anti-mycobacterial drugs Flashcards
Which drugs are used to treat mycobacterial infections?
isoniazid Pyrazinamide ethambutol rifampin/rifabutin clofazimine dapson
which drugs interfere with mycolic acid synthesis
isoniazid
pyrazinamide
ethambutol
which drugs interfere with DNA dependent RNA pol?
rifampin/rifabutin
which drug interferes with DNA template function
clofazimine
which drug inhibits DH synthase
dapsone
what is the treatment plan for M tuberculosis
6 month plan =
2 months isoniazid and rifampin, pyrazinamide
4 additional months isoniazid and rifampin
9 month plan =
isoniazid + rifampin
what is the treatment plan for M kansasii (pneumonia)
isoniazid + rifampin + ethambutol
treat until you have 12 months of negative sputum
what is the treatment plan for M avium complex (MAC) (pneumonia)
clarithromycin or azithromycin + ethambutanol +/- rifabutin
treat until six months after negative sputum
what is the treatment for M leprae
dapsone + rifampin +/- clofazimine
treatment for a min of 2 years
what is the treatment for M fortuitum
amikacin (aminoglycoside) + doxycycline (tetracycline)
4 months for cutaneous
6 months for bone
12 months for lungs
what is the treatment for M marinum
rifamin + ethambutol
3 months
isoniazid - mechanism
inhibits mycolic acid
bactericidal during long growth phase
bacteriostatic in resting organisms
what is mycolic acid?
a unique component of mycobacterial cell wall
isoniazid - side efects
hepatotoxicity (increases with age) peripheral neuritis (B6 given for prevention)
pyrazinamide - mechanism
inhibits mycolic acid synthesis
bactericidal
proposed mechanism for inhibition of mycolic acid synthesis
target fatty acid synthase I gene
except ethambutol - inhibits use of mycolic acid in cell wall synth
pyrazinamide - side effects
dose related hepatits
should only be used for short therapy; monitor liver function
ethambutol - mechainsm
interferes with mycolic acid
- inhibits incorporation of mycolic acid into cell wall
- bacteriostatic
ethambutol - side effect
optical neuritis (visual acuity and red/green discrimination) -dont use in children under 5
also rare side effect is gout due to inhibition of excretion of uric acid
ethambutol - excretion
renal
dose adjustment may be necessary - accumulation can happen in patients with impaired function
rifampin/rifabutin - mechanism
DNA dep RNA polymerase - inhibits
eukaryotic RNA pol is less sensitive to rifampin because of binding affinity differences so it is safe to use
rifampin/rifabutin - side effects
rifampin - substrate and inducer for CYP3A4
rifabutin is not as potent of an inducer
rifampin reduces HIV protease inhibitor levels by 80% - patients need to be switched to rifabutin (decreases by 20-40%)
also turns saliva, urine, tears orange-red
clofazimine - mechanismm
inhibits template function of DNA
binds to DNA and inhibits function
clofazimine - excretion
hepatic, to feces
little is excreted in the urine
clofazimine - side effect
brownish pink coloring of skin, cornea, urine
dapsone - mechanism
inhibits DH (dihydropterate) synthease interferes in folic acid synthesis
dapsone is a sulfone so mechanism is like other sulfonamides
dapsone - side effect
similar to sulfonamides
- anorexia, nausea
- hemolytic anemia is rare but more frequent in individuals with G6PDH deficiency
- sulfone syndrome (rare)
which drugs cause hepatotoxicity?
isoniazid
pyrazinamid
which drug should you not use in pregnant patients?
clofazimine
which drug can cause hemolytic anemia in G6PDH deficient patients
dapsone
