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Small Ruminant
Info Series |
Understanding anthelmintics (dewormers)
by Susan
Schoenian
Sheep and Goat Specialist
Western Maryland Research & Education Center
University of Maryland Cooperative Extension
Date created or last revised:
20-Oct-2009
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Anthelmintics
are usually administered orally to sheep and goats using a syringe with
a long metal nozzle.
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An anthelmintic is a substance that expels or destroys gastro-intestinal worms. The more common name is dewormer. Anthelmintics are also called parasiticides, endectocides, nematodcides, parasitics, antiparasitics, and drenches.
Before 1940, the only
compounds used to deal with parasitism were natural substances that had some
effect on parasites, but also risked some toxicity to the animal. The modern
age of deworming began with the introduction of phenothiazine, which was adminstered
to sheep as a drench and/or included in salt mixtures. It was sometimes combined
with lead arsenate to control tapeworms. In the 1960s and 70s, organophosphate
anthelmintics were introduced. Haloxon (Loxon) was an organophosphate anthelmintic
that was eventually removed from the U.S. market due to toxicity issues, especially
with Suffolk sheep and Angora goats.
Nowadays, anthelmintics are separated into classes on the basis of similar chemical structure and mode of action. Although anthelmintics are sold under many brand names, there are really only three chemical classes relevant to sheep and goat producers
All drugs in a chemical class kills worms in the same manner, though the effectiveness within chemical families varies. For drug rotation to be of any value, you need to switch chemical classes, not just brand name products. On the other hand, it is no longer recommended to rotate dewormers (in the traditional sense), but rather to selectively deworm sheep and goats, using specific dewormers for specific situations.
All anthelmintics essentially kill worms by either starving them to death or paralyzing them. Because worms have no means of storing energy, they must eat almost continuously to meet their metabolic needs. Any disruption in this process results in energy depletion . Interfering with feeding for 24 hours or less is sufficient to kill most adult parasites. Parasites will also die if they become paralyzed and temporarily lose their ability to maintain their position in the gut.
Benzimidazoles
The first chemical class of modern anthelmintics developed was the benzimidazoles
(BZD). The first drug in this class, thiabendazole (TBZ) was introduced in
1961. In addition to thiabendazole, this chemical class includes fenbendazole(Safeguard®),
albendazole(Valbazen®), and oxyfendazole (Synanthic®). Benzimidazoles
interfere with the worm's energy metabolism on a cellular level. They bind
to a specific building block called beta tubulin and prevent its incorporation
into certain cellular structures called microbutbules, which are essential
for energy metabolism. Interfering with energy metabolism is a much more basic
mode of activity than the other classes of dewormers. For this reason, benzimidazoles
are also able to kill worm eggs. Benzimidazoles have a wide margin of safety
and broad spectrum activity.
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Anthelmintics
commonly used in the U.S. sheep and goat industry
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Acronym
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Class
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Drugs
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Common
trade names
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1
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BZD
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Benzimidazoles | Thiabendazole Fenbendazole Albendazole Oxfendazole |
TBZ®1 Panacur®, Safeguard®2 Valbazen®1 Synanthic® |
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2
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IMID TETR |
Nicotinic
agonists Imidazothiaoles Tetrahydropyrimidines |
Levamisole Morantel Pytrantel |
Prohibit®1,
Levasol1, Tramisol®1 Rumatel®2, Nematel® Strongid® |
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3
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ML
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Macrolytic
Lactones Avermectins Milbemycins |
Ivermectin Eprinomectin Doramectin Moxidectin |
Ivomec®1,
Primectin™1 Eprinex® Dectomax® Cydectin®1, Quest® |
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1FDA-approved
for use in sheep. 2FDA-approved
for use in goats.
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Nicotinic agonists
Nicotinic agonists comprise the next class of anthelmintics. They include
imidazothiaoles (IMID) and tetrahydropyrimidines (TETR). The tetrahydropyrimidines
group includes pyrantel pamoate (Strongid®), pyrantel tartrate, and morantel
tartrate (Rumatel®). The tetrahydropyrimidines mimic the activity of acetylcholine,
a naturally occuring neurotransmitter that initiates muscular contraction.
The worm is unable to feed and quickly starves. Tetrahydroyrimidines only
affect adult populations of worms. They do not have activity against the larval
stages and are ineffective against cestodes (tapeworms) and trematodes (liver
flukes).
Imidazothiaoles have a similar mode of action as pyrantel and morantel, causing spastic paralyis of the worms. The group includes the drug levamisole (Prohibit®, Tramisol®, and Levasol®). In addition to being used as an anthelmintic for animals, levamisole has been used to treat various human diseases: colon cancer, melanoma and head and neck cancer, and influenza. It was discovered in 1966. Compared to other anthelmintics, levamisole has the narrowest margin of safety, though toxicity is usually the result of excess dosage. Levamisole has a broad spectrum of activity and is effective against many larval stages of parasites, though not arrested larvae.
Macrolytic lactones
The last chemical class to be introduced was the macrolytic lactones (MLs,
macrolides). The first drug, ivermectin was introduced in the early 1980s
by Merck. It was the first drug to kill migrating larval stages of worms,
as well as the adults. Ivermectin quickly dominated the market, leading to
its overuse.
Macrolytic lactones consist of two closely related chemical groups: avermectins and milbemycins. The avermectins include ivermectin (Ivomec®) and derivatives: doramectin (Dectomax®) and eprinomectin (Eprinex®) . Moxidectin (Cydectin®, Quest®) is the only milbemycin.
All of the macrolytic lactone compounds have the same mode of action. They are developed from the same genus of soil dwelling-organisms (genus Streptomyces). They interfere with GABA-mediated neurotransmission, causing paralysis and death of the parasite. Macrolytic lactones are the most potent killer of worms and are more persistent in their effect. The duration of persistant activity varies according to the drug and formulation. Macrolytic lactones slso have the unique quality of killing several external parasites such as lice, mites, and ticks.They have a wide margin of safety for livestock and are effective against all stages of worms, including inactive forms. However, they are ineffective against cestodes (tapeworms) and trematodes (liver flukes).
Ivermectin is also used as a broad-spectrum antiparasitic agent in humans. It is mainly used for the treatment of river blindness. Ivermectin is the primary ingredient used in several types of heartworm preventative. Collies and related breeds may be sensitive to ivermectin, though ivermectin-based heartworm preventatives deliver doses of ivermectin which are suitable for dogs with this sensitivity.
Moxidectin was introduced in 1997. It is the most potent of the ML group and able to kill some worms resistant to ivermectin. Moxidectin works like Ivermectin, but disrupts a different neurological chemical. Moxidectin is effective in the prevention of heartworm disease in dogs and cats.
Because moxidectin is so closely related to ivermectin, its overuse (and misuse) is expected to lead rapidly to resistance. As such, many experts recommend moxidectin only be used for clinically parsitized animals.
In 2007, Novartis presented research on a potential new class of anthelmintics. The new class called amino-acetonnitrile derivatives (AADs) has been shown to kill worms by acting on specific acetylcholine receptors. Field trials are on-going. This would be the first new drug class in 25 years.
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The
FAMACHA© system can be used to determine which animals require
anthelmintic treatment for Haemonchus contortus, the most common
parasite in warm, moist climates.
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Anthelmintic
resistance
Anthelmintic resistance was inevitable. It is a world wide problem, having
reached catastrophic proportions in some regions. Each time an anthelmintic
is administered to an animal, it eliminates parasites whose genotype renders
them susceptible and selects for parasites who are resistant and pass their
resistant genes onto the next generation of worms. Certain practices accelerate
the rate by which the worms become resistant to the anthelmintic(s). These
include frequent deworming, treating every animal in the flock, putting treated
animals immediately onto a clean pasture, underdosing the drug, injecting
the drug, and pouring the drug on the animal's back. Frequent treatments are
primary cause of resistance.
Understanding how anthelmintics work may help to devise strategies for slowing down the rate by which the worms develop resisistance. At the same time, producers need to limit their use of anthelmintics in order to prolong their effectiveness for as long as possible.
The level of drug resistance
can be determined by performing the fecal egg count reduction test (FECRT)
or by a larval
development assay (LDA, DrenchRite®). In fact, anthelmintics can only
be properly used IF their effectiveness (or lack of effectiveness) is known.
Each farm is different.
Natural dewormers
and other old-time remedies
With increasing levels of anthelmintic resistance and a movement towards more
sustainable farming practices, there is a renewed interest in natural dewormers.
Many universities are conducting experiments to determine the efficacy of
various natural dewormers and other old-time remedies.
Tobacco has historically been used as an anthelmintic for livestock. While nicotine does have some anthelmintic properties, it is extremely toxic in the doses needed to kill worms. Copper sulfate is another historical worm treatment. The problem is that sheep are very sensitive to copper sulfate and can die if they get too much of it. In more recent years, scientists have been investigating the use of copper oxide wire particles as an anthelmintic for sheep and goats. Due to a lower absortion rate, this form of copper is safer to administer. with less risk of copper toxicity. So far, the research looks promising. The mode by which copper kills abomasal parasites is unknown.
There are a number of herbs which are known to have anthelmintic properties (e.g. wormwood), but they have the same problem as tobacco - what's poisonous to the worms is also poisonous to the animal when given in a sufficient volume to kill the worms. Numerous plants are being tested for their anthelmintic properties (e.g. pumpkin seed, garlic). So far, none have been proven under formal research conditions to be effective anthelmintics. Diatomaceous earth (DE) is touted as an anthelmintic, but various studies have failed to prove its efficacy as an anthelmintic. DE is composed primarily of silica (the main component of glass). Their is some evidence that it might be abrasive to the integument of worms in the digestive tract.