Metronidazole

Question 1

MOA

Answer 1

damage bacterial DNA (inhibit nucleic acid synthesis) and subsequently cause cell death – metronidazole is rapidly bactericidal in a concentration-dependent manner.

towards anaerobic and microaerophilic bacteria is due to the presence of electron transport components such as ferredoxins within these bacteria. Ferredoxins are small Fe-S proteins that donate electrons to metronidazole to form a highly reactive nitro radical anion.

Question 2

MOR

Answer 2

resistance relatively uncommon

1. Altered growth requirements – organism grows in higher local oxygen concentrations causing decreased activation of metronidazole and futile recycling of the active drug

2.Altered levels of ferredoxin – reduced transcription of the ferredoxin gene

Question 3

Spectrum of activity

Answer 3

Gram-Negative Anaerobes – highly active against cocci and bacilli
Bacteroides fragilis
Bacteroides distasonis, ovatus, thetaiotamicron, bivius (B. fragilis group DOT organisms)
Fusobacterium
Prevotella spp. and Veillonella spp.
Helicobacter pylori (an obligate anaerobe)

Gram-Positive Anaerobes – active against cocci (variably) and sporulating bacilli
Clostridium spp. (INCLUDING Clostridium difficile*)Peptostreptococcus

Other organisms
Trichomonas vaginalis
Entamoeba histolytica
Giardia lamblia
Gardnerella vaginalis

Question 4

Absorption

Answer 4

Metronidazole is rapidly and almost completely absorbed (F = 90 to 100%) after oral administration, achieving peak concentrations within 0.25 to 3 hours.

2.Food does not affect the absorption of metronidazole, but may delay the Tmax.

Question 5

Distribution

Answer 5

Metronidazole is well distributed into body tissues and fluids, including vaginal secretions, seminal fluids, saliva, and breast milk. Repeated dosing results in some accumulation of the drug.

2. Metronidazole DOES penetrate into the CSF and brain tissue

Question 6

Elimination

Answer 6

Metronidazole is metabolized by the liver to several active metabolites; accounting for over 50% of the systemic clearance of metronidazole.

2. Metronidazole and its metabolites are primarily excreted in the urine; only 10% is recovered as unchanged drug in the urine; 6-15% of a dose is excreted in the feces.

Question 7

Adverse effects

Answer 7

1. Gastrointestinal - N/V/D, METALIC TASTE
2. Central nervous system - peripheral neuropathy
3. Mutagenicity and carcinogenicity
   - Metronidazole may be teratogenic – should be avoided during the first trimester and during breastfeeding (Pregnancy Category B)

Question 8

IX. DRUG INTERACTIONS

Answer 8

Warfarin- Increased anticoagulant effect
Alcohol - Disulfiram reaction