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Metronidazole

• It is a nitroimidazole antibiotic, highly effective against anaerobic bacteria and protozoa

Mechanism of action:
• Its nitro group is chemically reduced inside sensitive protozoa and anaerobic bacteria giving
reactive toxic oxygen products which damage DNA → bactericidal
• Metronidazole (prodrug) microorganism nitro group is
reduced by ferredoxins active metabolite damages microbial (cidal
effect)
• In the presence of oxygen (aerobes), metronidazole cannot be reduced to its active metabolite;
therefore it is ineffective against aerobes

Spectrum of activity
• Active against almost obligate anaerobic bacteria, and against protozoa such as Trichomonas,
Giardia lamblia and Entamoeba
• GP and GN anaerobes
– Bacteriodes spp
– Prevotella spp
– Clostridium spp (including C. difficle)
– Fusobacterium spp

Pharmacokinetics
• Metronidazole is available for oral, IV and topical administration
• Orally, well absorbed, poorly bound to plasma proteins
• It diffuses well into the tissues including brain; therapeutic levels are achieved in various body
fluids—saliva, semen, vaginal secretion, bile, breast milk and CSF
• Metabolized in liver and metabolites are excreted mainly in urine
• Elimination half life 7 hrs

Clinical uses
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• Urological indications
– Severe intra-abdominal infections - combined with e.g., cephalosporins
– Surgical prophylaxis in combination with a cephalosporin for procedures with opening of colon
- colorectal, vaginal, abdominal
• Amoebiasis:
– DOC for treatment of all forms of amoebiasis. It is useful in the treatment of both intestinal and
extraintestinal amoebiasis
• Giardiasis – DOC for treatment of Giardia lamblia
• Pseudomembranous enterocolitis – due to Clostridium difficile – effective, cheaper and less toxic than
vancomycin
• Bacterial vaginosis, trichomoniasis
• Severe pelvic inflammatory disease - with e.g., cephalosporins

Dosage
• By I.V. infusion, for adults 500 mg in 100 ml solution 8-hourly, administered at a rate of 5 ml per
minute.
• Adult oral dosage – 400 - 800 mg, 3 times daily for 7 days or longer according to the clinical response.
• In the prevention of anaerobic infection in surgery, 1g orally as a single dose followed when possible
by 200 mg orally, 3 times daily for up to 7 days after surgery

Adverse effects
• 1. Gastrointestinal: nausea, metallic taste, dry mouth, epigastric distress, abdominal cramps and
occasionally vomiting
– GIT disorders can be reduced if the drug is taken with meals
• 2. Allergic reactions: skin rashes, urticaria, itching and flushing.
• 3. CNS: dizziness, insomnia, vertigo, headache, paraesthesia, rarely convulsions.
• 4. Disulfiram-like reaction: if taken with alcohol; the patient should be warned to avoid alcohol during
treatment with metronidazole.
• 5. Neutropenia
• 6. Teratogenic effect in experimental animals; metronidazole should be avoided in pregnant women.

• Contraindications
– Pregnancy
– Alcohol consumption

Drug interactions
• 1. Warfarin and other oral coumarins -Potentiates anticoagulant effect by inhibiting their metabolism
→ prolongation of prothrombin time; reduction of warfarin dose may be needed
• 2. Lithium - potentiate lithium toxicity by decreasing renal clearance of lithium.
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• 3. Alcohol: severe alcohol intolerance

Tinidazole

• Similar to metronidazole
• Tinidazole has a longer duration of action and better tolerability than metronidazol but is
more expensive than metronidazole.
• Uses:
• 1. Orodental infections: for anaerobic infections of oral cavity
• Tinidazole 600 mg twice a day for 5 days or 2 g once daily orally for 3 days
• 2. Amoebiasis: 2 g once daily orally for 3 days or 600 mg twice daily for a week.