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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

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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”

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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?

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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?

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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

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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?

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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??