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ANTIAMOEBIC DRUGS

Learning objectives
Classify antiamoebic drugs according to the
targeted form of E. histolytica
Describe the pharmacological properties of
nitroimidazoles
Describe the pharmacological properties of
diloxanide furoate
List antibiotics used as adjuvant to antiamoebic
drugs
Describe the principles of treatment of amoebiasis
and giardiasis

Therapeutic Classification of Anti-Amebic Drugs


I. Intestinal and extraintestinal Amebiasis .
Nitroimidazoles
Metronidazole
Tinidazole
Secnidazole.

II. Extraintestinal Amebicides


Chloroquine

III. Luminal Amebicides

1.

2.

Dichloroacetamides
Diloxanide Furoate
Antibiotics: Tetracyclines

Metronidazole (prototype)
Most commonly used agent
Mixed tissue amebicide (Intestinal & extra
Intestinal)
Kills only trophozoites in intestinal wall but not the
cysts of E. histolytica.

Pharmacokinetics:
Oral, I/V infusion, topical gel, cream.
Absorption: Almost complete from GIT, some unabsorbed
drug reaches colon.
PPL:1- 3 hrs
Distribution: widely Distributed to all tissues & high
concentrations in body fluids CSF & brain. Also in Vaginal
secretions ,saliva etc.
t : 7.5 hrs

Prep:

Metabolism: In liver; may accumulate in hepatic


insufficiency
Excretion: urine.

Mechanism of action
Metronidazole kills protozoa & is bactericidal for anaerobic
bacteria.
Metronidazole is a pro drug requiring reductive activation of

the NITRO group.

This occurs in sensitive anaerobic protozoa & anaerobic

bacteria by Ferredoxins; which are electron transport


proteins.

These proteins can donate electrons to Metronidazole which

serves as electron acceptor.

The reduced product is cytotoxic, it targets DNA & other

biomolecules / proteins, resulting in cell death.

Antimicrobial Spectrum
Kills anaerobic protozoa & bacteria
Entameba Histolytica (Trophozoits only)
Trichomona Vaginalis
Giardia Lamblia
Clostridia C . difficile
Bacteroides fragilis
Helicobacter pylori

Therapeutic Uses
Versatile drug
1. Amebiasis: DOC in all tissue infections

Acute intestinal Amebiasis / Amebic colitis with


dysentery. 10 d course with a luminal amebicide
Not reliably effective against parasites in lumen,

Hepatic Amebiasis :10 d course cures 95 % cases


For cases in which initial therapy fails
Aspiration of abscess & addition of Chloroquine /
Dehydroemetine or Emetine--- toxic

2. Trichomoniasis : Treatment of choice single dose of 2g.


Vaginal & urethral Trichomoniasis. Can be used topically.
3. Giardiasis Treatment of choice--- single dose 90 % efficacy.
4. Bacterial vaginosis: Can be used topically as a gel.
5. Eradication of H. Pylori in Peptic ulcer--a component of 14
days triple therapy regimen. Metronidazole 500mg BD along
with a proton pump inhibitor BD, Clarithromycin 500mg BD
6. Pseudomembranous enterocolitis by Clostridium difficile.
DOC. (Vancomycin is the drug of second choice)

Anaerobic/ mixed intra abdominal infections.


Component of prophylaxis specially for colorectal
surgery.
7. Brain abscess.
8. Acute Ulcerative Gingivitis.
9. Facilitates extraction of adult guinea worm in
Dranculosis
10. Acne rosacae.
5.
6.

Adverse Effects
GIT:
Dry mouth, metallic taste --- most common.
Nausea, vomiting, abdominal cramps , Diarrhea.
Oral thrush--stomatitis
Neurotoxicity: Headache, Insomnia, numbness or
paraesthesias, weakness , dizziness.
Others: Disulfiram like action with alcohol.
Dysuria ,Dark urine.
Hypersensitivity reactions (rash, neutropenia)

Drug interactions
- Potentiate Anticoagulant effect of Warfarin.
- Metabolism of Metronidazole induced by
Phenytoin & Phenobarbitone &
Cimetidine may inhibit it.
- Metronidazole increases Lithium toxicity.

Contraindications
Patient with active disease of the CNS.
Hepatic Disease/Renal disease, dose
adjustment should be done.
Pregnancy/ Nursing Mothers.

Tinidazole :
Second- generation Nitroimidazole.
Congener of Metronidazole similar to
Metronidazole
Longer acting once daily dose.
Short course 2gm single dose orally X 3 days.
Secnidazole: Longer acting (t1/2 24 h)
2gm orally for 3 days

Chloroquine
Tissue Amebicide specially against
Amoebic Hepatitis & Liver Abscess.
Concentrated in liver; kills trophozoits
of E. histolytica
Th.use: Hepatic amebiasis / abscess;
not responding to Metronidazole

Diloxanide Furoate (Luminal amebicide)


Dichloroacetamide derivative
Pharmacokinetics:
Given orally, splits into Diloxanide & furoic acid in the
gut. 90% Diloxanide is absorbed & conjugated to form
glucuronide and excreted in urine (no antiamoebic activity)
MOA: Not understood.
Unhydrolysed Diloxanide furoate is directly amebicidal
against ameba in lumen (but not those in intestinal wall)
and produces high cure rate in mild intestinal amebiasis
and in asymptomatic cyst passers

Therapeutic uses
Drug of choice for Asymptomatic Luminal
Amoebiasis (cyst passers)
Alongwith tissue amebicide in severe intestinal &
extra intestinal amebiasis.
Adverse effects
Flatulence
Nausea, abdominal cramps
Skin rashes rarely.
Precautions: Pregnancy

Tetracyclines
Used as Luminal amebicide.
Does not kill bacteria directly but disturbs the
symbiosis between normal intestinal flora & E
.histolytica . The amebae grow at expense of
normal intestinal flora .
Tetracyclines are broad spectrum antibiotics & kill
these flora leading to death of E .histolytica also.

Used in resistant cases only

Treatment of specific forms of Amebiasis:


Asymptomatic intestinal infection.
Generally not treated in endemic area.
In non-endemic area treated with luminal
amebicide.
Dolixanide furoate : 500mg TDS X 7 days
May be combined with tetracyclines.

Amoebic Colitis with dysentery:


Moderate to severe intestinal infection:
DOC --- Metronidazole 400mg bid X 7 days
Alternative ---- Dolixanide furoate (Luminal
agent)

Hepatic abscess, ameboma & other Extra


intestinal Infections:
DOC : Metronidazole + luminal agent.
For unusual cases not responding to
Metronidazole Chloroquine + Luminal agent.

Thank you