Anti Amoebic Drugs
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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
++
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
++
A luminal agent (similar to no.1)A luminal agent (similar to no.1)
Thank YouThank You