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Over the Counter, Around the House, Out in the Garden - Trending Threats for Pets
Tina Wismer, DVM, MS, DABVT, DABT ASPCA Animal Poison Control Center
Urbana, IL
Marijuana (Cannabis sativa)
♦ MJ contains at least 61 cannabinoid compounds and > 300 other substances § THC (∆-9-Tetrahydro-cannabinol)
♦ Amount of resins will vary § Plant variety § Sex of plant (female plant,
"sensemilla" more toxic) § Geographic location § Growing season
Toxicity
♦ Fresh plant: minimally toxic ♦ Toxicity ↑
§ Heating, drying, smoking, aging § Fresh plant: predominant compounds are THCA,
CBDA and cannabinolic acid (CBNA) - cannabinoids in their acidic forms
♦ Transformation by decarboxylation into neutral forms (THC and CBD) § Non-enzymatic process that has two main catalysts;
heat and time
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Marijuana (Cannabis sativa)
♦ Medicinal § Anti-emetic § Analgesic/anti-inflammatory – dihydrostilibene
canniprene § Anticonvulsant - cannabidol § Muscle relaxant § Appetite stimulant § Decrease intra-ocular pressure
United States
♦ 33 + states allow medical use ♦ 11 + states legalized recreational use ♦ Schedule I controlled substance
Marijuana
♦ More cases § Truly an increase in intoxicated pets § Changing attitudes § More potent forms
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Potency
♦ Increasing Potency § Increased THC strains of cannabis hybrids § Selective breeding
♦ THC levels have more than doubled over the last 25 years § THC in plant material 1-8% § Extracts 28% § Hash oil up to 50%
Changing Exposures
♦ Past: plant material from baggies or joints ♦ Now: Edibles (cookies, brownies, etc.) and
concentrates (oils, waxes, shatters) ♦ Increase in marijuana butter based edibles
§ THC butter – heat MJ in butter to extract the lipophilic THC
♦ While both dogs and cats willing ingest plant material, dogs are the most likely to consume edibles § Many of the edibles also incorporate
chocolate
Human dosing of THC products
♦ THC 10 mg
4
Quality control
♦ 75 products were evaluated to determine the amount of cannabidiol and THC § 17% of products were accurately labeled § 23% were under labeled § 60% were over labeled (THC)
Toxicity ♦ Dose-related
§ Wide-range of variability among individuals § Hepatic impairment more sensitive?
♦ Behavioral effects can start at low doses § 3 mg THC/kg PO ??
♦ Lethal dose: > 3 g THC/kg PO § Lethal dose has not been established in dogs or cats § Fortunately death is rare § Published reports of two dog deaths after ingesting
edibles and a 12-week-old ferret after ingesting plant material
Kinetics
♦ THC well absorbed via inhalation and PO ♦ Signs may be seen 30-60 m after
ingestion § Last 18 - 36 h, may last 72 hours
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Marijuana - Clinical Signs ♦ Most common signs
§ Depression (25% agitated) § Ataxia § Bradycardia (occasional tachycardia) § Incontinence (dribbling urine) § Hyperesthesia § Disorientation
♦ Other signs § Vocalizing, vomiting, diarrhea, hypothermia,
hypersalivation, mydriasis, seizure (rare) § Coma, hypotension (concentrates, THC butter)
Decontamination
♦ If asymptomatic § Emesis
• Marijuana is an anti-emetic, inducing emesis may not be successful but can be tried with recent (< 30 minutes) oral exposures
• Better results with hydrogen peroxide vs apomorphine
♦ Activated charcoal is generally not needed ♦ Monitor for several hours
Marijuana Treatment
♦ Assess patient § Outpatient vs inpatient § Many cases with plant material ingestion can
be managed at home with confinement and monitoring the ability to ambulate
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Treatment
♦ Monitor HR, BP and temp ♦ Minimize sensory stimuli ♦ Fluids ♦ Diazepam (if agitated), Acepromazine? ♦ Rotate body position q 4 hours ♦ Assisted respiration ♦ No specific CBC or chemistry profile
abnormalities are expected § Monitor blood glucose levels in young animals
Treatment
♦ Comatose animals § Intralipids (20% solution) may be helpful
(some variable results) § THC is lipid soluble § 1.5 ml/kg initial bolus (over 20-30 minutes)
then a CRI of 0.25 ml/kg/min for 30-60 minutes. Repeat CRI in 4 hours provided there is no lipemia.
♦ Comatose ferrets and lipids § Great results, N=2
Lipid Therapy
♦ Lipid emulsion is commonly used as a fat component for parenteral nutrition
♦ Promising treatment for some toxicoses § Usage based on human research
investigating bupivacaine ♦ Mechanism for lipid rescue
§ Possible “lipid shuttle”
7
Lipid Therapy
♦ Positives § Can hasten recovery time (less $$) § Can administer via peripheral catheters
♦ Inexpensive § 100ml bags ~ $37 § 2-year shelf life
Lipid Therapy
♦ Product must be refrigerated § Open bag is good for 48hrs
♦ Possible complications: § Significant lipemia § Pancreatitis § Transient increased liver enzymes § Volume overload potential § Can also remove antidotes and other
therapies
Lipid Therapy ♦ Marijuana ♦ Ivermectin ♦ Moxidectin ♦ Calcium-channel blockers ♦ Local anesthetics ♦ Permethrin ♦ Antidepressant medications ♦ Baclofen ♦ Baytril?
8
Lipid Therapy
♦ Lipidrescue.org § Website with information and discussions on
lipid administration and treatments
Marijuana Prognosis
♦ If appropriate treatment is implemented, the prognosis is good and no permanent effects should be anticipated
Question
♦ Are OTC urine spot tests for marijuana a helpful diagnostic tool in dogs?
A. Yes, most of the time B. Rarely C. About half the time
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Diagnostic Testing
♦ Urine OTC drug screening tests have not been validated for use in dogs § Most = false negative for THC in dog urine § Thought to be due to different metabolites
produced by dogs when compared to humans • 8-OH-Δ9-THC produced by dogs, 11-OH-Δ9-THC
in humans
♦ Different metabolites may also explain the urinary incontinence that is seen in dogs and not in other species
OTC Drug Tests
♦ Urine test ♦ 2-5 minutes ♦ Cheap
§ $8.50 ♦ Tests available
§ AMPH, BAR, BZO, THC, COC, MDMA, METH, MTD, MOP, OPI, PCP, TCA
♦ Thanks to Dr. Rob Kessler, Las Vegas, NV
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False Positive for THC?
♦ Literature reports of false + screens
Ibuprofen Naproxen Efavirenz
THC
Niflumic acid
But what about the non-THC products?
♦ Legal status less clear § Hemp products legal in some states
♦ Hemp has THC < 0.3% on dry weight basis
Cannabidiol (CBD)
♦ CBDs do not have the psychoactive properties of THC § Suggested for pain control and appetite
stimulation in pets ♦ CB2 selective agonists have been shown
to be somewhat effective in the treatment of pain, various inflammatory diseases, and osteoporosis in humans
♦ CBD even has anticonvulsant-activity
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Clinical uses in humans ♦ Cannabidiol for seizures ♦ Dravet Syndrome (Severe Myoclonic Epilepsy of Infancy)
§ Rare and intractable form of epilepsy that begins in infancy, even while taking multiple anticonvulsant drugs, children may still experience multiple seizures each day
§ Parents of afflicted children seek out cannabidiol-enriched cannabis products to treat these resistant seizures
• 20-80% reduction seizure frequency reported • Rare reports of complete resolution of seizures
♦ FDA approved orphan drug status for cannabidiol for treatment of drug-resistant epilepsy for Dravet and Lennox-Gastaut syndromes (Schedule V)
CBD use in pets
♦ CBD oil 2 and 8 mg/kg § Half-life to be 4.2 hours at both doses § Elevated alkaline phosphatase in all 8 dogs
♦ Osteoarthritis § 2 mg/kg q 12 h or placebo oil § Cross over study § The results seem to support anecdotal reports
of CBD oil’s benefits of decreased pain
CBD in pets?
♦ There is no known appropriate dose for pets
♦ ASPCA Animal Poison Control Center has had dogs develop the same signs as THC ingestion after ingesting CBD only products § Quality control? § Different metabolites? § Too high dosage?
12
Mac
♦ DSH ♦ 6y MN ♦ 10# ♦ Good health
♦ History of vomiting today and lethargic tonight
♦ PE is WNL
♦ What would you like to do? § A. Radiographs § B. Blood work § C. Ultrasound § D. Euthanasia
♦ BUN 52 (14 – 36) ♦ Creat 4.9 (0.6 – 2.4)
♦ All other values WNL
♦ Diagnosis?
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History
♦ The owner said she sprayed Mac yesterday with flea spray
♦ Do you think the flea spray is involved?
♦ What other questions do you want to ask the owner?
Additional History
♦ Mac’s owner had a death in the family and brought home several plants from the funeral
♦ The owner has observed Mac chewing on some of the plants
♦ The owner is able to identify the plants from the internet
Plant #1
♦ What is this plant? § Peace Lily (Spathiphyllum sp.)
♦ Does it cause renal failure? § No § Insoluble calcium oxalates
• Drooling, oral irritation, vomiting • Pharyngeal swelling (rare)
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Plant #2
♦ What is this plant? § Cala Lily (Zantedeschia sp.)
♦ Does it cause renal failure? § No § Insoluble calcium
oxalates
Plant #3
♦ What is this plant? § White lily (Lilium sp.)
♦ Does it cause renal failure? § Yes § Unknown mechanism
Treatment
♦ IV fluids ♦ Monitor urine output ♦ Monitor electrolytes ♦ Antiemetics as needed
♦ Prognosis?
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Lilies (Lilium and Hemerocallis spp.)
♦ All parts of plant toxic § Pollen
♦ Only cats ♦ Acute renal failure
§ Necrosis of proximal renal tubular epithelial cells
§ Unknown water soluble toxin
Lilies: Lilium and Hemerocallis spp. Common Names Scientific Names • Easter lily Lilium longiflorum • Tiger lily Lilium tigrinum • Rubrum lily Lilium speciosum • Japanese show lily Lilium lancifolium • Day lily Hemerocallis spp.
Lilies
♦ By 2-6 hours: vomiting ♦ By 24-72 hours: ARF
♦ Delaying treatment results in death
♦ Activated charcoal ♦ IV fluids
16
Grapes and Raisins
♦ Vitis sp. ♦ Renal failure associated
with ingestion
♦ No age, breed, sex predisposition § Dogs § Cats, ferrets?
Grapes and Raisins
♦ Grapes from private vines, roadside stands (“organic”), wineries § fresh grapes and
pressings from wineries ♦ Commercial raisins of
varying brands ♦ “Home grown” raisins
from roadside stands
Grapes and Raisins
♦ MOA and toxic principle unknown § Histopath: damage to the
proximal tubules § Toxin is water soluble, in
fleshy part, possibly complex sugar
♦ Individual sensitivity?
17
Grapes and Raisins - Toxicity
♦ How much is too much? § Err on side of caution § 0.7 oz/kg of grapes § 0.1 oz/kg of raisins
Grapes and Raisins
♦ Clinical Signs § Vomiting and/or diarrhea (within 6 hours) § Depression, dehydration, anorexia, abdominal
pain ♦ Clinical Pathology
§ Elevated creatinine (w/in 12 hours) § Elevated BUN in most dogs § ↑ Ca, ↑P, elevated liver enzymes, elevated
lipase/amylase, hyperglycemia
Grapes and Raisins - Decontamination
♦ Decontaminate recent ingestions § induce emesis up to 6 hours post exposure
♦ Activated charcoal § within the first 12-24 hours
♦ Fluid diuresis for 48 hours § especially important if vomiting develops
♦ Monitor renal values § if normal after 48 hrs discontinue fluids
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Grapes and Raisins - Treatment
♦ Symptomatic and supportive care § GI protectants § antiemetics § phosphate binders
♦ Oliguric/anuric renal failure developed within 72 hours of ingestion § poorly responsive to treatment § dialyzed dogs had mixed results
Joint Nutraceuticals
♦ Glucosamine, chondroitin, dimethylsulfone perna
♦ Typically vomiting, diarrhea § Electrolyte issues with soft chews
• Loss of free water = hypernatremia
♦ Rarely – elevated liver enzymes § Liver necrosis
Joint Nutraceuticals
♦ Fluids and antiemetics if needed ♦ Liver support ♦ ALT up within 72 h ♦ Dogs > 7 years most at risk
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Hops - Humulus lupulus
♦ Malignant Hyperthermia-like syndrome ♦ Dogs ♦ Signs within 3 hours
§ Tachypnea, severe hyperthermia (108°F) ♦ Death within 6 hours
Hops
♦ Toxic principle § Unknown
♦ Treatment § Dantrolene (direct-acting skeletal muscle
relaxant) § Cyproheptadine
♦ Prognosis: Guarded to poor
Cycad palms, Sago palm
♦ Cycas spp., Macrozamia spp., Zamia spp. § Ornamental yard and garden plant § Ornamental house plant
♦ All parts of plant, especially nut § In dogs, as few as 1-2 seeds
have been fatal
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Sago Palms (Cycas, Zamia)
Cycas (false sago palm) Cycad seeds
Sago Palms (Cycas, Zamia)
♦ 3 toxins § Cycasin – GI irritation , hepatic necrosis § Beta-methylamino-L-alanine
(BMAA) – neurotoxic amino acid
§ Unidentified toxin – causes axonal degeneration in CNS
Sago palms – Clinical signs ♦ Vomiting (+/- blood) ♦ Depression ♦ Anorexia ♦ Elevated liver enzymes
§ 24-48 h ♦ Seizures ♦ Death
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Sago Palms (Cycas, Zamia)
♦ Decontamination ♦ Aggressive care often necessary
§ Transfusions § Fluid and electrolyte therapy § GI protectants § Liver protectants § Seizure control
♦ Management of liver failure, DIC, and renal disease
Sago Palms (Cycas, Zamia)
♦ Prognosis guarded to poor if severe signs occur
♦ Mortality rate ~10-32%
♦ May require long-term management of hepatic compromise
‘Laners
♦ Bravecto, Simparica, NexGard, Credelio § Isoxazoline insecticide § Bind insect and acarine ligand-gated chloride
channels, leading to hyperexcitation and uncontrolled activity
♦ FDA warning ‘adverse neurologic effects’
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‘Laners
♦ Seizures, ataxia § More common in known epileptics § More common in overdose situations § More common in cats § Typically within 24 hours § Duration 8-12 hours
Questions??