Tissue amebicides

Diloxanide furoate is considered by many the drug of choice for asymptomatic luminal infections. It is not available commercially in the USA, but can be obtained from some compounding pharmacies. It is used with a tissue amebicide, usually metronidazole, to treat serious intestinal and extraintestinal infections. Diloxanide furoate does not produce serious adverse effects. Flatulence is common, but nausea and abdominal cramps are infrequent and rashes are rare. The drug is not recommended in pregnancy. 

Clinical Use. lodoquinol (Diquinol, Yodoxin, other names) is used primarily to treat protozoal infections within the intestinal tract,51 and it is often combined with a second tissue amebicide, which kills protozoa at extraintestinal sites. For instance, iodoqui-nol may be combined with metronidazole to ensure the destruction of parasites throughout the body, lodoquinol is usually administered orally. Because iodoquinol is relatively toxic, the routine use of this drug has been replaced somewhat by other agents such as paromomycin, which may be somewhat safer. 

Tissue amebicides (chloroquine, emetines, metronidazole) act on organisms in the bowel wall and the liver luminal amebicides (diloxanide furoate, iodoquinol, paromomycin) act only in the lumen of the bowel. The choice of a drug depends on the form of amebiasis. For asymptomatic disease, diloxanide furoate is the first choice. For mild to severe intestinal infection, metronidazole is used with diloxanide furoate or iodoquinol. The latter regimen, plus chloroquine, is recommended in amebic liver abscess (Table 53-2). The mechanisms of amebicidal action of most drugs in this subclass are unknown. 

This drug has a direct amebicidal effect against trophozoites E. histolytica in tissues, and it is not active against cysts in either the lumen or intestinal walls, or in other organs. The mechanism of action of emetine consists of the blockage of protein synthesis in eukaryotic (but not in prokaryotic) cells. It inhibits the process of polypeptide chain formation. Protein synthesis is inhibited in parasite and mammalian cells, but not in bacteria. 

Metronidazole or tinidazole is the drug of choice in the treatment of all tissue infections with E histolytica. Neither drug is reliably effective against luminal parasites and so must be used with a luminal amebicide to ensure eradication of the infection. 

Diloxanide furoate is a dichloroacetamide derivative. It is an effective luminal amebicide but is not active against tissue trophozoites. In the gut, diloxanide furoate is split into diloxanide and furoic acid about 90% of the diloxanide is rapidly absorbed and then conjugated to form the glucuronide, which is promptly excreted in the urine. The unabsorbed diloxanide is the active antiamebic substance. The mechanism of action of diloxanide furoate is unknown. 

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