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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.