8a – Rodenticides II Flashcards
Anticoagulant rodenticides
- Widely available at home and garden/farm stores
- Numerous active ingredients
- First generation: warfarin, diphacinone (MULTIPLE ingestions required)
- Second generations: brodifacoum, bromadiolone
o “superwarfarins”
o Developed b/c of warfarin resistant rodents
o **ONE INGESTION CAN KILL
o Longer half life
Mechanism of anticoagulant rodenticides
- Defect in secondary hemostasis
- Inhibition of vitamin K epoxide reductase
o “1972”: 2, 7, 9, 10
o **factor 7 is first to be depleted=PT prolonged first
Which anticoagulant rodenticide has the lowest LD50?
- Brodifacoum
EXAM
Anticoagulant rodenticides: clinical features
- *Onset: delayed 3-5 days post-ingestion
- Anorexia, lethargy, exercise intolerance, weakness
- Pale MM
- Dyspnea, tachycardia
- Petechiae that progresses toe eccymoses, hematomas
- **bleeding into any body cavity possible
o Brain, anterior chamber, thorax, abdomen, GIT, joints (present lame)
Incidence of anticoagulant rodenticide toxicity in dogs in Saskatchewan
- Hemothorax most common
- *bromadiolone and brodifacoum=MOST COMMON
Anticoagulant rodenticides: management for asymptomatic and know they were exposed
- Decontamination: induce emesis, A/C
- Blood work: PCV/TP, PT/PTT
- *antidote: Vitamin K1 (give with fatty meal)
o Cheap and relatively easy to give
o Get every 12hrs for 4 weeks!
o Check PT 48-72hrs after last dose - Ex. phytonadione (some are in peanut oil)
Anticoagulant rodenticides: management for asymptomatic and don’t know if they were exposed
- Baseline PT and re-checked in 48-72 hours
- If normal after 72 hrs=NO treatment required
- *start Vit K1 if PT is prolonged
Anticoagulant rodenticides: management for symptomatic
- Decontamination=CONTRAINDICATED
- *immediate goal=stabilize animal
- **Hemorrhage +/- anemia (fresh plasma, frozen fresh plasma contains clotting factors)
o Whole blood
o Autotransfusion
o Oxygen
o Intrathoracic
o Intra-abdominal
o Cage rest - Once stabilize=give antidote
- Imaging depending on location of bleeding
- Bloodwork: PCV/TP, PT/PTT
Anticoagulant rodenticides: diagnosis
- Usually made clinically
o History of exposure, compatible clinical signs, **prolonged PT/PTT - Differential diagnosis:
o Prolonged PT/PTT: severe liver failure, DIC, Vit K deficiency
Phosphide rodenticides
- Long history of use
- Zinc phosphide, aluminum phosphide, magnesium phosphide
- Pellets, treated grain, powders
- 2-5% formulations
- *stable in dry environments for several years
- **dangerous for humans=gas
- LD50: 20-40mg/kg BW for most species
Phosphide rodenticides: mechanism
- *contact with stomach acid=release of phosphine gas
o Extremely toxic and irritating!
o Oxidative damage to multiple organ systems: liver, kidney, lungs, heart, brain - Zinc phosphide: pH<4
- Aluminum P and magnesium P: neutral pH
Phosphide rodenticides: onset
- As soon as 15mins post-ingestion
Phosphide rodenticides: clinical features
- Severe GI distress
o Animals that cannot vomit are at higher risk
o *horses: colic signs - Shock, pale MM
- Profuse sweating (horses)
- CNS: lethargy or hyperexcitation
- Pulmonary edema
- Death within 3-48 hrs
- *delayed onset kidney or liver failure is possible (if the animals survives)
Phosphide rodenticide: characteristic odour
- Rotten fish or garlic (acetylene)
- *human health risk=gas
Phosphide rodenticide: clinical pathology
- Dehydration
- Elevated liver enzymes
- Azotemia
- Metabolic acidosis
- Elevated blood zinc?
Phosphide rodenticides: management
- No specific antidote
- *Decontamination: WELL-VENTILATED AREA
- *zinc P: NEUTRALIZE STOMACH pH
o Carbonate antacids, dilute sodium bicarbonate - IVFT, gastroprotectants
- Tremor and seizure control
- Monitoring
Phosphide rodenticides: diagnosis
- History of exposure and compatible clinical signs
- PM lesions
o Hemorrhagic GIT, pulmonary edema, hepatocellular necrosis and steatosis - Confirmation: detection of phosphine gas in stomach contents, vomitus, liver, kidney
Phosphide rodenticides: prognosis
- Symptomatic patients that survive 24hrs have a better prognosis
Phosphide rodenticides: human health
- Phosphine gas is toxic to humans
- Careful when tubing a horse or a vomiting animal in clinic
- Symptoms
o Dizziness, lethargy
o Nausea, vomiting
o Liver failure
o Coma
Sources of Vitamin D
- Rodenticides
- Human ointments and supplements
- Certain plants
- Feed mixing errors
Cholecalciferol/Vitamin D3: toxicity
- Acute lethal oral dose >2mg/kg (dogs)
o But get clinical signs at less
Cholecalciferol/Vitamin D3: mechanism
- Disruption of Ca and phosphorous homeostasis
o *hypercalcemia=dystrophic mineralization and multi-organ damage - Toxicokinetic
o Lipophilic
o Long elimination half life
o EHC (entero-hepatic circulation)
Cholecalciferol/Vitamin D3: ‘breakdown’/metabolism
- Vitamin D3 to calcifediol in liver to calcitriol in kidney
- Calcitriol actions
o Increased intestinal absorption
o Increased tubular reabsorption
o Increase bone resorption
o *hypercalcemia and hyperphosphatemia
Cholecalciferol/Vitamin D3: onset
- 12+ hours post-ingestion
Cholecalciferol/Vitamin D3: clinical features
- Weakness, lethargy, anorexia
- Vomiting, diarrhea
- PU/PD
Cholecalciferol/Vitamin D3: clinical pathological changes
- Hyperphosphatemia, hypercalcemia, (azotemia, iso/hyposthenuria)
o 12, 24, 72 hours
o Ca*P>60mg/dL= METASTATIC CALCIFICATION
Kidneys, other soft tissues
Kidney injury and renal failure
Cholecalciferol/Vitamin D3: management
- Decontamination if NOT contraindicated
o Contraindicated: Ca-containing fluids (LRS), Thiazide diuretics) - Dose-dependent treatment
- Clinically affected
o Hypercalcemia: prednisone, furosemide
o Hypercalcemic gastritis: GI protectants
o CV monitoring
o IVLE?
Cholecalciferol/Vitamin D3: diagnosis
- History, bloodwork
o Serum 25 hydroxyvitamin D - Considerations
o Prolonged clinical signs
o Chronic consequences of tissue mineralization
What are some DDx for hypercalcemia?
- Neoplasia
- Hyperparathyroidism
- Kidney disease
o Acute kidney injury: ethylene glycol, grapes/raisins, lilies, NSAIDs, aminoglycosides
Cholecalciferol/Vitamin D3: prognosis
- Good with early decontamination and supportive therapy
- Guarded to poor with development of renal failure
Cholecalciferol/Vitamin D3: PM lesions
- Soft tissue mineralization
o Kidney
o GIT
o Aorta
o Striated muscle
Cholecalciferol/Vitamin D3: histologic lesions
- Degeneration and necrosis of renal tubules
- Calcium accumulation (Von kossa stain)
