Antimycobacterial Drugs - (TB and Leprosy)

Question 1

AE of Isoniazid

Answer 1

Lupus-like syndrome and Peripheral neuritis

Question 2

MOA of Isoniazid

Answer 2

Prodrug is activated by KatG (mycobacterial catalase peroxidase) –> targets InhA and KasA –> decreased mycolic acid synthesis –> decreased cell wall synthesis

Question 3

Isoniazid is a synthetic analog of ?

Answer 3

Pyridoxine; must supplement patient with Vitamin B6

Question 4

True or False: Isoniazid is safe in pregnancy.

Answer 4

True

Question 5

Name the Rifamycins

Answer 5

Rifampin, Rifabutin

Question 6

MOA of Rifamycins

Answer 6

Bind to beta subunit of bacterial RNA polymerase –> block transcription and therefore RNA synthesis

Question 7

AE of Rifamycins

Answer 7

Orange body fluids, proteinuria

Question 8

PK/PD of Rifamycins

Answer 8

CYP450 inducers

Question 9

PK/PD of Isoniazid

Answer 9

CYP450 inhibitor

Question 10

True or False: Rifampin is safe in pregnancy.

Answer 10

True

Question 11

Which forms of Mycobacteria are Rifamycins used against?

Answer 11

M. kansasaii, M. tuberculosis

Question 12

DOC for Tuberculosis in HIV patients because of reduced CYP450 effects

Answer 12

Rifabutin

Question 13

Resistance mechanisms against Rifamycins

Answer 13

rpoB gene mutations, decreased permeability

Question 14

Indications of Rifamycins

Answer 14

Meningitis prophylaxis, latent TB in patients who cannot tolerate Isoniazid, combined with Vancomycin for MRSA

Question 15

MOA of Ethambutol

Answer 15

Inhibits arabinosyl transferase

Question 16

AE of Ethambutol

Answer 16

Reversible red-green colorblindness, hyperuricemia, neuritis

Question 17

Resistance mechanisms against Ethambutol

Answer 17

emb gene mutations

Question 18

Indictations of Ethambutol

Answer 18

combination therapy with Pyrazinamide, Isoniazid, Rifampin

Question 19

Which forms of Mycobacteria is Ethambutol used against?

Answer 19

M. tuberculosis and M. kansasaii

Question 20

AE of Pyrazinamide

Answer 20

Non-gouty polyarthralgia, hyperuricemia

Question 21

Resistance mechanisms against Pyrazinamide

Answer 21

Resistant strains lack Pyrazinamidase, increased efflux

Question 22

MOA of Pyrazinamide

Answer 22

Enzymatically hydrolyzed to Pyrazinoic acid

Question 23

Is Pyrazinamide safe for use during pregnancy?

Answer 23

Yes, if benefits outweigh risk

Question 24

What are the first line drugs for TB?

Answer 24

Isoniazid, Rifamycins (Rifampin and Rifabutin), Pyrazinamide, Ethambutol

Question 25

What are the second line drugs for TB?

Answer 25

Amikacin (Aminoglycoside), Streptomycin (Aminoglycoside), Levofloxacin (3rd gen. Fluoroquinolone), Ethionamide

Question 26

True or False: 2nd line drugs for TB are safe for use in pregnancy.

Answer 26

False; all 2nd line Antimycobacterial drugs are teratogenic!

Question 27

MOA of Dapsone

Answer 27

Inhibits Dihydropteroate synthase --> decreases folic acid synthesis (like Sulfonamides)

Question 28

Besides Leprosy, which other disease can Dapsone be used to treat?

Answer 28

PCP

Question 29

Repository form of Dapsone

Answer 29

Acedapsone

Question 30

AE of Dapsone

Answer 30

Hemolytic Anemia (b/c it is sulfa-related), Erythema nodosum (treat with Steroids or Thalidomide)

Question 31

PK/PD of Dapsone

Answer 31

CYP450 Inhibition

Question 32

Phenazine dye that is bactericidal against M.leprae

Answer 32

Clofazimine

Question 33

MOA of Clofazimine

Answer 33

Binds DNA --> inhibits replication; may generate ROS

Question 34

AE of Clofazimine

Answer 34

Red-brown skin discoloration, Eosinophilic enteritis

Question 35

Treatment for pauci-bacillary skin lesions

Answer 35

Rifampin + Dapsone for 6 months

Question 36

Treatment for multi-bacillary skin lesions

Answer 36

Rifampin + Dapsone + Clofazimine for 12 months

Question 37

Treatment for latent TB

Answer 37

Isoniazid (6-9 months) + Rifampin (4 months)

Question 38

Treatment against M.kansasaii

Answer 38

Isoniazid + Rifampin + Ethambutol

Question 39

Treatment against M.marinum

Answer 39

2 drug combo: Rifampin, Ethambutol, Clarithromycin, Minocycline, Doxycycline, Sulfonamides

Question 40

Treatment against M.chelonae

Answer 40

Clarithromycin monotherapy

Question 41

M.avium complex

Answer 41

Clarithromycin + Ethambutol +/- Rifampin

Question 42

M. fortuitum

Answer 42

Amikacin, Cefoxitin, Levofloxacin, Sulfonamides, Imipenem