The same dose will be absorbed faster when administered parenterally than when administered topically, but signs of toxicity can be seen in all routes with high enough doses.
Toxicity may occur with products administered orally, topically, or parenterally.
When ivermectin, a macrocytic lactone, is present in sufficiently high concentrations to cross the blood–brain barrier, it can cause neurologic signs in dogs.
In nonsensitive breeds, a dose of >2000 µg/kg is required to produce signs of toxicosis. 3,4
In sensitive breeds, ivermectin toxicosis can be seen in doses as low as 100 µg/kg, although doses of 6 µg/kg have been shown to be safe in sensitive breeds.
Common breeds with this mutation include the border collie, Australian shepherd, long-haired whippet, silken windhound, rough- and smooth-coated collies, and associated mixed breeds.
Dogs with an ABCB1 mutation are also predisposed to increased sensitivity to moxidectin, loperamide, milbemycin, and chemotherapeutic agents.
Dogs with a mutation in the multidrug resistance gene (ABCB1, formerly MDR1) are especially sensitive to ivermectin. 1,2
Very young animals may have an increased risk because of their immature blood–brain barriers.
No gender or age predisposition.
Dogs can also be exposed to ivermectin through ingestion of feces from treated cows, horses, or pigs.
Dogs on farms or in rural settings are at greater risk for ivermectin toxicosis because they may be exposed to products formulated for large animals.
Most cases of ivermectin toxicosis result from administration of ivermectin-containing products.
pCO2 = partial pressure of carbon dioxide
When ivermectin binds to the receptors, the chloride channels open slowly and irreversibly, resulting in prolonged hyperpolarization or depolarization of the neuron or muscle cell, causing rapid paralysis. 5
At higher concentrations, glutamate-gated chloride channels are opened directly. 5,6
At low concentrations, ivermectin potentiates the effect of glutamate.
The primary mechanism of action for ivermectin is to potentiate glutamate-gated chloride receptors and g-aminobutyric acid (GABA)–gated chloride channels.
History
Examination Findings
Testing for the ABCB1 gene mutation is available at Washington State University Veterinary Clinical Pharmacology Laboratory, Gribbles Veterinary Services in Australia, and Genetic Counseling Services in The Netherlands.
Measurement of serum ivermectin concentration can confirm diagnosis, but usually results are not available immediately.
History and examination findings are vital.
Other causes of extracranial neurologic disease.
Exposure to other toxicants (eg, ethylene glycol, methanol, heavy metals, hallucinogens, marijuana, barbiturates, opioids, benzodiazepines, mycotoxins).
Respiratory acidosis caused by hypoventilation may be present. Partial pressure of carbon dioxide (pCO2) >60 mm Hg is diagnostic.
Venous blood gas analysis is recommended if the patient is moderately obtunded.
Urinalysis may help differentiate between renal and prerenal azotemia.
Nonspecific elevations in liver enzymes may be present.
Prerenal azotemia may occur if patient is adipsic or vomiting.
Hypoglycemia may be present if tremors/seizures are prolonged.
Hemoconcentration has been seen.
CBC, serum biochemistry profile, and urinalysis are usually nonspecific but may be helpful.
There are no specific antidotes for ivermectin toxicosis.
Oral:
Ivermectin is recirculated in the GI tract.
If ingestion occurred <1–4 hours before presentation:
Emesis should be induced with apomorphine (0.03 mg/kg IV or subconjunctivally once) or hydrogen peroxide (0.5 mL/kg PO up to 2 times).
Activated charcoal should be administered (1–2 g/kg PO once) with/without cathartic; subsequent doses without cathartic at 0.5–1 g/kg q8h.
Monitoring electrolyte concentrations, especially sodium, is important.
If oral ingestion occurred within 24–36 hours before presentation:
Activated charcoal should be administered once at 1–2 g/kg PO; subsequent doses at 0.5–1 g/kg q8h.
All routes:
Patients with topical ivermectin toxicosis should be washed with mild dishwashing detergent and water before initiating additional treatments.
Crystalloid fluid therapy should be initiated for maintenance requirements and any ongoing losses (lactated Ringer’s solution, Plasmalyte-148 [baxter.com], 0.9% saline solution).
If hypovolemia (tachycardia, hypotension, pale mucous membranes, prolonged capillary refill time) is present, circulating fluid volume should be replaced by administering crystalloid fluid via 20 mL/kg bolus, then reassess vital signs.
Bolus may be repeated up to 4 times. Colloids (Hetastarch [hydroxyethyl starch; HES]) at 5 mL/kg concurrently may help correct hypovolemia.
Endotracheal intubation and mechanical ventilation should be initiated for hypoventilation (pCO2 >60 mm Hg).
Consider referral for mechanical ventilation if unavailable at primary receiving practice. Intubate patient and begin manual ventilation for transportation to specialty practice.
Progression of clinical signs may be slow. Exposed animals should be monitored closely in the hospital or at home for at least 1 week, as more extensive therapy may be indicated.
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