ANTI AMOEBIC

DRUGS
Tissue amoebicides
- Intestinal & extraintestinal amoebiasis:
Nitroimidazoles: Metronidazole, Tinidazole,
Secnidazole, Ornidazole, Satranidazole
Alkaloids: Emetine, Dehydroemetine
- Extraintestinal amoebiasis only: Chloroquine
Luminal amoebicides
Amides: Diloxanide furoate, Nitazoxanide
8-Hydroxyquinolines: Iodochlorohydroxyquin
(Clioquinol), Diiodohydroxyquin (Iodoquinol)
Antibiotics: Tetracyclines, Paromomycin
 Metronidazole
 It has broad-spectrum cidal activity against
protozoa & anaerobes
 MOA: a prodrug, requires reductive
activation of nitro group (by accepting
electrons)- interfere with energy metabolism
 The highly reactive nitro radical kills
organisms by radical mediated mechanisms
targeting DNA and other biomolecules
 ↑ed level of O2 -↓ metronidazole cytotoxicity
 Absorbed completely in upper intestine
 Penetrate well in all body tissues (except
placenta) and fluids (saliva, CSF, semen,
vaginal fluid, breast milk)
 Metabolized in liver; t/2 – 8 hrs
 ADRs: MC are nausea, headache, metallic
taste;
Neurotoxicity (seizure, neuropathy etc.);
Disulfiram like reaction with alcohol;
Mutagenic potential
 Dose should be reduced in patients with
severe liver disease
 Rifampin/ phenobarbitone - ↑ clearance &
cimetidine ↓ clearance of metronidazole
 It retards metabolism of oral anticoagulant
 Uses: Metronidazole
 Amoebiasis
 Giardiasis
 Trichomoniasis
 H. pylori infection
 Pseudomembranous enterocolitis
 Infection with anaerobes
 Oral infections (ulcerative gingivitis, trench
mouth) caused by spirochete - fusobacterium
Tinidazole: As efficacious as metronidazole
 DOA is longer (t/2=12hr); better tolerated
 Once daily administration is possible
Secnidazole
 Slower metabolism (t/2 life up to 30 hrs)
 Single 2 g dose is effective in amoebiasis
Satranidazole
 Well tolerated: less nausea, vomiting or
metallic taste; lack of neurological SEs;
and no disulfiram-like reactions
 Emetine
 An alkaloid derived from Ipecac
 Directly kills trophozoites but not cysts
 Dehydroemetine is less toxic congener
 Acts by inhibiting protein synthesis
 Faster action than metronidazole
 Highly effective in liver abscess (reserve drug)
 Always given s.c/i.m
 Concentrated in liver and excreted very slowly
over 1 month (t/2 is 5 days)
 Not to be taken for > 10 days
 Cumulative toxicity: if repeated within 6
weeks
 ADRs: pain at injection site, nausea,
vomiting, cardiotoxicity (arrhythmia, CHF,
myocarditis, hypotension etc.),
neuromuscular weakness
 Contraindicated in pregnancy/cardiac/renal
dis.
 Give luminal amoebicide after emetine to
eradicate the cyst forming trophozoites
 Chloroquine
 Concentrated in liver, used in hepatic
amoebiasis only
 Completely absorbed in upper intestine, not so
concentrated in the intestinal wall, not
effective as intestinal or luminal agent
 Efficacy similar to emetine in abscess, but
duration of treatment is longer and relapses
more frequent
 A luminal agent must always be given with it
or after
 Diloxanide furoate
 Highly effective luminal amoebicide
 Directly kills trophozoites producing cysts
 No systemic antiamoebic activity despite
diloxanide absorption from GIT
 Diloxanide furoate exerts no antibacterial
action
 less effective in invasive amoebic dysentery
- poor tissue amoebicide
 SEs: flatulence (most common), nausea
 Given after tissue amoebicide to eradicate
cysts
 Nitazoxanide
 After oral administration converted to
active metabolite “tizoxanide”
 Interferes with PFOR enzyme dependent
electron transfer reaction
 Used for giardiasis and cryptospordiosis
and as luminal amoebicide in amoebiasis
 SEs: Greenish tint to urine
 Paromomycin
 An aminoglycoside – action confined to GIT
 Inhibits protein synthesis (30S ribosome)
 100% drug is recovered in faeces
 Ototoxic & nephrotoxic on parenteral use
 Effective against luminal forms of amoeba only
 Used alone to treat asymptomatic cyst passer
 Preferred agent during pregnancy
 Other uses: giardiasis during pregnancy;
cutaneous leishmaniasis (topical); visceral
leishmaniasis (parenteral)
 8-hydroxyquinolines
 Kill cyst forming trophozoites only
 Not effective in acute dysentery but effective in
chronic intestinal amoebiasis
 Less efficacious than D. furoate
 Iodoquinol is safer - Dose should not exceed 2g/d
 SEs: Subacute myelo-
myelo-optic neuropathy (SMON)
may lead to loss of vision; peripheral neuropathy;
Iodism (furunculosis, inflammation of mucous
membranes), acute hypersensitivity to iodine;
goiter on prolonged use
1. Asymptomatic intestinal infection
Diloxanide furoate, 500 mg TID for 10 days
OR
Paromomycin, 10 mg/kg TID for 7 days

2. Acute symptomatic intestinal infection

Metronidazole, 750 mg TID (or 500 mg IV every
6 hours) for 10 days OR
Tinidazole, 2 g OD for 3 days
+
A luminal agent (similar to No. 1)
3. Liver abscess, other extraintestinal dis.
Similar to No. 2 OR
Alternative therapy:
Dehydroemetine or emetine 1 mg/kg
SC/IM for 8–
8–10 days, followed by (liver
abscess only) chloroquine,
chloroquine, 500 mg BD for 2
days, then 500 mg daily for 21 days
+
A luminal agent (similar to no.1)
Thank You