The pharmacological action of Metronidazole is reflected in a selective toxicity to anaerobic or microaerophilic microorganisms and for anoxic or hypoxic cells. The nitro group of Metronidazole accepts electrons from electron transport proteins such as flavoproteins in mammalian cells and ferredoxins or their equivalent in bacteria and diverts them from normal energy yielding pathways. In the former case a nitro reductase catalyses the reaction of the flavin radical with the nitro compound. In the latter case, the reduction is catalysed by iron sulfur complexes.
Chemically reactive reduced forms of the drug lead to the formation of cytotoxic products that destroy the cell. The drug inhibits DNA synthesis in vaginalis and Clostridium bifermentans and causes degradation of existing DNA in the latter microorganism. Mammalian DNA indicates that reduced Metronidazole causes a loss of the helico structure of DNA, strand breakage and an accompanying impairment of its function. Metronidazole has antiprotozoal and antibacterial actions and is effective against Trichomonas vaginalis and other protozoa including Entamoeba histolytica, Giardia lamblia and against anaerobic bacteria.
Metronidazole is rapidly absorbed after oral administration with peak plasma concentrations occuring between 20 minutes and 3 hours post dose. Metronidazole is widely distributed in body tissues. The plasma half-life is of the order of 8.5 hours with at least half the dose being excreted in the urine as metabolites Metronidazole can be used in chronic renal failure; it is rapidly removed from the plasma by dialysis. Metronidazole diffuses across the placenta and is excreted in breast milk with levels equivalent to those seen in serum.
Metronidazole is indicated for the prevention of postoperative infections due to anaerobic bacteria, particularly species of bacteroides and anaerobic streptococci.
Metronidazole is indicated for the treatment of established anaerobic infections (septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis and post-operative wound infections from which pathogenic anaerobes have been isolated); urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male; bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginosis or Gardnerella vaginitis); all forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers); giardiasis; acute ulcerative gingivitis; anaerobically-infected leg ulcers and pressure sores; acute dental infections (e.g. acute pericoronitis and acute apical infections).
Metronidazole may cause nausea, vomiting, unpleasant taste,, furred tongue and gastrointestinal disturbances, urticaria, skin rashes, pruritus, angioedema and darkening of urine. Metronidazole may also cause dizziness, drowsiness, ataxia, headaches and incordination of movement.
Prolonged therapy may cause peripheral neuropathy or transient epileptiform seizures.
Known hypersensitivity to Metronidazole Tartrazine (E102) and sunset yellow (E110) may cause allergic reactions.
Hepatic impairment, pregnancy and breast-feeding, and renal failure. Anticoagulants prolong therapy therefore patients on anticoagulants require clinical check-ups. Alcohol should be avoided.
Dosage and administration
Megyl suspension should be taken at least one hour before a meal. Megyl tablets should be swallowed with water. It is recommended that the tablets should be taken during or after a meal.
Treatment of anaerobic infections:
Adults: 800mg initially followed by 400mg every 8 hours for 7 days.
Children: 7.5mg/kg every 8 hours for 7 days
Prevention of post-operative anaerobic bacterial infections:
400mg every 8 hours in the 24 hours before surgery followed post operatively by intravenous or rectal administration until oral therapy is possible
To be taken 5-10 days
Adults: 400-800mg three times a day. Or an alternate dose is 1.5 to 2.5g as a single dose daily for 2 or 3 days.
7-10 years: 200-400mg three times a day
3-7 years: 100-200mg three times a day
1-3 years: 100-200mg three times a day
To be taken daily as a single dose daily for 3 days
7-10 years: 1g
3-7 years: 600-800mg
1-3 years: 500mg
Adults: 2g as a single dose or 800mg in the morning and 1.20g in the evening for 2 days or 600mg-1g daily in two or three divided doses for 7 days. Sexual partners should be treated concomitantly.
Children: to be taken for 7 days
7-10 years: 100mg three times a day
3-7 years: 100mg two times a day
1-3 years: 50mg three times a day
It is treated similarly to vaginal trichomoniasis with which it may co-exist: Metronidazole is usually given by mouth as a single dose 2g dose or 400-500mg twice daily for 7 days.
Adults: 200mg 3 times a day for 3 days
Adults: 200mg, 3 times a day for 3 days
For leg ulcers and pressure sores
Adults: 400mg 3 times a day for 7 days
Patients should be advised not to take alcohol during therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effects) reaction. Psychotic reactions have been reported in patients who were using Metronidazole and disulfiram concurrently.
Patients receiving phenobarbital or phenytoin metabolise Metronidazole at a much greater rate than normally, reducing the half-life to approximately 3 hours.