Lecture 60 - Anti-TB Drugs Flashcards
The standard short-course of TB treatment is 2 months ______ and 4 months ___.
2 months RIPE (Rifampin, Isoniazid, Pyrazinamide, Ethambutol)
4 months of RI (RIfampin and Isoniazid)
Isoniazid inhibits ____ ____ synthesis by inhibiting mycolic acid synth. Is it bacteriocidal or baceriostatic?
Keep in mind Isoniazid is a ___-drug, meaning it is activated by Mtb metabolism. Thus, the bacteria can become resistant by acquiring a mutation in ___G, the enzyme that typically activates Isoniazid. Also keep in mind ALL front-line Mtb drugs are _______ bioavailable (this should make sense since treatment lasts for 6+ months –> IV would not be conducive to such a long course of therapy).
The main adverse effect of Isoniazid is ________, which is reversible upon cessation of the drug.
Cell wall synthesis
Bacteriocidal
Pro-drug
KatG
Orally bioavailable
Hepatotoxicity
Rifampin inhibits bacterial ____ pol, and it is _____ spectrum (acts on both Gram + and -). This is one of the drugs that can accumulate and have effective concentrations in the ______ (so what does it cross?)
Use of Rifampin colors all bodily excretions ____-___.
Keep in mind Rifampin may induce the CytP___ system, enhancin the metabolism of co-administered drugs.
RNA pol
Broad
CNS
Crosses the BBB
Orange-red
CytP450
Pyrazinamide is a bacteriocidal drug effective against _______-phase (Lag, Log, Stationary, or Death phase?) bacteria. Its mech of action is not well understood. This drug is especially good at crossing the _____, so it is effective for treating Mtb meningitis.
Stationary
BBB
Ethambutol is the only one of the front-line drugs that is bacterio_____. Like Isoniazid, it inhibits ____ ____ synthesis, and like ALL front-line drugs, it is _______ bioavailable.
Adverse effects of Ethambutol are vision related. It can cause _____ blindness and optic neuritis, so it is contraindicated in children under ___ years old.
BacterioSTATIC
Cell Wall
Orally bioavailable
Color blindness
6 years old
MDR TB is considered resistant to at least ____ (the drugs used in the 4 month segment of standard treatment.) So, which front-line drug might still be an option?
RI (Rifampin and Isoniazid)
Pyrazinamide might still be an option.
Thioamides are among the second-line drugs used to treat MDR TB. Ethioamide and prothioamide are in this class, and they act in the same way as _______ and are also ______ bioavailable. The difference is that they do not require activation by Mtb enzyme KatG.
Isoniazid
Orally
All the Fluoroquinolones have the “_____” suffix!! They are bacterio_____ drugs that inhibit DNA _______ II (aka gyrase) –> the eukaryotic homolog of this enzyme is 100-1000 times less sensitive. These are orally bioavailable drugs that are _____ spectrum (active against both Gram + and -).
Oxacin
Bacteriocidal
DNA Topoisomerase II (aka gyrase)
Broad spectrum
Polypeptide class of TB drugs include Capreomycin. It is NOT ______ bioavailable, so how is it administered?
NOT Orally, so parenteral (injected)
Aminoglycosides are also used as a second-line drug for TB (streptomycin is among them). They bind to and inhibit the _____S subunit of RNA –> so inhibit _____ synthesis. They are mostly used for AEROBIC, Gram - bacteria. These drugs can cause ___toxicity.
30S
Protein Synth
Ototoxicity
Diarylquinolines are another second-line class for TB treatment. _____ is among this class. They act by inhibiting ____ synthase, so no energy for the cell. These drugs are limited to use in ____ (adults or children with TB?) and can cause Prolonged ____ syndrome (heart problems). These drugs are ______ bioavailable.
Bedaquiline
ATP
Adult TB
Prolonged QT
Orally
Pretomanid is also a second-line drug for TB treatment. It is _____ bioavailable and acts by releasing ____ and inhibits mycolic acid synth.
Orally
NO
