Download Treatment of amebiasis

Treatment of amebiasis
Therapeutic agents are classified as luminal,systemic or mixed amebicides according to the site
where the drug is evective.
Mixed amebicides
Mechanism of action
Metronidazole
&
Tinidazole
Within anaerobic bacteria & sensitive
protozoa, the nitro group of the drug is
reduced into reactive cytotoxic
products, by pyruvate
ferredoxinoxidoreductaseenzyme,
which bind to DNA causing its damage,
disrupting transcription & replication of
the trophozoites.
Therapeutic uses
1- Antiprotozoal: as it is the drug of first
choice in treatment of
Amebiasis,Giardiasis , Trichomoniasis
pharmacokinetics
Side Effects
1. GIT disturbances, glossitis
with metalic taste in the mouth.
- effective orally, rectally and
IV infusion.
2. CNS manifestations:
headache, dizziness, insomnia
and sensory neuropathy.
- Widely distributed,
including CSF.
3. Dysuria and dark urine.
4. Rash & neutropenia.
- Metronidazole t1/2is 6-8 h.
- Tinidazole t1/2 is 12-14 h.
5. Mutagenic and carcinogenic
in mice, so not used in
pregnancy.
6. Enzyme inhibitor:
potentiating warfarin and
disulfiram-reaction with
alcohol.
2- Anti-anerobe:e.g.
dental infection, pseudomembraneous
colitis
tis and anerobic brain abscess
Luminalamebicides
- Iodoquinol is a halogenated hydroxyhydroxy
quinoline.
Idoquinol
DiloxanideFur
oate
- It is an effective luminal amebicide
that is commonly used
sed with
metronidazole to treat amebic
infections.
In the gut, diloxanidefuroate is split into
diloxanide and furoic acid.
- 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.
1- Direct amebicidal action, which
effects on cell membranes causing
leakage.
2- also, exerts its antiamebic actions by
reducing thee population of intestinal
flora
2- headache, rash, and pruritus.
- It has a half-life of 11–14
hours.
3-Thyroid enlargement.
90% is rapidly absorbed,
which is excreted in the
urine.
1- GIT disturbances and
flatulence.
- It is an aminoglycoside
antibiotic
1- Gastrointestinal distress &
diarrhea.
The unabsorbed diloxanide is the active
antiamebic substance.
Paromomycin
1- GIT disturbances:
which usually stops after
several days. It should be taken
with meals to limit
gastrointestinal toxicity.
- It's not significantly
absorbed from the
gastrointestinal tract, that's
way only effective against
luminal forms of
E.histolytica.
2- Teratogenic.
2- It accumulates with renal
insufficiency and contribute to
renal toxicity.
Systemic amebicides
- They inhibit protein synthesis by
blocking chain elongation.
- Effective against tissue trophozoites of
E. histolytica.
Emetine
&
Dehydroemetine
N.B.
Dehydroemetine is a
synthetic analog of
emetine.
Precautions
Used only if:
1- metronidazole or tinidazole can't be
used
2- or in severe amebic liver abscess.
- The natural alkaloid
emetine is too toxic for
clinical use.
- IM injection is preferred
route.
- Emetine is concentrated in
liver, where it persists for a
month after single dose.
1- Pain, tenderness, and sterile
abscesses at the injection site.
2- GIT disturbances and
diarrhea.
3- Muscle weakness and
discomfort.
4- Serious toxicities: cardiac
arrhythmias, heart failure, and
hypotension.
- It's slowly metabolized and
excreted.
3- Used for the minimum period needed
to relieve severe symptoms (usually 3–5 - It's 1/2 life is 5 days.
days).
4- Not be used in patients with cardiac
or renal disease, in young children, or in
pregnancy.
Chloroquine
- Used as tissue-amebicidal only in cases
of hepatitis or liver abscess.
- It is an anti-malarial dug.
Tetracycline
- Used in severe cases of amebic
dysentery.
- It decreases risk of opportunistic
infection, perforation and peritonitis.
- Given with systemic-amebicidals.
* Treatment of specific forms of amebiasis *
1- ASYMPTOMATIC INTESTINAL INFECTION (Bowel lumen amebiasis)
In which trophozoites (non-infective , active-invasive form)and
cysts (infective, non-invasive form)
are passed into the feces (i.e. carrier or cyst passer).
* Treatment is directed at eradicating cysts with a “luminal amebicide”.
2- AMEBIC COLITIS (Tissue-invading
(Tissue
amebiasis):
- Mild intestinal infection.
- Moderate intestinal infection.
- severe intestinal infection (dysentery).
• It can be in the form of:
- Acute intestinal amebiasis, or,
- Chronic intestinal amebiasis (amebic granuloma in the intestinal
wall, ameboma).
• Treatment is directed at eradicating trophozoites with systemic “tissue
amebicide” and should be followed by a course of “luminal amebicide” to
eradicate the source of infection.
• EXTRAINTESTINAL INFECTIONS (Tissue-invading
(Tissue invading amebiasis):
o It can bee in the form of hepatitis, liver abscess and other extraintestinal
diseases.
o Treatment is directed at eradicating trophozoites with systemic “tissue
amebicide” and should be followed by a course of “luminal amebicide” to
eradicate the source of infection.
o Aspiration of amebic abscess and addition of another “tissue amebicide”
are greatly helpful in curing this case.