Antimycobacterials

Question 1

what is the purpose of drug combinations in the chemotherapy of mycobacterial infections?

Answer 1

to delay the emergence of resistance and to enhance antimycobacterial activity

Question 2

what are the 5 major drugs used to treat TB?

Answer 2

INH, rifampin, ethambutol, pyrazinamide, and streptomycin

Question 3

initiation of treatment of pulmonary TB usually involves a __(#) combination regimen.

Answer 3

3 to 4 drug

Question 4

this drug is a structural congener to pyridoxine; its MOA involves inhibition of mycolic acids.

Answer 4

INH

Question 5

true or false: resistance to INH develops quickly when the drug is used alone

Answer 5

true

Question 6

deletions of the following genes are associated with what level of resistance? katG and inhA

Answer 6

high-level and low-level respectively

Question 7

true or false: INH is equally effective on both active and latent TB cells

Answer 7

false; bactericidal for growing cells, but LESS effective for dormant organisms

Question 8

the liver metabolism of INH follows what mechanism?

Answer 8

acetylation and is under genetic control (fast vs. slow acetylators)

Question 9

INH half life is approximately how long in fast acetylators? in slow?

Answer 9

60 to 90 minutes vs. 3 to 4 hours; note: population of fast acetylators is more common amongst Asians than Europeans or Africans

Question 10

will fast acetylators require lower or higher doses of INH to have the same therapeutic effect as slow acetylators?

Answer 10

higher

Question 11

which drug is given as the sole drug in treatment of latent TB?

Answer 11

INH

Question 12

what is the MC toxic effect of INH?

Answer 12

neurotoxicity including peripheral neuritis, muscle twitching and insomnia

Question 13

what is the treatment for the neurotoxicity associated with INH?

Answer 13

pyridoxine (25-50 mg/d orally)

Question 14

true or false: INH is hepatotoxic and may cause abnormal liver function tests

Answer 14

true - it may also inhibit hepatic metabolism of several drugs

Question 15

what is the expected manifestation of the use of INH in patients with G6PDH deficiency?

Answer 15

hemolysis

Question 16

what is the MOA for rifampin?

Answer 16

inhibition of DNA-dependent RNA polymerase

Question 17

true or false: rifampin is easily well distributed throughout the CNS

Answer 17

true

Question 18

what is the DOC for treatment of latent TB in INH intolerant patients?

Answer 18

rifampin; note, this will also be the DOC for INH resistant strains

Question 19

rifampin may be used in conjunction with what other Ab to treat MRSA and PRSP?

Answer 19

vancomycin

Question 20

true or false: rifampin strongly induces liver drug-metabolizing enzymes and enhances the elimination rate of many drugs.

Answer 20

true

Question 21

which drug, also a derivative of rifamycin, is equally effective as an antimycobacterial agent and is LESS likely to cause drug interactions?

Answer 21

rifabutin

Question 22

what is the name of the rifamycin derivative that has been used in travelers’ diarrhea?

Answer 22

rifamixin

Question 23

true or false: rifampin is the preferred DOC for the tx of TB or other mycobacterial infections in AIDS patients.

Answer 23

false; rifabutin is preferred

Question 24

this drug works by inhibiting arabinosyl transferases involved in the synthesis of arabinogalactan.

Answer 24

ethambutol

Question 25

the most common adverse effects of ethambutol are what?

Answer 25

dose dependent vision disturbances and possible retinal damage (only after prolonged use)

Question 26

what are the two most common toxic side effects of pyrzinamide?

Answer 26

polyarthralgia and hyperuricemia (asymptotic)

Question 27

what is the one aminoglycoside that is now commonly used to treat drug resistant strains of M. tuberculosis?

Answer 27

streptomycin (typically in combination)

Question 28

what is indicated for treatment of tuberculosis caused by streptomycin resistant strains?

Answer 28

amikacin

Question 29

what does the first-line standard regimen for pulmonary TB consist of?

Answer 29

INH, rifampin, and pyrazinamide - typically after 2 months pyrazinamide is stopped and the 2 drug regimen is continued for the next 4 months (in HIV negative patients)

Question 30

if resistance to INH is high, how is the initial regimen for pulmonary TB adjusted?

Answer 30

the initial drug regimen should now include ETB or streptomycin; TB resistant to only INH can be treated with 6 months of RIF+pyrazinamide+ETB or streptomycin.

Question 31

what is recommended as primary prophylaxis for pulmonary TB in patients with CD4 less than 50/μL?

Answer 31

clarithromycin or azithromycin with or without RIF