2. Objective
• List the drugs used for treatment of amebiasis/giardiasis,
their side effects
• Discuss different groups of drugs for treatment of amebiasis
3. Amebiasis
• Amebiasis caused by Entamoeba hystolytica
• E. dispar does not cause disease
• Around 10% world population affected by amebiasis
• 40-50 mil develop colitis or extraintestinal disease
• Around 40,000 annual death
• Types of diseases
• Colitis, amebic liver abscess
• Metronidazole and Tinidazole cornerstone of treatment
4. Amebiasis…
• Metronidazole so much absorbed
• Concentration may not be adequate in the colon lumen
• Luminal drugs may be required
• Metronidazole is also not effective against cysts
5. Giardiasis
• Giardiasis caused by Giardia intestinalis
• Infection results in either of the following
• An asymptomatic carrier state
• Acute self-limited diarrhea
• Chronic diarrhea, characterized by signs of malabsorption
(steatorrhea) and weight loss
6. Drugs for treatment of Amebiasis / Giardiasis
• Metronidazole/ Tinidazole
• Tinidazole has long half life and administered only for three days
• Paromomycin (luminal for amebic colitis/ liver abscess)
• Iodoquinol (luminal for amebic colitis/ liver abscess)
• Nitazoxanide
8. •The nitro-group very important for its effect against bacteria and
protozoa
•The nitro-group used as an electron sink
•Strict anaerobes and microaerophilic bacteria and protozoa generate
electron during their energy production
• Energy derived from pyruvate decarboxylation
• Reduced by the pyruvate:ferredoxin oxidoreductase system
•The nitro-group becomes activated becomes labile that like free
radicals and attacks important molecules such as DNA
•Metronidazole is bactericidal
9. Metronidazole…
• Resistance
• Eg. Reduction of ferredoxin production
• Less common in anaerobic bacteria
• Helicobacter resistance is more common
• Protozoan resistance is also seen
• Respond to higher dose
11. PK
• Two hallmarks of metronidazole
• High concentrations following oral administration
• Excellent tissue penetration
• Clindamycin does not effectively penetrates BBB
• When no meningeal inflammation, CSF level ~ 45% of
serum conc.
• During meningitis CSF conc. similar to serum conc.
12. PK…
• T1/2 = 8hrs and administration as TID
• Liver responsible for 50% clearance
• Dose adjustment in hepatic failure
• Administered PO, IV, Intravaginal
13. Therapeutic indication
• Anaerobic infections
• Brain abscess, with penicillin
• Lung abscess, with penicillin (clindamycin preferred choice)
• Clostridium difficile & Other types of anaerobic bacterial infections
• Helicobacter Pylori
• Protozoal infections
• Giardiasis
• Trichomoniasis
• Amoebiasis including amebic liver abscess
14. Side effects
• Mainly GI side effects including metallic taste
• Urine discoloration
• CNS side effects
• Dizziness, vertigo,
• Very rarely encephalopathy, convulsions, incoordination, and ataxia
• Numbness or paresthesia's of the extremities
• Disulfiram like reaction
• Disulfiram like effect = Nausea, vomiting, flushing, dizziness,
throbbing headache, chest and abdominal discomfort, and
general hangover-like symptoms
15. Paromomycin
• An aminoglycoside used as an oral agent to treat
• E. histolytica infection, cryptosporidiosis, and giardiasis
• Parenteral administration used to treat visceral leishmaniasis
• Not absorbed from the GI tract;
• the actions of an oral dose are confined to the GI tract
• 100% of the oral dose recovered in the feces
• MoA – protein synthesis inhibitor
• Drug of choice for treating intestinal colonization with E. histolytica
• Also used with metronidazole for amebic colitis & liver abscess.
• Disulfiram like effect = Nausea, vomiting, flushing, dizziness, throbbing
headache, chest and abdominal discomfort, and general hangover
like symptoms
16. Paromomycin…
• Also used for giardiasis when metronidazole / Tinidazole is
contraindicated
• Adverse effects are rare with oral usage
• Abdominal pain and cramping, epigastric pain, nausea and vomiting,
steatorrhea, and diarrhea.
• Rarely, rash and headache have been reported.
17. Iodoquinol
• Used as luminal agents to eliminate intestinal colonization with
E. histolytica
• Combined with metronidazole to treat amebic colitis or amebic liver
abscess
• Because of its superior adverse-event profile, paromomycin is preferred
• Safe when used at a dose of 2g/ day
• Most important toxicity myelo-optic neuropathy
• Also causes peripheral neuropathy
• Disulfiram like effect = Nausea, vomiting, flushing, dizziness, throbbing
headache, chest and abdominal discomfort, and general hangover-
like symptoms
