Antimycobacterial Drugs

Question 1

M. tuberculosis prophylaxis

Answer 1

Isoniazid

Question 2

M. tuberculosis treatment

Answer 2

Rifampin, Isoniazid, Pyrazinamide, Ethambutol

RIPE for treatment

Question 3

M. avium -intracellulare prophylaxis

Answer 3

Azithromycin, rifabutin

Question 4

M. avium - intracellulare treatment

Answer 4

More drug resistant than M. TB. Azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin.

Question 5

M. leprae treatment

Answer 5

Long-term treatment with dapsone and rifampin for TB form. Add clofazimine (turns skin red and GI symptoms) for lepromatous form.

Question 6

Isoniazid (INH) mech:

Answer 6

Decreased synthesis of mycolic acids. Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite.
Selective for mycobacteria, since mycolic acid is unique to mycobacteria

Question 7

Isoniazid (INH) uses:

Answer 7

Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB.
Diff INH half-lives in fast vs slow acetylators (serum transaminase should be monitored regularly)

Question 8

Isoniazid (INH) tox:

Answer 8

Neurotoxicity, hepatotoxicity. Pyridoxine (vit B6) can prevent neurotoxicity, lupus.
INH Injures Neurons and Hepatocytes
(Hepatitis is greater in slow acetylators)

Question 9

Isoniazid (INH) MOR:

Answer 9

mutations leading to underexpression of KatG (encodes catalase-peroxidase in bacteria that convert INH to active metabolite)

Question 10

Rifamycins:

Answer 10

Rifampin, Rifabutin

Question 11

Rifamycin mech:

Answer 11

Inhibits DNA-dependent RNA polymerase

Question 12

Rifamycin uses:

Answer 12

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 13

Rifamycin tox:

Answer 13

Minor hepatotoxicity and drug interactions (increased P-450); orange body fluids (nonhazardous side effect). Rifabutin favored over rifampin in patients with HIV infection due to less cytochrome P-450 stimulation.
GI disturbances.

Question 14

Rifampin’s 4 R’s:

Answer 14

RNA polymerase inhibitor
Ramps up microsomal cytochrome P-450
Red/orange body fluids
Rapid resistance if used alone
RifAMPin RAMPS up cytochrome P-450, BUT rifaBUTin does not

Question 15

Rifamycin MOR:

Answer 15

Mutations reduce drug binding to RNA polymerase. Monotherapy rapidly leads to resistance.

Question 16

Pyrazinamide: mech

Answer 16

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

Question 17

Pyrazinamide: uses

Answer 17

Mycobacterium TB

Question 18

Pyrazinamide: tox

Answer 18

Hyperuricemia, hepatotoxicity

Question 19

Ethambutol: mech

Answer 19

Decreased carobohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.

Question 20

Enthambutol: use

Answer 20

Mycobacterium TB

Question 21

Ethambutol: tox

Answer 21

Optic neuropathy (red-green color blindness). (reversible)