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1. Anusha Shaji, B.Pharm, M.Pharm
Assistant Professor
Department of Pharmacology
Nirmala College of Pharmacy,
Muvattupuzha, Ernakulam
2. AMEBIASIS
Amoebiasis also called amoebic dysentry
It 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
Transmitted through GIT.
3. ANTIAMOEBIC DRUGS
These are drugs useful in infection caused by the anaerobic
protozoa Entamoeba histolytica.
Other Entamoeba species are generally non-pathogenic
Poor environmental sanitation and low socio- economic status
are important factors in the spread of the disease
↓
Which occurs by faecal contamination of food and water
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:
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.
↓
6. 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.
↓
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
7. CLASSIFICATION
Classification of amoebicidal drugs
Therapeutic agents are classified as luminal, systemic, or mixed (luminal and
systemic) amebicides according to the site where the drug is effective (Figure 1).
8. Mixed Amebicides
Metronidazole
Mixed amoebicides are used for the treatment of amoebic
infections;
It kills the E. histolytica trophozoits.
Extensively used in the treatment of infections caused by Giardia
lamblia, Trichomonas vaginalis, Anaerobic cocci, and Anaerobic
gram negative bacilli.
Drug of choice for the treatment of pseudomembranous colitis
caused by the anaerobic, gram positive bacillus Clostridium difficile.
Activated by anaerobic organisms to a compound that damage
parasite DNA.
9. 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.
10. Pharmacokinetics
Completely and rapidly absorbed after oral administration
Little unabsorbed drug reaches the colon
It is widely distributed in the body
Therapeutic levels can be found in vaginal and seminal fluids,
saliva, breast milk, and cerebrospinal fluid (CSF)
Metabolism occurs in liver
Plasma half life- 8 hours
Uses
Amoebiasis, Giardiasis, Anaerobic bacterial infections,
pseudomembranous enterocolitis, Helicobacter pylori gastritis/
peptic ulcer
11. Adverse effects
An unpleasant metallic taste is often experienced.
The most common adverse effects are those
associated with the gastrointestinal tract, including
nausea, vomiting, epigastric distress, and abdominal
cramps.
Less frequent side effects are headache, glossitis,
dryness of mouth and dizziness
Urticaria, flushing, heat, itching and rashes
Thrombophlebitis of the injected vein occurs if the
solution is not well diluted
12. SYSTEMIC AMEBICIDES
These drugs are useful in treating liver abscesses or intestinal wall
infections caused by amebas.
Chloroquine
Used in combination with metronidazole and diloxanide furoate to
treat and prevent amebic liver abscesses.
It eliminates trophozoites in liver abscesses.
Also effective in treatment of malaria.
Emetine and Dehydroemetine
Used as alternative agents for the treatment of amebiasis.
These inhibit protein synthesis by blocking chain elongation.
13. Intramuscular injection is the preferred route.
Emetine is concentrated in liver, where it persists for a month after single
dose.
It is slowly metabolized and excreted, and it can accumulate.
Its half life in plasma is 5 days.
The use of these, are limited by their toxicities and close clinical
observations is necessary when these drugs are administered.
They should not be taken for more than 5 days.
Dehydroemetine is only available under a compassionate investigational
new drug protocol through the Centers of disease Control and Prevention.
The untoward effects are pain at the site of infection, transient nausea,
cardiotoxicity, neuromuscular weakness, dizziness, and rashes.
14. Luminal Amebicides
Iodoquinol
Iodoquinol, a halogenated 8- hydroxy quinolone.
It is effective against Entamoeba histolytica, luminal trophozite and
cyst form.
Side effects include rashes, diarrhea, dose- related neuropathy,
including rare optic neuritis. Long term use of drug should be avoided.
Paromomycin
Aminoglycosides antiamebicides; alternative agent for
cryptosporidiosis.
Not significantly absorbed from GIT, so effective against the intestinal
(luminal) form of E. histolytica and tapeworm.
15. Excreted in urine.
Its antiamoebic action is due to
effect on cell membranes, causing
leakage and by reducing the
population of intestinal flora.
Adverse effects
Gastrointestinal distress
Diarrhoea