DNA Function Inhibitors Flashcards
Fluoroquinolones MOA
Targets bacterial DNA gyrase, which is needed for DNA unwinding and normal replication
Bactericidal
Fluoroquinolone Examples
Ciprofloxacin [Cipro] - urinary
Levofloxacin [Levoquin] - urinary/respiratory
Moxifloxacin [Alvelox] - respiratory
Fluoroquinolone Absorption
well absorbed orally
cipro and levo are availaible parenteral
Fluoroquinolone Distribution
Good penetration into most tissues, CNS if inflammed, highly concentrates in the urine
Fluoroquinolone metabolism/excretion
primarily renal excretion
“respiratory” quinolones
Levofloxacin
Moxifloxacin
Fluoroquinolone Use, gram + cocci
Strep. pneumoniae (pneumonia, bronchitis, acute sinusitis)
“respiratory quinolones”
MSSA (skin infections)
Fluoroquinolone use, gram - cocci
Moraxella catarrhalis (sinusitis, bronchitis) --> Levofloxacin
Fluoroquinolone use, gram - bacilli
Haemophilis Influenzae (lower respiratory tract infection, pneumonia) Pseudomonas aeruginosa E. Coli (UTI*)
Fluoroquinolone use, atypicals
[Moxifloxcin]
Chlamydia (trachoma, urethritis, CAP)
Mycoplasma pneumoniae (CAP)
Fluoroquinolone ADR
C. Diff Colitis - N/V/D
Possible tendon rupture, rare
Limited use in pregnancy and
Fluoroquinolone DDI
theophyline metabolism is reduced
antacids reduce ABX metabolism
Nitrofurantoin
Macrobid, Macrodantin
“urinary tract antiseptic” because concentrate highly in renal tubules. Plasma levels can’t get high enough safely to treat systemic infections
Nitrofurantoin MOA
Bacterial enzymes reduce the drug into intermediates that damage DNA. Humans dont reduce as quickly.
Bactericidal - concentration dependant
Nitrofurantoin pharmacokinetics
ABS by GI system very well
Excreted into urine, rate linearly related to renal function
Turns urine brown color
Nitrofurantoin uses in UTI
Second line - proteus and pseudomonas are resistant
Very effective against E. Coli though, can be used when patients are resistant to TMP/SMX
Metronidazole
[Flagyl]
Metronidazole MOA
Prodrug that is transformed into a highly reactive nitro radical by organisms, especially anaerobes and protozoa. The anion targets DNA and is bactericidal
Metronidazole Pharmacokinetics
Absorbed well PO
Distribution is wide, including CSF and bone
Hepatic metabolism - adjust dose in liver dz
COntraindicated in breast feeding moms
Metronidazole uses, anaerobes
Clostridium difficile
Bacteroides fragilis
Helicobacter pylori
Metronidazole uses, protozoa
Trichomonas vaginalis
Sulfonamides
Sulfamethoxazole
Sulfonamide MOA
Inhibitors of folic acid production via inibiting the enzyme dihydropteroate synthetase organisms must use to create folic acid.
Bacteristatic, folic acid stores must be used up by the organism before the drug’s effects kick in
Sulfonamide plus trimethoprim (TMP) MOA
Trimethoprim is a dihydrofolate reductase inhibitor. These together are synergistic, acting on two sequential steps of folinic acid synthesis. TMP is NOT a sulfonamide
Sulfamethoxazole (SMX) plus trimethoprim (TMP)
Bactrim or Septra…. abbreviated TMP/SMX
Sulfonamide ABS/distribution
Well absorbed on an empty stomach
Well distributed in body water. Displaces bilirubin bound to protein that can cause kernicterus in neonates
Sulfonamide met/excr
Deactivated via acetylation, then excreted in kidneys
Need to change the dose in renal failure
Sulfonamide uses - general
BROAD SPECTRUM ABX, seldom used in a single drug form due to resistance and the availability of less toxic drugs.
TMP/SMX used most commonly together
TMP/SMX use, gram + cocci
MRSA (community acquired skin infection)
TMP/SMX use, gram - bacilli
Klebsiella, proteus, enterobacter (uncomplicated UTI)
Pseudomonas
TMP/SMX use, atypicals
Chlamydia - trachoma, CAP, urethritis
