Antibiotics V: Antimycobacterial Agents

Question 0

Adverse effect of ethambutol

Answer 0

Optic neuritis (loss of visual acuity and red-green color blindness)

Question 1

MOA of Ethambutol

Answer 1

Disrupts assembly of the mycobacterial cell wall

a) Inhibits mycobacterial arabinosyl transferase III; action is bacteristatic

Question 2

MOA of pyrazinamide

Answer 2

Prodrug that is converted to pyrazinoic acid (POA) by mycobacterial pyrazinamidase

Question 3

What drug in TB treatment acts as a “sterilizing” agent against residual organisms that may cause relapse?

Answer 3

Pyrazinamide

Question 4

Adverse effects of pyrazinamide

Answer 4

Hepatotoxicityand hyperuricemia

Question 5

Second line TB treatment

Answer 5

Streptomycin

Question 6

Drug that passively diffuses into the mycobacterium. It is a prodrug activated by mycobacterial catalase/peroxidase to a free radical. The free radical form covalently binds to NAD+ and NADP+ to form adducts that are inhibitors of enzymes involved in synthesis of mycolic acid

Answer 6

Isoniazid

Question 7

INH is bacteriostatic/bactericidal to active bacilli, but bacteriostatic/bactericidal to quiescent bacilli?

Answer 7

Bactericidal, Bacteristatic

Question 8

What is resistance to INH due to?

Answer 8

Mutation or deletion of katG gene

Question 9

Explain the metabolism of INH

Answer 9

Inactivated in the liver by acetylation, which is genetically determined. N-Acetyl-INH is excreted in the kidneys.
Half life is 1hr in rapid acetylators, 3 hr in slow acetylators.

Question 10

Adverse rxns of INH

Answer 10

1) Peripheral neuropathy- dose related parathesias in extremities; results from drug-imduced deficiency in pyridoxine (can be reversed by taking vitamin B6)
2) Hepatotoxicity(older pts)

Question 11

Name a rifamycin

Answer 11

Rifampin

Question 12

What drug inhibits DNA-dependent RNA polymerase by binding to the B subunit of bacterial RNA polymerase, inhibiting RNA synthesis; action is bactericidal

Answer 12

Rifampin

Question 13

The resistance to rifampin is caused by

Answer 13

mutation in rpoB, the gene for the B subunit that results in reduced binding affinity

Question 14

What TB drug can also be used to treat leprosy and is also considered a broad spectrum antibiotic with activity against Neiserria meningitis, H. flu, S. aureus, and Legionella sp.?

Answer 14

Rifampin

Question 15

What drug has these adverse rxns:

1) Hepatotoxicity
2) Discoloration of body fluids (Red-orange color)
3) Strong induction of many CYP isoforms (Oral contraceptives, warfarin, and HIV drugs are of special concern.

Answer 15

Rifampin