ANTHELMINTICS

2010

ANTHELMINTICS (anthelminthic drugs) are used to treat infections by parasitic organisms of the helminths family (helminthos, a worm). A large proportion of humankind harbours helminths of one species or another. In some cases there may only be minor discomfort, but in many cases there is serious morbidity. The form of treatment depends in part on the form of the infection. Intestinal forms include infection by tapeworms, including Taenia species. Tissue forms include Trematodes or flukes (genus Schistosoma, class Trematoda, phylum Platyhelminthes) cause schistosomiasis — or bilharziasis. The drugs that treat fluke infection by Schistosoma mansoni, S.japonicum and S. haematobium are called ANTISCHISTOSOMES. In all cases there is a complicated life cycle in which hosts other than humans are utilized. Treatment varies with the stage of the life cycle. Anthelmintic drugs, in order to act, must be capable of penetrating the cuticle of the worm or pass into its alimentary tract. They work in a variety of ways to damage the worm, causing paralysis, narcosis, or damaging its cuticle and so allowing partial digestion. Some drugs interfere with the metabolism, which may be very species-dependent.

Benzimidazoles include albendazole, mebendazole and thiabendazole and constitute a major class of broad-spectrum anthelmintics. They work through an effect on helminth microtubular function, with considerable selectivity in this respect for worms as compared to humans. Mebendazole is much used, and is usually the drug of choice, and is relatively free of side-effects. Albendazole is a more recent agent that is better absorbed. These agents can be used for most worm infections, but not for flukes.

Praziquantel is a broad-spectrum anthelmintic, and used in schistosomiasis (bilharziasis) infection by all three fluke species; and as a taenicide against tapeworm infection, including cysticercosis. It acts by altering calcium homeo-stasis in the parasites, which affects muscle in such a way that they are paralysed and die. Praziquantel is toxic to both adult and immature (cercaria) forms of flukes, and it is the latter that infects humans by penetrating the skin. This drug is remarkably free of serious unwanted effects in humans, and adverse effects at normal dose are due to reaction to dead organisms where infection has been extensive. Metriphonate is the drug of first choice for Schistosoma haematobium species. Piperazine can be used orally for roundworm {Ascarius lumbricoides) and threadworm (Enterobius vermicularis) infections. It paralyses the worm (possibly through acting as a GABA-mimetic) which is then expelled. It is particularly free of side-effects, and is an established drug that is inexpensive and available without prescription in many countries. However, it has been largely superseded by the benzimidazoles. Diethylcarbamazine is a piperazine derivative that can be used against filarial infections by Wuchereria bancwft or Loa loa. It is thought to work by altering the parasite in such a way as to enhance the host’s immune reaction. Levamisole is used orally for infection by the roundworm (Ascarius lumbricoides), which it paralyses. Niclosamide was the drug of choice for tapeworm, but praziquantel is now preferred. The drug causes separation of the head and body of the mature worm, and a purgative is required to pass the body parts before ova are released. Oxamniquine is used orally to treat schistosomiasis. and affects both mature and immature forms of Schistosoma mansoni. The parasite concentrates the drug which affects DNA intercalation. It has fairly obtrusive side-effects, including gastrointestinal disturbances in a significant proportion of patients, and some unwanted CNS effects. Metriphonate is the drug of choice to treat schistosomiasis of the Schistosoma haematobium species only. It is a prodrug that gives rise to the active form dichlorvos in vivo. It is thought to be an anticholinesterase in the parasite, causing paralysis. Pyrantel is a broad-spectrum anthelmintic that seems to paralyse the parasite by neuromuscular blockade, and is a relatively safe drug effective by mouth. Ivermectin is a semisynthetic derivative of the avermectins (macrolide antibiotics from Streptomyces avermitilis). It is the drug of choice for onchocerciasis (Onchocerca volvulus), which causes ‘river-blindness’, and may be used against Wuchereria bancrofti, which causes elephantiasis. It is thought to act by causing paralysis through chloride channel opening.