Transcript Ivermectin Toxicosis

Veterinary Specialists of South
Florida Presents:
Outline
 Clinical
Case Summary
 Definition
 Etiology and Pathophysiology
 Epidemiology
 Clinical Presentation
 Diagnosis
 Treatment/Prognosis
Chook
4 yo FS Australian Shepherd
 8 AM

 Owner dewormed horses with
2% Ivermectin Paste

10 AM
 Chook was normal when owner
left the house

12 PM
 Daughter found Chook wobbly
and stumbling around
Chook - Presentation
 Alert and hyper-responsive
 MM – pink & moist, CRT < 2 seconds
 Temp = 102.4 F
 HR = 200, RR = pant
 Absent menace and PLR’s bilaterally
 Mydriasis
Chook - Diagnosis
 Ivermectin Toxicity
○ History of exposure
○ Breed susceptibility
○ Physical exam findings
Chook - Treatment
IV catheter placed
IV fluids started
Owner decline further treatment
Ivermectin Toxicity - Definition

Ivermectin toxicity
 A clinical syndrome that is used to describe
an exposure to the macrocyclic lactone
antiparasitic drug ivermectin

Other drugs
 Milbemycin, moxidectin, selamectin,
doramectin, eprinomectin, abamectin
Etiology & Pathophysiology
Enhance the release of GABA (inhibitory
neurotransmitter)
 Parasites

 GABA mediated neurons present throughout
PNS -> enhanced GABA release -> paralysis

Mammals
 GABA mediated neurons restricted to CNS &
BBB excludes the drug at therapeutic dosages

Overdose
 With overdosages, or animals with a defect in
the BBB, drug enters the CNS and causes an
inhibitory effect -> CNS depression
Epidemiology
Young animals
 More likely in dogs, but cats can show
clinical signs as well
 Genetics and Breed predispositions
 Risk Factors

 LA formulations for SA
 CNS disease or BBB disruption
Genetics & Breed Predispositions

MDR-1 gene mutation
 Autosomal recessive
trait
 Defect in the Pglycoprotein multidrug
transporter in the BBB
 Defect allows
Ivermectin to pass into
the CNS at even low
doses, causing
toxicosis
Breeds Affected

www.vetmed.wsu.edu/depts-vcpl/breeds.aspx
Ivermectin Dosages

Heartworm prevention
 0.006 mg/kg PO q 30 days

Off-label use
 Dosage range from 0.05-0.3 mg/kg PO/SQ
Most dogs tolerate up to 2.5 mg/kg PO
 LD50 in Beagles = 80 mg/kg
 In MDR-1 gene mutation dogs

 Up to 0.1 mg/kg (16X label dose)
Clinical Presentation

History
 Exposure to ivermectin containing
compounds

Presenting Complaint
 Depression, disorientation,
vocalization, stupor, ataxia, tremors,
vomiting, anorexia, recumbency,
blindness, coma, seizure, death
Clinical Presentation

Physical Exam Findings
 Mydriasis +/- blindness
 CNS depression
 Ataxia
 Disorientation
 Hypersalivation
 Tremors
 +/- bradycardia, vomiting, seizures
 Hypothermia or hyperthermia
Differential Diagnosis
Other intoxications
 Brain neoplasia
 Encephalitis
 Hepatic encephalopathy
 Blue-green algae
 Hypoglycemia
 Hypocalcemia
 Phenobarbital toxicity

Initial Database
Neurological examination
 No specific clinical
pathologic alterations
expected
 Baseline

 CBC/Chem/UA
 Bile acids
 +/- thoracic/abdominal
imaging
Advanced Testing

Physostigmine
 1 mg/40 lbs or 0.06 mg/kg IV
 Supports diagnosis -> not confirmatory
 Not generally recommended

Ivermectin sensitivity testing
 Tests for the presence of the MDR-1 gene
mutation
 WSU

Other
 Liver, adipose tissue, brain or serum levels
Treatment - Goals
Manage life-threatening situations
 Supportive care
 Decrease absorption/enhance
elimination
 Nursing care – comatose patients

Treatment - Immediate

Induce emesis
 Recent ingestion
 No signs of respiratory
distress, comatose state

Gastric lavage
 Control airway and respiration

Activated charcoal
 Orogastric/nasogastric
intubation
Treatment – Supportive Care
Manage seizures
 Continue activated
charcoal administration
 Fluid therapy/Electrolyte
balance
 Manage comatose
patients

 Supportive care is the
mainstay of treatment
Prognosis

Largely dependent on
 Dose
 Relative individual sensitivity
 Provision of supportive care
May require supportive care for one day,
several days, or even several weeks
 Even those in a coma, or a seemingly
hopeless case, can have a full recovery

References
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Cote, Etienne. Interceptor toxicity. Cote Clinical Veterinary Advisor pp 610-611,
Copyright © 2009 Elsevier Inc.
Dowling P. Pharmacogenetics: It’s not just about ivermectin in collies. Clinical
Pharmacology Update; 47: 1165-1169, 2006.
Edwards G. Ivermectin: does P-glycoprotein play a role in neurotoxicity? Filaria
Journal, 2:58, 2003.
Hopper K, Aldrich J, Haskins SC. Ivermectin Toxicity in 17 Collies. J Vet Intern
Med; 16:89-94, 2002.
Mealey KL, Northrup NC, Bentjen SA. Increased toxicity of P-glycoproteinsubstrate chemotherapeutic agents in a dog with MDR1 deletion mutation
associated with ivermectin sensitivity. J Am Vet Med; 223(10):1453-5, 1434, 2003..
Merola V, Khan S, Gwaltney-Brant S. Ivermectin Toxicosis in Dogs: A
Retrospective Study. J Am Anim Hosp Assoc. 45:106-111, 2009.
Paul AJ, Tranquilli WJ. Ivermectin. Kirk RW, editor: Current veterinary therapy X,
Philadelphia, 1989, WB Saunders.
Peterson, Michael E.; Talcott, Patricia A. Small Animal Toxicology, 2nd Edition.
Elsevier, Missouri, 2006, pp 785-93.
Plumb, Donald C. Plumb’s Veterinary Drug Handbook, 5th Edition. Blackwell
Publishing, 2005, pp 763-4.
Shell, L. Ivermectin. VIN database, 2006.
Veterinary Clinical Pharmacology Laboratory. Affected Breeds. Washington State
University. 2010.
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