TB Drugs Flashcards
which drugs are mycolic acid synthesis inhibitors (what line are they)
- isoniazid (first line)
- dalamanid (second line)
- pretomanid (second line)
what drugs are cell wall synthesis inhibitors (what line are they)
- ethambutol (first line)
- cycloserine (second line)
what drugs are RNA polymerase inhibitors (what line)
- rifampin (first line)
- rifabutin (first line)
what drugs are protein synthesis inhibitors (what line)
aminoglycosides
- streptomycin (second line)
- amikacin (second line)
- kanamycin (second line)
what drugs are DNA synthesis inhibitors (what line)
- levofloxacin (second line)
- moxifloxacin (second line)
what drugs are ATP synthase inhibits (what line)
- bedaquiline (second line)
intensive phase uses which drugs
how long is intensive phase
- all 4 front line drugs
- H+R+Z+E
- 8 weeks
continuation phase uses which drugs
how long is continuation phase
- H+R
- 18 weeks
what drugs are effective against latent TB
- rifampin (also effective against active)
- rifabutin (also effective against active)
- pyrazinamide
isoniazid bacterial enzymes needed to convert it to active form
- KatG
what bacterial enzyme does isoniazid inhibit
result
- InhA
- prevents mycolic acid precursor from turning into mycolic acid
mutations in ______ and ______ confer resistance to isoniazid
- KatG
- InhA
isoniazid toxicities
- hepatotoxicity
- peripheral neuropathy
INH - INJURY TO NERVES AND HEPATOCYTES
how does isoniazid cause toxicities
- intermediate compounds produce toxic reactive metabolites which cause liver damage
which acetylators of isoniazid are less prone to toxicity
- fast acetylation
why are slow acetylators of isoniazid more prone to toxciity
- accumulate toxic metabolite
what is the polymorphism in isoniazid that can cause more toxicities
- NAT2
inductors of ______ also promote damage in isoniazid toxicities
how
example
- CYP2E1
- convert to toxic reactive metabolite faster
- alcohol
toxicities of delamanid
- no significant CYP-associated drug interactions
ethambutol MOA
- inhibits arabinosyltransferase
- inhibits synthesis of galactan portion of cell wall
cycloserine MOA
- inhibits cytoplasmic enzymes
mutations in _________ confer resistance to ethambutol
- arabinosyltransferase
ethambutol toxicities
is this reversible?
- optic neuritis (color blindness)
- reversible with removal of drug
cycloserine toxicities
- various neurologic symptoms
mutations in ____ confer resistance to rifampin and rifabutin
- RNA polymerase
interesting toxicity of rifabutin
- orange coloration of skin, urine, feces, saliva, tears
rifampin and rifabutin toxicities
- nephrotoxicity/interstitial nephritis
- drug interactions
how do rifampin and rifabutin interact with other drugs
which drugs
- induces important cytochromes that speed up metabolism of clinically relevant drugs
- reduces their effectiveness
- HIV protease/RT inhibitors
- Bedaquiline
RIFAMPIN REVS UP DRUG METABOLISM
how Pyrazinamide works
- enters bacterium and gets converted to charged form (negative form)
- trapped by higher pH and disrupts cell energetics
mutations in _______ confer resistance to Pyrazinamide
normal role
- PZase
- converts Pyrazinamide to charged negative form to keep it trapped in cell
Pyrazinamide toxicities
Pyrazinamide toxicities more common when
- hepatoxicity -> drug induced hepatitis
- drug dose used was higher
MOA of Bedequiline
- disrupts production of ATP within bacterial cells
Bedaquiline coadministration with _____ reduces its effectiveness
- rifampin
which drugs are only effective against active TB
- cell wall synthesis inhibitors
- ATP synthase inhibitor
which drugs are only effective against latent TB
- pyrazinamide
