Micro - Antimicrobials (Antimycobacterial drugs)

Question 1

What drug is used as prophylaxis for M. tuberculosis?

Answer 1

Isoniazid

Question 2

What 4 drugs are used as treatments for M. tuberculosis?

Answer 2

(1) Rifampin (2) Isoniazid (3) Pyrazinamide (4) Ethambutol; Think: “RIPE for treatment”

Question 3

What are 2 drugs used as prophylaxis for M. avium-intracellulare?

Answer 3

(1) Azithromycin (2) Rifabutin

Question 4

What is the treatment for M. avium-intracellulare? Include possible options.

Answer 4

Azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin.

Question 5

What is the prophylaxis for M. leprae?

Answer 5

N/A :-) Trick question!

Question 6

What is the treatment for M. leprae tuberculoid versus lepromatous form?

Answer 6

Long-term treatment with dapsone and rifampin for tuberculoid form. Add clofazimine for lepromatous form.

Question 7

How does M. avium-intracellulare compare to M. tuberculosis in terms of resistance?

Answer 7

More drug resistant than M. tuberculosis.

Question 8

What is the mechanism for Isoniazid (INH)? What is needed for INH to become active?

Answer 8

Decrease synthesis of mycolic acids; Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite

Question 9

What is the clinical use for Isoniazid (INH)?

Answer 9

Mycobacterium tuberculosis

Question 10

What is the only agent used as solo prophylaxis against TB?

Answer 10

Isoniazid (INH)

Question 11

How do the INH half-lives differ?

Answer 11

Different INH half-lives in fast vs. slow acetylators.

Question 12

What are 2 toxicities associated with INH?

Answer 12

(1) Neurotoxicity (2) Hepatotoxicity; Think: “INH Injures Neurons and Hepatocytes”

Question 13

What can prevent neurotoxicity due to Isoniazid (INH)? With what other condition can it help?

Answer 13

Pyridoxine (vitamin B6) can prevent neurotoxicity, lupus.

Question 14

What are 2 examples of Rifamycins?

Answer 14

(1) Rifampin (2) Rifabutin

Question 15

What is the mechanism of Rifamycins?

Answer 15

Inhibits DNA-dependent RNA polymerase

Question 16

What is the clinical use of Rifamycins?

Answer 16

Mycobacterium tuberculosis; delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B.

Question 17

What are 2 potentially hazardous toxicities of rifamycins? What is a nonhazardous side effect of rifamycin?

Answer 17

Minor hepatotoxicity and drug interactions (increased P-450); Orange body fluids (nonhazardous effects)

Question 18

Which rifamycin is favored in patients with HIV infection, and why?

Answer 18

Rifabutin favored over Rifampin in patients with HIV infection due to less cytochrome P-450 stimulation; Think: “RifAMPin RAMPs up cytochrome P-450, BUT rifaBUTin does not.”

Question 19

What are 4 R’s to associate with Rifampin?

Answer 19

Rifampin’s 4 R’s: (1) RNA polymerase inhibitor (2) Ramps up microsomal cytochrome P-450 (3) Red/orange body fluids (4) Rapid resistance if used alone

Question 20

What is the mechanism of pyrazinamide?

Answer 20

Mechanism uncertain. Thought to acidify intracellular environment via conversion to pyrazinoic acid.

Question 21

In what context is pyrazinamide effective, and what is its relevance to TB?

Answer 21

Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found.

Question 22

What is the clinical use for pyrazinamide?

Answer 22

Mycobacterium tuberculosis

Question 23

What are 2 toxicities associated with Pyrazinamide?

Answer 23

(1) Hyperuricemia (2) Hepatotoxicity

Question 24

What is the mechanism of Ethambutol?

Answer 24

Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase

Question 25

What is the clinical use for Ethambutol?

Answer 25

Mycobacterium tuberculosis

Question 26

What toxicity is associated with Ethambutol?

Answer 26

Optic neuropathy (red-green color blindness).

Question 27

What are 4 antimycobacterial drugs?

Answer 27

(1) Isoniazid (INH) (2) Rifamycins (3) Pyrazinamide (4) Ethambutol