Nucleic acid synthesis- individual facts Flashcards
Name the drugs that interfere with RNA polymerase
Rifampin, Fidaxomicin
Mechanism of Rifampin
Binds bacterial RNA pol at active center, blocks mRNA elongation
Spectrum of Rifampin
Mycobacterium tuberculosis (Treated with 4 total antibiotics)
Resistance to Rifampin
Intrinsic: Unable to bind to Beta subunit of RNA pol
Acquired: mutations in rpoB gene prevent binding
Side effects of Rifampin
Turns body fluids red/orange, Increased liver enzymes, GI upset
Mechanism of Fidaxomicin
Inhibits RNA pol
Spectrum of Fidaxomicin
C. diff, C. diff, C. diff, Gram+ anaerobes, Very narrow
Resistance to Fidaxomicin
Point mutation in RNA pol observed in vitro
Side effects of Fidaxomicin
very few due to low absorption
Name Fluoroquinolones
Ciprofloxacin, levofloxacin, moxifloxacin. FLOXACIN
Mechanism of Fluoroquinolones
Ciprofloxacin, levofloxacin, moxifloxacin
Binds topoisomerase which leads to DNA damage
Spectrum of Fluoroquinolones
Ciprofloxacin, levofloxacin, moxifloxacin
Broad, Gram+, Gram-, atypical organisms (Mycoplasma), Hospital-acquired pneumonia, UTIs
Resistance to Fluoroquinolones
Ciprofloxacin, levofloxacin, moxifloxacin
Active efflux of drug, changes in topoisomerase
Adverse effects of fluoroquinolones
Ciprofloxacin, levofloxacin, moxifloxacin
Gi, confusion, photosensitivity, C. diff colitis, Chelates Calcium, Iron, Aluminum and Zinc.
What is ciprofloxacin used for
intentionally spread diseases (biowarfare)
Mechanism of Sulfonamides
Folate antagonist, competes for active site of folate synthesis enzyme dihyropteroate synthetase
Spectrum of sulfonamides
Bacteria and fungi that synthesize their own FH2
Resistance to sulfonamides
Bacteria that uptake FH2, increase in PABA, increase in efflux of drug, change in the enzyme
Side effects of sulfonamides
Kernicterus, jaundice, complications with warfarin, hemolysis of G-6-p dehydrogenase deficiency
Mechanism of trimethoprim
Inhibits final step of FH2 synthesis
Resistance to trimethoprim
Altered enzyme, increased enzyme, alternative metabolic pathways
Side effects of trimethoprim
GI upset
Mechanism of action of Metronidazole and tinadazole
Acts as e- sink generating a free radical and leading to DNA damage
Spectrum of metronidazole and tinadazole
Protozoa, C. diff, anaerobic bacteria
Resistance to metronidazole and tinadazole
Down regulation of pyruvate:ferredoxin oxidoreductase, leading to decreased activation of drug
Side effects of metronidazole and tinadazole
Disulfiram-like reaction with EtOH, Nausea, diarrhea, headache, metallic tase
Other notes on metronidazole and tinadazole
Avoid during pregnancy, only anaerobic bacteria
Mechanism of Nitrofurantoin
Alters ribosomal proteins that inhibit synthesis of DNA, RNA, cell walls and proteins
Spectrum of action of nitrofurantoin
Broad, rapidly excreted in urine in active form
Resistance of nitrofurantoin
very rare since it affects so much
Side effects of nitrofurantoin
Vomiting and rash
Notes on nitrofurantoin
Only used for treating UTIs