TREATMENT OF

AMOEBIASIS &

GIARDIASIS

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

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

Classification Of Drugs

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

Metronidazole is selectively toxic to anaerobic microorganisms.

After entering the cell by diffusion, 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.

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.

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.

PHARMACOKINETICS

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.

Adverse Effects

It is contraindicated in: -

Neurological diseases

Blood dyscrasias

First trimester of pregnancy

Chronic alcoholism

CONTRAINDICATIONS

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.

INTERACTIONS

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

Trichomonas vaginitis

Anaerobic bacterial infections

Pseudomembranous enterocolitis

Ulcerative gingivitis, trench mouth

Peptic ulcer disease

ALSO USED IN…

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).

TINIDAZOLE

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.

SECNIDAZOLE

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.

ORNIDAZOLE

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.

SATRANIDAZOLE

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.

EMETINE

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.

CHLOROQUINE

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

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.

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

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 .

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.

TETRACYCLINES

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.

DRUGS FOR GIARDIASIS

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 tometronidazole or tinidazole.

• It has also been used in bacterial enteritis, foodpoisoning diarrhoeas & bacillary dysentery, but is nota first line treatment for any of these.

• Furazolidone is partly absorbed fromintestines & excreted in urine which turns orange.

• Side effects are mild & infrequent– nausea,headache, dizziness.