Metronidazole Flashcards
Metronidazole is bactericidal/bacteriostatic
bactericidal
Metronidazole structure
nitroimidazole, heterocyclic; imidazole based nucleus with a nitro group
Metronidazole MOA
- drug enters bacterial cell by passive diffusion
- electron is transferred to the nitro group of metronidazole and results in production of short-lived nitroso free radical, which is cytotoxic and can interact with cellular DNA
- produces cytotoxic effect of reduced product because the activated metronidazole compound can inhibit DNA synthesis and induce DNA damage via oxidation, resulting in single-strand double-straw breaks
- induces DNA degradation and cell death. finally there is the release of inactive end products of the drug.
Metronidazole is activated in _____ when it recipes an electron from ____ or ____
anaerobic bacteria; ferredoxin; flavodoxin
Aerobic bacteria are _____ to activate prodrug because
unable; they lack necessary electron transport proteins with sufficient negative redox potential
Metronidazole spectrum coverage
ANAEROBES ONLY
light purple: prevotella
dark red: bacteroides, clostridium
light red: fusobacterium
Metronidazole is available in these formulations:
oral capsules, tablets, IV solution, topical gels, creams, lotions and vaginal gels
Metronidazole needs/does not need renal adjustment t
does not
When should metronidazole be adjusted for hepatic impairment?
severe hepatic impairment; give 50% dose
Metronidazole oral absorption
really good 98-100%
Metronidazole 1/2 life
8 hours; long
Metronidazole is ____protein bound
<20%
Metronidazole volume of distribution
adult: 0.55 L/kg
neonatesL 0.54-0.81 L/kg
Metronidazole is metabolized by
oxidation, glucoronidation, by CYPs and yield 5 major metabolites which are excreted in the urine and feces
Metronidazole indications
Parasitic infections: trichomonas vaginalis, giardia, entamoeba histolytica
anaerobic infections: brain abscess, gynelogic, bacteremia, bone and joint, respiratory, intra-ab, lung abscess/nectrotizing pneumonia
C. diff: no longer recommended by IDSA as first line treatment for mild infections due to concern for failure
H.pylori: increasing resistance, part of a combo of 3-4 drugs
Metronidazole adverse effects
nausea, diarrhea, dry mouth, metallic taste, candidate vaginitis, stomatitis
CNS effects
peripheral neuropathy with prolonged use and is reversible
Metronidazole precautions
disulfiram-like reaction following consumption of alcohol
- flushing, hypotension, tachycardias, nausea
- hold metronidazole for 48 hours
- may occur with all routes of administration
pregnancy and lactation
- not associated with fetal harm and recommended doses
- it is secreted into breast milk but doses in breast milk are about 1/5 of that in plasma
- if giving larger doses (2g) defer breastfeeding for 12-24 hours
Tissue penetration
CSF (inflamed) =serum concentrations CSF (not inflamed)= 45% of serum concentration bile= serum epithelial lining fluid= serum peritoneal fluid= high pancreatic fluid= high
Metronidazole mechanisms of resistance in bacteroides strains
not common
Bacteroides use the ____ to induce reduction of nitrate residue of metronidazole into an inert amino acid derivative without and toxicity for bacterial chromosome
nim gene
Clostridiodes resistance is due to several alterations in yet-to-be defined ____, such as those involving the activity of nitroreductases, iron uptake, and DNA repair
metabolic pathways
