Metronidazole Flashcards
What is the mechanism of action of metronidazole?
Metronidazole is a prodrug that, in anaerobic environments, is reduced by bacterial/protozoal ferredoxin to reactive metabolites. These metabolites damage DNA through strand breakage and destabilization, leading to cell death (bactericidal).
Describe the antimicrobial spectrum of metronidazole.
Metronidazole is active against anaerobic bacteria (Bacteroides, Clostridioides difficile, Clostridium perfringens, etc.) and certain protozoa. It treats anaerobes ‘below the diaphragm’ (intra-abdominal infections) and protozoal parasites such as Giardia, Entamoeba histolytica, Trichomonas vaginalis. Also used for Gardnerella vaginalis and part of H. pylori combination therapy.
How can organisms develop resistance to metronidazole?
Resistance is uncommon, but can occur if organisms decrease production of the activating enzymes or have altered ferredoxin (reducing activation of the drug). Some H. pylori and Trichomonas strains have developed metronidazole resistance via these mechanisms.
Outline key pharmacokinetic features of metronidazole.
Metronidazole is well absorbed orally and distributes widely, including into the CNS (effective for brain abscesses). It is metabolized in the liver (via CYP450 oxidation and glucuronidation) and metabolites are excreted in urine (which may cause a harmless brownish coloration). It has a relatively short half-life (~8 hours) and is often dosed 2-3 times a day.
What major drug interactions are associated with metronidazole?
Metronidazole has a disulfiram-like effect: if combined with alcohol, it can cause flushing, tachycardia, nausea, vomiting. It may potentiate warfarin’s anticoagulant effect by inhibiting warfarin metabolism (CYP2C9). Also, concurrent use with lithium can raise lithium levels. Patients should avoid alcohol during therapy and up to 48 hours after.
What are common clinical indications for metronidazole?
Metronidazole is first-line for mild to moderate C. difficile infection. It’s also used for anaerobic infections like intra-abdominal abscesses, anaerobic periodontal infections, and aspiration pneumonia (often combined with a drug covering aerobes). It treats protozoal infections: trichomoniasis (both patient and partner), giardiasis, and amebiasis (Entamoeba). In combination therapy, it’s part of H. pylori treatment (‘triple therapy’) and used for Gardnerella vaginalis (bacterial vaginosis).
When should metronidazole be avoided or used with caution?
Avoid alcohol use during and shortly after therapy (due to disulfiram reaction). Use with caution in early pregnancy (especially first trimester) – although evidence is mixed, it’s usually avoided in 1st trimester trichomoniasis. Reduce dose in severe liver impairment since it’s hepatically metabolized. Discontinue if neurological symptoms like peripheral neuropathy occur.
List major adverse effects of metronidazole.
Common side effects include a metallic taste, GI upset (nausea, cramping). It can cause headache, dizziness, and rarely peripheral neuropathy (especially with prolonged use). A disulfiram-like reaction occurs with alcohol (flushing, vomiting). Dark urine can also occur (harmless).
What mnemonic can help recall metronidazole uses?
‘GET GAP on the Metro’ – Giardia, Entamoeba, Trichomonas, Gardnerella, Anaerobes (below diaphragm, e.g., Bacteroides, C. diff), and Pylori (H. pylori). This summarizes major organisms treated by metronidazole.
