1. Amoebiasis

2. An infection of the intestinal tract
AMEBIASIS
An infection of the intestinal tract
Occurs due to ingestion of foods or water
Contaminated with Entameba Histolytica cysts

3. AMEBIASIS
Was first described by Lambl and Losch in a dysenteric patient (1859)
Councilman and lafleur in described amoebic liver abscess.
Schauudinn (1903) differentiated pathogenic and nonpathogenic types of Amoebae
A disease caused by a one-celled parasite called Entamoeba histolytica.
More common in people who live in tropical areas with poor sanitary conditions.

4. AMOEBIASIS A MAJOR HEALTH PROBLEM
Estimated to cause 70,000 deaths per year world wide
Severe Amoebiasis infections (known as invasive amoebiasis).
Invasion of the intestinal lining causes amoebic dysentery or amoebic colitis.
Transmitted by :-
Fecal contamination of drinking water and foods
Direct contact with dirty hands or objects
By sexual contact
SYMPTOMS:-
Range from mild diarrhoea to dysentery with blood and mucus in the stool.
Gastrointestinal including
Diarrhoea, vomiting, abdominal pain or discomfort and fever.
Symptoms take from a few days to a few weeks to develop
Most infected people are asymptomatic but this disease has the potential to make the sufferer dangerously ill.

5. SYMPTOMS Gastrointestinal including
Diarrhoea, vomiting, abdominal pain or discomfort and fever.
Symptoms take from a few days to a few weeks to develop
Most infected people are asymptomatic but this disease has the potential to make the sufferer dangerously ill, especially if there is any suggestion of immunocompromised.

6. LIFE CYCLE Entamoeba histolytica exists in two forms:
1.Cysts (infective):
• Can survive outside the human body.
• Transform to trophozoites.
2. Trophozoites (non-infective; invasive):
•Reproduce
•They may feed on intestinal bacteria or
Invade and ulcerate wall of large intestine
May migrate to liver or other tissues.
•Transform to cysts which are excreted in feces.

7. LIFE CYCLE 1. Cysts ingestion. 2. Formation of trophozoites
3. Penetration of intestinal wall
4. Multiplication of trophozoites within colon wall.
5. Systemic invasion.
6. Cyst formation in rectum and excretion in feces.

9. EVENTS ON AMOEBIASIS

10. LIFE CYCLE Precystic stage:
Trophozoites living in the intestine undergo binary fission
Round and 10-20µ in size
Cystic stage:
Enters by forming a delicate cystwall around itself
Size is 12µ
Quadrinucleated cyst is the infective stage of the parasite
Ingested by human host pass along with food into the small intestine
Wall of cyst dissolved by trypsin
Tetranucleate emerges out from cyst into lumen of large intestine called excystment
The Trophozoite Stage:
10-40 µm, fragile.
Uninucleate
Erythrophagocytosis
Reside, feed and multiply by binary fission in lumen of colon.
May invade – Lytic & physical mechanisms and metastasize to liver and other extra- intestinal sites.

11. CLINICAL PRESENTATIONS
Asymptomatic Intestinal infection
(Carriers, passing cysts)
Mild to moderate intestinal disease
(Nondysenteric Colitis)
Severe Intestinal infection ( Dysentery)
Hepatic abscess, ameboma (localized granulomatous lesion of colon) and other extraintestinal disease

12. Light Microscopy of Stool
DIAGNOSIS
Light Microscopy of Stool
Identification of trophozoites / cysts in fresh stool
Serology
Stool antigen-detection test
Sensitive and Specific
A sample of freshly collected Fecal specimen

13. ANTIAMOEBIC DRUGS

14. CLASSIFICATION TISSUE AMEBICIDES For treating intestinal infections.
LUMINAL AMEBICIDES
For treating intestinal infections.
Amide:
Diloxanide furoate, Nitazoxanide
(b) 8-Hydroxyquinolines :
Quiniodochlor, Diiodohydroxyquin
(c) Antibiotics :
Tetracyclines
TISSUE AMEBICIDES
Used to destroy amoebae that have invaded tissue, rapidly absorbed into the bloodstream and transported to the site of infection.
(a) For both intestinal and extraintestinal amoebiasis:
A)Nitroimidazoles:
Metronidazole, Tinidazole, Secnidazole,Ornidazole, Satranidazole
B) Alkaloids:
Emetine, Dehydroemetine
(b) For extraintestinal amoebiasis only:
Chloroquine

15. METRONIDAZOLE Mixed amoebicide
Choice for intestinal &extraintestinal amoebiasis.
Acts on trophozoites.
Has no effect on cysts.
Mechanism:
Nitro group of metronidazole is reduced by protozoan.
Leading to cytotoxic reduced product
That binds to DNA and proteins
Resulting into parasite death.

16. MECHANISM Selectively toxic to anaerobic microorganisms.
After entering the cell by diffusion
Its nitro group is reduced by certain redox proteins (operative only in anaerobic microbes)
To highly reactive nitro radical which exerts cytotoxicity.
Acts as an electron sink
Competes with the biological electron acceptors of the anaerobic organism
For the electrons generated by the pyruvate : ferredoxin oxidoreductase (pfor) enzyme pathway of pyruvate oxidation.
The energy metabolism of anaerobes is, thus, disrupted.
Aerobic environment attenuates cytotoxicity

17. RESISTANCE:
Develop resistance become deficient in the mechanism that generates the reactive nitro radical from it.
PHARMACOKINETICS:
Given orally or IV.
Absorption is rapid and complete.
▪ Due to rapid absorption from GIT, not reliably effective against luminal parasites.
Wide distribution to all tissues and body fluids (CSF, saliva, milk).
Plasma protein binding is low ( < 20%).
Plasma half life is 8 h
Metabolized in liver
Excreted in urine

18. ADVERSE EFFECTS
Relatively frequent and unpleasant, but mostly nonserious.
Anorexia (an emotional disorder characterized by an obsessive desire to lose weight by refusing to eat)
Nausea
Metallic taste
Abdominal cramps
Looseness of stool.
Less frequent side effects are-
Headache,
Glossitis (inflammation of the tongue) ,
Dryness of mouth,
Dizziness(a feeling that you are about to fall),
Rashes
Neutropenia (abnormally low number of neutrophils).
Prolonged administration
Peripheral neuropathy (damage to nerves of the peripheral nervous system) and
CNS effects.
Very high doses:-
Seizures (Due to the electrical discharge in the nervous system)
If the solution is not well diluted:-
Thrombophlebitis of the injected vein (inflammation of the wall of a vein with associated thrombosis) occurs

19. Ulcerative gingivitis, trench mouth
CLINICAL USES
Extraluminal amoebiasis (combined with luminal amebicide).
Giardiasis
(Infection of the intestine with a flagellate protozoan which causes diarrhea and other symptoms.)
Trichomoniasis
(An infection caused by parasitic trichomonads (genus Trichomonas), chiefly affecting the urinary tract, vagina, or digestive system.)
Broad spectrum of Anaerobic bacteria
Helicobacter pylori infection
Pseudomembranous colitis (Clostridium defficile).
(is an infection of the colon.)
Ulcerative gingivitis, trench mouth
(a severe form of gingivitis that causes painful, infected, bleeding gums and ulcerations. )
Guinea worm infestation
(a painful and debilitating infestation contracted by drinking stagnant water contaminated with Guinea worm larvae that can mature inside a human's abdomen until the worm emerges through a painful blister in the person's skin)
CONTRAINDICATIONS / PRECAUTIONS
Pregnancy and nursing women.
Alcohol intake
CNS diseases
Severe hepatic disease
Severe renal disease

20. TINIDAZOLE Efficacious as metronidazole
Similar to it in every way except:
Metabolism is slower
T1/2 is -12 hr
Duration of action is longer
More suited for single dose or once daily therapy
better tolerated
Lower side effects
SECNIDAZOLE
A congener of metronidazole
Same spectrum of activity and potency.
Oral administration
Absorption is rapid and complete
Metabolism is slower
Plasma t1/2 of hours.
Side effect similar to metronidazole
USES:
Intestinal Amoebiasis
Giardiasis
Trichomonas Vaginitis
Nonspecific Bacterial Vaginosis
Hepatic Amoebiasis.

21. Activity similar to metronidazole Slowly metabolized-
SATRANIDAZOLE
Nitroimidazole
Longer t1/2 -14 hr.
ADVANTAGES ARE:
Better tolerability,
No nausea, vomiting or metallic taste,
Absence of neurological and disulfiram-like reactions.
USE :
Amoebiasis
Giardiasis
Trichomoniasis
ORNIDAZOLE
Activity similar to metronidazole
Slowly metabolized-
Longer t1/ hr
USES:
Amoebiasis,
Giardiasis,
Trichomoniasis,
Anaerobic Infections
Bacterial Vaginosis.
Side effect profile is also similar.

22. EMETINE AND DEHYDROEMETINE
CHEMISTRY :
Emetine hydrochloride is a plant alkaloid derived from Cephaelis ipecawanha.
Dehydroemetine is a synthetic analogue
PHARMACOKINETICS:
Variable oral absorption.
Given preferably S.C. but could be given by IM, NEVER I.V
Plasma half life is 5 days.
Concentrated in Liver, Lungs, Spleen, Kidney, Cardiac muscle and Intestinal wall.
MECHANISM
Act on tissue trophozoites
No effect on cysts
Acts by inhibiting protein synthesis in amoebae
By arresting intraribosomal translocation of trna- amino acid complex

23. Dehydroemetine is less toxic than emetine
ADVERSE EFFECTS
Dehydroemetine is less toxic than emetine
Pain at site of injection, abcesses.
GIT: Nausea, vomiting, diarrhoea.
Neuromuscular weakness
Serious toxicities:
Cardiotoxicity
- Cardiac arrhythmias,
- Hypotension
- Heart failure
CLINICAL USES
Amoebic liver abscess
Intestinal wall infections
Severe forms of amebiasis
Acute amoebic Dysentery
(dehydroemetine is preferable due to less toxicity)
CONTRAINDICATIONS
Heart disease
Kidney disease
Pregnancy

24. DEHYDROEMETINE Semisynthetic derivative of emetine Equally effective
Less toxic to the heart.
Thus, it is preferred over emetine by most physicians.

25. CHLOROQUINE Antimalarial drug Used in combination
For amebic liver Diseases
Followed by luminal amebicide.
Kills trophozoites
Highly concentrated in liver.
Therefore used in hepatic amoebiasis only.
Completely absorbed from the upper intestine and not so highly concentrated in the intestinal wall .
Amoebae do not develop resistance to chloroquine.
Because of safety of chloroquine, it may be given concurrently or immediately after a course of metronidazole
To ensure complete eradication of the trophozoites in liver.
A luminal amoebicide must always be given with or after chloroquine to abolish the luminal cycle.
It is now employed only when metronidazole is not effective or not tolerated.

26. DILOXANIDE FUROATE CHEMISTRY PHARMACOKINETICS PHARMACODYNAMICS
Ester of diloxanide + furoic acid
PHARMACOKINETICS
Given orally.
Split in the intestine
Diloxanide is absorbed, conjugated to form a glucoronide which is excreted in urine
Diloxanide is a weaker amoebicide than its furoate ester : no systemic antiamoebic activity.
PHARMACODYNAMICS
Highly effective luminal amoebicide: directly kills trophozoites responsible for production of cysts.
Diloxanide furoate exerts no antibacterial action.
Less effective in invasive amoebic dysentery, because of poor tissue amoebicidal action.
High cure rate in mild intestinal amoebiasis and in asymptomatic cyst passers.

27. THERAPEUTIC USES ADVERSE EFFECTS CONTRAINDICATIONS:
For mild intestinal/ asymptomatic intestinal infection
Given after any tissue amoebicide to eradicate cysts.
For eradication of infection given along with all forms of amebiasis.
Combined use with metronidazole/ tinidazole is quite popular.
Some chronic cases require repeat courses for eradication.
ADVERSE EFFECTS
Flatulence ( the accumulation of gas in the alimentary canal)
Nausea, vomiting, abdominal cramps.
No serious adverse effects
CONTRAINDICATIONS:
- Pregnancy
- Children (less than 2 years).

28. NITAZOXANIDE Salicylamide congener
Use in treatment of giardiasis is also active against E. Histolytica, T. Vaginalis, cryptosporidium, H. Pylori, ascaris, H. Nana and some other protozoa and helminths.
It is a prodrug which on absorption is converted to the active form tizoxanide.
MECHANISM OF ACTION:
An inhibitor of PFOR enzyme that is an essential pathway of electron transport energy metabolism in anaerobic organisms.
Tizoxanide produced in the body is conjugated and excreted in urine and bile.
USES:
Giardiasis (infection of the intestine with a flagellate protozoan, which causes diarrhoea and other symptoms.)
Cryptosporidiasis (is a parasitic disease caused by Cryptosporidium)
Amoebic dysentery as luminal amoebicide.
Against metronidazole- resistant giardia (an intestinal infection marked by abdominal cramps, nausea and watery diarrhea)
SIDE EFFECTS:
Abdominal pain
Vomiting
Headache

29. TETRACYCLINES Directly inhibit amoebae only at higher concentrations.
The older tetracyclines are incompletely absorbed in the small intestine, reach the colon in large amounts and inhibit the bacterial flora with which entamoebae live symbiotically.
Indirectly reduce proliferation of entamoebae in the colon
Especially valuable in chronic, difficult to treat cases with only the luminal cycle and little mucosal invasion.
Adjuvant role in conjunction with a more efficacious luminal amoebicide.
They are not good for acute dysentery and for hepatic amoebiasis.

30. 8-HYDROXYQUINOUNES Active against
USES
Lumen amoebicide.
For eradication of infection given along with tissue amoebicide (metronidazole).
ADVERSE EFFECTS
Peripheral neuropathy including optic neuritis
GIT: Nausea, vomiting, diarrhoea.
Enlargement of the thyroid gland.
Agranulocytosis (A deficiency of granulocytes in the blood).
Iodine sensitivity.
Drug interfere with thyroid function tests (increase protein- bound serum iodine thus decrease in measured 131I uptake).
SPECTRUM:
Active against
Entamoeba, giardia, trichomonas, some fungi (dermatophytes, candida) and some bacteria.
They kill the cyst forming trophozoites in the intestine
Do not have tissue amoebicidal action
Valueless in extraintestinal amoebiasis
Intestine absorption is variable.
Therapeutic concentrations are not attained in the intestinal wall or in liver.
The unabsorbed part reaches lower bowel and acts on luminal cycle of amoebae.

31. CONTRAINDICATIONS
Optic neuropathy (Disease or dysfunction of one or more peripheral nerves)
Thyroid disease
Sensitivity to iodine
Severe kidney disease
Discontinued if it produces persistent diarrhea or signs of iodine toxicity (dermatitis, urticaria (A rash of round, red welts on the skin that itch intensely), pruritus (Severe itching of the skin), fever)

32. TREATMENT OF AMOEBIASIS
1. INVASIVE INTESTINAL AMOEBIASIS
Metronidazole/tinidazole are the drugs of choice.
Secnidazole, ornidazole, satranidazole are the alternatives.
Adjuvant measures for diarrhoea and abdominal pain may be needed.
The above treatment should be followed by a course of luminal amoebicide to eradicate E. histolytica from the colon and to prevent carrier (cyst passing) state.

33. 2. CHRONIC INTESTINAL AMOEBIASIS/ASYMPTOMATIC CYST PASSERS
These cases are more difficult to treat, two or more repeated courses may be needed.
Diloxanide furoate produces high cure rates and is the drug of choice.
Nitazoxanide is an alternative.
A tetracycline may be given concurrently with the luminal amoebicide in cases which fail to clear completely.

34. 3. AMOEBIC LIVER ABSCESS A serious disease
Complete eradication of trophozoites from the liver is essential to avoid relapses.
Metronidazole/tinidazole are the first choice drugs effective in> 95% cases.
Dehydroemetine is to be used only if metronidazole cannot be given for one reason or the other, and in patients not cured by metronidazole.
A luminal amoebicide must be given later to finish the intestinal reservoir of infection.
A course of chloroquine may be administered after that to ensure that no motile forms survive in the liver.

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