Amoebiasis Useful drugs

Of the dichloroacetamides diloxanide furoate, clefamide, teclozan and etofamide the most frequently used agent is diloxanide furoate. It is the luminal amoebicide of choice in chronic intestinal amoebiasis, however it lacks efficacy acute intestinal amoebiasis. Its mechanism of action is unknown. Given orally, diloxanide is formed by bacterial hydrolases. Diloxanide is for 90% absorbed and then metabolized to diloxanide glucuronide. The remaining 10% remains in the intestine as the active drug. Diloxanide is generally well tolerated. Adverse effects include flatulence, nausea and abdominal cramps. 

Diloxanide furoate is the furoate ester of 2,3-dichloro-4-hydroxy-A-methyl acetanilide. This antiamoebic drug was developed as a result of the discovery that various a,a-dichloroacetamides possessed an amoebicidal activity [1]. Diloxanide furoate is considered as a safe and effective drug for the treatment of asymptotic or mildly symptomatic persons who are passing cysts of Entameba histolytica [2,3], It acts principally in the bowel lumen, and is used in the treatment of the intestinal amoebiasis. It is less effective in amebic dysentery than in asymptotic infection, but the furoate gives high intestinal concentrations and is possibly more effective than metronidazole in the treatment of cyst passers [4],... 

Amoebiasis is an infectious disease caused by Entamoeba histolytica. It can cause asymptomatic intestinal infection, colitis (mild to moderate), dysentery (severe intestinal infection), ameboma, liver abscess etc. The drugs used in chemotherapy of amoebiasis are classified as in table 9.9.1. 

Derivatives of 2-amino-5-nitrothiazole have antiparasitic activity. Niridazole (253) is used in the treatment of schistosomiasis, but its side-effects make it unattractive for treating other diseases, e.g. amoebiasis, for which safer drugs are available. The nitroimidazole metronidazole (254) is particularly useful in amoebiasis and trichomoniasis, and the latter disease may also be treated with nimorazole, l-morpholinoethyl-5-nitroimidazole. 

Bowel lumen amoebiasis is asymptomatic and trophozoites (noninfective) and cysts (infective) are passed into the faeces. Treatment is directed at eradicating cysts with a luminal amoebicide diloxanide furoate is the drug of choice iodoquinol or paromomycin is sometimes used. 

In practice, treatment of amoebiasis can be divided into treatment of bowel lumen amoebiasis, and tissue-invading amoebiasis. The bowel lumen infection, which is usually asymptomatic, may be in trophozoites form (non-infective) or in cysts form (infective) and treatment is directed at eradicating cysts with a luminal amoebicide (e.g. diloxanide). The tissue-invading amoebiasis (giving rise to dysentery, hepatic amoebiasis and liver abscess) must be treated with systemically active drugs (systemic amoebicides) active against trophozoites (e.g. metronidazole, tinidazole also, in dangerously ill patients dehydroemetine may be used, which is less toxic than the parent emetine (derived from ipecacuanha). Sometimes antibiotics (e.g. tetracycline) are used concurrently to stop opportunist infections. 

Salts of acetarsone are used in the treatment of intestinal amoebiasis, vaginal trichomoniasis, and necrotizing ulcerative gingivitis (Vincent s angina). The diethylamine salt (acetylarsan [534-33-8]) has antisyphilitic properties. Because of toxicity problems, safer drugs have been developed Oral LD q in rabbits is 150 mg/kg. 

Fumagillin (155) is known to be antibiotic (with antiphage activity) and amoebicide. It has been used locally for the treatment of drug-resistant intestinal amoebiasis [190]. 

Related drugs include nitrofurantoin 6.15) (a urinary antiseptic) and metronidazole 6.22) (a nitroimidazole much used in amoebiasis and trichomoniasis). 

Used in treatment of symptomatic trichomoniasis, acute intestinal amoebiasis, and serious anaerobic infKtions used to treat other sen-ous anaertdiic infiKtions Helidac b a combination drug of bismuth subsalicylate, tetracycline, and metronidazole for neatment of HelicobaaeT pylon. 

Related drugs include nitrofurantoin (6.74, p. 200) (a urinary antiseptic) and metronidazole (6.19, p. 205) (a nitroimidazole much used in amoebiasis and trichomoniasis). Clearly, there is much to be discovered before it can be said how any of these drugs act so selectively, but the recent link of nitrofurazone with inhibition of RNA synthesis seems an important clue. 

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