TB Drugs Flashcards
what are the two phases of TB drug treatment?
intensive and continuation phases
what drugs are used during intensive phase? how long is it for drug susceptible and drug resistant?
all four first line…isoniazid, ethambutol, rifampin, pyrazinamide
lasts 8 weeks
lasts 6 months
what drugs are used during continuation phase? how long is it for drug susceptible and drug resistant?
isoniazid and rifampin
18 weeks
18 months
what is the common toxicity with isoniazid?
hepatotoxicity
rate the types of drug resistant TB from best to worst to have
MDR…XDR…TDR
what drugs are you resistant to with MDR?
rifampin and isoniazid
what drugs are you resistant to with XDR?
rifampin isoniazid and 2 2nd class drugs
what drugs are you resistant to with TDR?
rifampin isoniazid, 2 2nd class, and others
do most TB drugs kill latent or proliferating bacteria?
proliferating
what is the mechanism of isoniazid and delamanid?
they block the synthesis of mycolic acid by inhibiting InhA
what are the two TB drugs that are mycolic acid synthesis inhibitors?
isoniazid and delamanid
what is unique about isoniazid and delamanid? what protein takes care of this?
they are pro drugs…converted by KatG in the TB
what two enzymes can pick up mutations to yield resistance to isoniazid and delamanid?
KatG and InhA
explain how isoniazid causes hepatotoxicity
there are two metabolic pathways…one a fast and one a slow acetylation…the slow leads to a toxic metabolite to the liver
what chemical induces the slow pathway for isoniazid metabolism?
ethanol
what is the mechanism of ethambutol and cycloserine?
they are cell wall inhibitors
what two TB drugs are cell wall inhibitors?
ethambutol and cycloserine
what is a toxicity of ethambutol?
optic neuritis…red/green color blindness
which of ethambutol and cycloserine is first and second line?
ethambutol is first and cycloserine is second
what two TB drugs are RNA polymerase inhibitors?
rifampin and rifabutin
what is a weird toxicity of rifabutin?
orange colorationof skin, urine, feces, saliva, tears
what is a common toxicity of rifampin and rifabutin related to their clearance?
nephrotoxicity
rifampin and rifabutin are inducers of what class of molecules that can lead to serious drug interactions?
CYPs
what class of drugs must you be careful with when giving rifampin or rifabutin because of the CYP induction?
HIV drugs…induces the CYPs that clear the HIV drugs…so they are gone quick
what TB drug is cleared by the CYPs that rifampin and rifabutin induce?
bedaquline
what is the mechanism of pyrazinamide?
it is unclear but it does get trapped in the myco TB cell and is effective there
what enzyme converts pyrazinamide into its active state in the TB cells?
PZase…mutations here yield resistance
what is the common toxicity with pyrazinamide?
hepatotoxicity
what is the mechanism of bedaquiline?
ATP synthase inhibition
what TB drug is an ATP synthase inhibitor?
bedaquiline
