Page 582 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Macrocyclic Lactone Endectocides Chapter | 43 547

VetBooks.ir liver tissues had elevated levels of doramectin. The effective if performed within 2 h of ingestion (Mealey,
For patients that can safely vomit, emesis may be
remaining lions made full recoveries. Dendrobatid frogs
administered ivermectin orally via micropipette (attempted
2006). If the patient is unable to safely vomit (e.g., is a
dosage 0.2 mg/kg) developed clinical signs of toxicosis species that cannot vomit or is symptomatic), gastric
24 48 h following administration (Clayton et al.,2012). lavage can be considered. Activated charcoal should be
Signs included ataxia, reduced/absent reflexes, lack of considered in addition to, or instead of, emesis or lavage.
righting reflex, reduced/absent buccal pumping, hydrocoe- It is important to mention that with xenobiotics like the
lom, and unresponsiveness; overall mortality was 68% and MLs, which are excreted in the bile, activated charcoal
surviving frogs remained symptomatic for up to 3 weeks. can be of benefit regardless of the route of the exposure.
In a reproduction study, Wise et al. (1997) demon- Thus if a patient received an overdose of injectable ML
strated that at a high dose, emamectin benzoate (deriva- subcutaneously, activated charcoal will still be a very
tive of avermectin B 1 ) exposure during gestation and valuable decontamination option. The ML molecules will
lactation in rats produced evidence of neurotoxicity in the be carried to the GI by the bile.
F 1 offspring. A no observed adverse effect level for devel- MLs undergo enterohepatic recycling; therefore, mul-
opmental neurotoxicity of emamectin was determined to tiple doses of activated charcoal will likely be beneficial.
be 0.6 mg/kg/day. In addition, the MLs are substrates for the p-glycoprotein
transport system (P-GP) that transports some drugs across
cell membranes. In the intestine, the MLs enter the enter-
Diagnosis ocyte by absorption from the GI. However, once in the
cell, the P-GP acts to move the ML across the membrane
Diagnosis of ivermectin, selamectin, and other MLs can
and back into the gastrointestinal lumen. This cycling
be based on history of exposure to a product, clinical
allows the ML molecules to have multiple opportunities
signs, and residue analysis in the body tissue or fluids.
to bind with the repeated doses of activated charcoal
These compounds are analyzed using high-performance
(Mealey, 2006). When repeated doses are indicated, half
liquid chromatograph coupled with a UV, fluorescence, or
the original dose should be given at 4 8 h intervals, often
photodiode array detector (Reising et al., 1988; Maynard
for 2 3 days (Peterson, 2006).
and Maynard, 1989; Rabel et al., 1993; Payne et al.,
The patient should be monitored for the development
1995; Anastaseo et al., 2002; Gupta et al., 2005). GI
of CNS effects including ataxia, lethargy, recumbency,
content, liver, fat, and feces are usually the specimens
tremors and seizing. Also monitor for bradycardia, gastro-
analyzed for MLs residue, while brain tissue would be uti-
intestinal upset, and respiratory depression. No specific
lized for confirming toxicosis.
chemistry panel changes are expected. If activated char-
Fatal doramectin toxicosis in two lions (Panthera leo)
coal is given, serial serum sodium tests should be run to
was associated with brain doramectin concentrations of
check for elevations, as hypernatremia has been associ-
0.082 and 0.183 ppm (Lobetti and Caldwell, 2012). Brain
ated with repeated doses of activated charcoal (Ball,
ivermectin concentrations reported in clinically normal cat-
2014).
tle are low (e.g., B0.004 ppm), while concentrations of
There is no specific antidote for ML toxicosis, so treat-
0.056 ppm have been associated with clinical toxicosis
ment is symptomatic and supportive. Patients who are
(Seaman et al.,1987). In dogs, 0.134 ppm of ivermectin in
recumbent or comatose will require good nursing care
brain tissue was associated with fatal toxicosis (Pullium
including thermoregulation, soft bedding, and frequent
et al., 1985), while in horses 0.131 ppm was associated
turning to prevent decubital ulcers and urine scalding since
with ivermectin-induced fatality (Swor et al., 2009).
the patient may be immobile for multiple days (Mealey,
2006). Patients that are experiencing tremors or seizures
can be treated with methocarbamol. Minimize sensory sti-
TREATMENT
muli since these patients can be hyperesthetic. Nutritional
Treatment for intoxication with MLs should include limit- support through tube feeding may also be necessary
ing systemic absorption of the xenobiotic, monitoring for (Mealey, 2006). Intravenous fluids should be given as
possible clinical effects, and managing any signs that needed for cardiovascular support and atropine can be used
develop. Symptomatic patients should be stabilized prior to for bradycardia. A respirator may be necessary if signifi-
performing decontamination procedures. For oral exposures, cant respiratory depression develops. Picrotoxin and pysos-
emesis, lavage and/or administration of activated charcoal tigmine have both been used to treat ivermectin toxicosis,
should be considered. If the exposure was by a recent sub- but have been associated with significant adverse effects
cutaneous injection and life-threatening toxicosis is possi- including seizures (Crandell and Weinberg, 2009).
ble, surgical excision of the injection site can be considered A promising new therapy, intravenous infusion of a
if the bleb can still be palpated (Beasley et al., 1999). lipid emulsion (ILE), has been used to treat ML toxicosis