Amebiasis

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  • Emetine & Dehydroemetine (Mebadin)
    •  Overview:
      •  Parenteral administration due to erratic oral administration
      •  Oral administration may cause vomiting (emetine (generic) can be derived from ipecac)
      •  Parenteral administration results and emetine (generic) stored mainly in the:
        • liver
        • lungs
        • spleen
        • kidneys
      •  Slow elimination (renal)
    • Pharmacological effects
      •  Blocks eukaryotic protein synthesis
      •  Animal-toxic doses:
        • renal common hepatic, skeletal, cardiac muscle cellular damage
        • cardiac induction/contraction depression -- arrhythmias
        • adrenergic/cholinergic-receptor locking activity
    • Anti-amebic Effects:-act only against trophozoites
    • Clinical Uses:
      •  Inappropriate management for mild/asymptomatic intestinal infection
      • Severe intestinal disease (amebic dysentery)
        •  parenteral emetine (generic)/dehydroemetine (Mebadin)
          • rapid improvement
          • usually not curative
          • reduced likelihood of toxicity of drugs used < seven days
      • Action against other parasites:
        •  secondary choices for management of infections due to:
          •  Balantidium coli
          •  Fasciola hepatica
          •  Paragonimus westermani
    •  Adverse/Side effects
      •  Short duration (3-5 days) --few/mild adverse effects
      •  Intermediate duration (up to 10 days) -- mild/severe side effects
      •  Extended duration > 10 days -- serious toxicity (contraindicated for prolonged administration)
      •  muscle weakness/tenderness/pain: injection region), common effect)
      •  occasional:
        • nausea/vomiting
        • sterile abscess
      •  diarrhea: more common, several days after treatment initiation
      •  minor ECG changes-frequent
      •  serious cardiac conduction defects-infrequent
      •  most serious symptoms/findings:
        •  tachycardia (other arrhythmias)
        •   precordial pain
        •   congestive heart failure {+dyspnea & hypotension}
      •  Frequent reported effects:
        •   muscle weakness/tenderness/stiffness/aching & tremor
        •   mild paresthesias
    •  Contraindications
      •  patients with cardiac/renal disease
      •  patients with recent history of polyneuritis
      •  in young children unless alternative drugs have been ineffective in managing liver abscess or severe dysentery
      •  pregnancy

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  • Diloxanide furoate (Furamide)
    • Overview:
      • directly amebicidal
      • few drug effects in animals
    • Pharmacokinetics:
      • diloxanide furoate (Furamide) is split into diloxanide and furoic acid {depth bacteria}
      • Most of the diloxanide is absorbed (and conjugated to the glucuronide-which is rapidly excreted in the urine)
      • unabsorbed diloxanide is amebicidal
    • Clinical Uses:
      • Drug of choice for asymptomatic intestinal amebiasis
      • Used in combination with another drug for mild intestinal amebiasis
      •  Diloxanide furoate (Furamide) can be used to eliminate luminal amebas in combination with a nitroimidazole which can eliminate luminal & tissue amebas
        •  diloxanide-not effective as the primary drug in severe/moderate intestinal amebiasis since it is not effective against tissue trophozoites.
    • Contraindications/Adverse Effects:
      •  Common: flatulence; uncommon/rare-- nausea,abdominal cramps, rash
      •  Diloxanide furoate (Furamide) should not be used in pregnancy or given the children < 2 years old.

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  • Iodoquinol (Yodoxin, Moebequin)
    • Overview:
      •  Effectiveness limited to bowel luminal organisms {i.e. not effective against intestinal wall/extraintestinal tissue trophozoites}
      •  poor absorption (90% unabsorbed)
      • renal excretion-following glucuronidation
      •  may interfere with some thyroid function tests {for up to six months buying increasing proteins-bound serum iodine, which decreases 131I uptake.
    • Clinical Uses: iodoquinol (Yodoxin, Moebequin)
      •  Intestinal Amebiasis
        •  alternative drug in treating asymptomatic/model/moderate disease
        •  ineffective an initial management of severe intestinal amebiasis {may be used later}
        •  may be used concurrent with other anti-amebiasis drugs {a target extraintestinal sites} to manage concurrent intestinal infection
      • Management of other Intestinal Parasites
        •  Effective as monotherapy or with a tetracycline for Dientamoeba fragilis treatment
        •  Effective as monotherapy for treating Balantidium coli.
    •  Adverse Effects:iodoquinol (Yodoxin, Moebequin)
      • Adverse effects associated with halogenated hydroxyquinolines (iodoquinol (Yodoxin, Moebequin) is an example of this group)
        •  Neurotoxicity (potentially severe)
          • More likely to occur with long dosing periods and at higher than recommended doses
          • Neurotoxicity not likely to occur at normal dosage and normal dosing duration
          •  At high doses/long periods:
            •  optic atrophy
            •  peripheral neuropathy
            •  visual loss
          • Neurotoxic effects tend to be reversible; however complete reversal may not occur
        • Other-typically mild/infrequent:
          •  diarrhea (several days)
          •  gastrointestinal symptoms
          •  headache
          •  slight thyroid enlargement
    • Contraindications/Cautions:iodoquinol (Yodoxin, Moebequin)
      • Should not be used for treatment/prophylaxis of travelers' diarrhea or nonspecific diarrhea
      • Use only recommended dosage
      • Cautious use in patients with preexisting:
        •  optic neuropathy
        •  renal disease
        •  thyroid disease
        •  hepatic disease {other than secondary to amebiasis}
      • Cause for discontinuation:
        •  persistent diarrhea
        •  symptoms of iodine reaction {urticaria, pruritus, fever, skin eruptions}
        •  hepatic disease unrelated to amebiasis
        •  renal disease
        •  thyroid disease
      • Cautious use in young children/infants-iodoquinol (Yodoxin, Moebequin) may be more toxic in the young
        • recommendation: careful opthalmological examination before & during iodoquinol administration.

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  • Metronidazole (Flagyl) in amebiasis & other protozoal infections
    • Overview-metronidazole (Flagyl)
      • Readily absorbed
      • urinary excretion of drug & drug metabolites
    • Mechanism of action: metronidazole (Flagyl)
      • Metronidazole (Flagyl) undergoes chemical reduction by ferredoxin or ferredoxin-related processes
        • reduced-products are responsible for bacteriocidal effects against anaerobic bacteria
        • Amebiasis: metronidazole (Flagyl) kills Entamoeba histolytica trophozoites (but not cysts)
        • In dracunculiasis: metronidazole (Flagyl) Effexor anti-inflammatory
      •  Clinical Uses:
        • Treatment of extraluminal amebiasis:
          •  eliminates tissue infections {hepatic abscess; intestinal wall/extraintestinal infections}
          •  Note: luminal amebicides should be used concurrently to insure cure of luminal infections
          •  metronidazole (Flagyl): kills trophozoites --does not kill E histolytica systems
        • Other Clinical uses:
          • Urogenital trichomoniasis
            • "Trichomonas vaginalis, a flagellate, is the most common pathogenic protozoan of humans in industrialized countries."-CDC
            • http://www.dpd.cdc.gov/DPDx/HTML/Trichomoniasis.htm
            • Life Cycle:Trichomonas vaginalis
              •  "Trichomonas vaginalis resides in the female lower genital tract and the male urethra and prostate, where it replicates by binary fission. 
              •  The parasite does not appear to have a cyst form, and does not survive well in the external environment. 
              • Trichomonas vaginalis is transmitted among humans, its only known host, primarily by sexual intercourse."-CDC
            • Geographic Distribution: Trichomonas vaginalis
              • "Worldwide.  Higher prevalence among persons with multiple sexual partners or other venereal diseases."-CDC
            • Clinical Features
            • Laboratory Diagnosis
            • Treatment:"The Medical Letter recommends metronidazole or tinidazole as drugs of choice.  To prevent reinfection, all sexual partners should be treated. 
              •  Metronidazole-resistant strains have been reported."-CDC
        • Metronidazole (Flagyl):Alternative drug in:
          • Giardia lamblia (Giardia lamblia, a protozoan flagellate (Diplomonadida).
            • Life Cycle
            • Giardia Clinical Features/Laboratory Diagnosis
              • Treatment
            • Microscopy
              • Trophozoites
              • Giardia in culture
              • Giardia cysts
          • Balantidium coli, a large ciliated protozoal parasite.
            • Life Cycle
            • Clinical Features/Laboratory Diagnosis
            • Microscopy
          • Blastocystis hominis-"Whether or not Blastocystis hominis can cause symptomatic infection in humans is a point of active debate.  This is due to the common occurrence of the organism in both asymptomatic and symptomatic individuals, parasitized or not."-CDC http://www.dpd.cdc.gov/DPDx/HTML/Blastocystis.htm 
          • Dracunculus mediensis-Dracunculiasis (guinea worm disease) is caused by the nematode (roundworm) Dracunculus medinensis
            • http://www.dpd.cdc.gov/DPDx/HTML/Dracunculiasis.htm
            • "An ongoing eradication campaign has dramatically reduced the incidence of dracunculiasis, which is now restricted to rural, isolated areas in a narrow belt of African countries and Yemen."-CDC
            • Life Cycle/Geographic Distribution
            • Clinical Features
            • Treatment:
              • "Local cleansing of the lesion and local application of antibiotics. 
              • Mechanical, progressive extraction of the worm over a period of several days. 
              • No active antihelminthic treatment is available. 
              • The Medical Letter recommends metronidazole (Flagyl) , not as a curative drug, but as a drug that decreases inflammation and facilitates removing the worm."-CDC-
              • http://www.dpd.cdc.gov/DPDx/HTML/Dracunculiasis.htm
          •  Not effective (significantly) against:
            • facultative anaerobes
            • obligate aerobes
            • Candida albicans
      • Adverse Effects:metronidazole (Flagyl)
        •  Common:
          •  headache, dry mouth, nausea, metallic-taste
          •  Urine:-dark/reddish-brown
        •  Uncommon:
          •  vomiting, diarrhea, dizziness, weakness, stomatitis, urethral burning, vertigo paresthesias, insomnia {reduced gastrointestinal irritation if taken with food}
        •  Rare:
          • pancreatitis
          • Severe CNS effects, i.e. mental changes, ataxia, peripheral neuropathy, seizures
        •  Unusual effect:disulfram (Antabuse)-like, causes vomiting/nausea if alcohol is consumed during metronidazole
      • Cautions/Contraindications:
        •  long-term used in patients with a history of:
          • blood dyscrasias
          • severe liver dysfunction
          • organic brain disease
        •  Cautious use in pregnancy-particularly first trimester

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Primary Reference: Goldsmith, R. S., Antiprotozoal Drugs in Basic and Clinical Pharmacology (Katzung, B. G., ed) Appleton-Lange, 1998, p. 838-861.
Primary Reference: Morgan, Juliette and del Rio, Carlos, Amebiasis in Medicine for the Practicing Physician (Hurst, J. W., ed) Appleton-Lange, 1996, pp. 457-459.