ANTI-AMOEBIC DRUGS

Madan Sigdel
Lecturer
Department of Pharmacology
Gandaki Medical College
Amoebiasis is protozoal infection caused by
Entamoeba histolytica, which are transmitted
through fecal-oral route.

CLASSIFICATION
1. Tissue amoebicides
(a) For both intestinal and extraintestinal amoebiasis:
Nitroimidazoles: Metronidazole,
Tinidazole, Secnidazole, Ornidazole,Satranidazole
Alkaloids: Emetine, Dehydroemetine
(b) For extraintestinal amoebiasis only: Chloroquine
2. Luminal amoebicides
(a) Amide : Diloxanide furoate, Nitazoxanide
(b) 8-Hydroxyquinolines: Quiniodochlor
(Iodochlorohydroxyquin, Clioquinol),
Diiodohydroxyquin (Iodoquinol)
(c) Antibiotics: Tetracyclines
Life cycle of E. histolytica, showing the sites of action of amebicidal drugs.
Metronidazole
 Highly effective against most of the anaerobic
bacteria and several protozoa such as E.
histolytica, Giardia Lambia and Trichomonas
Vaginalis. it is also effective against
Dracunculas medinensis.
Mechanism of action
 The E. hystolytica possess an enzyme, pyruvate-
ferrodoxin oxido-reductase, which participates in
metabolic electron transfer reactions.
 These electrons are captured or accepted by the
nitro group of metronidazole. As a result
metronidazole itself become reduced.
 The reduced metronidazole binds to DNA of the
E. hystolytica. this disrupt replication and
transcription. This results in the death of E.
hystolytica.
Metronidazole (prodrug)

enters
Microorganism

Nitro group reduced by

ferredoxins and Fe-S proteins

Active Metabolite

Breaks and damage microbial DNA

Death of organism (bactericidal effect)

 Pharmacokinetics
 After oral administration, it is nearly completely
absorbed. After absorption, it is distributed well in
the different tissues and fluids of the body.
 Therapeutic levels can be found in vaginal,
seminal fluids, CSF, saliva and breast milk.
After absorption some part (20%) gets bound to
plasma proteins.
 Metabolised by oxidation followed by
glucuronidation in the liver. The parent drug and
it's metabolites are excreted in the urine.
Adverse effects
Side effects to metronidazole are relatively frequent and
unpleasant, but mostly nonserious.
 Most common - Nausea, Vomiting, abdominal cramps
and metallic taste
 Less frequent – headache, glossitis, rashes and
dryness of mouth
 Prolonged administration – Peripheral neuropathy and
CNS effects
 Seizures at high dose
 Contraindications:
 Metronidazole is contraindicated in neurological disease,
blood dyscrasias, first trimester of pregnancy and chronic
alcoholism.

Interactions:
 Disulfiram-like intolerance to alcohol occurs in some
patients taking metronidazole
 Enzyme inducers (phenobarbitone, rifampin) may reduce its
therapeutic effect.
 Cimetidine can reduce metronidazole metabolism: its dose
may need to be decreased.
 Uses
1. Amoebiasis: DOC 400-800 mg t.d.s for 7 days
2. Trichomonas vaginitis : DOC 400 mg t.d.s orally 7
days. Both the sexual partners should be treated
simultaneously.
3. Giardiasis: 400 mg t.d.s for 7 days OR 2 g/day for 3
days.
4. Guinea worm infestation: 200-400 mg t.d.s for 7 days
5. Anaerobic infection: highly effective against most of the
anaerobic infections- pelvic inflammatory disease, lung
abscess, intra- abdominal infection etc. caused by B.
fragilis, clostridium and anaerobic organisms.
a. in aerobic brain abscess it is used in combination
with 3rd generation cephalosporin.
b. In antibiotic associated pseudomembranous
colitis metronidazole is more effective and
less toxic than vancomycin.
c. In the treatment of H. Pyroli infection
metronidazole is used in combination with
clarithomycin or amoxicillin and a proton
pump inhibitor
Tinidazole
 Most features are similar to metronidazole.
Tinidazole has longer duration of action and
better tolerability than metronidazole.
 Secnidazole
 same spectrum of activity and potency as
Metronidazole
 oral administration is rapid and complete, but
metabolism is slower resulting in a plasma t½ of
17–29 hours.
Emetine and dehydroemetine

 Emetine, alkaloid derived from Cephaelis

ipecacuanha and dehydroemetine, a synthetic
analog – kills trophozoites of E histolytica

 MOA: Inhibiting intra-ribosomal

translocation of tRNA-amino acid complex
→ inhibition of protein synthesis
 Emesis
 Muscle weakness
 ECG changes: T wave inversion and prolongation of PR
interval
 Tachycardia
 Itching and skin rashes
 Nausea
 Eczematous lesions may occur at injection site.
Chloroquine
 Kills trophozoites of E. histolytica
 Concentrates in liver – used in hepatic
amoebiasis
 Completely absorbed from upper intestine – not
effective in invasive or luminal dysentery
 Used after a course of Metronidazole – but a
luminal amoebicide must be added
Amides
Diloxanide furoate
  Highly effective luminal amoebicide

 Kills trophozoites responsible for production of cyst – however no

antibacterial action
 MOA: gets hydrolyzed into diloxanide and furoic acid. .

 Diloxanide moeity is partly absorbed, the unabsorbed portion in the

gut exerts anti-amoebic activity.

 Uses: Mild tissue amoebiasis/asymptomatic cyst passers, Tissue

amoebiasis and liver abscess with Metronidazole
 ADRs: Well tolerated, only falatulence, nausea, itching and rarely
urticaria
Thank you