Ivermectin, a mixture between 22,23-dihydro-avermectin B1a (≥ 80%) and B1b (≤ 20%), is produced by an actinomycete (Streptomyces avermitilis). Structurally, it is a disaccharide macrocyclic lactone, chemically related to milbemycin (Fig. 1). Ivermectin is active against nematodes and arthropods.
MECHANISM OF ACTION
Ivermectin activates the gamma-aminobutyric acid (GABA) receptor causing release of GABA from the pre-synaptic membrane and facilitating the binding of GABA to the post-synaptic membrane of inhibitory interneurones.
GABA opens post-synaptic chloride channels, favouring an increase in the intracellular level of this ion with consequent hyperpolarisation of the cell membrane.
TOXICITY
The exclusion of ivermectin from the central nervous system is mediated by P-glycoprotein at the blood-brain barrier. Some breeds of dogs (collies, Shetland sheepdog, English sheepdog) have a deficiency of this protein and are, therefore, unable to prevent ivermectin from crossing the blood-brain barrier: these breeds are, therefore, predisposed to poisoning following exposure to ivermectin.
The peak plasma concentration of ivermectin occurs 3 hours after its ingestion; the half-life in dogs is 2-3 days.
The LD50 in the dog (Beagles) is 80 mg/kg.
CLINICAL SIGNS
The clinical signs usually develop within a few hours of ingestion of ivermectin.
The most commons signs in the dog are:
- Anorexia, vomiting
- Ataxia
- Behavioural disturbances
- Depression
- Mydriasis
- Sialorrhoea/hypersalivation
- Hyperaesthesia
- Absent/fixed stare
- Repetitive pedalling movements or head swaying
- Hyperactivity, agitation, aggressiveness
- Hyperthermia
- Weakness
- Difficulty with breathing and cyanosis
Following severe intoxication by ivermectin or as a reaction to the death of the microfilariae during antinematode treatment, the typical signs of shock can be found in the dog:
- Collapse
- Pallor
- Cold extremities
- Increased capillary filling time
- Weak pulse
Signs in the cat include:
- Ataxia
- Vocalisation
- Disorientation
- Stupor
- Generalised tremors
- Mydriasis, apparent blindness (loss of the reflex to threat, slow and incomplete papillary reflexes)
- Repetitive movements and circling
- Bradycardia
- Hypothermia
- Coma and death
DIAGNOSIS
The diagnosis is based on the history and clinical signs.
LABORATORY TESTS
Liver, adipose tissue, brain and plasma can be analysed to determine the concentrations of ivermectin present.
TREATMENT
Recovery can take a long time (weeks or months). The treatment is symptomatic.
The toxic substances can be removed by:
- Inducing vomiting with apomorphine 0.04 mg/kg i.v. or 0.08 mg/kg i.m. or s.c. in the dog
- Gastric lavage
- Activated charcoal every 3-4 hours
The use of diazepam and other diazepines should be avoided.
Oral or parenteral administration of fluids and nutrients is very important.
Suggested readings
- Hopper K, Aldrich J, Haskins SC. Ivermectin toxicity in 17 collies. J Vet Intern Med 2002;16:89-94.
- Lewis DT, Merchant SR, Neer TM. Ivermectin toxicosis in a kitten. J Am Vet Med Assoc 1994;205:584-6.
- Lovell RA. Ivermectin and piperazine toxicoses in dogs and cats. Vet Clin North Am Small Anim Pract 1990;20:453-68.
- Merola V, Khan S, Gwaltney-Brant S. Ivermectin toxicosis in dogs: a retrospective study. J Am Anim Hosp Assoc 2009;45:106-11.
- Muhammad G, Abdul J, Khan MZ, Saqib M. Use of neostigmine in massive ivermectin toxicity in cats. Vet Hum Toxicol 2004;46:28-9.
- Pulliam JD, Preston JM. Safety of ivermectin in target animals: safety in dogs. In: Ivermectin and Abamectin. Ed. Campbell WC. Springer-Verlag edition. 1989;157-61.
- Roder JD, Stair EL. An overview of ivermectin toxicosis. Vet Hum Toxicol 1998;40:369-70.
Useful links
Pesticide Database, Ivermectin