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 = 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 P- glycoprotein multidrug transporter in the BBB Defect allows Ivermectin to pass into the CNS at even low doses, causing toxicosis
Breeds Affected
Ivermectin Dosages Heartworm prevention mg/kg PO q 30 days Off-label use Dosage range from mg/kg PO/SQ Most dogs tolerate up to 2.5 mg/kg PO LD 50 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 Cote, Etienne. Interceptor toxicity. Cote Clinical Veterinary Advisor pp , Copyright © 2009 Elsevier Inc. Dowling P. Pharmacogenetics: It’s not just about ivermectin in collies. Clinical Pharmacology Update; 47: , Edwards G. Ivermectin: does P-glycoprotein play a role in neurotoxicity? Filaria Journal, 2:58, Hopper K, Aldrich J, Haskins SC. Ivermectin Toxicity in 17 Collies. J Vet Intern Med; 16:89-94, Mealey KL, Northrup NC, Bentjen SA. Increased toxicity of P-glycoprotein- substrate chemotherapeutic agents in a dog with MDR1 deletion mutation associated with ivermectin sensitivity. J Am Vet Med; 223(10):1453-5, 1434, Merola V, Khan S, Gwaltney-Brant S. Ivermectin Toxicosis in Dogs: A Retrospective Study. J Am Anim Hosp Assoc. 45: , 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, 2 nd Edition. Elsevier, Missouri, 2006, pp Plumb, Donald C. Plumb’s Veterinary Drug Handbook, 5 th Edition. Blackwell Publishing, 2005, pp Shell, L. Ivermectin. VIN database, Veterinary Clinical Pharmacology Laboratory. Affected Breeds. Washington State University
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