Cestode

Cestibtantite Cesto cida Cestode infections Cestodes Cetadol Cetal... 

Niclosamide [50-65-7] (2/5-dichloro-4 -nitrosahcylanihde) has been commonly used against tapeworms in small animals (5). Although tapeworms (cestodes) are frequently refractory to anthelmintics highly active against other intestinal parasites, they are sensitive to niclosamide as well as pra2iquantel [55268-74-1] and epsirantel. Pyrantel pamoate [22204-24-6] is probably the most common animal wormer used in the 1990s. 

More then a dozen representatives of the above ring systems were introduced into the human therapy. Actisomide (2) and trequinsin (3) are used as antiarrhytmic and antihypertensive agents, respectively. Sunepitron (4), a a 2-adrenoceptor antagonist, is under clinical trials for the treatment of anxiety and depression. Representatives of the third generation of antibacterial quinolone-3-carboxylic acids the blockbluster ofloxacin (5), its levorotatory enantiomer, levofloxacin (6), and rufloxacin (7) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (8) is under development. Praziquantel (9) is widely applied for the treatment of schistosomes- and cestode-caused infection in both veterinary and human therapies (Scheme 4). 

Gasser, R.B. and Chilton, N.B. (1995) Characterisation of taeniid cestode species by PCR-RFLP of ITS2 ribosomal DNA. Acta Tropica 59, 31—40. 

Okamoto, M., Bessho, Y., Kamiya, M., Kurosawa, T. and Horii, T. (1995) Phylogenetic relationships within Taenia taeniaeformis varian Is and other taeniid cestodes inferred from the nucleotide sequence of the cytochrome c oxidase subunit I gene. Parasitology Research 81, 451-458. 

The remaining major classes of water-soluble lipid transporter proteins (other than the polyproteins of nematodes see below) come from plants and helminths. Plants possess very small (approximately 9 kDa) helix-rich, fatty-acid-binding proteins, the structures of some of which are known (Lerche and Poulsen, 1998). A recently described class comes from cestodes these are also very small (approximately 8 kDa), presumably intracellular, and helix-rich, and bind anthelmintic drugs in addition to fatty acids (Janssen and Barrett, 1995 Barrett et al., 1997). The only helix-rich small (approximately 14 kDa) lipid transporter from vertebrates is the acetyl-CoA-binding protein (Kragelund et al., 1993). 

Janssen, D. and Barrett, J. (1995) A novel lipid-binding protein from the cestode Moniezia expansa. BiochemicalJournal ill, 49—57. 

Polarographic studies of a mitochondrial fraction from Hymenolepis diminuta showed that of four substrates tested, DL-glycerol-3-phosphate was the most rapidly oxidized, but the highest respiratory control ratio (1.7) was obtained with dl-isocitric acid. With isocitrate as substrate oxyclozanide at 1.61 nM stimulated O uptake and relieved oligomycin inhibition of adinosine diphosphate-stimulated respiration, but at concentrations above 2 pM progressively inhibited O uptake. Rafoxanide, niclosamide, 3,4,5-tribromo-salicylanilide, nitroxynil, resorantel, di-chlorophen, and 2,4-dinitrophenol exhibited effects similar to those of oxyclozanide on the respiration in cestode mitochondria. The relative potencies were compared and the possible mode of action discussed [38]. 

Khloshchanov [64] indicated by photometric analysis that the greatest concentration of phenasal was observed in cestodes of the lower third of the small intestine of sheep 4 h after oral administration of 0.2 g of the anthelmintic/kg. Increasing the dose of phenasal to 1 g/kg increased shedding of the cestodes. 

Niclosamide inhibits oxidative phosphorylation and stimulates adenosine tripho-sphatese activity in the mitochondria of cestodes, killing the scolex and proximal segments of the tapeworm both in vitro and in vivo. The scolex of the tapeworm, then loosened from the gut wall, may be digested in the intestine and thus may not be identified in the stool even after extensive purging [90,91], Niclosamide is not appreciably absorbed from the gastrointestinal tract [92,93] and the side effects have primarily been limited to gastrointestinal symptoms. 

The answer is d. (Hardman, p 1019J Niclosamide is a halogenated salicylanilide derivative. It exerts its effect against cestodes by inhibition of mitochondrial oxidative phosphorylation in the parasites. The mechanism of action is also related to its inhibition of glucose and oxyrgen uptake in the parasite. 

Tests using helminth infections in a variety of laboratory animals soon revealed that the avermectins had activity against a variety of nematodes but lacked activity toward cestodes and trema-todes. During the course of testing in a number of other assays, they were found active against the flour beetle, Tribolium confusum (14). This activity against arthropods was confirmed in mice infected with larvae of the bot fly, Cuterebra fontinella. 

The absence of GABA-mediated neurotransmission in cestodes and trema-todes explains the lack of activity of the avermectins against these organisms. 

Flatworms (platyhelminths) tape worms (cestodes) flukes (trematodes) e.g.. Schistosoma species (bilharziasis) praziquantel praziquantel... 

Agents used in the treatment of cestodal infections include praziquantel (see Section Vll.a.l), niclosamide and the benzimidazoles such as albendazole and mebendazole (see Section vn.b.l). Niclosamide and praziquantel are effective against Taenia solum (pork tapeworm). Taenia saginata (beef tapeworm). Taenia latum (fish tapeworm) and Hymenolepis nana (dwarf tapeworm). Praziquantel is a second choice drug after albendazole for cys-ticercosis caused by Taenia solum. Albendazole and mebendazole are alternatives. 

Several benzimidazoles are in use for the treatment of helminthic infections. Three of these, mebendazole, thiabendazole and albendazole, are described in this section. They have a broad range of activity against many nematode and cestode parasites, including cutaneous larva migrans, trichinosis, disseminated strongyloidiasis, and visceral larva migrans. A fourth, triclabendazole, is considered as the drug of choice for Easciola hepatica therapy. 

Albendazole has a broad spectrum of activity against intestinal nematodes and cestodes, as well as the fiver flukes Opisthorchis sinensis, Opisthorchis viverrini, and Clonorchis sinensis It also has been used successfully against Giardia lambfia. Albendazole is an effective treatment of hydatid cyst disease (echinococcosis), especially... 

For many years, niclosamide (Niclocide) was widely used to treat infestations of cestodes. Niclosamide is a chlorinated salicylamide that inhibits the production of energy derived from anaerobic metabolism. It may also have adenosine triphosphatase (ATPase) stimulating properties. Inhibition of anaerobic incorporation of inorganic phosphate into ATP is detrimental to the parasite. Niclosamide can uncouple oxidative phosphorylation in mammalian mitochondria, but this action requires dosages that are higher than those commonly used in treating worm infections. 

The drug affects the scolex and proximal segments of the cestodes, resulting in detachment of the scolex from the intestinal wall and eventual evacuation of the cestodes from the intestine by the normal peristaltic action of the host s bowel. Because niclosamide is not absorbed from the intestinal tract, high concentrations can be achieved in the intestinal lumen. The drug is not ovicidal. 

Ammann RW and Eckert J. Cestodes Echinococcus. Gastroenterol Clin North Am 1996 25 655-689. 

Tapeworm. A parasitic intestinal cestode worm having a flattened, band-like form. The eggs of tapeworms are ingested by the intermediate host, they produce the larval stage in tissues. When the flesh of intermediate host is eaten, the larvae develop within the alimentary canal of the definitive host into adult tapeworms. 

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