This document discusses amebiasis, an intestinal infection caused by the protozoan Entamoeba histolytica. It describes the life cycle and symptoms of E. histolytica, from ingesting cysts to formation of trophozoites that penetrate the intestinal wall and may cause liver abscesses. Diagnosis involves isolating E. histolytica from feces. Treatment aims to eliminate actively infected and asymptomatic carriers to prevent future infections. Several antiamoebic drugs are discussed including metronidazole, diloxanide, and 8-hydroxyquinolines that act on intestinal and extraintestinal amebiasis. Metronidazole's mechanism of action involves reductive activation by susceptible
2. AMEBIASIS
Amebiasis (also called amebic dysentry) is
an infection of intestinal tract caused by
Entamoeba histolytica.
The disease can be acute or chronic, with the
patients showing varying degrees of illness,
from no symptoms to mild diarrhea to
fulminating dysentery (Dysentery in which
the symptoms are intensely acute, leading to
prostration, collapse, and often death).
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3. The diagnosis is established by isolating
E. histolytica from fresh feces.
Therapy is aimed not only at the acutely
ill patients but also at those who are
asymptomatic carriers, because
dormant E. histolytica may cause future
infections in the carrier and be a
potential source of infections for
others.
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5. Life cycle of
Entamoeba histolytica
Entamoeba histolytica exists in two forms:
1. Cysts form (That can survive out side the
body).
2. Trophozoites form (That are labile and don’t
persist outside the body).
Life cycle
Life cycle consists of following steps:
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6. 1. Ingestion of cysts
Cysts are ingested through feces, contaminated food or
water.
2. Formation of trophozoites
Cysts are passed into the lumen of intestine, where the
trophozoites are liberated.
3. Penetration and multiplication of trophozoites
Trophozoites are penetrated in intestinal wall and
multiply within colon wall. They either invade and
ulcerate the mucosa of large intestine or simply feed
on intestinal bacteria.
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7. 4. Systemic invasion
Large numbers of trophozoites within the
colon wall can also lead to systemic
invasion and caused liver abscess.
5. Cysts discarded
The trophozoites within the intestine are
slowly carried toward the rectum, where
they return to cyst form and are excreted
in feces.
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8. Antiamoebic drugs
• These are drugs useful in infection caused by the protozoa
Entamoeba histolytica.
A. Tissue amoebicides
a) For both intestinal and extraintestinal amoebiasis:
I. Nitroimidazoles: Metronidazole,Tinidazole, Secnidazole,
Ornidazole,Satranidazole
II. Alkaloids: Emetine, Dehydroemetine
b) For extra intestinal amoebiasis only:Chloroquine
B. Luminal amoebicides
a) Amide : Diloxanide furoate, Nitazoxanide
b) 8-Hydroxyquinolines: Quiniodochlor(Iodochlorohydroxyquin,
Clioquinol),Diiodohydroxyquin (Iodoquinol)
(c) Antibiotics: Tetracyclines
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11. 4.Alkaloids: Emetine, Dehydroemetine
N
N OCH3
OCH3
H3CO
H3CO
CH3
H
H
H
(2S,3R,11bS)-2-((6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-3-ethyl-9,10-dimethoxy-
2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinoline
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14. Mechanism of action of Metronidazole
Metronidazole is a prodrug. It requires reductive activation
of nitro group by susceptible organism. Its selective toxicity
towards anaerobic and microaerophilic pathogens such as
E. histolytica, G. lamblia, etc.
These organisms contain electron transport components
such as ferridoxin, small Fe-S proteins that have sufficiently
negative redox potential to donate electrons to
metronidazole.
The single electron transfer forms a highly reactive nitro
radical anion that kills susceptible organisms by radical-
mediated mechanisms that target DNA, resulting in cell
death.
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17. Competes with biological
electron acceptor
Acts as electron sink –
electrons by PFOR p/w
Energy metabolism
disrupted
Reduced to highly
reactive nitro radicals
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18. Therapeutic Uses
Amoebiasis: DOC in all tissue infections
Acute intestinal Amoebiasis / Amoebic colitis with
dysentery-- 800 mg TDS-10 d course with a luminal
amoebicide
Mild intestinal amoebiasis-400mg TDS for 5-7 days
Hepatic Amoebiasis :1g iv followed by 0.5g every 8-12 hr
till oral therapy-------------10 d course cures 95 % cases
For cases in which initial therapy fails –
Aspiration of abscess & addition of Chloroquine
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19. • Giardiasis
Treatment of choice--- 400mg TDS
7days or 2g/d for 3 days
• Trichomoniasis : DOC, 400mg TDS
7days
Vaginal & urethral Trichomoniasis-----
topically.
• Bacterial vaginosis: Can be used
topically as a gel.
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20. • Anaerobic bacterial infection-after pelvic
surgery, appendicectomy
• 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
• Pseudomembranous enterocolitis by
Clostridium difficile. DOC. (Vancomycin is the
drug of second choice)
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21. • Ulcerative Gingivitis, Trench mouth
• Facilitates extraction of adult
guinea worm in Dranculosis
• Acne rosacae.
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22. emetine
• MOA-These inhibit protein synthesis by
blocking chain elongation.
• Uses- used as alternative agents for the
treatment of amebiasis.
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