Chemotherapy

AMOEBIASI
of

S
- Viral Bakhai and Drashti Pate
 AMOEBIASIS
Amoebiasis (also called amoebic dysentery) is an infection of the intestinal tract
caused by Entamoeba histolytica.

Humans are the only known hosts for these protozoa

transmitted almost exclusively by the fecal-oral route. Ingested E. histolytica

cysts from contaminated food or water survive acid gastric contents and
transform into trophozoites that reside in the large intestine.

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 AMOEBIASIS
Many individuals may remain asymptomatic but excrete the infectious cyst form,
making them a source for further infections.

In other individuals, E.histolytica trophozoites invade into the colonic mucosa

with resulting colitis and bloody diarrhea (amebic dysentery).

Occasionally, E.histolytica trophozoites invade through the colonic mucosa,

reach the portal circulation, and travel to the liver, where they establish an amebic
liver abscess.

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 EPIDIMIOLOGY
Tropical Regions
Humans and Animals
Protozoal Diseases (amebiasis <20%)

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 CLASSIFICATION
Therapeutic agents for amoebiasis are classified as:

Luminal - which act on the parasite in the lumen of the bowel .

(Diloxanide furoate, Iodoquinol, paromomycin)

Systemic - which are effective against amoebas in the intestinal wall and liver.
(Emetine, dehydroemetine)

Mixed amoebicides - effective against both the luminal and systemic forms of the
disease.
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(Metronidazole, Tinidazole)
 DILOXANIDE FUROATE

It is the drug of choice for mild intestinal/asymptomatic amoebiasis

and is given after any tissue amoebicide to eradicate cysts.

MECHANISM
OF ACTION:

It
is a highly effective luminal amoebicide which directly kills tropozoites
responsible for production of cysts.

It
exerts no antibacterial action and is less effective in invasive amoebic
dysentery.
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 DILOXANIDE FUROATE

METABOLISM:
It is primarily metabolized by glucoronidation and is excreted in urine.

SIDE EFFECTS:
Diloxanide furoate is very well tolerated, the only side effect are nausea, itching and
rarely urticarial

CONTRAINDICATION:
The drug is contraindicated in pregnant women and children under two years of age.

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 IODOQUINOl

MECHANISM OF ACTION:
Unknown, It is effective against organisms in the bowel lumen but not against the
trophozites in the intestinal wall.

PHARMACOKINETICS:
Poorly absorbed.
90% of the drug is retained in the intestine & excreted in the faeces.
T1/2 of 4-11 hours.
Excreted in the urine as glucoronides.

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 IODOQUINOl

SIDE EFFECTS:
Anorexia, nausea, vomiting, abdominal pain, headache, rash and pruritus.
(Iodism may occur due to chronic iodine overload, Goitre may occur.)

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 PAROMOMYCIN

It is an aminoglycoside antibiotic, is only effective against the intestinal (luminal) forms

of E.histolytica and tapeworms, because it is not significantly absorbed from the GIT.

MECHANISM OF ACTION:
It acts as direct amoebicidal which is probably due to the effects it has on cell
membranes, causing leakage.

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 PAROMOMYCIN
METABOLISM:
Very little of the drug is absorbed on oral ingestion, but that which is absorbed is
excreted in urine.

ADVERSE EFFECTS:
Gastrointestinal distress and diarrhoea are the principal adverse effects.

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TETRACYCLINES

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 EMETINE

MECHANISM OF ACTION:
Directly acting amoebicide kills trophozoites but has no effect on cysts.
Acts by inhibiting protein synthesis in amoeba by arresting intraribosomal
translocation of tRNA - amino acid complex.

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 EMETINE
SIDE EFFECTS:
Local irritant and has high systemic toxicity,
Nausea, vomiting, gastric irritation, abdominal cramps, diarrhoea, stiffness of muscle,
hypotension and myocarditis.

USES:
Now rarely used for amoebic dysentery or amoebic liver abscess.
Also effective for liver fluke infestation.

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DEHYDROEMETINE

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 METRONIDAZOLE
MECHANISM OF ACTION
After entering the cell by diffusion its nitro group is reduced by certain redox
proteins operative only in anaerobic microbes to highly reactive nitro radical
which exerts cytotoxicity.

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 METRONIDAZOLE
PHARMACOKINETICS:

Metronidazole is almost completely absorbed from the small intestines;

It is widely distributed in the body, attaining therapeutic concentration in vaginal secretion,

semen, saliva and CSF.

t1/2 is 8 hours.

METABOLISM:
1. Oxidation
2. Glucoronide conjugation. 20
 METRONIDAZOLE
ADVERSE EFFECTS:
Anorexia, nausea, metallic taste and abdominal cramps are the most common.

Looseness of stool is occasional.

Less frequent side effects are - headache, dryness of mouth, dizziness, rashes and transient neutropenia.

Prolonged administration may cause peripheral neuropathy and CNS effects. Seizures have followed very
high doses.

USES:

Amoebiasis, Giardiasis, Trichomonas vaginitis, Anaerobic bacterial infections, Pseudomembranous

enterocolitis, Ulcerative gingivitis, Helicobacter pylori gastritis/peptic ulcer
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 TINIDAZOLE
It is an equally efficacious congener of metronidazole, similar to it in every
way except:

Metabolism is slower
t 1/2 is 12 hr
duration of action is longer
dosage schedules are simpler. Thus, it is more suited for single dose or once daily
therapy.

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 Summary
Amoebiasis Entamoeba histolytica
Route Fecal or oral
Drugs Depending on site of infection

References:
Wilson and Gisvolds Textbook of ORGANIC MEDICINAL AND
PHARMACEUTICAL CHEMISTRY- 12th Edition, Antihelmintics, pg. 224-
226
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Thank you!
- Viral Bakhai and Drashti Pate