Metronidazole is an antiprotozoal, antibacterial and antihelminthic nitroimidazole agent.
The chemical formula is C6H9N3O3 and the molecular weight is 171.2.
Metronidazole is reduced to disrupt energy metabolism of anaerobes by hindering the replication, transcription and repair process of DNA results in cell death. Presence of oxygen prevents reduction of metronidazole and so reduces its cytotoxicity.
Plasma concentration and clearance of metronidazole is dose dependent. Reddish brown discoloration of urine in some patients may be due to the presence of unidentified pigments derived from the drug.
Metronidazole is active against T.vaginalis, E. histolytica, Giardia lamblia, Blastocystis hominis, Balantadium coli,spirochaetes and anerobic streptococci. Clostridia induced pseudomembranous colitis responds to metronidazole.
Amoebiasis - Metronidazole is a first line drug for all forms of amoebic infection. For invasive dysentery and liver abscess-800 mg TDS (children 30-50 mg/kg/day) for 7-10 days.
Giardiasis - It is highly effective in a dose of 400 mg TDS for 7 days.
Trichomonas vaginitis – Metronidazole is drug of choice; 400 mg TDS for 7 days achieves nearly 100% cure.
Helicobacter pylori gastritis/peptic ulcer - Metronidazole 40 mg TDS.
Metronidazole is also useful in treatment of pseudomernbranous enterocolitis, ulcerative gingivitis, trench mouth.
Metronidazole sensitizes tumour cells for ionizing radiation but is not used clinically for this purpose.
Metronidazole is contraindicated in patients with prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives, patients with neurological disease, blood dyscrasias and in first trimester of pregnancy. Disulfiram-type reaction can occur if metronidazole is received by alcoholics.
Common side effects of metronidazole are nausea, vomiting, dry mouth, abdominal cramps, metallic taste, headache, anorexia. Other side effects include vomiting, diarrhea, rashes, furry tongue, glossitis, dizziness, vertigo, dysuria, cystitis.
Metronidazole is an antiprotozoal drug but it is also active against bacteria and it belongs to the nitroimidazole group.
Chemically it is 1-(beta-hydroxyethyl)-2-methyl-5-nitroimidazole.The chemical formula is C6H9N3O3 and the molecular weight is 171.2.
Oral: 375 mg capsules; 250 and 500 mg tablets; extended-release 750 mg tablets
Parenteral: 5 mg/mL
Metronidazole is not active by itself; its nitro group gets activated to convert it into the active form. This activation is done by the micro-organisms. It is selectively toxic to anaerobic and micro-aerophilic pathogens. After entering the cell by diffusion its nitro group is reduced by certain redox proteins functional only in anaerobic microorganisms to extremely reactive nitrogen radical that is cytotoxic. The nitro radical of metronidazole acts as an electron sink which competes with the biological electron acceptors of the anaerobic organism for the electrons produced by the pyruvate: ferrodoxin Oxidoreductase (PFOR) enzyme pathway of pyruvate oxidation. The energy metabolism of anaerobes is, thus, disturbed and replication, transcription and repair process of DNA is hindered leading to cell death. Metronidazole and oxygen both strive for the electrons formed during metabolism of energy. Hence oxygen decreases the cytotoxic action caused by metronidazole and also reduces its activation. Anaerobes which develop metronidazole resistance become deficient in the mechanism that generates the reactive nitro radical from it.
Metronidazole has activity against many of the obligate group of anaerobes. Anerobic bacteria which are facultative, aerobic and non-sporulating gram-positive bacilli are mostly resistant.
Resistance can occur to metronidazole due to following properties in organisms:
Some microaerophilic and anerobic bacteria, Giardia lamblia, Trichomonas vaginalis, and Giardia intestinalis are resistant to metronidazole.
Orally administered metronidazole is readily absorbed. The t1/2 is ~8 hours. Some accumulation of the drug occurs if doses are repeated every 6-8 hours. Plasma protein binding is < 20%. Except placenta, metronidazole penetrates well into body tissues and fluids, including vaginal secretions, seminal fluid, saliva, breast milk, and CSF.
After an oral dose, >75% metronidazole is metabolized and is excreted through the kidney in urine. It is mainly metabolised in the liver by glucuronidation and oxidation. An acid and hydroxy metabolite are formed which are the major metabolites. More than half of the activity of metronidazole against trichomonas is exerted by the hydroxy metabolite. It also has a extended t1/2 of approximately twelve hours.
1. Amoebiasis - Metronidazole is a first line drug for all forms of amoebic infection. For invasive dysentery and liver abscess-800 mg TDS (children 30-50 mg/kg/day) for 7-10 days. In serious cases of liver abscess 1 g may be infused i.v. slowly followed by 0.5 g every 8-12 hour till oral therapy is instituted. For mild intestinal disease - 400 mg TDS for 5-7 days.[>
2. Giardiasis - It is highly effective in a dose of 400 mg TDS for 7 days.
3. Trichomonas vaginitis – It is the drug of choice; 400 mg TDS for 7 days achieves nearly 100% cure. Nonspecific bacterial vaginosis also responds.
4. Anaerobic bacterial infections -Metronidazole is effective drug and is generally used along with gentamicin or cephalosporins. For serious cases i.v. administration is recommended: 15 mg/kg infused over 1 hour followed by 7.5/mg/kgevery6hours till oral therapy can be started with 400-800 mg TDS.
5. Pseudomembranous enterocolitis- Oral metronidazole 800 mg TDS preferred over vancomycin as it is more effective, more convenient, and less toxic.
6. Ulcerative gingivitis, trench mouth: 200-400 mg TDS (15-30 mg/kg/day) is quite effective because anaerobes are involved. Metronidazole /tinidazole are the drugs of choice for acute necrotizing ulcerative gingivitis, in which they are often combined with amoxicillin, tetracycline or erythromycin.
7. Helicobacter pylori gastritis/peptic ulcer - metronidazole 40 mg TDS or tinidazole 500 mg BD is frequently used along with amoxicillin/clarithromycin and omeprazole/pantoprazole/lansoprazole in triple drug 2 week regimens.