In this article we will discuss about:- 1. Structure of Metronidazole 2. Mechanism of Action of Metronidazole 3. Adverse Effects.
Structure of Metronidazole:
Metronidazole is a nitroimidazole, the class of therapeutic drugs used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa.
Metronidazole (1-(β-hydroxyethyl)-2-methyI-5-nitroimidazole), the chemical structure of which is given in Fig. 45.17 and the chemical formula is C6H9N3O3, was determined to be therapeutic against Trichomonas vaginalis and Entomoeba histolytica following its discovery in the late 1950s.
Later in 1962 Darbon et al. reported that it could be used to treat giardiasis, a diarrhoeal disease, caused by Giardia lamblia. Metronidazole is marketed under the trade name Flagyl. It is also used in the treatment of the dermatological condition rosacea, where it is marketed under the trade names Rozex and MetroGel.
Metronidazole is quickly and completely absorbed after oral administration and penetrates body tissues and secretions such as saliva, breast milk, semen, and vaginal secretions.
The drug is metabolized mainly in the liver and is excreted in the urine. Metronidazole is selectively taken up by anaerobic bacteria and sensitive protozoal organisms because of the ability of these organisms to reduce metronidazole to its active form intracellularly.
Mechanism of Action of Metronidazole:
The mechanism of action of metronidazole has been thoroughly studied, particularly in Giardia—the cause of giardiasis. The drug enters the pathogen, and once it is within the pathogen, electron transport protein ferredoxin from the pathogen donates electrons to the nitro group of the drug.
The drug becomes “activated” by reduction of this nitro group and a gradient favouring the intracellular transport of metronidazole is established in this reduction reaction. Reduced metronidazole serves as a terminal electron acceptor which binds covalently to DNA molecule.
This results in DNA damage in the form of loss of helical structure, impaired template function, and strand breakage, with subsequent death of the pathogen. In addition to this effect, metronidazole inhibits pathogen’s respiration. The reductive activation of metronidazole may also need to toxic radicals, which react with essential cellular components of the pathogen.
Adverse Effects of Metronidazole:
Common adverse effects (≥ 1% of patients) of metronidazole therapy include nausea, diarrhoea, and/or metallic taste. Intravenous administration of drug is commonly associated with thrombophlebitis.
In frequent adverse effects include hypersensitivity reactions (rash, itch, flushing, fever), headache, dizziness, vomiting, etc. International Agency for Research on Cancer (IARC) has listed metronidazole as a potential human carcinogen.
Although some of the testing methods have been questioned, it has been demonstrated to cause cancer in experimental animals. Nevertheless, metronidazole appears to possess a fairly low potential for cancer risk and under most circumstances the benefits of treatment outweighs the risk.