The actual disulfiram-alcohol reaction is caused by inhibition of hepatic aldehyde dehydrogenase and build up of acetaldehyde after ingestion of alcohol. At the same time, this potential reaction is included as a precaution in the drug insert and is commonly discussed with patients by prescribers. There are case reports that when metronidazole was mixed with alcohol it led to a disulfiram-like reaction, including flushing, nausea/vomiting, and headaches, though the level of evidence of supporting the existence of this association is limited. This leaves aerobic cells utilizing PDC (e.g., human cells) unaffected. In effect, PFOR converts metronidazole into a DNA-damaging toxin, but only does so in anaerobes that utilize PFOR. Metronidazole then accumulates electrons, forms superoxide anions, damages DNA, and kills the organism. Here’s the key: metronidazole acts as a target for PFOR and gets reduced, effectively activating the drug. They still convert pyruvate to acetyl-CoA but they use a different enzyme called pyruvate:ferredoxin oxidoreductase ( PFOR), which catalyzes a red-ox reaction that moves electrons around. Acetyl-CoA then then goes into the Krebs Cycle and ultimately generates ATP.Īnaerobic bacteria and parasites have a completely different mechanism for processing pyruvate.
Homo sapiens or aerobic bacteria) use the pyruvate dehydrogenase complex ( PDC) to convert pyruvate to acetyl-CoA. In particular, one must understand the different ways that aerobes and anaerobes metabolize pyruvate.Īerobes (e.g. Pyruvate metabolism is key to understanding metronidazole’s mechanism of action. In a way, metronidazole is a remarkably selective drug, treating only anaerobic organisms. But, it is also used to treat anaerobic parasites like Entamoeba histolytica and giardia. It is bactericidal against anaerobic bacteria (includes gram positives and gram negatives) as well as microaerophilic bacterial like Helicobacter pylori. Metronidazole is interesting in that it treats BOTH bacteria and parasites (trimethoprim-sulfamethoxazole is another example). It then became widely used as an antibiotic to treat anaerobic bacterial infections. Only in the 1970s was it noted to be active against Bacteroides fragilis. Metronidazole was developed in the 1950s to treat the parasite trichomonas and then was used in the 1960s to treat other parasitic infections, like giardia and amoebiasis. #tweetorial #medtwitter /IewcNO2hYF- Avraham Z. The answer may also explain the infamous disulfiram-like reaction that can occur when metronidazole is mixed with alcohol.
Ever wonder why metronidazole (Flagyl) treats both bacteria and parasites?
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