Good ol’ Metronidazole … friend or foe ?

Good ol’ Metronidazole … friend or foe ?

Metronidazole is a Nitroimidazole derivative that has been used as an antibacterial and antiprotozoal agent for more than 45 years. It was originally indicated for the management of infection caused by Trichomonas vaginalis but was then shown to be effective against other protozoal infections, such as amoebiasis and giardiasis.

The first report on the effect of metronidazole for the management of anaerobic infections was published in 1962 [Shinn], wherein acute ulcerative gingivitis was successfully treated by using metronidazole therapy. However, major advances were made by Tally et al at the Wadsworth Veterans Hospital in Los Angeles 10 years later; Tally and colleagues showed that metronidazole is useful in the treatment of systemic anaerobic infections, including those caused by Bacteroides fragilis. Later, metronidazole was introduced for the management of Clostridium difficile infection and is still recommended as an alternative to vancomycin for treatment of this infection. Treatment regimens for the eradication of Helicobacter pylori still include metronidazole in combination with other agents. Metronidazole is also indicated for the treatment of bacterial vaginosis caused by Gardnerella vaginalis. Despite 45 years of extensive use, metronidazole remains the criterion standard for the management and prophylaxis of anaerobic infections.

The efficacy of metronidazole against anaerobic bacteria can be explained by its mechanism of action where the nitro group of metronidazole reacts with ferredoxin present in anaerobic parasites to inhibit nucleic acid synthesis.

Metronidazole is absorbed by the small intestine, metabolised by the liver and excreted by the kidneys.

Why do I need to know about metronidazole?

  • Metronidazole is a hepatic enzyme inhibitor (CYP2C9). It can potentiate actions of local anaesthetics and induction agents. Lignocaine toxicity can occur in normal doses in patients on long term metronidazole.
  • Interacts with – alcohol, lithium, phenytoin, phenobarbitone, busulphan and warfarin.
  • Concurrent use of alcohol and metronidazole can produce a disulfiram-like reaction. Most manufactures advise abstinence from alcohol for 48 hours prior to consumption of alcohol.
  • Metronidazole increases the anticoagulant effect of warfarin.

Pharmacology: Remember “12Bs”

  • B : Basic formula – C6H9N3O3
  • B : Binding to protein – 20 per cent
  • B : Bioavailability – 80 per cent Oral, 60 per cent Rectal, 25 per cent Vaginal
  • B : Biological T1/2 – 8 hours
  • B : Blocker/ inhibitor of Liver enzymes
  • B : Biliary/ hepatic metabolites
  • B : Bactericidal
  • B: Breakage of DNA strands is the mechanism
  • B : Breakdown products in urine
  • B : Breast milk contain metronidazole
  • B : Beyond (post-antibiotic) effect up to 3 hours after concentration falls below MIC
  • B : Bio-active hydroxyl metabolites (30-65 per cent of parent compound)

 

Indications:

Remember “FLAGYL”

  • F : Fistulating crohn’s disease
  • L : Liver abscess
  • A : Anaerobes and protozoa
  • G : Giardiasis
  • Y : Yeast infections
  • L : Leg ulcers

 

Side Effects:

Side effects are not serious but the interaction with alcohol and some pharmacological agents could be life threatening. Also as a result of chronic metronidazole usage, drug toxicity could happen. To mention a few side effects, remember “FLAGYLEM

  • F : Furred tongue
  • L : Liver (hepatocellular) injury
  • A : Anorexia
  • G : GI – pancreatitis
  • Y : Yellow/ dark urine
  • L : Leucopenia/ pancytopenia
  • E : Ethanol + Metronidazole —Stomach upset

                                                              Sickness/ vomiting

Sweating

Skin flush

Shortness of breath

Sinus tachycardia

Seizures

  • M : Metallic taste

                  Meningitis (aseptic)

Monitoring required if used for long time.

 

Authors:

Dr.Sher Mohammad1 Dr.Prateek Verma2 Dr.Danish Siddiqi3

  1. Consultant anaesthetist
  2. MTI

Royal Hallamshire Hospital, STH Glossop Road Sheffield

  1. Clinical Fellow Anaesthetics, Sheffield Children Hospital.

Email:sher.mohammed@sth.nhs.uk

Phone:0114 2712381

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