Antimycobacterials Flashcards
what is the purpose of drug combinations in the chemotherapy of mycobacterial infections?
to delay the emergence of resistance and to enhance antimycobacterial activity
what are the 5 major drugs used to treat TB?
INH, rifampin, ethambutol, pyrazinamide, and streptomycin
initiation of treatment of pulmonary TB usually involves a __(#) combination regimen.
3 to 4 drug
this drug is a structural congener to pyridoxine; its MOA involves inhibition of mycolic acids.
INH
true or false: resistance to INH develops quickly when the drug is used alone
true
deletions of the following genes are associated with what level of resistance? katG and inhA
high-level and low-level respectively
true or false: INH is equally effective on both active and latent TB cells
false; bactericidal for growing cells, but LESS effective for dormant organisms
the liver metabolism of INH follows what mechanism?
acetylation and is under genetic control (fast vs. slow acetylators)
INH half life is approximately how long in fast acetylators? in slow?
60 to 90 minutes vs. 3 to 4 hours; note: population of fast acetylators is more common amongst Asians than Europeans or Africans
will fast acetylators require lower or higher doses of INH to have the same therapeutic effect as slow acetylators?
higher
which drug is given as the sole drug in treatment of latent TB?
INH
what is the MC toxic effect of INH?
neurotoxicity including peripheral neuritis, muscle twitching and insomnia
what is the treatment for the neurotoxicity associated with INH?
pyridoxine (25-50 mg/d orally)
true or false: INH is hepatotoxic and may cause abnormal liver function tests
true - it may also inhibit hepatic metabolism of several drugs
what is the expected manifestation of the use of INH in patients with G6PDH deficiency?
hemolysis
what is the MOA for rifampin?
inhibition of DNA-dependent RNA polymerase
true or false: rifampin is easily well distributed throughout the CNS
true
what is the DOC for treatment of latent TB in INH intolerant patients?
rifampin; note, this will also be the DOC for INH resistant strains
rifampin may be used in conjunction with what other Ab to treat MRSA and PRSP?
vancomycin
true or false: rifampin strongly induces liver drug-metabolizing enzymes and enhances the elimination rate of many drugs.
true
which drug, also a derivative of rifamycin, is equally effective as an antimycobacterial agent and is LESS likely to cause drug interactions?
rifabutin
what is the name of the rifamycin derivative that has been used in travelers’ diarrhea?
rifamixin
true or false: rifampin is the preferred DOC for the tx of TB or other mycobacterial infections in AIDS patients.
false; rifabutin is preferred
this drug works by inhibiting arabinosyl transferases involved in the synthesis of arabinogalactan.
ethambutol
the most common adverse effects of ethambutol are what?
dose dependent vision disturbances and possible retinal damage (only after prolonged use)
what are the two most common toxic side effects of pyrzinamide?
polyarthralgia and hyperuricemia (asymptotic)
what is the one aminoglycoside that is now commonly used to treat drug resistant strains of M. tuberculosis?
streptomycin (typically in combination)
what is indicated for treatment of tuberculosis caused by streptomycin resistant strains?
amikacin
what does the first-line standard regimen for pulmonary TB consist of?
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)
if resistance to INH is high, how is the initial regimen for pulmonary TB adjusted?
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.
what is recommended as primary prophylaxis for pulmonary TB in patients with CD4 less than 50/μL?
clarithromycin or azithromycin with or without RIF
