Anti-TB (Antimycobacterials)

Question 1

What three characteristics are specific to Mycobacterium?

Answer 1

• Acid-fast staining
• Mycolic acid
• Arabinogalactin

Question 2

What is the DOC for ACTIVE TB?

Answer 2

RIPE

• Rifampin
• Isoniazid
• Pyrazinamide
• Ethambutol

Question 3

Under what conditions would you substitute Rifabutin for Rifampin in the treatment of TB? Why (2)?

Answer 3

Rifabutin for Rifampin if HIV+ or concerned about drug interactions (other med is an inducer of CYP3A4)

Question 4

What is the DOC for LATENT TB? What are two alternative options?

Answer 4

Isoniazid + Rifapentine

• Isoniazid monotherapy
• Rifampin monotherapy

Question 5

What is the MOA of Isoniazid? What is it activated by?

Answer 5

Inhibition of mycolic acid

- Activated by KatG (possible MOR)

Question 6

What should be considered with metabolism of Isoniazid, and why is this important?

Answer 6

Fast vs. Slow acetylators

- Changes toxicity…

Question 7

What are the three primary toxicities associated with Isoniazid?

Answer 7

• Hepatotoxicity
• Hemolysis and G6PD deficiency
• Peripheral neuritis

Remember INH (injury to nerves and hepatic)

Question 8

What is the MOA of the Rif family? What three drugs are included in this family and how is each used?

Answer 8

Rif MOA: inhibit RNA polymerase via rpoB subunit (possible MOR)

• Rifampin: active TB (RIPE) OR mono latent TB
• Rifabutin: substitute for Rifampin if HIV+ or drug interactions in active TB
• Rifapentine: latent TB (combine with Isoniazid)

Question 9

What are the three primary toxicities associated with Rifampin?

Answer 9

• Drug interactions (induces CYP3A4)
• Orange-colored secretions
• Decreased BP effectiveness

Question 10

What is the MOA of Ethambutol?

Answer 10

Inhibition of arabinogalactin synthesis

Question 11

What is the primary toxicity associated with Ethambutol?

Answer 11

Visual issues (R/G color blind, blindness)

Question 12

What is the MOA/what conditions are necessary for Pyrazinamide to be active?

Answer 12

MOA: unknown…

- Requires acidic environment

Question 13

What is the primary toxicity associated with Pyrazinamide?

Answer 13

Hepatotoxicity

Question 14

What two antimycobacterials are associated with Hepatotoxicity?

Answer 14

• Isoniazid

- Pyrazinamide

Question 15

Why is Isoniazid PLUS Rifapentine considered the DOC for latent TB over monotherapy Isoniazid or Rifampin (2)?

Answer 15

Rifapentine has a longer half-life so fewer doses AND reduced side effects (compared to monotherapies)

Question 16

Why are the second line antimycobacterials considered second line?

Answer 16

Less effective AND more toxic

Question 17

What is the DOC for MAC (Mycobacterium avium complex) - think ___ + ___ + ___)?

Answer 17

- Azithromycin OR Clarithromycin 
PLUS
- Ethambutol
PLUS
- Rifampin OR Rifabutin OR Cipro

Question 18

In the treatment of MAC (Mycobacterium avium complex), why would you choose Azithromycin over Clarithromycin?

Why would you choose Rifampin OR Rifabutin over Cipro, and vice versa?

Answer 18

• Azithromycin over Clarithromycin if drug interactions
• Rifampin OR Rifabutin if patient is <18 (Cipro is contraindicated)
• Cipro if drug interactions (Rifampin, Rifabutin are strong inducers of CYP3A4)

Question 19

What is the DOC to treat Leprosy (Mycobacterium leprae) - think ___ + ___)?

Answer 19

Rifampin + Dapsone

Question 20

What is the MOA for Dapsone? What is Dapsone’s primary toxicity?

What does is treat?

Answer 20

• MOA: Inhibits folic acid synthesis
• Toxicity: nasal obstruction

Treats Leprosy (Mycobacterium leprae)

Question 21

What drug is used to treat the symptoms of Leprosy (Mycobacterium leprae), and what is that symptom? What should be considered with the use of this drug?

Answer 21

Thalidomide treats ENL

- VERY TOXIC - Teratogenic (not for pregnancy