This document discusses treatments for amoebiasis and giardiasis. Metronidazole is the first-line treatment for both infections. It is effective against protozoa including Entamoeba histolytica and Giardia lamblia. For amoebiasis, metronidazole is used to treat intestinal and invasive forms at doses of 400-800 mg daily for 5-10 days. Tinidazole and secnidazole are alternatives with longer half-lives allowing single or once daily dosing. Diloxanide furoate is also used for mild intestinal amoebiasis. Nitazoxanide is a newer treatment effective against various proto

1. TREATMENT OF
AMOEBIASIS &
GIARDIASIS

2. It is the infection caused by protozoa Entamoeba
histolytica.
 It is usually transmitted by faecal transmission of
food & water.
 Mostly present in the areas with poor environmental
sanitation.
AMOEBIASIS

3. Classification Of Drugs
Tissue Amoebicides
A. For both Intestinal & Extraintestinal Amoebiasis:
i. Nitroimidazoles: Metronidazole, Tinidazole,
Secnidazole, Ornidazole, Satranidazole
ii. Alkaloids: Emetine, Dehydroemetine
B. For extraintestinal amoebiasis only: Chloroquine
Luminal Amoebicides
A. Amide: Diloxanide furoate, Nitazoxanide
B. 8-Hydroxyquinolines: Quiniodochlor,
Diiodohydroxyquin
C. Antibiotics: Tetracyclins

4. METRONIDAZOLE
 It has broad spectrum cidal activity against protozoa
including Giardia lamblia & Amoeba.
 Many anaerobic bacteria are sensitive.
 Anaerobic bacteria & G. lamblia also can develop
metronidazole resistance, but this is a clinical
problem only in the case of H.pylori.

5.  Metronidazole is selectively toxic to anaerobic
microorganisms.
 Af ter entering the cell by dif fusion, its nitro gp. is
reduced by certain redox proteins operative only in
anaerobic microbes to highly reactive nitro radical
which exerts cytotoxicity.
 The nitro radical of metronidazole acts as an electron
sink which 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.

6.  Aerobic environment attenuates cytotoxicity of
metronidazole by inhibiting its reductive activation.
Anaerobes which develop metronidazole resistance
become deficient in the mechanism that generates
the reactive nitro radical from it.

7. PHARMACOKINETICS
 Metronidazole is almost completely absorbed from
the small intestines; little unabsorbed drug reaches
the colon.
 It is widely distributed in the body, attaining
therapeutic concentration in vaginal secretion,
semen, saliva & CSF.
 It is metabolized in liver primarily by oxidation &
glucoronide conjugation & excreted in urine.
 Plasma t-half is 8hrs.

8. Adverse Effects
Side ef fects to metronidazole are: -
 Anorexia, nausea, metallic taste & abdominal
cramps.
 Less frequent are– Headache, glossitis, dryness of
mouth, dizziness, rashes & transient neutropenia.
 Prolonged administration may cause peripheral
neuropathy and CNS ef fects.

9. CONTRAINDICATIONS
It is contraindicated in: -
 Neurological diseases
 Blood dyscrasias
 First trimester of pregnancy
 Chronic alcoholism

10. INTERACTIONS
 A disulfiram-like intolerance to alcohol occurs in
some patients taking metronidazole; they should be
instructed to avoid drinking.
 Enzyme inducers may reduce its therapeutic ef fect.
 Cimetidine can reduce metronidazole metabolism.
 Metronidazole enhances war farin action by
inhibiting its metabolism.

11. Amoebiasis:
 Metronidazole is a first line drug for all forms of
amoebic infections.
 For invasive dysentery & liver abscess- 800mg
TDS( children 30-50 mg/kg/day) for 7-10 days.
 For mild intestinal disease—400mg TDS for 5-7
days.
USES

12. ALSO USED IN…
 Trichomonas vaginitis
 Anaerobic bacterial infections
 Pseudomembranous enterocolitis
 Ulcerative gingivitis, trench mouth
 Peptic ulcer disease

13. TINIDAZOLE
It is an equally ef ficacious congener of
metronidazole, similar to it in every way except:
 Metabolism is slower; t1/2 is—12hr; duration of
action is longer; dosage schedules are simpler. Thus
it is more suited for single dose or once daily
therapy.
 Better tolerated
 Side ef fects are lower: metallic taste, nausea, rash.
 For Amoebiasis: 2g OD for 3 days( children 30-
50mg/kg/day).

14.  A congener of metronidazole.
 Absorption af ter oral administration is rapid &
complete.
Metabolism is slower resulting in a plasma t1/2 of
17-29 hrs.
 Dose-- 2g stat.
SECNIDAZOLE

15. ORNIDAZOLE
 It is slowly metabolized.
 Has longer t1/2(12-14hr).
 Dose & duration of regimens for amoebiasis,
giardiasis, trichomoniasis,anaerobic infections &
bacterial vaginosis resemble those for tinidazole.

16. SATRANIDAZOLE
 Another nitroimidazole having longer t1/2(14hr).
 Advantages are: better tolerability– no nausea,
vomiting or metallic taste, absence of neurological &
disulfiram-like reactions & that it does not produce
the acetamide metabolite which is a weak
carcinogen.
 Dose– 300mg BD for 3-5 days in Amoebiasis.

17. EMETINE
 It is potent & directly acting amoebicide– kills
trophozoites but has no ef fect on cysts.
 It acts by inhibiting protein synthesis in amoeba by
arresting intraribosomal translocation of t-RNA-amino
acid complex.
Toxic Effects Of Emetine
 Nausea & vomiting are frequent.
 Abdominal cramps & diarrhoea
 Weakness & stif fness of muscles
 Hypotension, tachycardia, ECG changes &
myocarditis.

18. CHLOROQUINE
 It kills trophozoites of E.histolytica
 Highly concentrated in liver.
 Used in hepatic amoebiasis only. Because it is
completely absorbed from the upper intestine & not
so highly concentrated in intestinal wall– it is neither
ef fective in invasive dysentry nor in controlling the
luminal cycle.
 Dose for amoebic liver abscess: 600mg for 2 days
followed by 300mg daily for 2-3 weeks.

19. DILOXANIDE FUROATE
 It is highly ef fective luminal amoebicide
 Directly kills trophozoites responsible for production
of cysts.
 Furoate ester is hydrolyzed in intestine & the
released diloxanide is largely absorbed.
 Diloxanide is a weaker amoebicide than its furoate
ester & is primarily metabolized by glucuronidation &
is excreted in urine.
 Diloxanide furoate is less ef fective in invasive
amoebic dysentery, bcoz of poor tissue amoebicidal
action. However, a single course produces high(80-
90%) cure rate in mild intestinal amoebiasis.

20.  Diloxanide furoate is very well tolerated
 Side ef fects are flatulence, occasional nausea,
itching & rarely ur ticaria.
 It is the drug of choice for mild intestinal/
asymptomatic amoebiasis.
 Combined use with metronidazole/tinidazole is
quite popular.
 Dose: 500mg TDS for 5-10 days; children
20mg/kg/day.

21. NITAZOXANIDE
 Recently introduced for the treatment of giardiasis
but is also active against E.histolytica, T.vaginalis,
Cryptosporidium, Ascaris.
 It is a prodrug which on absorption is converted to
the active form tizoxanide, an inhibitor of PFOR
enzyme that is an essential pathway of electron
transpor t energy metabolism in anaerobic
organisms.
 Tizoxanide produced in the body is conjugated &
excreted in urine and bile.

22.  Nitazoxanide is indicated in giardiasis,
cryptosporidiosis, as well as in amoebic dysentery as
luminal amoebicide.
 Abdominal pain, vomiting & headache are mild &
infrequent side ef fects.
 Dose: 500mg (children 7.5 mg/kg) BD for 3 days .

23. TETRACYCLINES
 They directly inhibit amoebae only at higher
concentrations.
 The older tetracyclins are incompletely absorbed in
the small intestine, reach the colon in large amounts
 Inhibit the bacterial flora with which Entamoebae
live symbiotically.
 Thus, they indirectly reduce proliferation of
Entamoebae in the colon.
 They are not good for acute dysentery & for hepatic
amoebiasis.

24. DRUGS FOR GIARDIASIS
 Giardia lamblia is a flagellate protozoon which
mostly lives as a commensal in the intestine.
 Invades the mucosa
 Causes diarhhoea requiring treatment.
DRUGS:-
 Metronidazole:- 200mg TDS (children 15mg/kg/day)
for 7 days or 2g daily for 3 days
 Or Tinidazole 0.6g daily for 7 days or 2g single dose
 Or Secnidazole 2g single dose may be considered as
the drugs of choice.

25.  Nitazoxanide:- This prodrug of the PFOR enzyme
inhibitor tizoxanide has recently become available
for the treatment of diarrhoea & dysentery caused by
Giardia lamblia, E.histolytica, C.parvum.
 The dosage schedule is convenient– 500mg (children
7.5mg/kg) twice daily for 3 days, ef ficacy high(80-
90%) & tolerability good.
 Quiniodochlor:- 250mg TDS for 7 days is a
somewhat less ef fective alternative.

26.  Furazolidone: - It is a nitrofuran compound active
against many gram –ve bacilli including Salmonella
& Shigella, also Giardia & Trichomonas.
• For Giardiasis 100mg TDS for 5-7 days is inferior to
metronidazole or tinidazole.
• It has also been used in bacterial enteritis, food
poisoning diarrhoeas & bacillary dysentery, but is not
a first line treatment for any of these.
• Furazolidone is partly absorbed from
intestines & excreted in urine which turns orange.
• Side ef fects are mild & infrequent– nausea,
headache, dizziness.