Antiprotozoal agents 2&3

• Anti-protozoal agents

  • Amoebiasis
  • Giardiasis
  • Trichomoniasis
  • Trypanosomiasis
  • Leishmaniasis
  • Babesiosis
• Approximately 500 million people harbour amoebiasis
• Amoebiasis causes 40,000-100,000 deaths annually
• Amoebiasis is the 2nd leading cause of death from parasitic diseases
• Amoebiasis

  • Simple life cycle; humans chief hosts
  • Infection generally spreads by poor hygiene
  • Infection normally follows ingestion of mature cysts in contaminated food or water
• E. histolytica

  Bowel lumen commensal - causative organism of amoebiasis
• Cyst

  Inactive; infectious form of amoebiasis
• Trophozoite

  Active, invading host tissue form of amoebiasis
• Amoebiasis infection process

  1. Ingestion of cysts

  2. Excystation in small intestine

  3. Trophozoites mature

  4. Invasion of host tissue
• Trophozoites

  • Capable of invading host tissue
  • Ingest bacteria, other protozoa, host RBC's inside human body
  • Convert to binucleated cyst form
• Trophozoites convert to tetranucleated cyst
• Manifestations of amoebiasis

  • Asymptomatic colonization
  • Intestinal amoebiasis
  • Liver abscess
• Asymptomatic infection occurs when ingested cysts excyst in small intestine and do not invade intestinal mucosa
• Invasive disease occurs when active trophozoites invade intestinal epithelium
• Invasive disease outcomes

  • Asymptomatic colonization
  • Intestinal amoebiasis
  • Liver abscess
• Giardiasis characteristics

  • Giardia intestinalis
  • Transmitted from man to man via fecal-oral route
  • Ingestion of cysts in contaminated water or food
  • Asymptomatic carrier state
  • Acute self-limited diarrhoea
  • Chronic diarrhoea
• Trichomoniasis


  • Commonest form is Trichomonas vaginalis
  • Spread by sexual intercourse
  • Intense vaginitis with purulent discharge
• Trichomoniasis may be difficult to differentiate clinically from candida vaginitis
• Lack of symptoms in men hinders effort to eradicate trichomoniasis
• Drugs used in chemotherapy of amoebiasis

  • Imidazole derivatives
  • Quinoline derivatives
  • Antibiotics
  • Miscellaneous
• Imidazole derivatives

  • Metronidazole
  • Tinidazole
  • Secnidazole
• Quinoline derivatives

  • Halogenated hydroxyquinolines
  • 4-aminoquinolines
• Halogenated hydroxyquinolines

  • Diiodohydroxyquinoline
  • Iodochlorohydroxyquinoline
  • Broxyquinoline
• 1. aminoquinolines

  • Chloroquine
• Antibiotics

  • Paromomycin
  • Tetracycline
• Miscellaneous drugs

  • Nitazoxanide
  • Diloxanide
• Classification of drugs used in amoebiasis

  • Drugs used only in intestinal amoebiasis
  • Drugs used in both intestinal and extraintestinal amoebiasis
  • Drugs used only in extraintestinal amoebiasis
• Drugs used only in intestinal amoebiasis

  • Halogenated oxyquinolines
  • Diloxanide
  • Antibiotics
• Drugs used in both intestinal and extraintestinal amoebiasis

  • Metronidazole
  • Tinidazole
  • Secnidazole
• Drugs used only in extraintestinal amoebiasis

  • Chloroquine
• E. histolytica and other luminal parasites lack enzymes of fermentation, oxidative phosphorylation, and Kreb's cycle
• E. histolytica utilizes novel enzymes to provide a source for electron transfer to drive metabolism
• Metronidazole

  Pro-drug activated by nitro group reduction in susceptible organisms
• Metronidazole mechanism

  • Electron transfer forms highly reactive nitroso radical anion
  • Function occurs only when partially reduced
  • Sensitivity is directly related to presence of PFOR activity
• PFOR

  Pyruvate-ferredoxin oxidoreductase
• Metronidazole activation process

  1. Drug entry into anaerobic cell

  2. Nitro group reduced by redox proteins

  3. Reactive nitro radical exerts cytotoxic action
• Metronidazole is active against E. histolytica trophozoites but not cysts
• Metronidazole is the drug of choice in invasive amoebiasis
• Metronidazole is effective in trichomoniasis, amoebiasis, and giardiasis
• Tinidazole characteristics

  • 2nd generation nitroimidazole
  • Similar mechanism of action as metronidazole
  • Longer T1/2
  • Shorter treatment course
  • Better tolerability