Metronidazole

Question 1

MOA

Answer 1

Prodrug activated by ferredoxins whose activated metabolites damage bacterial DNA

Bactericidal->Concentration-dependent

Question 2

MOR

Answer 2

Altered growth requirements

Altered levels of ferredoxin–>reduced transcription of the ferredoxin gene

Question 3

Spectrum of activity

Answer 3

Gram (-) anaerobes–>highly active
- Bacteroides fragilis (B.fragilis group DOT organisms)

Gram (+) anaerobes–> C. DIFF

Question 4

Absorption

Answer 4

Rapidly and completely absorbed after oral administration (F=90-100)

Question 5

Distribution

Answer 5

Well distributed into tissues and fluids

DOES penetrate into the CSF and brain tissue

Question 6

Metabolism/excretions

Answer 6

Metabolized by liver to several active metabolites; primarily excreted by the urine

6-15% of a dose is excreted in the feces

The t1/2 is prolonged in the presence of renal or hepatic dysfunction, dose adjustments are required

Removed during hemodialysis

Question 7

Clinical uses

Answer 7

Infections due to anaerobes–>polymicrobial and additional antibiotics are necessary for coverage of aerobic bacteria

Typical adult dose is 500 mg every 6 hours, maximum dose is 4 grams daily

C. diff

Trichomonas vaginalis

Question 8

Adverse effects

Answer 8

GI–> nausea, diarrhea, anorexia, metallic taste

CNS–> peripheral neuropathy

Teratogenic (Pregnancy category B)

Question 9

Drug interactions

Answer 9

Warfarin

Alcohol