ANTI AMOEBICANTI AMOEBICDRUGSDRUGSDRUGSDRUGS

Tissue amoebicides

- Intestinal & extraintestinal amoebiasis:

Nitroimidazoles: Metronidazole, Tinidazole,

Secnidazole, Ornidazole, SatranidazoleSecnidazole, Ornidazole, Satranidazole

Alkaloids: Emetine, Dehydroemetine

- Extraintestinal amoebiasis only: Chloroquine

Luminal amoebicides

Amides: Diloxanide furoate, Nitazoxanide

8-Hydroxyquinolines: Iodochlorohydroxyquin(Clioquinol), Diiodohydroxyquin (Iodoquinol)

Antibiotics: Tetracyclines, Paromomycin

MetronidazoleMetronidazole

It has broad-spectrum cidal activity againstprotozoa & anaerobes

MOA: a prodrug, requires reductiveactivation of nitro group (by acceptingactivation of nitro group (by acceptingelectrons)- interfere with energy metabolism

The highly reactive nitro radical killsorganisms by radical mediated mechanismstargeting DNA and other biomolecules

↑ed level of O2 -↓ metronidazole cytotoxicity

Absorbed completely in upper intestineAbsorbed completely in upper intestine

Penetrate well in all body tissues (exceptPenetrate well in all body tissues (exceptplacenta) and fluids (saliva, CSF, semen,placenta) and fluids (saliva, CSF, semen,vaginal fluid, breast milk)vaginal fluid, breast milk)vaginal fluid, breast milk)vaginal fluid, breast milk)

Metabolized in liver; t/2Metabolized in liver; t/2 –– 8 hrs8 hrs

ADRs:ADRs: MC are nausea, headache, metallicMC are nausea, headache, metallictaste;taste;

Neurotoxicity (seizure, neuropathy etc.);Neurotoxicity (seizure, neuropathy etc.);Disulfiram like reaction with alcohol;Disulfiram like reaction with alcohol;Mutagenic potentialMutagenic potential

Dose should be reduced in patients withDose should be reduced in patients withsevere liver diseasesevere liver disease

Rifampin/ phenobarbitoneRifampin/ phenobarbitone -- ↑ ↑ clearance &clearance &ccimetidineimetidine ↓↓ clearance of metronidazoleclearance of metronidazoleccimetidineimetidine ↓↓ clearance of metronidazoleclearance of metronidazole

It retards metabolism of oral anticoagulantIt retards metabolism of oral anticoagulant

Uses: MetronidazoleUses: Metronidazole

AmoebiasisAmoebiasis

GiardiasisGiardiasis

TrichomoniasisTrichomoniasis

H. pylori infectionH. pylori infection H. pylori infectionH. pylori infection

Pseudomembranous enterocolitisPseudomembranous enterocolitis

Infection with anaerobesInfection with anaerobes

Oral infections (ulcerative gingivitis, trenchOral infections (ulcerative gingivitis, trenchmouth) caused by spirochetemouth) caused by spirochete -- fusobacteriumfusobacterium

Tinidazole: As efficacious as metronidazole

DOA is longer (t/2=12hr); better tolerated

Once daily administration is possible

SecnidazoleSecnidazole

Slower metabolism (t/2 life up to 30 hrs)

Single 2 g dose is effective in amoebiasis

Satranidazole

Well tolerated: less nausea, vomiting ormetallic taste; lack of neurological SEs;and no disulfiram-like reactions

EmetineEmetine

An alkaloid derived from IpecacAn alkaloid derived from Ipecac

Directly kills trophozoites but not cystsDirectly kills trophozoites but not cysts

Dehydroemetine is less toxic congenerDehydroemetine is less toxic congener

Acts by inhibiting protein synthesisActs by inhibiting protein synthesis

Faster action than metronidazoleFaster action than metronidazole

Highly effective in liver abscess (reserve drug)Highly effective in liver abscess (reserve drug)

Always given s.c/i.mAlways given s.c/i.m

Concentrated in liver and excreted very slowlyConcentrated in liver and excreted very slowly

over 1 month (t/2 is 5 days)over 1 month (t/2 is 5 days)

Not to be taken for > 10 daysNot to be taken for > 10 days

Cumulative toxicity: if repeated within 6Cumulative toxicity: if repeated within 6weeksweeks

ADRs:ADRs: pain at injection site, nausea,pain at injection site, nausea,vomiting, cardiotoxicity (arrhythmia, CHF,vomiting, cardiotoxicity (arrhythmia, CHF,vomiting, cardiotoxicity (arrhythmia, CHF,vomiting, cardiotoxicity (arrhythmia, CHF,myocarditis, hypotension etc.),myocarditis, hypotension etc.),neuromuscular weaknessneuromuscular weakness

Contraindicated in pregnancy/cardiac/renalContraindicated in pregnancy/cardiac/renaldis.dis.

Give luminal amoebicide after emetine toeradicate the cyst forming trophozoites

ChloroquineChloroquine

Concentrated in liver, used in hepaticamoebiasis only

Completely absorbed in upper intestine, not soconcentrated in the intestinal wall, noteffective as intestinal or luminal agenteffective as intestinal or luminal agent

Efficacy similar to emetine in abscess, butduration of treatment is longer and relapsesmore frequent

A luminal agent must always be given with itor after

Diloxanide furoate

Highly effective luminal amoebicide

Directly kills trophozoites producing cysts

No systemic antiamoebic activity despitediloxanide absorption from GIT

Diloxanide furoate exerts no antibacterial Diloxanide furoate exerts no antibacterialaction

less effective in invasive amoebic dysentery- poor tissue amoebicide

SEs: flatulence (most common), nausea

Given after tissue amoebicide to eradicatecysts

NitazoxanideNitazoxanide

After oral administration converted toAfter oral administration converted toactive metabolite “tizoxanide”active metabolite “tizoxanide”

Interferes with PFOR enzyme dependentInterferes with PFOR enzyme dependentelectron transfer reactionelectron transfer reactionelectron transfer reactionelectron transfer reaction

Used for giardiasis and cryptospordiosisUsed for giardiasis and cryptospordiosisand as luminal amoebicide in amoebiasisand as luminal amoebicide in amoebiasis

SEs: Greenish tint to urineSEs: Greenish tint to urine

ParomomycinParomomycin

An aminoglycosideAn aminoglycoside –– action confined to GITaction confined to GIT

Inhibits protein synthesis (30S ribosome)Inhibits protein synthesis (30S ribosome)

100% drug is recovered in faeces100% drug is recovered in faeces

Ototoxic & nephrotoxic on parenteral useOtotoxic & nephrotoxic on parenteral use Ototoxic & nephrotoxic on parenteral useOtotoxic & nephrotoxic on parenteral use

Effective against luminal forms of amoeba onlyEffective against luminal forms of amoeba only

Used alone to treat asymptomatic cyst passerUsed alone to treat asymptomatic cyst passer

Preferred agent during pregnancyPreferred agent during pregnancy

Other uses: giardiasis during pregnancy;Other uses: giardiasis during pregnancy;cutaneous leishmaniasis (topical); visceralcutaneous leishmaniasis (topical); visceralleishmaniasis (parenteral)leishmaniasis (parenteral)

88--hydroxyquinolineshydroxyquinolines

Kill cyst forming trophozoites onlyKill cyst forming trophozoites only

Not effective in acute dysentery but effective inNot effective in acute dysentery but effective inchronic intestinal amoebiasischronic intestinal amoebiasis

Less efficacious than D. furoateLess efficacious than D. furoate Less efficacious than D. furoateLess efficacious than D. furoate

Iodoquinol is saferIodoquinol is safer -- Dose should not exceed 2g/dDose should not exceed 2g/d

SEs:SEs: Subacute myeloSubacute myelo--optic neuropathy (SMON)optic neuropathy (SMON)may lead to loss of vision; peripheral neuropathy;may lead to loss of vision; peripheral neuropathy;Iodism (furunculosis, inflammation of mucousIodism (furunculosis, inflammation of mucousmembranes), acute hypersensitivity to iodine;membranes), acute hypersensitivity to iodine;goiter on prolonged usegoiter on prolonged use

1.1. Asymptomatic intestinal infectionAsymptomatic intestinal infection

Diloxanide furoate, 500 mg TID for 10 daysDiloxanide furoate, 500 mg TID for 10 daysOROR

Paromomycin, 10 mg/kg TID for 7 daysParomomycin, 10 mg/kg TID for 7 days

2.2. Acute symptomatic intestinal infectionAcute symptomatic intestinal infectionMetronidazole, 750 mg TID (or 500 mg IV everyMetronidazole, 750 mg TID (or 500 mg IV every6 hours) for 10 days6 hours) for 10 days OROR

Tinidazole, 2 g OD for 3 daysTinidazole, 2 g OD for 3 days

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A luminal agent (similar to No. 1)A luminal agent (similar to No. 1)

3.3. Liver abscess, other extraintestinal dis.Liver abscess, other extraintestinal dis.

Similar to No. 2Similar to No. 2 OROR

Alternative therapy:Alternative therapy:

DehydroemetineDehydroemetine oror emetineemetine 1 mg/kg1 mg/kgDehydroemetineDehydroemetine oror emetineemetine 1 mg/kg1 mg/kgSC/IM for 8SC/IM for 8––10 days, followed by (liver10 days, followed by (liverabscess only)abscess only) chloroquinechloroquine, 500 mg BD for 2, 500 mg BD for 2days, then 500 mg daily for 21 daysdays, then 500 mg daily for 21 days

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A luminal agent (similar to no.1)A luminal agent (similar to no.1)

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