Exam 3: Antituberculotics

Question 1

How is TB spread?

Answer 1

Droplet nuclei, expelled when a person with infectious TB sneezes, speaks, sings, or coughs

Question 2

What drugs are multi drug resistance TB resistant to?

Answer 2

Isoniazid and rifampin

Question 3

What drugs are extreme drug resistant TB resistant to?

Answer 3

Isoniazid, rifampin, any fluoroquinolone, and injectable second line drugs (Kanamycin, capreomycin, and amikacin)

Question 4

How is active TB treated?

Answer 4

Isoniazid, rifampin, ethambutol, and pyrazinamide (HRZE)

***All 4 for the first 2 months, then only isoniazid and rifampin for 4 months

Question 5

Why is TB treated with 4 different drugs?

Answer 5

Helps reduce Multiple drug resistant bacteria and significantly reduces transmission rates to other people with the first two months of treatment

Question 6

What are the 3 ways to treat latent TB?

Answer 6

1) isoniazid + rifapentine 1 a week for 12 weeks
2) Rifampin daily for 4 months
3) Isoniazid either daily or twice weekly (76-270 doses)

Question 7

What is the MOA of isoniazid?

Answer 7

Inhibits synthesis of mycolic acid- a prodrug that is activated by KatG

Question 8

When is isoniazid used?

Answer 8

• Monotherapy for latent TB

- Used in combination for active TB

Question 9

What is the route of administration of Isoniazid?

Answer 9

Oral

Question 10

How is isoniazid metabolized?

Answer 10

Metabolized by acetylation in the liver inactivates the drug.
Excretion is though urine.
Metabolic rate of INH is dependent on genetic makeup (there are fast and slow acetylators)

Question 11

What are the toxicities of isoniazid?

Answer 11

-Hepatitis (fast acetylators) peripheral neuritis (in slow acetylators), hemolysis, drug induced lupus, and CNS stimulation (Convulsions, insomnia, vertigo)

Question 12

What is the MOA of Rifampin?

Answer 12

Inhibits DNA dependent RNA polymerase

-Taken orally

Question 13

Aside from TB, what else is Rifampin effective against?

Answer 13

Leprosy, most G+ cocci, and some G- microbes

Question 14

How is rifampin used in the treatment of TB?

Answer 14

• Monotherapy for latent TB

- Combination therapy for active TB

Question 15

What are the toxicities associated with Rifampin?

Answer 15

• Hepatic enzyme induction: potent inducer of P450, drug interactions
• Harmless orange color to urine, sweat, and tears
• Decreased effectiveness of birth control

Question 16

Who is rifampin not recommended for?

Answer 16

HIV-treated individuals due to drug interactions

Question 17

What is the MOA of Ethambutol?

Is it static or cidal?

Answer 17

Inhibits arabinosyl transferases involved in the synthesis of arabinogalactan.

-Bacteriostatic

Question 18

Out of the 4 drugs used in combination therapy to treat active TB, which ones have CNS penetration?

Answer 18

Ethambutol and Pyrazinamide

Question 19

What are the toxicities associated with ethambutol?

Answer 19

-Decrease in visual acuity and loss of green-red perception.

Question 20

Who is ethambutol not recommended for, why?

Answer 20

Children below the age 13 due to effect on vision

Question 21

When is pyrazinamide most active?

Answer 21

At an acidic pH

-greatest activity against dormant organisms

Question 22

What are the toxicities associated with pyrazinamide?

Answer 22

Hepatic dysfunction, hyperuricemia –> gout, myalgias, GI upset, and photosensitivity

Question 23

Why is pyrazinamide a critical first line drug for TB?

Answer 23

It is responsible for reducing therapy to the current standard of 6 months (previously 9-12 months)

Question 24

What is the MOA of streptomycin? Static or cidal?

Answer 24

Protein synthesis inhibitor (30s)

Bactericidal

Question 25

What are the toxicities associated with streptomycin?

Answer 25

Ototoxicity and nephrotoxicity

Question 26

What is the MOA of rifabutin?

Answer 26

Inhibits DNA dependent RNA polymerase

Question 27

What is the DOC for HIV-TB coinfected individuals and why?

Answer 27

Rifabutin (instead of rifampin) because it is a less potent inducer of P450 enzymes and has less drug interactions

Question 28

What is the MOA of Rifapentine?

Answer 28

Inhibits DNA dependent RNA polymerase

Question 29

What side effect is seen in rifampin, rifabutin, and rifapentine?

Answer 29

They cause orange colored metabolites

Question 30

What is the preferred therapy for latent TB, even in HIV+ patients?

Answer 30

Rifapentine and isoniazid

Question 31

What is the treatment for Mycobacterium Avium Complex?

Answer 31

1) Either clarithromycin OR azithromycin
2) Include ethambutol
3) Add third oral drug (rifabutin, rifampin, or ciprofloxacin)

12 month treatment

Question 32

What happens if you treat Mycobacterium leprae with only one antileprosy drug?

Answer 32

It will ALWAYS develop resistance. This is considered an unethical practice!

Question 33

What is the treatment for PB leprosy?

Answer 33

Rifampin and dapsone for 6 months

Question 34

What is the treatment for MB leprosy?

Answer 34

Rifampin and dapsone for 6-12 months

Question 35

What kind of leprosy has 1-5 patches?

Answer 35

PB leprosy

Question 36

What kind of leprosy has more than 5 patches?

Answer 36

MB leprosy

Question 37

What is the MOA of Dapsone?

Answer 37

Similar to sulfas (PABA antagonist), inhibits folate synthesis

** why sulfa drugs are not effective against leprosy is not known.

Question 38

What are the toxicities associated with Dapsone?

Answer 38

• Nasal obstruction that improves after 3-6 months
• Dose related hemolysis
• Peripheral neuritis
• Methemoglobinemia, leukopenia, allergic dermatitis

Question 39

What is the DOC for moderate to severe Erythema Nodosum Leprosum (ENL)?

Answer 39

Thalidomide

Question 40

What is thalidomide used to treat?

Answer 40

ENL, lepromatous leprosy, treatment of mycobacterium infections, and primary brain malignancies

Question 41

What is the main adverse effect of thalidomide?

Answer 41

Teratogenic, should not be used at any time during pregnancy