Metronidazole amoebiasis

Metronidazole is a nitro-imidazole. It is a mixed amoebicide, i.e. it acts at all sites of infection. It has to be activated in the parasite. By reduction in the amoeba of its nitro group reactive intermediates are formed, resulting in oxidative damage and ultimately cell kill. It is effective against many parasitic intestinal and tissue infections such as trichomoniasis, giardiasis and amoebiasis. It is the drug of choice for amoebic dysentery and amoebic liver abscess. 

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],... 

It is also used in combination with tinidazole (TINIBA DF) and metronidazole (ENTAMIZOLE) in the treatment of intestinal amoebiasis, hepatic amoebiasis and other systemic diseases due to E. histolytica. 

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. 

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. 

Biocidal compounds against Entamoeba histolytica, a parasite causing amoebiasis. The Schiff base-related complexes 26 and 27 are active in vitro, metronidazole, (28) is commonly used in the medication of amoebiasis. In the diagram on the left, the activities of metronidazole, the complexes 26, 27 and VO(acac)2 and the free ligands (L) of 26 and 27 are compared. The IC50 values indicate the concentrations at which growth of 50% of the amoebae is inhibited. 

For several other protozoan diseases there is adequate chemotherapy the 5-nitroimidazoles (for example, metronidazole) for the treatment of amoebiasis, giardiasis and trichomoniasis, the hydroxy-naphthoquinone bupravaquone for theileriosis in cattle and other ungulates, and the polyene ionophores (for example monensin, lasalocid, narasin and salinomycin) for the prophylaxis of avian coccidiosis. However, improved therapies are required for some opportunistic parasites that cause disease in immunocompromised humans. Paromomycin and nitazoxanide have some effect in the treatment of cryptosporidiosis and albendazole appears to be effective for microsporidiosis caused by Encephalitizoon intestinalis. 

A retrospective study in children who had not responded to metronidazole for giardiasis or amoebiasis found that 80% of them had been taking long-term phenobarbital. In a prospective study in 36 children the normal recommended metronidazole dosage had to be increased approximately threefold to 60 mg/kg to achieve a cure. The half-life of metronidazole in 15 other children taking phenobarbital was found to be 3.5 hours compared with the normal half-life of 8 to 9 hours. ... 

Amoebiasis, due to infection with Entamoeba histolytica, is conveyed between humans by its cysts which are 10 microns in diameter. They survive well outside the body and are ingested in water and uncooked food. In the colon, the larger vegetative forms (trophozoites) emerge and cause chronic diarrhoea and, often, ulceration of the bowel wall. Unlike bacterial dysentery, this disease is seldom self-limiting without proper medication. Abscesses in the liver form a common complication. A ready cure can be effected with metronidazole (Section 6.3.3). 

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. 

There is little doubt that the compound around which most attention currently centres is metronidazole. As well as being an effective trichomonicide this compound has been found to have considerable antibacterial activity against anaerobic species. It is also being increasingly used in the treatment of amoebiasis and giardiasis, and recently has been used in the treatment of Crohn s disease. 

A trial reported from Ceylon (22 ) in which metronidazole was compared, in the treatment of hepatic amoebiasis, with emetine and chloroquine, showed that adverse effects were encountered more commonly in patients who received chloroquine and emetine. Anand and Punjani(23 ) reported a study of metronidazole in the treatment of giardiasis in children. All the patients were aged under 13 years and the majority under 10 years. The only adverse effects observed were nausea, and a bitter after-taste in the mouth. 

A few reports have appeared on the use of other related compounds. Most of them concern the treatment of trichomoniasis and amoebiasis. All of the other nitro-imidazole compounds appear to exhibit a similar range of adverse effects to metronidazole (30 , 31<=). 

Jayawickrema, U. S. and Lionel, N. D. W. (1975) Comparison of metronidazole with emetine and chloroquine in the treatment of hepatic amoebiasis - a controlled double blind study. Ceylon med. J., 20, 99. 

Amoebiasis, common in many tropical countries but not confined to them, responds well to drugs, particularly metronidazole (Section 6.3c). 

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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