Toxins in Small Animal Medicine

Toxinsin

Small Animal Medicine Stacy Simmonds, DVM,

DACVECC

Top 10 Toxins2014

ASPCA 1. Human Medications2. OTC medications3. Insecticides4. Household items 5. Human foods 6. Veterinary medications 7. Chocolate8. Plants9. Rodenticide10. Home and Garden

Pet Poison Hotline 1. Chocolate2. Rodenticide3. Ibuprofen/Acetaminophen 4. Insecticidal Products5. Xylitol 6. Household cleaners 7. Antidepressants8. Fertilizers and Plant Food9. Grapes and Raisins10. De-wormer products

Lecture Topics• Options for

decontamination

• Human anti-inflammatory medications

• Antidepressant medications

• Sympathomimetic drugs

• Ethylene glycol

• Lily plants

• Rodenticides

• Chocolate

• Xylitol

• Tremorgenic mycotoxins

• Pyrethrins

• Batteries

• Toxins grouped by clinical signs

• Low toxicity substances

• Do you have original container• More than one active ingredient? • Was it an extended release product?• What is the possible timeframe of ingestion?• What was the potential lowest vs highest dose

ingested?• Has your pet vomited?• How was your pet acting at home?

Be Sure to Ask!

Dermal Decontamination

• Water soluble toxicants - Insecticide/pesticide• Bathe with dishwashing detergent (Dawn)

• Oily or Sticky substances (tar, glue, gum)• Avoid solvents (gasoline, turpentine)• Trim affected hair coat• Vegetable oil, mineral oil, peanut butter – rub

into hair coat until little ‘gummy balls’ develop – then rinse with detergent

Oral Decontamination

• Insoluble calcium oxalates - philodendron, dieffenbachia, calla lily, etc• Dilute with milk, yogurt, cottage cheese

• Irritants or Corrosives: lye, drain cleaners, detergents, bleach, chewed batteries• 2-6 ml/kg water or milk

Greengardening.com Wikipedia.org

Ourhouseplants.com

Emesis

• Dogs, cats, ferrets, pot-bellied pigs• Potential side effects: • Apomorphine – CNS depression• Protracted vomiting • Aspiration pneumonia• Gastritis• Increased vagal tone

Myassistancedog.org

• Best results if administered within one hour• Recovery < 80%

• Delayed emesis induction (4-6 hours): • Salicylates, opiods, anticholinergics, tricyclic

antidepressants, iron tablets, sugar coated substances

• Large amounts of xylitol• Grapes/raisins/chocolate

• Small moist meal prior to emesis may improve results

Emesis Timing

Fastcodesigns.com

Emesis Contraindications

• Species: rabbits, rodents• Already symptomatic • Underlying medical concerns: • History of laryngeal paralysis,

megaesophagus, brachycephalic syndrome

• Contraindicated toxins: • Corrosives, acids: lye, bleach, batteries, oven cleaners• Hydrocarbons/petroleum distillates: tiki-torch oil,

gasoline, kerosene, mineral spirits, furniture polish oils

Mysticcat.sg

Emesis TechniquesApomorphine

• Stimulates dopamine receptors on CRTZ zone• Mean time of emesis – 18 minutes

• Side effects: • Protracted vomiting (IM administration)• CNS depression

• Plumb’s Dose for Dogs: • 0.03 mg/kg IV; 0.04 mg/kg IM• or crush a tablet and dissolve in saline (0.9% NaCl) solution,

instill in the conjunctival sac, and rinse away after emesis• Dissolve one 6 mg tab in 6 cc sterile water water then place in

1ml tubes with a filter and freeze; thaw and give 0.3mg/kg IV

Wedgewoodpetrx.com

Emesis Techniques3% Hydrogen Peroxide

• Not first line method and for some contraindicated• Cats: “generally not recommended” due to

hemorrhagic gastritis and/or esophagitis• Use: Delayed evaluation by a veterinarian

• Mechanism of action: thought to be gastric irritation• Dose: (extra-label): 2.2 mL/kg PO• After 10 -15 minutes – can repeat dose once • Or 1 tsp/5 lbs with max of 3 tablespoons if >45 lbs

Emesis TechniquesCats

• Dexmedetomidine -VIN doses:• 1-2 ug/kg IM • 40 ug/cat IM (Plumb’s sedation dose)• 0.1ml/cat IM• Side effects• respiratory depression, bradycardia, hypertension

• Atipamezole

• Xylazine 0.44 mg/kg: (Plumbs – extra label):• 1.1 mg/kg IM or SQ• 0.44 mg/kg IM• Side effects: • respiratory depression, bradycardia, and hypotension.

• Yohimbine

Conciouscat.net

Assessment of dexmedetomidine and other agents for emesis induction in cats: 43 cases (2009-2014)

V. Thawley; JAVMA: December 2015

• Hydrogen peroxide (3), Xylazine (25), Demedetomidine (16)• Emesis effectiveness: • Hydrogen peroxide: 0/3• Xylazine: 11/25 - 44% • Demedetomidine: 13/16 - 95%

• Dose range: • Xylazine: 0.4-0.5 mg/kg• Dexmedetomidine: 0.96 – 10 mcg/kg

• Side effects: sedation• Suggested dosing for feline emesis: • Dexmedetomidine 7.0 mcg/kg IM• Dexmedetomidine 3.5 mcg/kg IV

Emesis Techniques Not recommended

• Syrup of ipecac

• Salt

• Dry powdered mustard

• Liquid dish detergent

• Digital induction

www.pe.com

Gastric Lavage • May have poorer recovery

of gastric contents than emesis

• Contraindications: • Caustic or corrosive

substance ingestion• Hydrocarbons

Indications: • Emesis has failed or is

contraindicated• Severe

organophosphate/carbamate toxicosis

• Severe metaldehyde or tremorgenic mycotoxin toxicosis

• Ivermectin ingestion• Sago palm ingestion• Bromethalin ingestion

• Increases surface area for toxin• Most effective within 1 hour of toxin ingestion• Poor binding with:• ‘ols’ – alcohol, ethylene glycol, xylitol• Metals – ferrous sulfate, lithium, zinc

• FIRST dose: sorbitol as cathartic • Cathartics enhance delivery through GI tract• Dose: 1 – 5 grams/kg – 2 g/kg is “standard” • Enterohepatic circulation: ½ original dose every 6-8

hours• Risks • Aspiration pneumonia • Electrolyte abnormalities

Activated Charcoal

Shopmedvet.com

** DVM 360.com When and How to Give Activated Charcoal, Justine Lee, DACVECC, DABT; 2013

• Goal: maintain renal perfusion and maintain hydration

• Does not enhance excretion of toxins more quickly

Fluid diuresis

Na+ mmol/L

Cl- mmol/L

K+ mmol/L

Ca++ mmol/L

pH

0.9% NaCl 154 154 5.0

LRS 130 109 4 ~ 3 6.5P-lyte 148

Norm R

140 98 5 5.5

P-lyte A 140 98 5 7.4

Intravenous Lipid Emulsion Therapy

• Potential mechanism(s): • Lipid sink• Improve cardiac performance in cardiotoxic drug overdoses

• USE: Hasten recovery in toxicities related to fat-soluble compounds

• 20% Intravenous lipid emulsion: • 1.5 ml/kg IV bolus over 1-2 mins then 0.25ml/kg/min CRI x 30-

60 mins• Can repeat bolus but check peripheral blood sample for lipemia• Max dose suggested: 8ml/kg/day

Intravenous Lipid Emulsion Therapy

• Baclofen• Ivermectin• Permethrin• Local anesthetics • Calcium channel blockers• NSAIDs

Intravenous Lipid Emulsion Therapy

• Potential side effects: • Phlebitis• Intravascular hemolysis• Hyperlipidemia/Pancreatitis

• Management: • Dedicated IV line• Sterile administration set• Central line not necessary

Anti-inflammatory medications(Human)

• Naproxen (Aleve®)

• Ibuprofen (Motrin®)

• Acetaminophen (Tylenol®)

Non-steroidal Anti-inflammatory medications

• Inhibit conversion of arachidonic acid to prostaglandins • Prostaglandins: • Maintain protective mucous layer in GI tract• Maintain normal blood flow to gastric mucosa• Maintain afferent arteriolar blood flow• Supports normal platelet function

• General treatment: • Decontamination and fluid diuresis• GI protectants: Misoprostol, Carafate, Prilosec• Enterohepatic recirculation: • Repeated charcoal doses• Cholestyramine

Emcrit.com

Non-steroidal Anti-inflammatory medications

Naproxen (Aleve®)• Tablet size: 200 mg and higher • Dogs• > 5mg/kg – GI • > 10 - 25 mg/kg – acute renal failure• > 50 mg/kg – CNS signs

• Cats• Any dose is potentially toxic (GI and renal)

• Long ½ life - • Multiple doses of charcoal• IV fluids x 72 hours at 2 x maintenance

• GI protectants x 2 weeks post hospital discharge

Non-steroidal Anti-inflammatory medicationsIbuprofen

• Tablet size: 200mg, 800mg, 1000mg • Dogs:

• ~25 – 50 mg/kg : GI• >125mg/kg: renal• > 400mg/kg: CNS

• Cats: • >87mg/kg: renal toxicity

• Treatment: • Repeated doses of charcoal• IV fluids x 48 hours• Misoprostol x 3 days

• Evaluate chemistry at baseline, 36, 48, 72 hours• GI protectants x 2 weeks (Carafate, Prilosec)

• Therapeutic dose in dogs: extralabel: 10-15 mg/kg• Toxic dose in dogs: > 100 mg/kg – ADR, GI signs• Recovery time is dose dependent

• > 100mg/kg: Hepatic disease/necrosis• > 200mg/kg: methemoglobinemia, heinz body hemolytic

anemia; KCS• May take 36-48 hours to appreciate elevated liver values • Treatment• * Cimetidine no longer recommended • SAM-E 20mg/kg • Vitamin C: 20 – 30 mg/kg PO every 4 -8 hours ~ 3 days• Methylene blue: not needed if NAC administered; don’t give pre-emptively

Non-steroidal Anti-inflammatory medications

Acetaminophen

Non-steroidal Anti-inflammatory medications

Acetaminophen

• All doses toxic in cats• More likely to develop methemoglobinemia• Usually seen within 2-4 hours

• Heinz body anemia• Hepatotoxicity • If no clinical or clin path signs in 36-48 hours,

not likely to develop complications.

Adelaidevet.com

N-acetylcysteine(NAC, Mucomyst)

• Ideally started within 16 hours of acetaminophen exposure

• Oral: should be diluted to 5% when given orally due to corrosive injury

• IV: dilute to 5% and give 140mg/kg IV followed by 70mg/kg q 6 hours x 7 treatment. • Use bacteriostatic filter and consider pre-dose

with Benadryl

Cholestyramine• MOA: binds bile acids which are then removed via

feces and not reabsorbed

• Toxin Indications: • Enterohepatic circulation• Vitamin D, Naproxen, Indomethacin, Piroxicam,

Diclofenac, sago palm

• Consider charcoal alternating with Cholestyramine 4 hours later – varies with toxin and patient case

Serotonin SyndromeOverdose vs. Drug interactions

• Clinical signs: initially sedation followed by agitation, disorientation, hyperactivity, vocalization, vomiting/diarrhea, tachycardia, hyperthermia, muscle tremors, hyperesthesia, seizures

• Human prescription medications• SSRI’s, SNRI, MAOI’s, TCA, antipsychotics

• Veterinary medications• Fluoxetine, Clomipramine, Mirtazapine, Tramadol

• Illicit drugs• Amphetamines, NMDA agonists

• Holistic supplements• Serotonin• 5 hydroxytryptophan (5 HTP)

Serotonin Syndrome Treatment

• Serotonin antagonists: • Cyproheptadine: • Dog - 1.1 mg/kg PO or PR and Cat – 2 – 4 mg PO • Phenothiazines – non-selective serotonin antagonists• Acepromazine 0.03-0.1 mg/kg (not more than 3 mg/day)• Chlorpromazine 0.5mg/kg IM or IV

• Manage tremors: • Methocarbamol

• Seizures • Diazepam• Anticonvulsants

• Cardiovascular abnormalities• Propanolol for sustained tachycardia or HTN• Atropine for bradycardia Healthtap.com

Differential for SSRI’s• Sleep medications (zolpidem)• Illicit drugs• Wild mushrooms• Tremorgenic mycotoxins (compost/moldy food)• Opiods• Sympathomimetics• Insecticides (carbamates/organophosphates)• Rodenticides (bromethalin, zinc phosphide)• Metaldehyde• Other metabolic causes

Effexor® Venlafaxine

• Cats seem to like venlafaxine• Clinical signs: ~ 2 mg/kg • Mydriasis, vomiting, tachypnea, tachycardia, ataxia, agitation• TX: emesis in asymptomatic patients• AC if extended release formulation• Monitor HR and BP• Antagonizing serotonin effects• Cyproheptadine• Acepromazine

• Lipid emulsion therapy since lipid soluble

Sympathomimetics• Amphetamines (adderall), Methamphetamines

(crystal meth), MDMA (ecstasy), Pseudoephedrine, phenolpropalnolamine, ephedrine, ma huange

• Treat with phenothiazines and barbituates• Diazepam can increase morbidity and mortality• Consider Cyproheptadine• Elevated BP or agitated • Consider Ace or Torbugesic

Urine Drug Tests

Consider Cyproheptadine

• Drug interactions where cyprohepatadine may help without pharmacologic basis.

• SSRI’s • Tricyclic antidepressants• Monoamine oxidase inhibitors• Amphetamines• Pseudoephedrine• Phenylpropanolamine• Baclofen• Drug combinations – Tramadol and Antidepressants

Ethylene Glycol• Antifreeze

• Brake fluids

• De-icers

• Condensers

• Home solar units

• Portable basket ball post bases

• Recreational vehicles

• Paints

• Cleaners

• Solvents

Ethylene Glycol • Ethylene glycol

glycoaldehyde in the liver by the enzyme alcohol dehydrogenase.

• Glycoaldehyde glycolic acid = metabolic acidosis and renal epithelial damage

• Glycolic acid oxalic acid – combines with serum calcium to form calcium oxalate complexes that crystallize in the renal tubular lumen

Ethylene Glycol • 3 clinical stages that can overlap• Neurologic • ~ 30 mins – 12 hours

• Cardiopulmonary – • ~ 12 – 24 hours • acidosis and electrolyte disturbances

• Renal – • ~ 12-72 hours• renal tubular injury from calcium oxalate crystals

Wcrah.com

Ethylene GlycolDiagnosis

• Acute Kidney Injury – but may take >12 hours post exposure

• Hypocalcemia

• PRN® EG kit: blood test • Cats may show signs below

the detectable level

• Kacey® EG test: • Can test positive for any

alcohol

• Woods lamp: urine or haircoat may fluorescence

• UA: dilute USG, glucosuria, +/- crystalluria

• Ultrasound: may reveal hyperechoic renal cortices

• Osmolality: • 1.86 (Na+ + K+) +

glucose/18 + BUN/2.8• > 320 mOsm/kg in dogs; >

330 mOsm/kg in cats

• Anion Gap: > 25 mEq/L

Ethylene GlycolTreatment

• Induce emesis • IVF diuresis • Activated charcoal – controversial effectiveness• 4-methylpyrazole (4-MP)• Ethanol • Dogs: negative EG test – can discontinue Fomepizole or

Ethanol • If azotemic, oliguric/anuric grim prognosis• Peritoneal or Hemodialysis – Gold Standard

Ethylene Glycol 4-methylprazole (4-MP)

• FDA withdrew Antizol - Vet approval in early 2015• Road Runner pharmacy – Compounded -

104$/1.5gm vial• Dose Cats: 126mg/kg IV slowly initial dose; 31.25

mg/kg IV @ 12 hours; 31.25 mg/kg @ 24 hours; 31.25 mg/kg @ 36 hours

• Dogs: 20mg/kg IV first dose; 15mg/kg @ 12 hrs, 15mg/kg @ 24 hrs, 5mg/kg @ 36 hrs

Ethylene GlycolEthanol

• Ethanol – prevents further metabolism of EG via inhibiting alcohol dehydrogenase

• Plumb’s – dosing recommendations• Monitor glucose, electrolytes, IV site• Side effects: • CNS Depression• Worsening metabolic acidosis• Hyperosmolarity

Lily Non-toxic

Calla lilies Peace lilies

Renal Toxic Lily Species

Hemerocallis spp.

• Daylily

• Lemon daylily

• Red lily

• Western lily

Lilium spp.

• Easter lily

• Tiger lily

• Asiatic hybrid lilies

• Japanese lilies

• Stargazer lilies

Encinavet.com

Lily toxicity • All parts toxic – including the pollen• GI signs – vomiting, hypersalivation• Neurologic signs• Acute kidney injury within 12 -72 hours

• Casts can be seen in 12 hours

• No known antidote• Decontamination and supportive care x 48 - 72 hours• Good prognosis with treatment if within ~18 hours and not

azotemic or oliguric• Dialysis may aid in managing the renal failure until tubular

regeneration occurs

RodenticideAnticoagulants

• Restricting production since 2011• Mechanism: inhibits Vitamin K epoxide

reductase (prevents recycling of Vitamin K1)• Second generation rodenticides have long

duration of action (30 days or more)• Some products carry >1 type

of rodenticide

RodenticideAnticoagulants

• Factor VII is first parameter affected – short ½ life (PT) – 36 – 72 hours – may appear clinically normal.

• After ~ 72 hours other factors become depleted and increase the possibility of hemorrhage

• Clinical signs: bleeding anywhere!• Vitamin K1 – dose 3-5 mg/kg/day split orally • Caution with SQ injection

• Whole blood or FFP• Check PT 48-72 hours after discontinuation of Vitamin K

Anticoagulant Rodenticide

Autotransfusion

• USE: Sterile collection set and blood administration set or in-line blood filter

Petplace.com

RodenticideBromethalin

• Toxic principle: leads to reduction of body ATP. • Na+/K+ pumps are depleted and myelin cells develop

edema decreased nerve impulse conduction• Cats more sensitive

• Clinical signs: within hours to 2 weeks (acute/chronic)• Muscle tremors, seizures, excitability, ataxia,

paresis/paralysis, seizures, death• Prognosis: poor with significant neurologic

signs & can have permanent motor damage

RodenticideCholecalciferol -Vitamin D toxicosis

• Increases calcium absorption in GI tract, bone and in kidneys

• Doses > 0.1 – 0.5 mg/kg necessitate treatment - decontaminate• Most commercial rat baits: 0.075 %

concentration• Half life 17 days!• Cats: ½ teaspoon of ingestion

may warrant treatment

Vitamin D3• Vitamin D supplementation (cholecalciferol)• 1 IU = 0.000002mg• 40,000 IU = ~ 1 mg cholecalciferol

• Vitamin D • Decontaminate if dose > 0.1 mg/kg (4,000 IU/kg)• 0.5 mg/kg

• Calcipotriene: psoriasis cream• Calcitriol 0.5 mcg tablets• Decontaminate if > 2.5 ng/kg

Vitamin D toxicosisTreatment

• Baseline Ca+ and renal values every 24 hrs x 3 - 4 days• Can see elevated Ca++ in 24 hours with AKI in 24 hours• Ca++ x Phosphorus ratio > ~ 60 leads to minimally reversible soft tissue

mineralization

• Admit for fluid diuresis (0.9% NaCl) – sometimes to 4-5 times maintenance• If hypercalcemic:

• Prednisone – 1-3 mg/kg PO BID• Furosemide – PO and IV • Consider: • Calcitonin 4-6 IU/kg SQ every 2-3 hours• Pamidronate

• Cholestyramine• 0.3 – 1gm/kg PO every 8 hours x 3 - 4 days. Separate from charcoal x 4 hours.

• Monitor serum calcium daily for 5-7 days, then at least twice a week if needed. Continue Lasix, Prednisone, phosphate binder if needed until calcium level improved.

Chocolate toxicity• Toxic ingredients: Theobromine and caffeine• Highest in darker chocolates

• Ingestion delays gastric emptying• Can induce even 6 hours post ingestion

• Undergoes enterohepatic circulation• Can repeat doses of AC if symptomatic

• Excreted in urine & reabsorbed in bladder• frequent walks or urinary catheter

Xylitol • Sweetener for sugar free products• Clinical signs variable (15 mins – 8 hours)• Hypoglycemia• Acute hepatic necrosis

• Dextrose often recommended even if normoglycemic• Monitor BG every ~ 2 hours and monitor liver values at

baseline and at 24 hours

Tremorgenic MycotoxinsMold

• Penitrem A• Inhibit glycine and GABA (inhibitory neurotransmitters)• Excreted in bile • Decontamination: Activated charcoal – repeated doses may

be beneficial• Clinical signs: hypersalivation, agitation, hypersensitivity• Treatment: • Methocarbamol• Diazepam/Phenobarbital• Propofol

• Insecticides – flea control• Common occurrence in cats getting spot on

treatment for dogs

• Clinical signs: mydriasis, hypersalivation, twitching, tremors, seizures

• Dermal decontamination• Methocarbamol• Intravenous lipid emulsion can be considered

Pyrethrins

• Alkaline dry cell batteries and Button or disc battery or lithium• Potential sequela -• Mucosal burns – may be delayed by 12-24 hours• Tissue liquefaction• Severe esophagitis

• Treatment • Dilute corrosive material w/ milk or water x 15 mins• Emesis – contraindicated with leaking battery • Activated charcoal – not beneficial• If lodged in esophagus – endoscopy to remove• If chewed up – surgical removal ideal• If intact – surgical removal vs bulk diet and gastroprotectants

Batteries

Enterohepatic Recirculation

• NSAID’s• Naproxen• Acetominophen

• Digoxin

• Marijuana

• Caffeine/Theobromine

• Theophylline

• Bromethalin

• Pyrethrins

• Ivermectin

• Antidepressants

• Phenobarbitol

• Organophosphate insecticides

• Vitamin D rodenticide

Hemolytic Anemia

• Allium• Brown recluse spider• Methylene blue• Propylene glycol• Zinc• Phenols• Napthalene

Methemoglobinemia

• Acetaminophen• Phenols - disinfectants and antiseptics,

mouthwash and sore throat lozenges• Chlorate salts - pyrotechnics• 3-chloro-p-toluidine hydrochloride

(Starlicide)

Tremors/Seizures • Ethylene glycol• Hypoglycemic agents (xylitol,

diabetic medications, Alpha lipoic acid)

• Bromethalin• Methylxanthine• Stimulants (amphetamines,

cocaine, antidepressants)• Paintballs• Paintball• Tetanus• Bromethalin

• Lead• Avicide • Toxic lily plants • Tremorgenic mycotoxins• Permethrin (cats)• Nicotine• Metaldehyde• Chocolate • Strychnine

Liver Injury

• Acetaminophen• Sago palm• Xylitol• NSAID’s - many• Mushroom –

Amanita

• Phenols• Castor bean

(Ricinus)• Blue green algae• Iron overdose• Aflatoxin

Renal Injury• Ethylene glycol

• Lilies (cats)

• Grapes/raisins

• NSAIDs

• Oxalic acid – rust remover

• Vitamin D metabolites

• Rhubarb, shamrock

• Mycotoxins

• Sulfonaminds

• Tetracyclines

• Amphotericin B

• Cisplatin

• Alpha-lipoic acid

• Phenols

• Pine oils

• Metals – Arsenic

Low toxicity

• Silica gel packs and litter • Ant and roach baits• Glow in the dark sticks/jewelry• Toilet bowl drop ins• Super glue • Paints • Firestarter logs

Toxin Resources

• Pet Poison Helpline • # 855 - 764 - 7661• # 800 - 213 - 6680• $49 fee

• Animal Poison Control: ASPCA • #888 – 426 - 4435• $65 fee• ASPCA Poison Control mobile app