Anthelmintics

Pharmaceutical Applications

The helminths, or parasitic worms, comprise the nematodes (roundworms), trematodes (flukes), cestodes (tapeworms) and acanthocephalans (thorny-headed worms). Most anthelmintics were discovered and developed for use in the veterinary field, where helminths significantly impact health and productivity. Few companies are searching for new compounds for use in human medicine, but commercial competition has produced a steady supply of new products for the veterinarian. Three new classes of anthelmintic (cyclic octadepsipeptides, amino-acetonitrile derivatives and paraherquamides) have entered or will soon enter the veterinary market and these have potential for human medicine. In addition, some members of established classes have exhibited promising results in preliminary investigations (moxidectin for filariasis; artemisinins for schistosomiasis).
Despite the lack of new anthelmintics for human treatment, satisfactory results can be achieved with current products for nearly all helminth infections. In some cases such as for filariasis, combinations of available drugs are being used to enhance treatment. Side effects usually include gastrointestinal upsets, but these are as likely to be related to the worm burden as to the drug. As helminths are often large and/or present in large numbers, their death and disintegration after chemotherapy can result in an obstruction or an allergic–anaphylactic type reaction.
The biggest problems still remaining to be solved are treatment of infections with larval cestodes, especially Echinococcus spp. There is no satisfactory drug against these parasites; although benzimidazole carbamates have useful activity, they are poorly absorbed from the gut when administered orally and painful injection-site reactions preclude parenteral use. Praziquantel also may be useful in some cases for larval cestodes. Another problem is the treatment of disseminated strongyloidiasis, which occurs when patients with a latent infection are immunosuppressed. No satisfactory chemotherapy is available for the macrofilarial stages in filarial infections, or to treat Guinea worm (Dracunculus medinensis) infection, although an eradication program has greatly reduced its incidence.
Although drug resistance is common in the veterinary field it is not yet a problem in human medicine, except with regard to schistosomiasis where resistance is known for hycanthone and praziquantel. This discrepancy is because anthelmintics are very widely and frequently used in the veterinary world but much less so in human medicine, in part due to the poverty of most of the people who are infected. With increasing wealth in tropical countries where these infections are common, anthelmintics are being used much more widely and there is concern that drug resistance will develop.