Metronidazole

Question 1

Metronidazole is bactericidal/bacteriostatic

Answer 1

bactericidal

Question 2

Metronidazole structure

Answer 2

nitroimidazole, heterocyclic; imidazole based nucleus with a nitro group

Question 3

Metronidazole MOA

Answer 3

1. drug enters bacterial cell by passive diffusion
2. 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
3. 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
4. induces DNA degradation and cell death. finally there is the release of inactive end products of the drug.

Question 4

Metronidazole is activated in _____ when it recipes an electron from ____ or ____

Answer 4

anaerobic bacteria; ferredoxin; flavodoxin

Question 5

Aerobic bacteria are _____ to activate prodrug because

Answer 5

unable; they lack necessary electron transport proteins with sufficient negative redox potential

Question 6

Metronidazole spectrum coverage

Answer 6

ANAEROBES ONLY

light purple: prevotella
dark red: bacteroides, clostridium
light red: fusobacterium

Question 7

Metronidazole is available in these formulations:

Answer 7

oral capsules, tablets, IV solution, topical gels, creams, lotions and vaginal gels

Question 8

Metronidazole needs/does not need renal adjustment t

Answer 8

does not

Question 9

When should metronidazole be adjusted for hepatic impairment?

Answer 9

severe hepatic impairment; give 50% dose

Question 10

Metronidazole oral absorption

Answer 10

really good 98-100%

Question 11

Metronidazole 1/2 life

Answer 11

8 hours; long

Question 12

Metronidazole is ____protein bound

Answer 12

<20%

Question 13

Metronidazole volume of distribution

Answer 13

adult: 0.55 L/kg

neonatesL 0.54-0.81 L/kg

Question 14

Metronidazole is metabolized by

Answer 14

oxidation, glucoronidation, by CYPs and yield 5 major metabolites which are excreted in the urine and feces

Question 15

Metronidazole indications

Answer 15

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

Question 16

Metronidazole adverse effects

Answer 16

nausea, diarrhea, dry mouth, metallic taste, candidate vaginitis, stomatitis

CNS effects

peripheral neuropathy with prolonged use and is reversible

Question 17

Metronidazole precautions

Answer 17

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

Question 18

Tissue penetration

Answer 18

CSF (inflamed) =serum concentrations
CSF (not inflamed)= 45% of serum concentration
bile= serum 
epithelial lining fluid= serum
peritoneal fluid= high
pancreatic fluid= high

Question 19

Metronidazole mechanisms of resistance in bacteroides strains

Answer 19

not common

Question 20

Bacteroides use the ____ to induce reduction of nitrate residue of metronidazole into an inert amino acid derivative without and toxicity for bacterial chromosome

Answer 20

nim gene

Question 21

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

Answer 21

metabolic pathways