Fluoroquinolones + Metronizadole Flashcards
Name some fluoroquinolones (4):
Ciprofloxacin
Levofloxacin
Moxifloxacin
Gemnifloxacin
Fluoroquinoloes: MOA
Inhibits DNA synthesis
Targets two enzymes:
- DNA gyrase (topo II) - mostly for gram neg
- DNA Topo IV - mostly for gram positive
Concentration-dependent
bacteriCIDAL
By binding these enzymes, it prevents them from maintaining DNA in the appropriate DNA state of supercoiling in both replicating and non-replicating regions
Action at DNA gyrase:
- prevents relaxation req for normal transcription/translation/replication thus halting DNA rep
Action at Top IV:
- interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division
Fluoroquinoloes: Mechanism of Resistance
Three major MXNS of resistance:
1. Altering binding sites
chromosomal mutations in genes that code
for the topoisomerase decreases binding
affinity of FQ to target site
2. Expression of active efflux pumps
enhances transfer OUT of FQs
3. Altered cell wall permeability
chrom mutation that decrease expression of
porins
plus some plasma mediated resistance
*cross-resistance observed in FQs
Fluoroquinoloes: Spectrum of Activity OVERALL
Gram +, Gram -, anaerobes and atypical
Gram +
- MSSA, PRSP, Strep pneumo
- Levo or Moxi NOT: Cipro*
Gram -
**Pseudomonas (Cipro>Levo NOT moxi, gent)
Enterobacteriae (Cipro & Levo»_space;»moxi)
Anaerobes
b. fragilis
Atypical
Legionella
Chlamydiaphilia, chlamydia, mycoplasma, ureaplasma
Others:
M. Tb
B. anthracis
Fluoroquinoloes: Clinical Use (7+)
Community acquired pneumo Acute exacerbations of chronic bronc/sinu Bacterial-ex in Cystic Fibrosis pts nosocomial pneumonia UTIs Chronic bacterial prostatitis Bone/osteomyelitis
Other: intra-abdominal infections, travelers’ diarrhea, TB, STDS
Fluoroquinoloes: AEs (2 big + 3 impt)
- GI - N/V/D, dyspepsia, C. DIFF COLITIS
- CNS - h/a, dizziness, confusion, agitation, insomnia, rare-hallucinations, seizures
Hepatotoxicity
- increases transanimase
Cardio-
- prolongs QTc (can lead to torsades)
- Articular damage
- caution with patients in other concominant drugs, and those who have HYPOkalemia
Arthropathy
Affects tendons - rupture or tendonitis
Other: hypersensitivity, rash
**Contraindicated in: Old, pregnant, kids, **
Fluoroquinoloes: Drug Interactions ( min 4)
“WTC”
Warfarin, increases conc
Theophyline (cipro only, increases conc)
Cyclosporine (cipro only, increases conc)
Not recommended to intake with divalent and trivalent cations, zinc, iron, calcium, mg, and antiacids, ddI, enteral feeds
–> can impair absorption of any FQ taken orally via chelation and cause clinical failure
Fluoroquinoloes: Pharmocology
Absorption: good overall
Distribution: good
- Urine and Prostate (Cipro and Levo)
- CNS MOXI
- Lungs, bones, alveolar macrophages, some cool fluids - saliva, speutum, bile, mucosa + SST
Elimination: Renal + Hepatic Renal - levo **adjust for RI** Hepatic - moxi Both hepatic + renal - cipro and gemi *Adjust only for RI*
NOT removed by HD
Fluoroquinoloes: Pharmacokinetics
Displays PAE
about 2 hours for gram +
about 2-4 hours for gram -
PIC/MIC approx. clinical efficacy
AUC/MIC
30-50 S. Pneumo
100-125 gram -
Fluoroquinoloes:
Spectrum of Activity (3) + clinical use (6)
Ciprofloxacin
Spectrum of Activity:
YES: gram - and atypical bacteria, PSEUDO
NO: gram positive, anaerobic
Clinica Use:
- UTI
- health-care associated pneumonia (BEST!)
- Travelers diarrhea/E.Coli ONLY ONE
- Prostatitis
- Osteomyelitis
- intra-abdominal infections (with metro)
Fluoroquinoloes:
Spectrum of Activity (4) + clinical use (7)
Levofloxacin
Spectrum of Activity:
YES: gram -, gram +, atypical, pseudo
NO: anaerobic
Clinical Use:
- UTI
- HCAPneumonia
- CApneumonia
- M.TB
- Prostatitis
- Osteomyelitis
- intra-abdominal infections (with metro)
Fluoroquinoloes:
Spectrum of Activity (4) + clinical use (5)
Moxifloxacin
Spectrum of Activity:
YES: gram -, gram +, anaerobic (ONLY FQ), atypical
NO: pseudo
Clinical Uses:
- CSF (ONLY FQ)
- CApneumo
- M. TB
- Osteomyelitis
- intra-abdominal infection (+metro)
Fluoroquinoloes:
Spectrum of Activity (3) + clinical use (1)
Gemifloxacin
Spectrum of Activity:
YES: gram +, gram -, atypical
NO: pseudo, anaerobic
Clinical Uses:
CA-pneumonia
Major advantages of FQs:
Broad activity
excellent oral availability
extensive tissue penetration
rel. long serum half lives
disadvantage: increasing resistance
Metronidazole: MOA
- inhibits DNA synthesis *
Prodrug, becomes activated when it is reduced by ferredoxins, which in the process of donating electrons, itself (ferre), becomes a reactive NITRO ANION –> damages bacterial DNA, inhibits synthesis –> cell death
BacterioCIDAL
concentration-dependent
