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Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms ( helminths) and other internal parasites from the body by either stunning or killing them without causing significant damage to the host. They may also be called vermifuges (those that stun) or vermicides (those that kill). Anthelmintics are used to treat people who are infected by helminths, a condition called helminthiasis. These drugs are also used to treat infected animals, particularly small
ruminant Ruminants are herbivorous grazing or browsing artiodactyls belonging to the suborder Ruminantia that are able to acquire nutrients from plant-based food by fermenting it in a specialized stomach prior to digestion, principally through microb ...
s such as
goat The goat or domestic goat (''Capra hircus'') is a species of Caprinae, goat-antelope that is mostly kept as livestock. It was domesticated from the wild goat (''C. aegagrus'') of Southwest Asia and Eastern Europe. The goat is a member of the ...
s and sheep. Anthelmintic medication is also used in mass deworming campaigns of school-aged children in many developing countries. Anthelmintics are also used for mass deworming of livestock. The drugs of choice for soil-transmitted helminths are mebendazole and albendazole; for schistosomiasis and tapeworms it is praziquantel.


Types

Many early treatments were herbal, such as the oil of herbs of the genus '' Chenopodium'' that were given as anthelmintic treatment for centuries. In 1908 it was found that the active constituent was ascaridole. From the 1920s to the 1970s, halogenated hydrocarbons (such as chloroform, carbon tetrachloride, tetrachloroethylene and hexachloroethane) were used in a string of continually more efficacious anthelmintics, until their underlying host toxicity was revealed. The modern broad-spectrum anthelmintics were developed by pharmaceutical companies that can afford the screening programs and testing systems that modern drug development involves. Historically, there have been three main classes of broad-spectrum anthelmintics. These are benzimidazoles, imidazothiazoles/tetrahydropyrimidines, and macrocyclic lactones. *
Benzimidazoles Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals. Preparation Be ...
disrupt parasitic worms'
microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nanometer, nm and have an inner diameter bet ...
s, a critical part of their cells'
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
s. Drugs in this category include: ** Albendazole – effective against threadworms, roundworms, whipworms, tapeworms, hookworms ** Mebendazole – effective against various nematodes **
Thiabendazole Tiabendazole (International Nonproprietary Name, INN, British Approved Name, BAN), also known as thiabendazole (Australian Approved Name, AAN, United States Adopted Name, USAN) or TBZ and the trade names Mintezol, Tresaderm, and Arbotect, is a pr ...
– effective against various nematodes **
Fenbendazole Fenbendazole is a broad-spectrum benzimidazole anthelmintic used against gastrointestinal parasites including: roundworms, hookworms, whipworms, the tapeworm genus '' Taenia'' (but not effective against '' Dipylidium caninum'', a common dog ...
– effective against various parasites **
Triclabendazole Triclabendazole, sold under the brand name Egaten among others, is a medication used to treat fascioliasis and paragonimiasis. It is very effective for both conditions. Treatment in hospital may be required. It is taken by mouth with typicall ...
– effective against
liver fluke Liver fluke is a collective name of a polyphyletic group of parasitic trematodes under the phylum Platyhelminthes. They are principally parasites of the liver of various mammals, including humans. Capable of moving along the blood circulation, ...
s ** Flubendazole – effective against most intestinal parasites * Imidathiazoles/tetrahydropyrimidines are
nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...
agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
s, including: **
Levamisole Levamisole, sold under the brand name Ergamisol among others, is a medication used to treat parasitic worm infections, specifically ascariasis and hookworm infections. It is taken by mouth. Side effects may include abdominal pain, vomiting, ...
** Pyrantel pamoate – effective against most parasitic nematodes of the GIT * Macrocyclic lactones are
glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...
-gated chloride channel agonists, and include: ** Avermectins (including ivermectin and moxidectin) - effective against most common intestinal worms, except tapeworms, for which praziquantel is commonly used in conjunction for mass dewormings * Drugs not members of these three main categories include: ** Diethylcarbamazine – effective against '' Wuchereria bancrofti'', '' Brugia malayi'', '' Brugia timori'', and '' Loa loa'' ** Salicylanilide – mitochondrial un-couplers such as Niclosamide and Oxyclozanide, and are used only for flatworm infections **
Nitazoxanide Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is ...
– readily kills ''
Ascaris lumbricoides ''Ascaris lumbricoides'' is a large parasitic worm, parasitic Nematoda, roundworm of the genus ''Ascaris.'' It is the most common parasitic worm in humans. An estimated 807 million–1.2 billion people are infected with ''Ascaris lumbricoides'' ...
'', and also possesses antiprotozoal effects. This is also an ascaricide. ** Oxamniquine – effective against flatworms (e.g., tapeworms and
schistosoma ''Schistosoma'' is a genus of trematodes, commonly known as blood flukes. They are Parasitism, parasitic flatworms responsible for a highly significant group of infections in humans termed ''schistosomiasis'', which is considered by the World H ...
) ** Praziquantel – effective against flatworms (e.g., tapeworms and
schistosoma ''Schistosoma'' is a genus of trematodes, commonly known as blood flukes. They are Parasitism, parasitic flatworms responsible for a highly significant group of infections in humans termed ''schistosomiasis'', which is considered by the World H ...
) ** Octadepsipeptides (e.g. Emodepside) – effective against a variety of gastrointestinal helminths ** Monepantel (aminoacetonitrile class) – effective against a variety of nematodes including those resistant to other anthelmintic classes ** Spiroindoles (e.g. derquantel) – effective against a variety of nematodes including those resistant to other anthelmintic classes ** Artemisinin – shows anthelmintic activity


Anthelmintic resistance

Anthelmintic resistance occurs when a heritable genetic change occurs in the parasite's DNA, rendering it insensitive to a previously effective anthelmintic drug. This is a particularly serious problem in helminth parasites of small ruminant farm animals. There are many factors that contribute to anthelmintic resistance, such as frequent, mass anthelmintic treatment, underdosing, treating repeatedly with only one anthelmintic, and resistance being transmitted during transfer of animals. Anthelmintic resistance in parasites is widespread; drug resistance exists in all livestock hosts and to all anthelmintic drug classes. This is a major threat to the sustainability of modern ruminant livestock production, resulting in reduced productivity, compromised animal health and welfare, and increased greenhouse gas emissions through increased parasitism and farm inputs. A database of published and unpublished European AR research on gastrointestinal
nematodes The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (he ...
was collated in 2020. A total of 197 publications were available for analysis, representing 535 studies in 22 countries and spanning the period 1980–2020. Results in sheep and goats since 2010 reveal an average prevalence of resistance to
benzimidazoles Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals. Preparation Be ...
of 86%, moxidectin 52%, and
levamisole Levamisole, sold under the brand name Ergamisol among others, is a medication used to treat parasitic worm infections, specifically ascariasis and hookworm infections. It is taken by mouth. Side effects may include abdominal pain, vomiting, ...
48%. All major gastrointestinal
nematode The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...
genera survived treatment in various studies. In cattle, prevalence of anthelminthic resistance varied between anthelmintic classes from 0–100% (benzimidazoles and macrocyclic lactones), 0–17% (levamisole) and 0–73% (moxidectin), and both '' Cooperia'' and '' Ostertagia'' survived treatment. However, resistance is not seen as often in the parasitic helminths that affect cattle, compared to sheep. Reasons for this include the fact that cattle receive anthelminthic drugs less frequently than sheep, and the different nature of their faecal pats that could leave different numbers of resistant infective larvae on the pasture. Unlike sheep, cattle can develop sufficient immunoprotection against such parasites. Both ''in vitro'' (egg hatch assay, larval development test, larval motility test,
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
and ''in vivo'' methods ( fecal egg count reduction test) can be used to detect anthelmintic resistance. 1/sup>   Treatment with an antihelminthic drug kills worms whose phenotype renders them susceptible to the drug, but resistant parasites survive and pass on their "resistance" genes. Resistant varieties accumulate, and treatment failure finally occurs. The ways in which anthelmintics are used have contributed to a major anthelmintic resistance issue worldwide. From the 1950s to the 1980s, new classes of effective and inexpensive anthelmintics were made available every decade, leading to excessive use throughout agriculture and disincentivizing alternative anti-nematodal strategies. Developing new anthelmintics is time-consuming and expensive therefore, it is important to use the ones that currently exist in a way that will minimize or prevent the development of anthelmintic resistance. 1/sup> Some of these methods are ensuring animals are not being underdosed, rotating the anthelmintics that are being used, and rotation of grazing land to reduce the parasite population. Other methods include using a combination of multiple different anthelmintics, and the use of ''refugia'' based strategies. R''efugia'' refers to the portion of the parasite population not being exposed to anthelmintics. This population is therefore not undergoing selection for resistance. Use of ''refugia'' helps to slow down the speed of evolution of resistance to anthelmintic drugs. Due to the problem of anthelmintic resistance, research into alternatives is continuing, including in the field of rational drug design.


See also

* '' Dysphania ambrosioides'', an herb native to Central and South America * Santonin, a historical anthelmintic no longer in use * 4-Hexylresorcinol


References


External links

* * Holden-Dye, L. and Walker, R. J
Anthelmintic drugs
(November 2, 2007), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.143.1 {{Authority control * Articles containing video clips