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Toxins in Small Animal Medicine

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1 Toxins in Small Animal Medicine
Stacy Simmonds, DVM, DACVECC

2 Top 10 Toxins 2014 ASPCA Pet Poison Hotline Human Medications
OTC medications Insecticides Household items Human foods Veterinary medications Chocolate Plants Rodenticide Home and Garden Pet Poison Hotline Chocolate Rodenticide Ibuprofen/Acetaminophen Insecticidal Products Xylitol Household cleaners Antidepressants Fertilizers and Plant Food Grapes and Raisins De-wormer products

3 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

4 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?

5 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

6 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 Ourhouseplants.com Greengardening.com Wikipedia.org

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

8 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

9 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 Symptomatic: tremoring, agitated, seizuring, weak Predispose to aspiration: megaesophagus, lar par Hydrocarbons/petroleum distillates: easy to aspirate due to low viscocity Hydrocarbons: liquid fuels such as kerosene, engine oil, tiki torch fuels, paint solvents, wood stains and strippers, lighter fluid; roofing tar Induction of emesis is contraindicated with ingestion of corrosive agents including alkalis and acids. The protective epithelial lining of the esophagus may be damaged initially when one of these products is swallowed. The muscular layer of the esophagus may be exposed and at risk for ulceration, perforation and scarring if vomiting does occur. The clinician must also take into account when deciding whether to induce emesis, any pre-existing conditions of the patient that can cause vomiting to be hazardous including severe cardiac disease or seizure disorder. Emesis may not be needed if the animal has already vomited and is not appropriate if the animal is already exhibiting clinical signs such as coma, seizures or recumbency, which make emesis hazardous. Additionally, if the patient has ingested a CNS stimulant and is already agitated, the additional stimulation of vomiting could lead to seizures.

10 Emesis Techniques Apomorphine
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 Naloxone reverses CNS effects but not nausea Not effective in cats; not recommended Injectable form can be given SQ and via conjunctival sac

11 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 minutes – can repeat dose once Or 1 tsp/5 lbs with max of 3 tablespoons if >45 lbs Best advice – bring in for emesis induction Best for patients that can’t be seen by vet in timely manner Kahn 2012 – H2O2 had similar effectiveness as apo Cats: Plumbs: “generally not recommended”

12 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 In plumbs Analgesia up to 30mins but sedation up to 2 hours SE: bradycardia, hypotension, respiratory depression

13 Assessment of dexmedetomidine and other agents for emesis induction in cats: 43 cases ( ) V. Thawley; JAVMA: December 2015 Hydrogen peroxide (3), Xylazine (25), Demedetomidine (16) Emesis effectiveness: Hydrogen peroxide: 0/3 Xylazine: 11/ % Demedetomidine: 13/ % Dose range: Xylazine: 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 Retrospective study from Penn – recommendation for inducing emesis

14 Emesis Techniques Not recommended
Syrup of ipecac Salt Dry powdered mustard Liquid dish detergent Digital induction Ipecac: delay in onset of vomitng and little efficacy; no longer available for purchase in US; cardiotoxic potential

15 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 Sago palm, bromethalin** Agitated, seizing or recumbent patients Hydrocarbons- petroleum distillates: kerosene, gasoline, naphtha Wood derived hydrocarbons – turpentine and pine oil Chlorinated hydrocarbons: used as insecticided, solvents and fumigants – affect CNS and pulmonary – chlorinated hydrocarbon toxicosis 2006

16 Dose of AC may be higher on bottle
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 Dose of AC may be higher on bottle AC useful in vet medicine for delayed release medications, enterohepatic circulation, lack of antidote Many products – toxiban Charcoal tablets less effective and not recommended Causes false positive on ethylene glycol tests

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

18 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 5.0 LRS 130 109 4 ~ 3 6.5 P-lyte 148 Norm R 140 98 5 5.5 P-lyte A 7.4 methylzanthines

19 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 mins Can repeat bolus but check peripheral blood sample for lipemia Max dose suggested: 8ml/kg/day Lipophilic compound is compartmentalized and results in decreased drug concentration Alter cardiac performace by providing energy to myocardial cells Same 20% used to provide lipids in parenteral nutrition Max dose: case report in dog of 18 ml/kg without issue Cost: Human adverse effects: hypersensitivity reaction to egg stabilizer and thrombophlebitis at cath site

20 Intravenous Lipid Emulsion Therapy
Baclofen Ivermectin Permethrin Local anesthetics Calcium channel blockers NSAIDs Vet literature: 2009 Crandal et al – moxidectin toxicity in a puppy Javma 2010 – SQ lidocaine overdose in a cat JVECCS 3 dogs case series naproxen: paper showed documented decrease in Naproxen concentrations in short time after ingestion Lipids can also bind the medications used to treat the toxin

21 Intravenous Lipid Emulsion Therapy
Potential side effects: Phlebitis Intravascular hemolysis Hyperlipidemia/Pancreatitis Management: Dedicated IV line Sterile administration set Central line not necessary

22 Anti-inflammatory medications (Human)
Naproxen (Aleve®) Ibuprofen (Motrin®) Acetaminophen (Tylenol®)

23 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 Toxic effects from decreased prostaglandins Doses listed that are known to cause side effects are for healthy pets with no previous comorbidity Emcrit.com

24 Non-steroidal Anti-inflammatory medications Naproxen (Aleve®)
Tablet size: 200 mg and higher Dogs > 5mg/kg – GI > 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 Anything smaller than an 88lb dog that gets the smallest tablet possible has the potential to be affected. Source: plumbs

25 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)

26 Non-steroidal Anti-inflammatory medications Acetaminophen
Therapeutic dose in dogs: extralabel: 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 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 Therapeutic dose: 10mg-15mg/kg – less than 5 days (if greater than 5 days consider BID) Decontamination: enterhepatic circulation – repeated charcoal can bind to oral NAC Need to do follow up bloodwork due to delay of lab evidence of hepatotoxicity NAC > ~ 100mg/kg Methemoglobinemia with 2-6 hours KCS usually resolves within 2 weeks Cimetidine: can inhibit the P450 enzyme responsible for the production of NAPQI, current evidence indicates this requires doses up to 10X of recommendations and inhibition takes several days to become clinically relevant; some research shows it may delay recovery SAMe – replenish glutathione Vit C: effectiveness to convert methemoglobin to hemoglobin Can take days for methemolobinemia to resolve and for hepatic injury to improve Vitamin C can be PO or IV Good prognosis if treated promptly; severe methemoglobinemia or severe hepatic damage – poor to guarded prognosis

27 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 hours, not likely to develop complications. Adelaidevet.com Cats can develop liver injury but if severe may succomb to methg before liver damage becomes apparent. For cats with acetaminophen toxicosis, N-acetylcysteine is a specific antidote because it provides sulfhydryl groups which directly bind to toxic acetaminophen metabolites to enhance elimination, and serves as a glutathione precursor. 2 newer thoughts regarding tylenol toxicity: Cimetidine isn’t as helpful at reducing NAPQI production as originally thought Methemoglobinemia may be due to formation of the PAP – paraaminophenol from acetominophen, not due to formation of NAPQI

28 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 NAC in 10% - 20% - dilute to 5% Small risk of anaphylaxis and risk of bacterial contamination unless you have the human IV formulation (Acetadote) ** Type of filter and who predose with Benadryl Millipore filter

29 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 Vitamin D most common use

30 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) Most common cause of SS is ingestion of human medications – prevalence has increased due to increased use of human SSRI’s SSRI: selective serotonin reuptake inhibitors, serotonin norepireuptake inhibitor - SNRI

31 Serotonin Syndrome Treatment
Serotonin antagonists: Cyproheptadine: Dog mg/kg PO or PR and Cat – 2 – 4 mg PO Phenothiazines – non-selective serotonin antagonists Acepromazine 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 Decontamination – AC charcoal beneficial and repeated doses ideal (especially if extended release or TCA’s) Treatment focuses on treating CNS, GI, cardiac signs, as well as hyperthermia Cyproheptadine – serotonin antagonist Chlorpromazine 0.5mg/kg IM or IV Phenothiazines: also some serotonin antagonist properties but can cause hypotension Esmolol for tachycardia if needd – give test dose Decrease sensory stimuli Agitation: reach for ace or chlorpromazine Tremors: methocarbamol Seizures: Pheno and if severe propofol 0.1 – 0.6 mg/kg/min – caution if other meds on board Outcome depends on dose, treatment, overall health of patient and if significant renal or liver dysfunction (most metabolized in the liver and renally excreted) Usually discharged within hours Clinicans Brief 2013 J. Lee Toxicology SSRI: prozac, zoloft, paxil – also Trazodone and Venlafaxine Healthtap.com

32 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 Ingestions of or overdose of

33 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 Effexor – bicyclic antidepressant - potent serotonin and noradrenaline reuptake inhibitor – has extended release tabs (signs can last 72 hours)

34 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 Ectasy Humans have a lower incidence of idiosyncratic reactions to benzodiazepines than vet patients. In humans and amphetamines get barbituates Sometimes the clinical signs are related to serotonin excess, consider cyproheptadine

35 Urine Drug Tests *** FIRST CHECK TEST for marijuana Control region
Test region Positive: NO line in the TEST region Check each test for potential cross reactions

36 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

37 Ethylene Glycol Antifreeze Recreational vehicles Brake fluids Paints
De-icers Condensers Home solar units Portable basket ball post bases Recreational vehicles Paints Cleaners Solvents Products <10% EG are less likely to cause issues

38 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 Complete excretion within 24 hoursEthylene glycol metabolized to glycoaldehyde in the liver by the enzyme alcohol dehydrogenase. Glycoaldehyde is metabolized to glycolic acid = metabolic acidosis and renal epithelial damage Glycolic acid metabolized to glyoxylic acid is converted to oxalic acid – combines with serum calcium to form calcium oxalate complexes that crystallize in the tubular lumen

39 Ethylene Glycol 3 clinical stages that can overlap Neurologic
~ 30 mins – 12 hours Cardiopulmonary – ~ 12 – 24 hours acidosis and electrolyte disturbances Renal – ~ hours renal tubular injury from calcium oxalate crystals Neuro – can be missed GI as well as neuro signs/lethargy initially Stages related to alcohol intoxication Wcrah.com

40 Ethylene Glycol Diagnosis
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 AC can cause false positive PRN: Ethanol, methanol, isopropal will not interfere with PRN test Formaldehyde, metaldahyde, diethlene glycol may cause false + Kacey: has 3 pads – 20mg/dl, 50mg/dL, 75 mg/dl – cats can use 20mg/dl pad Dye added to antifreeze to help in detecting leaks High AG metabolic acidosis from glycolic and lactic acid accumulation (EG metabolites are unmeasured anions). Can remian increased for 48 hours in untreated animals

41 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 Emesis and AC: may not be beneficial as alcohol rapidly absorbed. Goal: inhibit alcohol dehydrogenase 4MP – most effective in dogs within 8 hours of ingestion; needs high dose in cats and should be started within 3 hours of ingestion Ethanol:

42 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; mg/kg 12 hours; hours; hours Dogs: 20mg/kg IV first dose; 12 hrs, 24 hrs, 36 hrs Paladin Labs requested that the FDA withdraw approval because the company has not manufactured or marketed the drug since october 2014 – current lots are to expire 2017. 4MP inhibits ADH Should be started within 3 hours of ingestion (<4 hours) Will not worsen metabolic acidosis

43 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 Alcohol must be administered early to be effect – allows EG to be excreted in urine unchanged. Not to use with Fomepizole – alcohol poisoning Can be used if ingestion > 3 hours ago (but within 8 hours). Dose reduction if CNS depression is severe. 7%: 5% dextrose in 0.9NaCl and 8.6 ml/kg given slowly followed by CRI of 1.4 ml/hr ~ hours. 20% ethanol at 5ml/cat

44 Lily Non-toxic Calla lilies Peace lilies

45 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 * Cardiac glycoside

46 Encinavet.com

47 Lily toxicity All parts toxic – including the pollen
GI signs – vomiting, hypersalivation Neurologic signs Acute kidney injury within hours Casts can be seen in 12 hours No known antidote Decontamination and supportive care x 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 Clinical signs within a few hours of ingestion – lethargy, vomiting, hypersalivation Oliguric RF can be in 24 hours If tx in 18 hours of ingestion, px can be good. Since tubular injury from lily ingestion spares the renal tubular basement membrane, regeneration of damaged tubules may be possible.

48 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 Sold only to Commercial users (bulk such as 8lbs) – professional rodent companies or agriculture supply stores Bromethalin – intended for use in homes within bait stations Decontamination – AC every 6 – 8 hours for 2-3 treatments at dose of 1-3 g/kg. Color does NOT indicate active ingredient. (EPA registration # is linked to active ingredient) Vitamin K dependent factors: 2, 7 9, 10. PT – extrinsic pthway; then Factor II becomes depleted prolonging the PTT Clinically, hemorrhage not typically seen until both PT and PTT prolonged.

49 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 hours after discontinuation of Vitamin K Vitamin K with food – faster absorption IV – risk of anaphlaxis

50 Anticoagulant Rodenticide
Redundant tracheal membrane

51 Autotransfusion USE: Sterile collection set and blood administration set or in-line blood filter Fenestrated catheters Sterile collection set Iv tubing Blood filter (blood administration line) In line filters* Kangaroo bag (with sterile suction) with a filter Petplace.com

52 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 Since no antidote – aggressive decontamination – long half life and enterohepatic recirculation – AC every 8 hours for 3-6 treatments. Bring in container There are cases of severe paresis or paralysis that survived If mild depression or mild ataxia, prognosis is improved.

53 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: % concentration Half life 17 days! Cats: ½ teaspoon of ingestion may warrant treatment Sold mainly for commercial use Net result: elevations in the serum calcium and phophorous leading to soft tissue mineralization and renal injury/failure Repeated AC 1-3 g/kg every 8 hours x 2-3 treatments. Can check values daily X 4 days and if normal clin path parameters in asymptomatic patient – no further monitoring necessary

54 Vitamin D3 Vitamin D supplementation (cholecalciferol) Vitamin D
1 IU = mg 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 D3 supplements: have 5,000 – 50,000 IU per cap; multivitamin ~ 400 IU Worry at about 0.1 mg/kg (4000 IU/kg) ** Vitamin D drops in water* acute vs chronic intake

55 Vitamin D toxicosis Treatment
Baseline Ca+ and renal values every 24 hrs x 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 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. IVF – promote calcuresis NaCl to decrease renal tubular reabsoption of Ca++ (avoid fluids with Ca++) Pred: decreases gi absorption, bone resorption, increase renal excretion Furosemide mg/kg TID or QID or 5 mg/kg/hr CRI Pamidronate – inhibits osteoclastic bone resorption – 1.3 – 2.0mg/kg over 2 hours IV. May need to repeat in 5-7 days. Pamidronate – bisphosphate – refractory hypercalcemia – NOT in conjuction with Calcitoninc Calcitonin: 4-6 IU/kg SQ every 2-3 hours Michigan State parathyroid panel

56 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 Methylxanthines If no signs in 6-12 hours not going to (keep 4 hours and send home) Place u cath if severe

57 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 Put dextrose in IV (5%) 72 hours for LE’s Hypoglycemia – don’t develop hepatic necrosis Elevated LE – start denamarin

58 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

59 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

60 Batteries Alkaline dry cell batteries and Button or disc battery or lithium Potential sequela - Mucosal burns – may be delayed by 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 Button battery – give serial doses of water to dilute (hearing aids, watches) If in plastic housing may be difficult to see via radiographs (get rads of lateral chest to ensure not in esophagus) Disc battery: can cause necrosis from electric current AC – not likely to bind corrosive material and may make endoscopy difficult if concerned about severe esophagitis Leaking battery – how do we know? – owners choice based on awareness of complications of emesis Endoscopy – in basket or condom Lithium: can cause severe necrosis within mins of contact 1998 American college of vet toxicologists: Lithium batteries fixed in esophagus. Necrosis through esophagus and extended to trachea after 1 hours (lithium worse than alkali). Diluting with tap water decreased esphageal injury

61 Enterohepatic Recirculation
NSAID’s Naproxen Acetominophen Digoxin Marijuana Caffeine/Theobromine Theophylline Bromethalin Pyrethrins Ivermectin Antidepressants Phenobarbitol Organophosphate insecticides Vitamin D rodenticide Per plumbs Tricyclic antidepressants High doses Vit D rodenticide

62 Hemolytic Anemia Allium Brown recluse spider Methylene blue
Propylene glycol Zinc Phenols Napthalene Zinc – pennies after 1982

63 Methemoglobinemia Acetaminophen
Phenols - disinfectants and antiseptics, mouthwash and sore throat lozenges Chlorate salts - pyrotechnics 3-chloro-p-toluidine hydrochloride (Starlicide) Chlorates prevent plant growth

64 Tremors/Seizures Ethylene glycol Lead
Hypoglycemic agents (xylitol, diabetic medications, Alpha lipoic acid) Bromethalin Methylxanthine Stimulants (amphetamines, cocaine, antidepressants) Paintballs Paintball Tetanus Lead Avicide Toxic lily plants Tremorgenic mycotoxins Permethrin (cats) Nicotine Metaldehyde Chocolate Strychnine Avicide - birds

65 Liver Injury Acetaminophen Sago palm Xylitol NSAID’s - many
Mushroom – Amanita Phenols Castor bean (Ricinus) Blue green algae Iron overdose Aflatoxin

66 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 2nd column – toxins affecting kidneys 2013 Wismer Vit D: rodenticides and human psoriasis creams

67 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 Toilet bowl drop in’s – ok when dilute Super glue – remove with vegetable oil Paints – don’t use solvents to remove paint from fur; mild GI upset if ingested; very small amount of ethylele glycol Logs: mostly FB risk

68 Toxin Resources Pet Poison Helpline Animal Poison Control: ASPCA
# # $49 fee Animal Poison Control: ASPCA #888 – $65 fee ASPCA Poison Control mobile app Aspca – pics of toxic/nontoxic plants


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