Side-effects of Metronidazole

Metronidazole is a nitroimidazole drug similar to tinidazole. It has the chemical formula 1-(2-hydroxyethyl)- 2-methyl-5-nitroimidazole (C6H9N3O3) and a low molecular weight of 171.15 kDa. Following the discovery that azomycin, a nitroimidazole drug isolated from a Streptomyces species, was weakly active against Trichomonas vaginalis, many similar drugs were synthesized at Rhone-Poulenc Research Laboratories in France.

Mechanism of action

Metronidazole is a prodrug that diffuses into the cell and in the low redox potential environments of anaerobic bacteria and protozoa. It is activated by reduction (i.e. acceptance of electrons) of its nitro group. This process occurs as a single reduction step and involves the transfer of one electon. The source of electrons is the pyruvate oxidase or POR complex, which decarboxylates pyruvate, generating electrons that are passed onto ferredoxin and flavodoxin. 

Metronidazole is activated by accepting electrons from reduced ferredoxin or flavodoxin. This biochemical reaction probably creates a gradient which promotes further uptake of the drug into anaerobic organisms. A product of metronidazole reduction, likely the anionic nitro radical, interacts with DNA and produces cell death. Sigeti et al. showed that metronidazole was rapidly bactericidal against B. fragilis by an immediate inhibition of DNA synthesis.

Uses

Metronidazole is primarily used to treat: bacterial vaginosis, pelvic inflammatory disease (along with other antibacterials like ceftriaxone), pseudomembranous colitis, aspiration pneumonia, rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung abscess, periodontitis, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused by susceptible anaerobic organisms such as Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus, and Prevotella species.It is also often used to eradicate Helicobacter pylori along with other drugs and to prevent infection in people recovering from surgery.

Metronidazole is bitter and so the liquid suspension contains metronidazole benzoate. This may require hydrolysis in the gastrointestinal tract and some sources speculate that it may be unsuitable in people with diarrhea or feeding-tubes in the duodenum or jejunum.

Side-effects

Gastrointestinal side-effects 

Metronidazole has been occasionally associated with an unpleasant metallic taste in the mouth, a furred tongue, nausea (rarely vomiting), and abdominal pain. Doses as high as 180 mg/kg body weight per day, when used in oncology patients as an adjunct to radiotherapy, produced slight nausea; higher doses of up to 300 mg/kg body weight per day were progressively less well tolerated and produced severe anorexia, nausea, and vomiting, which often persisted for 24–48 h after the last dose. Pseudomembranous colitis due to C. difficile which was susceptible to metronidazole has been described in a patient in association with metronidazole administration as the sole antimicrobial. 

Hematologic effects 

A transient and reversible neutropenia has been occasionally observed during metronidazole therapy.