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Toxins in Small Animal Medicine Stacy Simmonds, DVM, DACVECC Top 10 Toxins 2014 ASPCA Pet Poison Hotline 1. Human Medications 1. Chocolate 2. OTC medications 2. Rodenticide 3. Insecticides 3. Ibuprofen/Acetaminophen 4. Household items 4. Insecticidal Products 5. Human foods 5. Xylitol 6. Veterinary medications 6. Household cleaners 7. Chocolate 7. Antidepressants 8. Plants 8. Fertilizers and Plant Food 9. Rodenticide 9. Grapes and Raisins 10. Home and Garden 10. De-wormer products Lecture Topics • • Chocolate • Xylitol Human anti-inflammatory medications • Tremorgenic mycotoxins • Antidepressant medications • Pyrethrins • Sympathomimetic drugs • Batteries • Ethylene glycol • Toxins grouped by clinical signs • Lily plants • Low toxicity substances • Rodenticides • Options for decontamination Be Sure to Ask! • 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? 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 Ourhouseplants.com • 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 Emesis • Dogs, cats, ferrets, pot-bellied pigs • Potential side effects: • • • • • Apomorphine – CNS depression Protracted vomiting Aspiration pneumonia Gastritis Increased vagal tone Myassistancedog.org Emesis Timing • 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 Fastcodesigns.com Emesis Contraindications • Species: rabbits, rodents • Already symptomatic • Underlying medical concerns: • History of laryngeal paralysis, megaesophagus, brachycephalic syndrome Mysticcat.sg • Contraindicated toxins: • Corrosives, acids: lye, bleach, batteries, oven cleaners • Hydrocarbons/petroleum distillates: tiki-torch oil, gasoline, kerosene, mineral spirits, furniture polish oils Emesis Techniques Apomorphine • Stimulates dopamine receptors on CRTZ zone • Mean time of emesis – 18 minutes • Side effects: • Protracted vomiting (IM administration) • CNS depression Wedgewoodpetrx.com • 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 Emesis Techniques 3% 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 Techniques Cats • 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 Indications: • Emesis has failed or is contraindicated • Severe organophosphate/carbamate toxicosis • Severe metaldehyde or tremorgenic mycotoxin toxicosis • Ivermectin ingestion • Sago palm ingestion • Bromethalin ingestion • May have poorer recovery of gastric contents than emesis • Contraindications: • Caustic or corrosive substance ingestion • Hydrocarbons Activated Charcoal • 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 Shopmedvet.com ** DVM 360.com When and How to Give Activated Charcoal, Justine Lee, DACVECC, DABT; 2013 Fluid diuresis • Goal: maintain renal perfusion and maintain hydration • Does not enhance excretion of toxins more quickly Na+ mmol/L Cl- mmol/L K+ mmol/L Ca++ mmol/L pH 0.9% NaCl 154 154 LRS 130 109 4 P-lyte 148 140 98 5 5.5 140 98 5 7.4 5.0 ~3 6.5 Norm R P-lyte A 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 medications Ibuprofen • 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) Non-steroidal Anti-inflammatory medications Acetaminophen • 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 • All doses toxic in cats • More likely to develop methemoglobinemia Adelaidevet.com • 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. 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, Diclofenac, sago palm Piroxicam, • Consider charcoal alternating with Cholestyramine 4 hours later – varies with toxin and patient case Serotonin Syndrome Overdose 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 • Recreational vehicles • Brake fluids • Paints • De-icers • Cleaners • Condensers • Solvents • Home solar units • Portable basket ball post bases 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 – Wcrah.com • ~ 12-72 hours • renal tubular injury from calcium oxalate crystals Ethylene Glycol Diagnosis • Acute Kidney Injury – but may • UA: dilute USG, glucosuria, +/take >12 hours post exposure crystalluria • 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 • 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 Glycol Treatment • 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 Glycol Ethanol • 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. Lilium spp. • Daylily • Easter lily • Lemon daylily • Tiger lily • Red lily • Asiatic hybrid lilies • Western lily • 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 Rodenticide Anticoagulants • 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 Rodenticide Anticoagulants • 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 Rodenticide Bromethalin • 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 Rodenticide Cholecalciferol -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 toxicosis Treatment • 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 Mycotoxins Mold • 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 Pyrethrins • 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 Batteries • 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 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 • Lead • Hypoglycemic agents (xylitol, diabetic medications, Alpha lipoic acid) • Avicide • Bromethalin • Toxic lily plants • Methylxanthine • Tremorgenic mycotoxins • Stimulants (amphetamines, cocaine, antidepressants) • Permethrin (cats) • Nicotine • Metaldehyde • Chocolate • Strychnine • Paintballs • Paintball • Tetanus • Bromethalin Liver Injury • Acetaminophen • Phenols • Sago palm • Castor bean (Ricinus) • Xylitol • Blue green algae • NSAID’s - many • Iron overdose • Mushroom – Amanita • Aflatoxin Renal Injury • Ethylene glycol • Sulfonaminds • Lilies (cats) • Tetracyclines • Grapes/raisins • Amphotericin B • NSAIDs • Cisplatin • Oxalic acid – rust remover • Alpha-lipoic acid • Vitamin D metabolites • Phenols • Rhubarb, shamrock • Pine oils • Mycotoxins • 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