Rodenticides Flashcards
Why are rodenticides dangerous?
- Designed to attract and kill mammals
- Widely sold - recommended safety often ignored
- occasionally used for malicious poisoning
What are the different kinds of Rodenticides?
- Anticoagulants
- Bromethalin
- cholecalciferol
- strychnine
- Zinc phosphate
What are the first generation anticoagulants?
- Often contain 0.05%
-
Warfarin
- ID at Wisconsin Animal Research Farm
- From dicoumarol found in hemorrhagic disease of cattle
- Grazing moldy sweet clover
- Diphacinone - Tomcat, Ramik, Mousemaze
- Chlorophacinone - Rozol
What are the second generation anticoagulants?
- Efficacious against resistant rats
- More potent (lethal in single feeding)
- Longer acting
- Possible relay toxicosis (mouse ⇢predator)
- Typical concentration is 0.005%
-
Brodifacoum (most common, highly toxic)
- Talon, Havoc, Bolt, Volid, D-con Mouse-Pruf II
- Maki, Contrac, One-Bite, Hawk
-
Diphethialone
- D-Cease, Hombre, Generation
What are the Toxicokinetics of anticoagulants?
- Oral absorption levels peak in minutes to hours
- Plasma half life:
- Warfarin - 14 hours
- effects last a few days
- Diphacinone - 4.5 days
- effects last 12-30 days
- Brodifacoum - 6 days
- effects last 12-30 days
- Warfarin - 14 hours
What is the normal clotting mechanism?
- Prothrombin II
What is the MOA of Anticoagulants?
- Vitamin K1 is regenerated by Vit K1 epoxide reductase
- Anticoagulants block this recycling
- also interfere with utilization by blocking synthesis of Vit K dependent clotting factors
- Facto VII (PT) affected early
- Factor IX (PTT) later on
What are the different toxicity levels of anticoagulants?
- Acute oral LD50 in dog (mg/kg)
- Warfarin 20-300
- Brodifacoum 0.22-4 (LD10 0.20)
- Bromadiolone 11-15
- Diphacinone 0.9-8
- Therapy should be started if dosage estimate is ¼ of LD10
What factors increase a mammals risk of anticoagulant poisoning?
- Geriatric or neonatal animals
- Concurrent liver disease
- Ruminants, horses - moldy sweet clover
- Protein displacing drugs
- Phenylbutazone
- Also Corticosteroids, Aspirin
- Impaired platelet function or low counts
What are the clinical effects of Anticoagulants?
- Related to hemorrhage and blood loss
- Often weak, anemic, dyspnea, epistaxis, melena, lameness, ataxia
- Occasional CNS signs (subdural bleeding)
- hemothorax (dyspnea, sudden death)
- May be acute death with no early signs
What necropsy lesions are common with anticoagulant toxicosis?
- Hemorrhage, hematomas, hemothorax
- Hemarthrosis; subdural hematomas
- Occur in a variety of tissues, organs, spaces
- platelet function normal
describe the clinical picture of anticoagulant toxicosis?
- Clinical signs delayed
- Initial sins are non-specific
- Lethargy, depression, pallor
- Varied Sx of bleeding tendency
- Anemia
- Melena, bloody vomit/diarrhea, point/area bleeding on mucous membranes, epistaxis, hematomas etc.
- Bleeding into joints/sc bleeding in feet can cause lameness
- Persistent bleeding rom venipuncture sites
How is anticoagulant toxicosis diagnosed?
- Presence of hemorrhagic syndrome
- Clotting time prolonged
- Prothrombin time (@2-3 days) post exposure
- Activated partial thromboplastin time (@3-5 days)
- PIVKA-Proteins Induced by Vit K Antagonists (aka Thrombotest)
- detects precursor proteins of clotting factors
- Detection of active ingredient in liver, blood, bait
- Liver - sample of choice in deceased animals
- Blood - sample of choice in live animals
- Hay - for dicoumarol
What are the typical clinical pathology results of acute anticoagulant toxicosis?
- PCV < 30
- Whole blood clotting - delayed
- Clot retraction - normal
- ACT - 2-10x normal
- PT - 2-6x normal
- APTT - 2-4x normal
- Platelets - normal
- FDP’s - normal
- Regen/non-regenerative normocytic, normochromic anemia
- Often leukocytosis
- +/- thrombocytopenia
- Abnormal clotting profile
- One-stage prothrombin time (OSPT) (most sensitive)
- Activated partial thromboplastin time (APTT)
- Thrombin time (TT)
- Activated clotting time (ACT)
What are the differential diagnoses for anticoagulant toxicosis?
- Dicoumarol - livestock via moldy hay
- Idiopathic coagulopathy
- Autoimmune thrombocytopenia
- DIC
- Hereditary (Von willebrand’s Disease)
- Liver disease (⇣ clotting factor synthesis)
What is the treatment for anticoagulant toxicosis?
- Supportive:
- Relieve hemothorax, raise PCV, Rx shock
-
Vit K1 (K3 ineffective)
- PO with fatty food preferred
- 3-5 mg/kg/d for 10 days (Warfarin)
- 3-5 mg/kg/d 2-4 weeks (Brodifacoum)
- 5 mg/kg/d 3-4 weeks (diphacinone)
- Horses 2mg/kg/d max
- Time lag 3-6+ hours for effective coagulation
- PO with fatty food preferred
- Blood or plasma transfusion - immediate clotting factors
- Monitor clotting function for 1 week
- Prognosis is good to excellent
Why is Vitamin K1 NOT given IV?
- high incidence of anaphylaxis
- When phytonadione is given with a high fat meal, rapid absorption and activation of Vit K1 is nearly equal to IV admin without the risks
- Also risks of puncturing a vein with a coagulopathy
Why should vit K3 be avoided in horses?
nephrotoxic
What is Bromethalin?
- Rodenticide
- Blocks mitochondrial energy production
- especially in the CNS
- Major toxic effect is cerebral edema
- LD50: 0.3 mg/kg cats ; 2.5 mg/kg dogs
What is the clinical picture of high dose bromethalin toxicosis?
- >0.5 mg/kg
- Above LD50
- Signs develop 4-24 hourse after ingestion
- Muscle tremors, hyperthermia, hyperesthesia, excitability, seizures
What is the clinical picture of low dose bromethalin toxicosis?
- Below LD50
- Signs develop within 2-7 days
- Progressive CNS depression with ataxia, paresis, hind limb paralysis, coma
What are the toxicity levels of Bromethalin?
(0.01% bait)
- Dogs:
- LD50 - 3.65 mg/kg
- Min toxic - 16.7 g/kg
- Cats
- LD50 - 0.54 mg/kg
- Min toxic - 3.0 g/kg
What is the MOA of Bromethalin?
- Metabolized to desmethylbromethalin
- Parent and metabolite uncoupled oxidative phosphorylation especially in the CNS
- Reduced ATP impairs sodium pump & leads to fluid accumulation in myelin sheaths and CNS
- Edema of myelin tracts leads to paralysis
What histopathology is common with bromethalin toxicosis?
- Edema and spongiform change of myelin
- Brain and spinal cord
What are the clinical signs of low dose bromethalin toxicosis?
- Onset @ 24-36 hrs
- Tremors
- Ataxia
- Vomiting
- Anisocoria
- Progressive depression
- Hind limb paralysis
- Lateral recumbency
- Coma
What are the clinical signs of high dose bromethalin toxicosis?
- Onset in 4-36 hrs
- Muscle tremors
- convulsions
- hyperexcitability
- running fits
- hyperesthesia
- focal or generalized motor seizures precipitate by light/noise
How is Bromethalin toxicosis diagnosed?
- History of exposure
- Characteristic microscopic lesions in brain and spinal cord
- Chemical detection of bromethalin in tissues (Brain, fat, liver, kidney)
- Possible hyperglycemia
- EEG:
- Spike & wave activity, voltage depression, abnormal Hi voltage slow wave typical of cerebral edema
What is the treatment of Bromethalin toxicosis?
- Early - before seizures - emetics
- limit absorption
- Repeat activated charcoal, saline cathartic (q12hrs for 6x) at half the original dose
- Dexamethasone prolongs survival time but does not reverse syndrome
- Mannitol/furosemide for cerebral edema
- Diazepam, methocarbamol, or phenobarbital as needed for seizures
- Supportive care - up to 3 weeks for recovery (if ever)
- ILE
What is the prognosis of bromethalin toxicosis?
- Very guarded in moderate to severe cases
What are the environmental and Food safety concerns of bromethalin?
- All animals species are targets
- Low probability for relay toxicosis
- Food safety impact is not known
- Fat soluble so can pass through milk
What is Strychnine?
- Extract of Stychnos-nuz vomica
- Indole Alkaloid
- Rodenticide - gophers and ground squirrels
- underground use only
- 0.5% or less
- Red/Green dye
What is the MOA of Strychnine?
- Rapidly absorbed
- Antagonizes glycine (neurotransmitter in inhibitory neurons)
- Renshaw Cells in spinal cord and medulla
- Inhibitory effects of reflex arcs are lost
- Uncontrolled excitation of spinal reflexes
- Predominantly extensor muslces
- Excreted via urine
What are the toxic levels of strychnine?
- Dogs:
- LD50: 0.5-1.2 mg/kg BW
- Cats:
- LD50: 2 mg/kg BW
What is the clinical picture of strychnine toxicosis?
- Acute onset - 15min - 2 hours
- Nervousness, restless, tremors early after exposure
- Rarely vomit
- Sensitive to external stimuli - especially loud noises, touch, light
- Saw horse stance
- Explosive onset of tetanic seizures - whole body rigidity
- Death from anoxia
How is Strychnine toxicosis diagnosed?
- Does not reliably produce lesions
- bruising, hemorrhage from trauma
- Finding bait in stomach is common
- dogs rarely vomit
- Dye from baits is a clue
- Detection of strychnine in stomach
- Urine too
- Liver last resort
What are possible differential to strychnine toxicosis?
- Tetanus, Metaldehyde, Penitrem A, Roquefortine, Avitrol, Theobromine, Nicotine, Caffeine, Amphetamines, Cocaine, OPs, carbamates, pyrethrin, mushrooms, Blue-green algae, chlorinated hydrocarbons, water deprivation, etc
- DDX for seizures is tough
- Strychnine intoxications are exceptionally sensitive to external stimuli
- start a violent seizure with a loud clap
- Strychnine intoxications are exceptionally sensitive to external stimuli
What is the treatment for strychnine toxicosis?
- Control seizures
- Diazepam, phenobarbital, methocarbamol, gas
- Supportive care - respiratory
- Decontamination
- lavage, charcoal
- Fluids
- Diuresis, acidic urine ⇢ion trapping
What is Vitamin D3?
- “cholecalciferol”
- Vit D2 - “ergocalciferol” - plant derived form
- Vit D2 = 40,000units Vit D/mg
- Vit D3 - 40,000IU of Vit D
- 1 USP or international unit = 25 ng D3/D2
Sources of cholecalciferol?
- Pellet or cereal based baits (0.075%)
- Place packs (10-30g)
- Careless placement often leads to toxicosis in non-target species
- Calcipotrience (Donovex lotion for psoriasis)
- Potent, high risk for dogs
- Vit D3 supplements
- Plants:
- S. malacoxylon, C. diurnum, T. flavescens
How much more potent is D3 to D2?
10x more potent for calcium uptake
What are the kinetics of Cholecalcipherol?
- Dog daily req is 22 IU (0.55ug/kg/day)
- Absorption- rapid and complete in SI
- Circulates in plasma to liver and kidney
- Liver: Metabolized to Calcifediol (25-hydroxy D3)
- Cytochrome P450 dependent
- Kidney: Converted to toxic metabolite calcitriol (1, 25 dihydroxy D3)
- Rate-limiting step
- D3 metabolites excreted in bile
- Liver: Metabolized to Calcifediol (25-hydroxy D3)
What are the toxic levels of cholecalcipherol?
- Minimum lethal dose: 5 mg/kg
- 1-3 mg/kg toxic = 2.6 g bait/kg BW
- Calcipotriol toxic at 50 ug/kg
What animals are most sensitive to cholecalcipherol?
cats>>puppies>adult dogs
What is the MOA of Cholecalcipherol toxicosis?
- 1, 25 dihydroxy D3 in kidney
- Increase serum calcium in 3 ways
- Increasing absorption (Ca & P) from gut
- Increase bone resorption via PTH
- Increase renal retention via distal tubule resorption
- Persistent hypercalcemia and hyperphosphatemia
- Early renal tubular damage and necrosis
- Abnormal soft tissue mineralization
What is the pathohysiology of Cholecalciferol toxicosis?
- Hypercalcemia - Conduction disturbances
- Shortened Q-T segment and increased P-R
- Bradycardia
- Vasoconstriction and hypertension
- Reduces cAMP ⇢ low ADH
- Decreased NaCl absorption ⇢ Diuresis
- Renal tubular degeneration
- Polyuria & hypsthenuria
- Azotemia
What are the clinical pathology presentations of Cholecalciferol toxicosis?
- Hypercalcemia >12mg/dL
- Hyperphosphatemia > 7 mg/dL
- Increased BUN and creatinine
- USG 1.002 - 1.006 ⇢ hyposthenuria
What is the clinical picture of cholecalciferol toxicosis?
- Delayed 12-36 hours post-ingestion
- Progressive signs
- Anorexia, vomiting (+/- blood), depression, muscle weakness
- Cardiac and renal changes
- Bradycardia, heart failure
- Hypertension, PU/PD
What lesions are common to cholecalciferol toxicosis?
- Renal tubular necrosis
- Soft tissue mineralization
- Kidney, heart, lung, stomach, intestine
- Aortic plaques
- Thyroid changes - uncommon
How is cholecaciferol toxicosis diagnosed?
- Serum calcium >12 mg/dL
- Bradycardia
- Azotemia
- Elevated D3 metabolites: 25-dihydroxy D3
- not all diagnostic labs test for these
- Serum iPTH depressed
- Tissue mineralization
- Elevated kidney Ca & P
- Ca >2,000 ppm (normal <600ppm)
What are the possible differentials for cholecalciferol toxicosis?
- Hypercalcemia of Malignancy
- Chronic Renal Failure
- Primary hyperparathyroidism
- Feline idiopathic hypercalcemia
What is the treatment for cholecalciferol toxicosis?
- Extended regimen - weeks, $$$
- Recent ingestion - Emetics, cathartics, activated charcoal ASAP (continued 1-2 days)
- Saline Diuresis (0.9% at 2-3x maintenance)
- Furosemide - 5mg/kg IV then 2.5 mg/kg PO
-
Prednisone - 2-3 mg/kg oral
- Block osteoclasts, GI and renal uptake
- Calcitonin- 4-6 IU/kg SQ @ 2-3 hours initially
-
Pamidronate- IV infusion 1.3-2 mg/kg over 2 hours
- inhibits bone resorption
- Calcium restriction, anti-emetics, GI protectants
What are the environmental and Food Safety concerns with cholecalciferol toxicosis?
- All species are susceptible
- Secondary intoxication can happen
- Excreted in milk
What is Zinc/Aluminum Phosphide?
- Rodenticide 2-5% in baits
- Limited Use - underground
- Grey-black powder (76% Zn)
- Decomposes in moist, acidic environments (ie stomach)
- Becomes phosphine gas
- Pungent odor (acetylene/garlic/fish)
- Also used as a grain fumigant
What are the kinetics of Zinc/Aluminum Phosphide
- Hydrolyzed in acidic stomach
- full stomach ⇡ reaction
- Zn3P2 ⇢ PH3 (phosphine gas) + Zn + 2
- Phosphine gas is the main toxicant
- Zn moiety is a strong emetic
- Protective in dogs
- Rats can’t vomit
What is the MOA of Phosphine gas?
- Blocks cytochrome oxidase - (cellular respiration)
- Blocks membrane ion transport in myocardium
What are the toxic levels of Zn/Al Phosphide?
- More toxic when consumed with food
- Gastric acid = hydrolysis
- Dogs:
- 300 mg/kg empty
- 40 mg/kg consumed with food
- Sheep- LD50 60mg/kg
- Birds- LD50 7-10 mg/kg
What is the clinical picture of Zn/Al Phosphide toxicosis?
- Acute onset- 15mins - 6 hours
- Notably variable clinical signs:
- Vomiting +/- blood
- Anorexia
- Lethargy
- Rapid respirations
- Abdominal pain
- Ataxia
- Seizures
- Hyperesthesia
How is Zn/Al Phosphide toxicosis diagnosed?
- Non-specific and variable clinical signs
- History of exposure
- Myocardial and renal tubular damage, pulmonary edema
- Volatile - collect, seal, freeze samples
- Phosphine gas in stomach can be a necropsy hazard (Large animals)
- Detection of elevated Az and P in stomach content
What is the treatment for Zn/Al Toxicosis?
- Detoxification/symptomatic/Supportive Care
- Activated charcoal and cathartics
- Antacids - raise stomach pH over 5
- Combat acidosis, hypocalcemia
- GI protectants
- Guarded prognosis, hypocalcemia
- GI protectants
- Guarded prognosis
What are the environmental and food safety concerns with Zn/Al toxicosis?
- Necropsy hazard
- All animals
- susceptible
- Mass deaths reported in birds
- Potential for secondary toxicosis
- Food safety impact unknown
