Pharm - tuberculosis part 2 Flashcards
SE pyrazinamide
not really specific - malaise, fever, etc
spectrum of pyrazinamide
ONLY used for TB
in what conditions is pyrazinamide most effective
ACIDIC CONDITIONS
explain the tb regimen in which pyrazinamide is administered
either with isoniazid + rifampin or isoniazid + rifampin + ethambutol
ALWAYS at least with both isoniazid and rifampin
does pyrazinamide get into cells?
yes - it has to to be active against TB.
it’s a small molecule - can penetrate macrophages and lysosomes by passive diffusion
pyrazinamide is preferentially active against what kind of bacilli?
NON REPLICATING
Pyrazinamide targets ________, which is important for the synthesis of acetyl CoA
aspartate decarboxylase
2 resistance mechanisms against pyrazinamide
-decreased uptake into cells
-mutations that inhibit the conversion of the prodrug into the active form - pyrazinoic acid
does pyriazinamide have cross resistance with other tuberculosis agents?
why or why not
NO
has a very unique MOA
*****important AE of pyrazinamide
hyperuricemia, which can develop into acute gouty arthritis
this is bc pyrazinamide and uric acid compete for the same transporter, and thus the secretion of uric acid from the body is decreased
is pyrazinamide well absorbed? well distributed? can it penetrate BBB?
yes to all
only penetrates CNS when meninges are inflamed tho
1-5% of patients on pyrazinamide experience
hepatotoxicity
MOA ethambutol
inhibits the synthesis of arabinogalactan - an important component of the m. tb cell wall
does so by competitively inhibiting arabinosyl transferase
3 main AE ethambutol*
hyperuricemia
joint pain
optic neuritis (reversible if we discontinue the drug or lower the dose)
2 1st line TB agents that can cause hyperuricemia
pyrazinamide
ethambutol
what enzyme does ethambutol inhibit
arabinosyl transferase
leads to diruption of arabinogalactan synthesis, and thus increased permeability of the cell wall
spectrum ethambutol
m. tuberculosis and other mycobacterial organisms
regimen in which ethambutol is given
in combo therapy - w 2 or 3 other 1st lines
arabinosyl transferase is encoded by the ______ operon
explain this operon
embCAB operon
EmbA and EmbB are involved in arabinogalactan synthesis
EmbC involved in lipoarabinomannan synthesis (LAM)
2 resistance mechanisms for ethambutol
-overproduction of arabinosyl transferase (emb gene products)
-mutate EmbB gene structure mutants – drug may not be able to bind enzyme
very important pharmacokinetic situation for ethambutol
it can accumulate in renal failure patients - need to reduce the dose for them
can ethambutol be adminstered orally?
YES
well absorbed from GI
**very important AE ethambutol
AFFECTS THE EYES:
-retrobulbar neuritis – loss of vision and develop red-green color blindness
streptomycin AE
is it 1st line?
do we really use anymore?
it is 1st line but we don;t really use - very toxic and can cause permanent hearing loss
kanamycin is _____ line for tuberculosis
SECOND LINE
adverse effects kanamycin
hearing loss
kidney damage
contraindicated in pregnancy
how is tb diagnosed
THREE THINGS
-chest x ray
-sputum sample
-skin or blood test
how is tb treated
with antibiotics
3 symptoms of active tb
weight loss
loss of appetite
night sweats
how is TB transmittied
ONLY through the air - nothing else
what does isoniazid inhibit in mycobacterium tuberculosis
mycolic acids
common side effect isoniazid
hepatotoxicity
what enzyme in the liver metabolizes isoniazid
NAT2 (n-acetyl transferase)
true or false
rifampin causes increased plasma levels of drugs metabolized by the CYP system
FALSE
decreases their serum levels by increasing CYP activity
true or false
rifampin is a potent inducer of the CYP system
TRUE
