TREATMENT OF

AMOEBIASIS &
GIARDIASIS
 AMOEBIASIS

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.
 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
 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.
 Metronidazole is selectively toxic to anaerobic
microorganisms.
 After entering the cell by diffusion, its nitro 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.
 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.
 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.
 Adverse Effects

Side effects 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 effects.
 CONTRAINDICATIONS

It is contraindicated in:-
 Neurological diseases

 Blood dyscrasias

 First trimester of pregnancy

 Chronic alcoholism
 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 effect.

 Cimetidine can reduce metronidazole metabolism.

 Metronidazole enhances warfarin action by
inhibiting its metabolism.
 USES

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.
ALSO USED IN…

 Trichomonas vaginitis

 Anaerobic bacterial infections

 Pseudomembranous enterocolitis

 Ulcerative gingivitis, trench mouth

 Peptic ulcer disease

 TINIDAZOLE

It is an equally efficacious 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 effects are lower: metallic taste, nausea, rash.
 For Amoebiasis: 2g OD for 3 days( children 30-
50mg/kg/day).
 SECNIDAZOLE

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

 It is potent & directly acting amoebicide – kills

trophozoites but has no effect 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 & stiffness of muscles
 Hypotension, tachycardia, ECG changes &
myocarditis.
 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
effective 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.
 DILOXANIDE FUROATE

 It is highly effective 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 effective in invasive
amoebic dysentery, bcoz of poor tissue amoebicidal
action. However, a single course produces high(80 -
90%) cure rate in mild intestinal amoebiasis.
 Diloxanide furoate is very well tolerated
 Side effects are flatulence, occasional nausea,
itching & rarely urticaria.
 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.
 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
transport energy metabolism in anaerobic
organisms.
 Tizoxanide produced in the body is conjugated &
excreted in urine and bile.
 Nitazoxanide is indicated in giardiasis,
cryptosporidiosis, as well as in amoebic dysentery as
luminal amoebicide.
 Abdominal pain, vomiting & headache are mild &
infrequent side effects.
 Dose: 500mg (children 7.5 mg/kg) BD for 3 days.
 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.
 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.
 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, efficacy high(80 -
90%) & tolerability good.
 Quiniodochlor:- 250mg TDS for 7 days is a
somewhat less effective alternative.
 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 effects are mild & infrequent– nausea,
headache, dizziness.