If you have given your Collie
this drug and your pet is starting to behave strangely please print out and take
this information to your Vet to help him treat your dog.
- 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
- 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
- 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
- Formulations of Ivermectin :
- Ivomec (Merck) - injectable, 10 mg/ml for swine and
- Equvalan (Merck) - oral paste, 8.7 mg/ml for
- Ivomec (Merck) - oral drench, 0.8 mg/ml for
- Heartguard (Merck) oral tabs, 68, 136, and 272
micrograms of ivermectin for dog for the prevention of Canine Heartworm
- 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
- Cattle: 4 - 8 mg/kg (20 - 40 times the therapeutic
- Horses: 2 mg/kg (10 times the therapeutic dose)
- Pigs: 30 mg/kg (100 times the therapeutic dose)
- Collies: 0.1 - 0.2 mg/kg (15 - 30 times the
- Beagles: 2.5 - 40 mg/kg (greater than 200 times the
- Cats: there is a report of a kitten exhibiting
toxicosis following administration of 0.3 mg/kg of body weight,
subcutaneously. Adult cats seem to be less sensitive.
- Chelonians (red-footed and leopard tortoises): 0.1 -
- Leopard frogs: 2.0 mg/kg intramuscular resulted in
death while 20 mg/kg cutaneous had no effect
Note: Convulsions & seizures are NOT commonly
associated with Ivermection toxicosis.
Ivermectin is a GABA agonist, which will increase the effects of
inhibitory neural pathways in the CNS leading to depression and
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
- This difference in location of GABA receptor may be
the reason for the large margin of safety of ivermectin-containing products
- 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
- 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)
- There is no safe specific antidote for ivermectin toxicosis
- Initially following an oral exposure the focus should be on ivermectin
- activated charcoal
- saline cathartic
- Symptomatic and Supportive care can help the majority of intoxicated
- treatment could be prolonged (days to weeks)
- intravenous fluids
- 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.
- Button C, Barton R, Honey P, Rickford P; Avermectin
toxicity in calves and an evaluation of picrotoxin as an antidote. Aust Vet
J 1988 May;65(5):157-158, 1988.
- Godber LM, Derksen FJ, Williams JF, Mahmoud B;
Ivermectin toxicosis in a neonatal foal. Aust Vet J 72(5):191-192,
- Hadrick MK, Bunch SE, Kornegay JN; Ivermectin
toxicosis in two Australian shepherds. J Am Vet Med Assoc
- Hopkins KD, Marcella KL, Strecker AE; Ivermectin
toxicosis in a dog. J Am Vet Med Assoc 197(1):93-94, 1990.
- Houston DM, Parent J, Matushek KJ; Ivermectin
toxicosis in a dog. J Am Vet Med Assoc 191(1):78-80, 1987.
- Jongen,MJ; Engel,R; Leenheers,LH: High-performance
liquid chromatographic method for the determination of occupational exposure
to the pesticide abamectin. Am. Ind. Hyg. Assoc. J. 52(10), 433-437,
- Letcher J, Glade M. Efficacy of ivermectin as an
anthelmintic in leopard frogs. J Am Vet Med Assoc 200(4):537-538,
- Lewis DT, Merchant SR, Neer TM; Ivermectin toxicosis
in a kitten. J Am Vet Med Assoc 205(4):584-586, 1994.
- Li,J; Qian,C: Determination of avermectin B1 in
biological samples by immunoaffinity column cleanup and liquid chromatography
with UV detection. J. AOAC. Int. 79(5): 1062-1067, 1996.
- Lovell RA; Ivermectin and piperazine toxicoses in dogs
and cats. Vet Clin North Am Small Anim Pract 20(2):453-468,
- Mitsui,Y; Tanimori,H; Kitagawa,T; Fujimaki,Y; Aoki,Y :
Simple and sensitive enzyme-linked immunosorbent assay for ivermectin. Am.
J. Trop. Med. Hyg. 54(3): 243-248, 1996.
- Paul AJ, Tranquilli WJ, Seward RL, Todd KS Jr,
DiPietro JA; Clinical observations in collies given ivermectin orally. Am J
Vet Res 48(4):684-685, 1987.
- Ristic Z, Medleau L, Paradis M, White-Weithers NE;
Ivermectin for treatment of generalized demodicosis in dogs. J Am Vet Med
Assoc 207(10):1308-1310, 1995.
- Sams,R: Chemical assay of avermectins by high
performance liquid chromatography with fluorescence detection. Vet.
Parasitol. 48:59-66, 1993.
- Skopets B, Wilson RP, Griffith JW, Lang CM; Ivermectin
toxicity in young mice. Lab Anim Sci 46(1):111-112, 1996.
- Teare JA, Bush M; Toxicity and efficacy of ivermectin
in chelonians. J Am Vet Med Assoc 183(11):1195-1197, 1983.
- Tranquilli WJ, Paul AJ, Seward RL, Todd KS, Dipietro
JA; Response to physostigmine administration in collie dogs exhibiting
ivermectin toxicosis. J Vet Pharmacol Ther 10(1):96-100, 1987.
- Tranquilli WJ, Paul AJ, Seward RL; Ivermectin plasma
concentrations in collies sensitive to ivermectin-induced toxicosis. Am J
Vet Res 50(5):769-770, 1989.
- Yamazaki J, Matsumoto K, Ono H, Fukuda H; Macrolide
compounds, ivermectin and milbemycin D, stimulate chloride channels sensitive
to GABAergic drugs in cultured chick spinal neurons. Comp Biochem Physiol
C 93(1):97-104, 1989.
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