Antimycobacterial Drugs

Question 1

what is the most common site of mycobacterial infection?

Answer 1

lungs

Question 2

in which patients is multi-drug resistance TB seen?

Answer 2

HIV/AIDS +

Question 3

asymptomatic, no radiographic abnormalities, and all bacteriological studies are negative

Answer 3

latent TB

Question 4

what is the cell wall of mycobacteria made of? (3)

Answer 4

peptidoglycan
arabinogalactan
mycolic acid

Question 5

single most important anti-T drug that inhibits synthesis of mycolic acid, destroying the cell wall

Answer 5

isoniazid (INH)

Question 6

when is isoniazid the most potent?

Answer 6

during initial 2-5 days of therapy

Question 7

6 ADRs of isoniazid?

Answer 7

“the sons are so neurotoxic (muscle twitching, insomnia), that they cause hepatotoxicity and hemolysis”

neurotoxic
muscle twitching
insomnia
hepatotoxicity
hemolysis

Question 8

what enzyme does isoniazid induce in alcoholics?

Answer 8

CYP2E1

Question 9

in which patients is hemolysis to occur when taking isoniazid?

Answer 9

those with G6PD deficiency (protects RBCs from damage)

Question 10

what should be added when a patient is taking isoniazid? why?

Answer 10

vit B6
INH blocks metabolic activation of pyridoxine (vit B6)

Question 11

which enzyme does isoniazid INHIBIT?

Answer 11

CYP450

Question 12

which 4 drugs have increased side effects in patients who are slow acetylators (AKA have an absence or deficiency in the N-acetyltransferase 2 enzyme)? why?

Answer 12

Sulfapyridine
Hydralazine
Isoniazid
Procainamide

they all go through N-acetyltransferase 2 pathway

Question 13

what effect does sulfapyridine have on slow acetylators?

Answer 13

liver damage

Question 14

what effect do hydralazine and procainamide have on slow acetylators?

Answer 14

lupus-syndrome

Question 15

what effect does isoniazid have on slow acetylators?

Answer 15

peripheral neuropathy

Question 16

Rifa-

Answer 16

rifamycins

Question 17

block RNA polymerase from initiating transcription by binding to and inhibiting it

Answer 17

rifamycins (rifa-)

Question 18

4 ADRs of rifamycins?

Answer 18

“Rifa has alot of HOGS”

Hepatotoxicity
Orange
GI
Skin rash

Question 19

ADR from weekly high doses of a rifamycin?

Answer 19

flu-like syndrome

Question 20

which enzyme do rifamycins INDUCE?

Answer 20

CYP450

Question 21

which rifamycin should be used in a patient with TB + co-infection with HIV? why?

Answer 21

rifabutin
less DDI

Question 22

since rifamycin have biliary excretion and enterohepatic recirculation, which drug’s effectiveness will be decreased?

Answer 22

oral contraceptives

Question 23

bacteriostatic agent that inhibits arabinosyl transferase (who is required for synthesis of arabinogalacatan, which links mycolic acid to mycobacterial cell wall)

Answer 23

ethambutol

Question 24

what is a dose dependent ADR of ethambutol?

Answer 24

visual disturbances

Question 25

ADR d/t prolonged high dose of ethambutol?

Answer 25

retinal damage

Question 26

6 ADRs of ethambutol?

Answer 26

optic neuritis red-green colorblindness headache confusion peripheral neuropathy hyperuricemia

Question 27

bactericidal agent against semi-dormant form of TB in macrophage

Answer 27

pyrazinamide

Question 28

4 ADRs of pyrazinamide?

Answer 28

"the pyraz's want to HASH it out" **Hepatotoxicity Arthralgia Skin rash Hyperuricemia**

Question 29

name the most frequently used 2nd line Rx for TB

Answer 29

IM streptomycin amikacin/kanamycin

Question 30

aminoglycosides that inhibit protein synthesis

Answer 30

streptomycin amikacin/kanamycin

Question 31

ADR of streptomycin + amikacin?

Answer 31

nephrotoxicity ototoxicity

Question 32

in which patients should streptomycin and amikacin be avoided in?

Answer 32

pregnant patients

Question 33

which 3 fluoroquinolones can be used to treat TB?

Answer 33

"Moxi and Levo need their Cipro to treat their TB" Moxi- Levo- Cipro-

Question 34

7 ADRs of fluoroquinolones?

Answer 34

Skin rash/sun sensitivity Prolonged QT/Peripheral neuropathy Ruptured tendon Increased risk of C. diff Neurotoxic GI intolerance +Weak cartilage

Question 35

2nd line tx for TB that inhibits mycolic acid synthesis

Answer 35

ethionamide

Question 36

2nd line tx for TB that inhibits protein synthesis

Answer 36

capreomycin

Question 37

2nd line treatment for TB that interferes with proton pump for ATP synthase

Answer 37

bedaquiline

Question 38

2nd line tx for TB that inhibits mycobacterial cell wall synthesis; similar to INH

Answer 38

delamanid

Question 39

2 ADRs for bedaquiline and delamanid?

Answer 39

increased QT CYP3A4

Question 40

used to treat persistent and latent TB

Answer 40

pretomanid

Question 41

what should pretomanid be used with to treat extensively drug-resistant TB? (2)

Answer 41

bedaquiline + linezolid x 6mo

Question 42

8 ADRs for combination treatment: pretomanid + bedaquiline + linezolid

Answer 42

nerve damage hepatotoxicity prolonged QT lactic acidosis myelosuppression acne headache N/V/D

Question 43

what drugs should be used during the first 2 months of tx for TB? AKA the intensive phase

Answer 43

Rifamycins Isoniazid Pyrazinamide Ethambutol

Question 44

what drugs should be used for the 2nd phase of TB? AKA the continuation phase

Answer 44

Rifamycin Isoniazid

Question 45

what is the monotherapy #1 for TB prophylaxis?

Answer 45

isoniazid daily x 6 months

Question 46

what is the monotherapy #2 for TB prophylaxis?

Answer 46

isoniazid x 9 months

Question 47

what is the monotherapy #3 for TB prophylaxis?

Answer 47

rifampin daily x 4 months

Question 48

what is the monotherapy #4 for TB prophylaxis, especially for latent TB with HIV?

Answer 48

isoniazid daily + weekly rifapentine x 3 months

Question 49

vaccine for TB that protects children but not adults

Answer 49

bacile calmette guerin

Question 50

what is the most common pattern of resistance in TB treatment?

Answer 50

isoniazid resistance

Question 51

treatment for resistant TB disease? what is an alt? what is added in severe disease?

Answer 51

rifampin + pyrazinamide + ethambutol alt: streptomycin in place of etham. quinolone for severe

Question 52

what is the treatment rule for multi-drug resistant TB?

Answer 52

at least 4 drugs x 18-24 months 3 PO, 1 injection

Question 53

what should be included for treatment of mycobacterium avium complex?

Answer 53

azithromycin OR clarithromycin