• Chloroquine (Aralen)

  • High liver concentrations (concentrates in liver)

  • Very effective in combination with dehydroemetine (Mebadin) (or emetine (generic)) for:

    • Prevention/treatment of amebic liver abscess

  • Ineffective for intestinal amebiasis-drug inactive against luminal amebas

• Emetine and 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 and hypotension)

    •  Frequent reported effects:

      •   Muscle weakness/tenderness/stiffness/aching and 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

• 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 and 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.

• 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

      •  Hhyroid disease

    • Cautious use in young children/infants-iodoquinol (Yodoxin, Moebequin) may be more toxic in the young

      • Recommendation: careful opthalmological examination before and during iodoquinol administration.

• Metronidazole (Flagyl) in amebiasis and other protozoal infections

  • Overview: metronidazole (Flagyl)

    • Readily absorbed

    • Urinary excretion of drug and 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

          • 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

            • 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 lambliaI; Giardia duodenalis, 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

        • Dracunculus mediensis  Dracunculiasis (guinea worm disease) is caused by the nematode (roundworm) Dracunculus medinensis

          • "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

        •  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

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.