General:

• Ivermectin toxicosis is more likely in dogs following overzealous treatment with an ivermectin containing product formulated for horses or cattle.
• The breeds of dogs most commonly affected are collies and collie-crosses.
• Small birds such as parakeets (due to their body weight and difficulty in delivering the appropriate dose) can easily be overdosed with ivermectin following treatment for scaly leg mites.
• Ivermectin has a broad spectrum of activity against many internal and external parasites.

• Ivermectin is a macrolide antibiotic produced from a fungus first isolated from a soil sample in Japan - Streptomyces avermitilis .
• The avermectins are a class of chemicals that have a novel mode of action against nematode and arthropod parasites.
• Ivermectin is a mixture of the 22, 23-dihydro derivative of avermectin B1.
• Ivermectin was licensed for use in the United States in 1983.
• Formulations of Ivermectin :
• Ivomec (Merck) - injectable, 10 mg/ml for swine and cattle
• Equvalan (Merck) - oral paste, 8.7 mg/ml for horses
• Ivomec (Merck) - oral drench, 0.8 mg/ml for sheep
• Heartguard (Merck) oral tabs, 68, 136, and 272 micrograms of ivermectin for dog for the prevention of Canine Heartworm disease

• Dogs are usually intoxicated with ivermectin from the inappropriate, extra-labeled use of cattle, sheep or horse product.
• Well-intentioned, yet uninformed, owners may "worm" the dog with a large animal formulation.
• Any species may be affected if the dose is large enough to penetrate the Blood-Brain-Barrier

The following doses of ivermectin are those reported in the literature that cause clinical signs (most commonly ataxia or depression).

• Cattle: 4 - 8 mg/kg (20 - 40 times the therapeutic dose)
• Horses: 2 mg/kg (10 times the therapeutic dose)
• Pigs: 30 mg/kg (100 times the therapeutic dose)
• Dogs
• Collies: 0.1 - 0.2 mg/kg (15 - 30 times the therapeutic dose)
• Beagles: 2.5 - 40 mg/kg (greater than 200 times the therapeutic dose)
• Cats: there is a report of a kitten exhibiting toxicosis following addministration of 0.3 mg/kg of body weight, subcutaneously. Adult cats seem to be less sensitive.
• Chelonians (red-footed and leopard tortises): 0.1 - 0.4 mg/kg
• Leopard frogs: 2.0 mg/kg intramuscular resulted in death while 20 mg/kg cutaneous had no effect

• mydriasis
• depression
• coma
• tremors
• ataxia
• stupor
• emesis
• drooling
• death

Mode of Action:

• Ivermectin is an agonist for the neurotransmitter gamma-aminobutyric acid (GABA).
• GABA is a major inhibitory neurotransmitter.
• In mammals, GABA-containing neurons and receptors are found in the Central Nervous System; while in arthropods and nematodes GABA is found primarily in the Peripheral Nervous System (neuromuscular junction).
• This difference in location of GABA receptor may be the reason for the large margin of safety of ivermectin-containing products in mammals.
• The binding of ivermectin to a neuronal membrane increases the release of GABA.
• GABA binds to the GABA receptor-chloride channel complex of postsynaptic neuronal membranes causing an influx of chloride ions.
• The influx of chloride ions hyperpolarize the neuronal membrane making them less excitatory and decreasing nerve transmission.
• The hyperpolarization of neuronal membranes (at the NMJ) mediate a flaccid paralysis in arthropods and nematodes.

• Clinical Signs
• History of exposure to ivermectin-containing products
• Chemical analysis for ivermectin (generally not needed)
• Methods used:
• high-pressure liquid chromatography (HPLC)
• enzyme-linked immunoassay (ELISA)
• Samples:
• liver
• body fat
• gastrointestinal contents (low GI absorption)
• feces
Ivermectin is metabolized only slightly by the liver. The majority of ivermectin is excreted in the feces. In cattle, sheep and horses significant amounts of ivermectin can remain in fecal 'pats' leading to reduced numbers of dung beetles.

• There is no safe specific antidote for ivermectin toxicosis
• Initially following an oral exposure the focus should be on ivermectin removal:
• activated charcoal
• saline cathartic
• Symptomatic and Supportive care can help the majority of intoxicated animals
• treatment could be prolonged (days to weeks)
• intravenous fluids
• pads
• turning affected animals to prevent pressure sores
• treat possible bradycardia
• Picrotoxin has been proposed as a specific antidote. There are some reports of using picrotoxin to treat ivermectin toxicosis. It is generally titrated to effect. Picrotoxin is a potent GABA antagonist that causes an increase in the excitability of neurons in the CNS which leads to convulsions. Seizures caused by picrotoxin administration may be treated with barbituates. Picrotoxin has a narrow margin of safety and is not the best treatment for ivermectin toxicosis.
• Physostigmine - is an uncharged, reversible inhibitor of acetylcholinesterase that can penetrated the Blood-Brain-Barrier.Physostigmine has been shown to have some effect in the comatose animal. This may be due to an increased concentration of acetylcholine in affected neurons. The comatose animal may exhibit a transient increase in metal alertness. This may be beneficial to the veterinarian by: confirming the diagnosis of ivermectin toxicosis, possibly treating the more severe cases and giving the owners hope for their comatose dog.

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Original Article:  http://www.abvt.org/iverm.html

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Ivermectin and Animals | Ivermectin Death Rates | Ivermectin Warnings | Not Fully Tested