E.

histolytica exists in two forms: the inactive

but infective cyst and the active trophozoite
Drugs Colonic infection with E. histolytica occurs as
for a result of ingestion of cysts through the
fecal-oral route, for example, drinking
Amebiasis contaminated water.
Intestinal invasion occurs may be
a function of the number of cysts ingested
the strain of the parasite
the motility of the host gastrointestinal
tract
the presence of appropriate enteric
bacteria to serve as nourishment for the
ameba.
 Disease results when active trophozoites
invade the intestinal epithelium, and
secondary spread to the liver can occur via
the portal circulation
E. histolytica lyses and destroys human
tissue.
Trophozoites typically multiply superficial to
the muscularis mucosae of the intestines
and spread laterally. They may also
penetrate more deeply, occasionally
perforating the intestinal wall and spreading
locally
 The trophozoite form is capable of
invading host tissue.
Inside the human body, the trophozoites
move using pseudopods and ingest
bacteria, other protozoa, and host red
blood cells.
A trophozoite can convert to a binucleated
cyst form, which matures into a
tetranucleated cyst that travels through the
colon but is not capable of mucosal
invasion
Pharmacology of Antiprotozoal
Agents
Tissue-acting agents
Metronidazole (Flagyl)
Dehydroemetine
Chloroquine
Luminal amebicides
Iodoquinol
Diloxanide furoate (Furamide),
Paromomycin
 A systemic agent may be so well absorbed
that only small amounts of the drug stay in
the bowel, which might prove ineffective as
a luminal agent.
A luminal-acting agent, on the other hand,
may be too poorly absorbed to be effective
in the tissue
In the asymptomatic cyst passer, it is
necessary to eradicate the causative agent
from the lumen to prevent intestinal
amebiasis or the development of amebic
liver abscess
METRONIDAZOLE
Metronidazole, a nitroimidazole is the drug
of choice in the treatment of extraluminal
amebiasis.
It kills trophozoites but not cysts of E
histolytica and effectively eradicates
intestinal and extraintestinal tissue
infections
Tinidazole, a related nitroimidazole have
similar activity and a better toxicity profile
than metronidazole
 Mechanism of Action
Metronidazole is inactive until it is
reduced within host or microbial cells
possessing a large negative redox
potential; such redox potentials are
present in many anaerobic or
microaerophilic luminal parasites/
protozoans.
Activated metronidazole forms reduced
cytotoxic compounds that bind to proteins,
membranes, and DNA in target cells,
causing severe damage
Reactive reduction products appear to be
responsible for antimicrobial activity
 Adverse Effects
Nausea, headache, dry mouth, or a
metallic taste in the mouth occurs
commonly.
Infrequent adverse effects include
vomiting, diarrhea, insomnia,
weakness, dizziness, thrush, rash,
dysuria, dark urine, vertigo,
paresthesias, and neutropenia
Metronidazole has a disulfiram-like
effect, so that nausea and vomiting can
occur if alcohol is ingested during
therapy
EMETINE &
DEHYDROEMETINE
an alkaloid derived from ipecac
effective against tissue trophozoites of E.
histolytica, but because of major toxicity
concerns their use is limited to unusual
circumstances in which severe amebiasis
requires effective therapy and
metronidazole cannot be used
The drugs should be used for the
minimum period
 Adverse effects, include pain,tenderness,
and sterile abscesses at the injection site;
diarrhea, nausea, and vomiting; muscle
weakness and discomfort; and minor
electrocardiographic changes.
Serious toxicities include cardiac
arrhythmias, heart failure, and hypotension
IODOQUINOL
a halogenated hydroxy-quinoline
90% of the drug is retained in the intestine
and excreted in the feces.
The remainder enters the circulation, and
is excreted in the urine as glucuronides
 The mechanism of action of iodoquinol
against trophozo-ites is unknown.
It is effective against organisms in the
bowel lumen but not against
trophozoites in the intestinal wall or
extraintestinal tissues
Adverse effects include diarrhea, anorexia,
nausea, vomiting, abdominal
pain,headache, rash, and pruritus
DILOXANIDE FUROATE
a dichloroacetamide derivative
In the gut, diloxanide furoate is split into
diloxanide and furoic acid;
about 90% of the diloxanide is rapidly
absorbed and then conjugated to form the
glucuronide, which is promptly excreted in
the urine.
The unabsorbed diloxanide is the active
antiamebic substance.
 The mechanism of action of diloxanide
furoate is unknown
Adverse effects; flatulence is common, but
nausea and abdominal cramps are
infrequent and rashes are rare.
PAROMOMYCIN SULFATE
an aminoglycoside antibiotic that is not
significantly absorbed from the
gastrointestinal tract
The small amount absorbed is slowly
excreted unchanged, mainly by glomerular
filtration
Adverse effects include occasional
abdominal distress and diarrhea