Anti-Amoebic Drugs

Anti-Amoebic Drugs


       Antiamoebic Agents – Classification

       Pharmacology of Metronidazole

At the end of this lecture, the student will be able to:

       Describe the Pharmacology of Metronidazole

       Explain the ADR and drug interactions of Metronidazole


       Amoebiasis (Amoebic dysentry) is an infectious disease caused by protozoa, Entamoeba histolytica, which is produced by the ingestion of cysts of this organism

       The ingested cysts develop into trophozoites and adhere to the colonial epithelial cells in the intestine

       These trophozoites then lyses the host cell and invades the submucosa

       This produces the amoebic ulcers and cause acute dysentery or chronic intestinal amoebiasis

       The parasite may also pass into blood steam and invades the liver causing liver abscesses


1. Systemic Amoebicides

     a) For both intestinal and extra intestinal amoebiasis

      - Nitromidazoles: Metronidazole, Tinidazole, Secnidazole, Ornidazole

      - Alkaloids: Emetine, Dehydroemetine

     b) For extra intestinal amoebiasis: Chloroquine

2. Luminal Amoebicides

     a) Amides: Diloxanide furoate

     b) 8-Hydroxyquinolines: Diiodohydroxyquin

     c) Antibiotics: Tetracyclines, Paromomycin


       Metronidazole is the drug of choice in the treatment of different forms of amoebiasis

       It kills the trophozites of E. histolytica but has no effects on the cysts

       It is often used in combination with Diloxanide furoate for the treatment of amoebiasis

Mechanism of Action

Metronidazole is a pro durg.

It is converted in anaerobic organism by the redox enzyme pyruvate-ferredoxin oxidoreductase. The notro group of metronidazole is chemically reduced by ferredoxin or a ferredoxin linked metabolic process and the products are responsible for disrupting the DNA helical structure, thus inhibiting nucleic acid synthesis.


       Disposition of metronidazole in the body is similar for both oral and intravenous dosage forms

       Following oral administration, metronidazole is well absorbed

       Plasma concentrations of metronidazole are proportional to the administered dose

       Metronidazole is the major component appearing in the plasma, with lesser quantities of metabolites also being present

       Less than 20% of the circulating metronidazole is bound to plasma proteins

       Metronidazole appears in cerebrospinal fluid, saliva, and breast milk in concentrations similar to those found in plasma

       Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses.

       The major route of elimination of metronidazole and its metabolites is via the urine (60% to 80% of the dose)

Anti microbial spectrum

       Metronidazole has a broad-spectrum cidal activity against protozoa and many anaerobic bacteria

       It is drug of choice in treatment of infections caused by E. histolytica, Giardia lamblia and Trichomonas vaginalis

       It is also active against Gram-positive bacilli such as Clostridia

Adverse Effects

       The most common unwanted effects are gastrointestinal disturbances

       It has a metallic, bitter taste in the mouth

       CNS symptoms such as dizziness, headache and sensory neuropathies are rarely observed

       If taken with alcohol a disulfiram like effect occurs


Metronidazole is contraindicated in:

       Neurological disease

       Blood dyscrasias

       First trimester of pregnancy (though no teratogenic effect has yet been demonstrated, its mutagenic potential warrants caution)

       Cautious use in chronic alcoholics.


       Disulfiram-like intolerance to alcohol occurs in some patients taking metronidazole

       Alcohol-metronidazole interaction occurs only in some individuals, while majority of those taking it can consume alcohol without any reaction

       There is no convincing evidence of disulfiram-like action of metronidazole, but manufactures advise caution in drinking during metronidazole therapy

       Enzyme inducers (phenobarbitone, rifampin) may reduce its therapeutic effect

       Cimetidine + metronidazole can reduce metronidazole metabolism: its dose may need to be decreased

       Metronidazole enhances warfarin action by inhibiting its metabolism

       It can decrease renal elimination of lithium and precipitate toxicity

Clinical Uses

       It is used in the treatment of amoebiasis, giardiasis, trichomonas vaginitis and pseudomembranous enterocolitis

       Also used in the treatment of many anaerobic bacterial infections and in peptic ulcers


       Amoebiasis (Amoebic dysentry) is an infectious disease caused by protozoa, Entamoeba histolytica, which is produced by the ingestion of cysts of this organism

       The nitro group of metronidazole is chemically reduced by ferrodoxin and the product of the reaction disrupts nucleic acid synthesis

       ADR of metronidazole- causes metallic, bitter taste in the mouth; dizziness, headache and sensory neuropathies are rarely observed; causes a disulfiram like effect with alcohol



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