Entamoeba histolytica is a protozoan parasite that causes amoebiasis. It is transmitted through the oral-fecal route by ingesting cysts from contaminated food or water. In the intestines, cysts excyst into trophozoites which multiply and may invade the intestinal wall, causing dysentery. Trophozoites can spread to other organs through the bloodstream. Metronidazole is effective against both intestinal and tissue infections, as it is activated by anaerobic metabolism and kills the trophozoites. Other nitroimidazole derivatives like tinidazole and ornidazole are also used to treat amoebiasis.

1. OM NAMAH SHIVAYAH, SHREE KRISHAN SHARNAM MAMAH

2. LIFE CYCLE OF Entamoeba histolytica

3. Amoebiosis
 Amebiasis is an infectious disease caused by a free-living amoebic parasite
called Entamoeba histolytica (Protozoa)
 It is a Protozoal disease.
 The organism infects the bowel and causes gastroenteritis.
 Mode of transmission- Oro- fecal route means infection occurs by ingestion
of cysts (generally from fecally contaminated food or water)
 Excystation occurs in the ileum of the small intestine.
 Trophozoites multiply by binary fission in the large intestine. Most remain
in the lumen of the intestine, however, some may invade the intestinal
mucosa, enter the bloodstream and develop in extraintestinal sites.
Symptoms----Cyst formation is triggered by the dehydration of gut
contents in asymptomatic carriers.
 It is more common in countries with poor sanitation.
 The incubation period may last from days to weeks before symptoms
appear.
 This disease spread through food and drinks that are contaminated by
Entamoeba histolytica.

4. Invasive forms of the disease lead to amoebic dysentery in which the trophozoites
invade the intestinal wall, leading to the formation of amoebic ulcers. This results
in severe diarrhea with blood and mucus present. In such cases it is important to
identify E. histolytica in the stools to differentiate among other causes of
dysentery.
If trophozoites penetrate the intestinal wall, serious problems can occur,
including liver abcesses, or spread to the lungs and brain, usually resulting in
death.
Asymptomatic infections are responsible for the spread of the parasite with
numerous cysts being passed in normal stools. Diarrheic stools primarily contain
trophozoites which cannot persist in the environment.
Infections of E. histolytica vary in intensity from asymptomatic to severe or fatal
invasions.
Symptoms/Pathology

5. Classification of Anti- amoebic drugs
Drugs effective in intestinal or luminal or local amoebiosis
Diloxanide
Iodoquinolone
Drugs effective only in tussue or hepatic amoebiosis
Chloroquine
Dihydroemetine
Drugs effective in both intestinal and Hepatic amoebiosis
Nitroimidazole dvt
Eg. Metronidazole
Tinidazole
Ornidazole

6. Intestinal amebiasis-
 Asymptomatic intestinal infection-eg. Diloxanide fuorate
 Mild/Moderate/Severe intestinal infection(Dysentery)-
eg. Nitroimidazole dvt. (Metronidazole, Tinidazole, Ornidazole)
Other pattern of classification
Hepatic amebiasis-
 Nitroimidazole dvt. (Metronidazole, Tinidazole,
Ornidazole)

7. Drugs effective in intestinal or luminal or local
amoebiosis
 Diloxanide
Directly amebicidal
MOA-
 Diloxanide furoate (Furamide) is split into diloxanide and furoic acid
(depth bacteria)
 Most of the diloxanide is absorbed (and conjugated to the
glucuronide-which is rapidly excreted in the urine)
 Unabsorbed diloxanide is amebicidal
S/e- Flatulance
Diloxanide (IUPAC Name)-
4-[(Dichloroacetyl)(methyl)amino]phenyl
furan-2-carboxylate

8. Iodoquinolone(IUPAC Name)-
5,7 di-iodo-8- hydroxy quinoline
Iodoquinolone
Quinoline ring system is present in this drug.
Effectiveness limited to bowel luminal organisms (i.e. not
effective against intestinal wall/extra intestinal tissue trophozoites)
Poor absorption (90% unabsorbed)
Renal excretion-following glucuronidation
May interfere with some thyroid function tests (for up to six months buying
increasing proteins-bound serum iodine, which decreases 131I uptake.
S/E- On long term use-Goiter
Neurotoxicity (potentially severe)
Green stool
Note- Green stool is an indication of Iodoquinolone therepy
C/I- Optic neuropathy
Renal disease
Thyroid disease
Hepatic disease (other than secondary to amebiasis)

9. Drugs effective only in tissue or hepatic
amoebiosis
Chloroquine
MOA-High liver concentrations (concentrates in liver) So
effective against hepatic amoebiosis
Note-Very effective in combination with dihydroemetine or
emetine for Prevention/treatment of amebic liver abscess
Emetine & Dehydroemetine
Parenteral administration because oral administration may cause
vomiting (emetine can be derived from ipecac)
MOA-By Parenteral administration drug stored mainly in the Liver
So effective against hepatic amoebiosis
Use-act only against trophozoites

10. Drugs effective in both intestinal and Hepatic
amoebiosis
Nitroimidazole dvt-
 highly effective against anaerobic micro
organism and parasitic infection.
 Nitro group is highly reactive in nature and
responsible for its Pharmacological action
(Cidal in nature)
MOA- Metroinidazole represents its category
Nitroimidazole dvt/Metronidazole is reduced by the pyruvate:ferredoxin
oxidoreductase system in obligate anaerobes, which alters its chemical
structure. Reduction of Nitroimidazole dvt/Metronidazole creates a
concentration gradient that drives uptake of more drug and promotes
formation of intermediate compounds and free radicals that are toxic to
the cell.
IUPAC name-
5-Nitro-1H-imidazole

11. Metronidazole
2-(2-methyl-5-nitro-1H-
imidazol-1-yl)ethanol
MOA
Metronidazole undergoes chemical reduction by ferredoxin or ferredoxin-
related processes
Reduced-products are responsible for bacteriocidal effects against
anaerobic bacteria
Amebiasis: metronidazole (Flagyl) kills Entamoeba histolytica trophozoites (but
not cysts)
Note-In dracunculiasis: metronidazole (Flagyl) Effexor anti-inflammatory

12. Metronidazole
S/e-
Carcingenic
 Mutagenic
 Cell mediated immunity suppression
 Metalic Taste
 Alcohal intolerance
Reddish brown coloration of urine
 Stevens–Johnson syndrome -Metronidazole alone rarely causes Stevens–
Johnson syndrome, but is reported to occur at high rates when combined with
mebendazole
Reddish Brown coloration of Urine- indication of metronidazole
therapy
Alcohol intolerance- Avoid alcohal during therapy (24hrs before and
48 hrs after last dose of metronidazole
Note- Disulfiram (Use in treatment of alcohol addicts) and Niclosemide
(Antiworm) –Also show alcohol intolerance

13. Metranidazole Uses
 Amoebic dysentry and Hepatic Abscess
 Trichomonas infection (T. vaginititis)
 Giarrdia infection (Giardia lambelis)
 Ulceration of gums (Gingivitis)
D/I-
 Metranidazole potentiate anticoagulant effect of coumarin anticoagulant.
Tinidazole
1-(2-ethylsulfonylethyl)-2-
methyl-5-nitro-imidazole
It is chemically similar to
metronidazole
It is prefer over metronidazole as it is
more potent, longer acting and less
side effects

14. Ornidazole
1-Chloro-3-(2-methyl-5-nitro-1H-
imidazol-1-yl)propan-2-ol
MOA
After passive absorption into bacterium cell, the nitro group of ornidazole
is reduced to amine group by ferrodoxin type redox system.
The formation of redox intermediate intracellular metabolites is believed
to be the key component of microorganism killing for Ornidazole.
The drug is active against anaerobic bacteria