question 12

Side effect of Ethambutol*

Answer 12

1. Optic neuritis

* NOT heptaotoxic

Question 13

MOA of Pyrazinamide*

Answer 13

Blocks s my colic acid synthesis by inhibit FA synthesis I; bactericidal

Question 14

What is Pyrazinamide* important for

Answer 14

short-term multi-drug therapy

Question 15

Absorption of Pyrazinamide*

Answer 15

Widely distributed, including CSF

Question 16

Adverse side effects of Pyrazinamide*

Answer 16

Hepatic damage

Question 17

MOA of Streptomycin*

Answer 17

1. binds to several ribosomal sites
2. stops initiation
3. causes mRNA misreading

Question 18

What is Streptomycin* used for

Answer 18

Reserved for most serious forms of TB

Question 19

Side effects of Streptomycin*

Answer 19

1. Ototoxicity

2. Nephrotoxicity

Question 20

What are “atypical” mycobacterial infections?

Answer 20

MOTT (mycobacteria other than tubercle bacilli) is responsible for infection

Question 21

What treatments are available for “atypical” mycobacterial infections?

Answer 21

Rifabutin, Clarithromycin

Question 22

What is Rifabutin*

Answer 22

Rifampin* analog for single-agent prophylaxis of M. avium-intracellulare (MAC) in AIDS patients

Question 23

Toxicities of Rifabutin*

Answer 23

• Similar to Rifampin* but less frequent

- Drug interactions similar to Rifampin* but less potent CYP inducer

Question 24

What is Clarithromycin* used for

Answer 24

1. part of multi-drug regimen for M. avium-intracellulare in AIDS patients
2. also used for MAC prophylaxis

Question 25

Is Clarithromycin* bacteriostatic or bactericidal?

Answer 25

Bactericidal

Question 26

What are some drugs used for the treatment of leprosy?

Answer 26

Dapsone*, Clofazimine*, Rifampin*

Question 27

MOA of Dapsone*

Answer 27

structural analog of para-aminobenzoic acid (PABA); inhibits synthesis of folic acid; bacteriostatic

Question 28

What are the uses of Dapsone*

Answer 28

1. Used in combination w/ other drugs (such as rifampin*) | 2. prophylaxis (and treatment) of Pneumocystis jiroveci in AIDS patients

Question 29

Side effects to Dapsone*

Answer 29

Hemolytic anemia, methemoglobinemia

Question 30

MOA of Clofazimine*

Answer 30

Binds to mycobacterial DNA interfering with reproduction and growth

Question 31

Uses of Clofazimine*

Answer 31

combination therapy

Question 32

Side effects of Clofazimine

Answer 32

potential red-brown pigmentation of the skin

Question 33

Treatment regimen for Lepromatous disease

Answer 33

Dapsone* + Rifampin* + Clofazimine* (daily for 2yr)

Question 34

Treatment for tuberculoid disease

Answer 34

Dapsone* + Rifampin* (daily for 1 yr)