Week 4 - Nucleic Acid Inhibitors Flashcards
What is the mechanism of action for Rifampin?
bactericidal – binds RNA pol at the active center, blocks elongation
What is Rifampin used to treat?
TB
What drug has the side effect of turning body fluids orange-red?
Rifampin
Why would Rifampin not be prescribed for someone who is taking organ rejection meds?
induction of Cyp450 enzyme can induce metabolism of other drugs at higher rate, leading to lower drug amounts in your system
How does impaired liver function lead to higher blood levels of Rifampin?
no deacetylation –>Rifampin remains hydrophobic–>decreased excretion through feces–>build up in blood
What is the mechanism of action for Fidaxomicin?
bactericidal - inhibits RNA pol
What is the spectrum for Fidoxamicin?
narrow, Gram + anaerobes (C. diff)
Why is Fidoxamicin used to treat C. diff?
low absorption
What are the fluoroquinolones?
Ciprofloxacin, levofloxacin, moxifloxacin
What is the mechanism of action for the fluoroquinolones?
Bactericidal – bind topo II and IV
What is the spectrum for Fluoroquinolones?
broad, Gram+ and Gram -
Mycoplamsa, hospital acquired Pneumonia
Resistance of Fluoroquinolones:
overprescribed for UTIs, resp, and acute GI infections
- active efflux of drug
- mutations in Topo
Which topo inhibition strategy is most important for each of the classes of bacteria?
Topo II (gyrase)- Gram - Topo IV - Gram +
How do fluoroquinolones lead to cell death?
cause dsDNA breaks
What are a few adverse effects for fluoroquinolones?
arthropathy (don’t use with kids or prego)
confusion and photosensitivity
C. diff, fungal infections
What shouldn’t be consumed with fluoroquinolones?
calcium, ion, aluminum, zinc because they can prevent drug absorption by binding drug
-avoid milk, fortified juice
What is the general mechanism of action for Sulfonamides and Trimethoprim?
indirect inhibition of DNA synthesis by blocking dihydrofolic acid synthesis
What is the mechanism of action for sulfamethoxazole?
bacteriostatic - it is a PABA analog, acts as a competitive inhibitor for Dihydropteroate synthetase
Adverse effects of Sulfonamides:
Hypersensitivity (Stevens-Johnson), crystalluria, hemolysis if G-6-P dehydrogenase deficient, Kernicterus (jaundice in newborns)
Mechanism of action for Trimethoprim:
bacteriostatic - inhibits dihydrofolate reductase (low affinity for mammalian)
What is the sequential blockade used to treat UTIs and Pneumocystis?
TMP-SMX = Bactrin
- blocks folate synthesis twice to be bactericidal
- don’t use with sulfa allergy
What is the mechanism for Metronidazole/tinidazole?
bactericidal - drug is reduced to generate free radicals that lead to DNA strand breaks and cell death
Spectrum fro Metronidazole:
anaerobic, includes C. diff and Protozoa
What is a unique side effect of Metronidazole?
disulfiram-like rxn when taken with alcohol – it blocks ALDH
**avoid with prego
Why doesn’t metronidazole work on aerobes?
metro needs reduced form of ferredoxin
-aerobes have mostly oxidized ferredoxin
Mechanism of Nitrofurantoin:
bactericidal – drug is reduced by flavoproteins to reactive intermediates –>alters/inactivates ribosome
-inhibits DNA, RNA, cell wall, and protein synthesis
What is the spectrum for nitrofurantoin?
broad, rapidly excreted in active form so used primarily for UTIs
Resistance mechanisms for nitrofurantoin:
none known right now – blocks many vital processes
What would be the best empiric treatment for a patient showing symptoms of UTI?
TMP/SMX
What drugs will have increased efflux as the resistance mechanism?
Fluoroquinolones, Sulfonamides
What drugs will have decreased uptake as the resistance mechanism?
Sulfonamides
What drugs will have an altered target as the resistance mechanism?
Rifampin, Fluoroquinolones, Sulfonamides, Trimethoprim
