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Res: Tb treatments

Terms in this set (33)

with antimicrobials
mycobacterium tuberculosis
How is the respiratory disease of tuberculosis treated? What is the name of the organism that causes tb?
multiple
TB treatment ALWAYS involves _________ drugs to avoid driving the development of resistance
For Intensive phase: Isoniazid, Rifampin, Pyrazinamide, and Ethambutol (H, R, Z, E) for 8 weeks

For Continuation phase: Isoniazid, Rifampin (H, R) for 18 weeks
What are the drug combinations for drug susceptible TB?
an intensive phase of 6 months with 5 drugs
a continuation phase of 18 months with 4 drugs
What are the drug combinations for drug resistant TB? (MDR, XDR)
Isoniazid and Rifampin
What is MDR TB resistant to?
Isoniazid and rifampin
2 classes of 2nd line drugs
What is XDR TB resistant to?
Isoniazid and rifampin
2 classes of 2nd line drugs
others
What is TDR TB resistant to?
rifampin and rifabutin
1st line
target both!
Which TB drugs target bacterial RNA polymerase? Do they target proliferating or latent TB?
streptomycin
kanamycin
amikacin
2nd line
Which TB drugs target bacterial ribosomes?
ciprofloxacin
ofloxacin
levofloxacin
2nd line
Which TB drugs target bacterial DNA Gyrase?
ethambutol
isoniazid
1st line

delamanid
2nd line

target proliferating
Which TB drugs target bacterial cell wall synthesis? Do they target proliferating or latent TB?
bedaquiline
2nd line

target proliferating
Which TB drugs target bacterial ATP synthase? Do they target proliferating or latent TB?
pyrazinamide
1st line

target latent
Which TB drugs target bacterial proton motive force? Do they target proliferating or latent TB?
the inability of some drugs to kill latent TB
What necessitates long treatment times for TB?
isoniazid (1st line)
dalamanid (2nd line)
What are the mycolic acid synthesis inhibitors?
this prodrug gets converted by KatG (from M. Tb), and the product inhibits InhA, which normally gives the final mycolic acid product

mutations in KatG or InhA confer resistance
Isoniazid MoA? Resistance?
hepatotoxicity (3%)
peripheral neuropathy
Nephrotoxicity- NAT2 is a slow acetylator or if CYP2E1 is induced by alcohol- toxic metabolites
Isoniazid toxicity?
none!
Delamanid CYP-associated drug interactions?
ethambutol (1st line)
cycloserine (2nd line)
What are the cell wall synthesis inhibitors?
ethambutol inhibits arabinosyltransferase (no arabinogalactan made)
cycloserine inhibits cytoplasmic enzymes responsible for peptidoglycan synthesis

mutations in arabinosyltransferase confer resistance
Ethambutol and cycloserine MoA? Resistance?
optic neuritis (R-G colorblindness)
ethambutol toxicities?
various neurological symptoms
cycloserine toxicities?
Rifampin/rifampicin
rifabutin
1st line
what are the RNA polymerase inhibitors?
inhibit RNA polymerase

RNA polym mutations confer resistance
Rifampin/rifabutin MoA? resistance?
nephrotoxicity/interstitial nephritis
rifabutin has orange coloration of skin and fluids
other symptoms like rash, vomiting, fever, etc
Rifampin/rifabutin toxicities?
rifampin induces lots of CYPs, so it reduces the effects of drugs, importantly bedaquiline and causes "TB-HIV syndemic"
Rifampin/rifabutin drug interactions?
HIV immunosuppression greatly increases the risk of TB reactivation, and TB medication (rifampin, rifabutin) makes HIV medications work less well.
What is the TB-HIV syndemic?
unknown.
it's a prodrug that gets converted by PZase in M. TB and gets pH trapped

PZase mutations confer resistance
Pyrazinamide MoA? Resistance?
hepatotoxicity > drug-induced hepatitis
less common now due to lower dosages
Pyrazinamide toxicities?
Class C, but CDC suggests women still get treated with the usual drugs
What is the pregnancy risk of these drugs?
bedaquiline
What is the ATP Synthase Inhibitor drug?
Weakens M. Tb by not allowing for the formation of ATP
Bedaquiline MoA?
Rifampin inducing CYPs causes bedaquilines to be less effective
Bedaquiline drug interactions?
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