Antimycobacterial Drugs

Question 1

90 pct of primary tb infections lead to latent, asymptomatic tb. What causes this to happen?

Answer 1

Development of cell-mediated immunity (which keeps the Tb in check)

Question 2

Are pts with latent Tb contagious?

Answer 2

No

Question 3

How large does the induration have to be for a PPD test to be positive?

Answer 3

Immunocompromised pts or suspicion of Tb - gt 5 mm, Low risk populations - gt 15 mm, All others - gt 10 mm

Question 4

There is an alternative to PPD for testing for Tb. What is the alternative and for whom is it recommended?

Answer 4

T cell-based inteferon gamma testing. Recommended for those who received BCG vaccine or those unlikely to return for PPD reading

Question 5

List first line drugs for Mycobacterium tuberculosis

Answer 5

Isoniazid, Rifampin, Ethambutol, Pyrazinamide, Streptomycin

Question 6

List second line drugs for Mycobacterium tuberculosis

Answer 6

Ethionamide, Capreomycin, Cycloserine, Aminosalicylic acid (PAS), Kanamycin, Amikacin, Quinolones (cipro, levofloxacin, moxifloxacin)

Question 7

One anti-tb drug is recommended for use during entire duration of therapy due to efficacy, tolerability, and low cost. Which drug?

Answer 7

Isoniazid

Question 8

Is isoniazid bactericidal or bacteriostatic?

Answer 8

Bactericidal

Question 9

What is the mechanism of isoniazid (INH)?

Answer 9

Prodrug, converted by mycobacteria to active form, inhibits mycolic acids, which mycobacteria need for cell wall

Question 10

AEs of isoniazid

Answer 10

Peripheral neuropathy (due to altered vit B6 metabolism) and Hepatitis (can be fatal)

Question 11

When treating tb is rifampin bactericidal or bacteriostatic?

Answer 11

Bactericidal

Question 12

Mechanism of rifampin

Answer 12

Binds to beta subunit of bacteria DNA-dependent RNA pol

Question 13

AEs of rifampin

Answer 13

Drug-drug interactions (CYPs), imparts orange color to urine, sweat and tears. Also GI upset

Question 14

Is pyrazinamide bactericidal or bacteriostatic?

Answer 14

Bactericidal in acid environments (such as where tb lives, in phagosomes of macrophages)

Question 15

Mechanism of pyrazinamide

Answer 15

Inhibits mycolic acid biosynthesis by targeting fatty acid synthase I gene

Question 16

AEs of pyrazinamide

Answer 16

Hepatotoxicity and hyperuricemia (may induce gout)

Question 17

Is ethambutol bactericidal or bacteriostatic?

Answer 17

Bacteriostatic

Question 18

echanism of ethambutol

Answer 18

Disrupts polymerization of cell wall

Question 19

What effect does ethambutol administration have on rifampin and ofloxacin activity

Answer 19

Increases their anti-tb activity by disrupting the cell wall (they are lipophilic)

Question 20

AEs of ethambutol

Answer 20

Decrease in visual acuity and loss of discrimination between green and red (dose-dependent)

Question 21

To what does streptomycin bind

Answer 21

The S12 subunit of ribosomal proteins (different target than other aminoglycosides)

Question 22

Is the effect of streptomycin on tb bactericidal or bacteriostatic?

Answer 22

Bacteriostatic (has bactericidal effects in vitro, but not enough reaches the tb to be cidal)

Question 23

When is streptomycin primarily used in tb cases now?

Answer 23

For drug-resistant TB or when pts are unable to take oral meds (its only available IM and IV)

Question 24

Compared to rifampin, rifabutin has more AEs and slightly worse tb activity. In what cases of tb would it be preferred over rifampin despite this?

Answer 24

In HIV positive patients also taking protease inhibitors, clarithromycin and azole antifungals, because it has far fewer drug-drug interactions

Question 25

Rifampin is a first line drug for tb. What two other first line anti-tb drugs are similar to rifampin

Answer 25

Rifabutin - same MoA and resistance, Rifapentine - same efficacy and side effect profile (but longer half-life)

Question 26

Ethionamide is a 2nd line drug for tb. What is its mechanism and what are its AEs?

Answer 26

Inhibits mycolic acid synthesis. Intense GI irritation, postural hypotension, mental depression, asthenia

Question 27

Para-aminosalicylic Acid (PAS) is a 2nd line anti-tb drug. What is its mechanism and what are its AEs?

Answer 27

Folate synthesis antagonist (similar to sulfonamides). Severe gastric irritation (limits compliance) and hypersensitivity reactions

Question 28

Which second line tb drug is associated with high incidence of ototoxicity and nephrotoxicity?

Answer 28

Capreomycin

Question 29

Cycloserine is a second line anti-tb drug. Give the mechanism and AEs of cycloserine

Answer 29

Inhibits incorporation of d-alanine into bacterial cell walls. AEs are neuologic (somnolence, vertigo, confusion, psychosis). Only used in treatment failures

Question 30

Which drugs of the same class as streptomycin are used as second line anti-tb agents?

Answer 30

Amikacin and Kanamycin (are both proper aminoglycosides) and capreomycin (is often grouped with the aminoglycosides)

Question 31

What drugs are typically used in the initial phase (2 months) and the follow up phase (4 or 7 months) for treating Tb?

Answer 31

Initial - Isoniazid, Rifampin, Pyrazinamide, Ethambutol (or streptomycin in children), Follow up - just Isoniazid and Rifampin

Question 32

What drugs are used to treat leprosy?

Answer 32

Dapsone, Rifampin and Clofazimine. Also ofloxacin, minocycline, thalidomide, and ethionamide

Question 33

Dapsone is used to treat leprosy. What are the mechanism and AEs of dapsone?

Answer 33

Mechanism similar to sulfonamides. AEs include hemolysis (high doses) and Jarish-Herxheimer reaction (immune response to sudden increase in bacterial kill products)

Question 34

What is ROM therapy?

Answer 34

Rofampin-Ofloxacin-Minocycline. Advocated by WHO as single dose therapy for a single paucibacillary (tuberculoid leprosy) skin lesion

Question 35

Treatment of mycobacterium avium-intracellulare complex (MAC) in HIV-negative patients

Answer 35

Clarithromycin (or azithromycin), Ethambutol, and Rifampin for one year after cultures are negative

Question 36

Treatment for mycobacterium kansasii

Answer 36

INH, rifampin, and ethambutol for 12-18 months

Question 37

Treatment for mycobacterium marinum

Answer 37

Clarithromycin or doxycycline or trimethoprim-sulfamethoxazole or rifampin and ethambutol