Anti-Amoebic Drugs
Contents
• 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
Introduction
• 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
Classification
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
• 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.
Pharmacokinetics
• 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
Contraindications
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.
Interactions
• 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
Summary
• 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
0 Comments: