4.5 Lab

Question 1

most common types of rodenticide?

Answer 1

Anticoagulants are the most common type of rodenticide
 First generation: Warfarin and indanedione (less common)
 Second generation: bromadiolone, brodifacoum

Question 2

toxicokinetics of anticoagnulant rodenticides? average duration?

Answer 2

 Well absorbed orally
 Highly bound to plasma proteins
 Metabolized in liver and excreted in urine

Average duration of toxicosis:
 14 days, warfarin
 21 days, bromadiolone
 30 days, brodifacoum

Question 3

mechanism of toxicity of anticoagulant rodenticides

Answer 3

 Blocks vitamin K-dependent clotting factor (prothrombin) synthesis in the liver by inhibiting vitamin K epoxide reductase
 Stops vitamin K recycling needed for factors II, VII, IX and X synthesis –
 Clinical signs appear 3-7 days after ingestion (i.e. after activated clotting factors are depleted by natural degradation)

• Anticoagulants antagonize vitamin K, which interferes with the normal synthesis of coagulation proteins factors I, II, VII, IX, and X in the liver
• thus, adequate amounts are not available to convert prothrombin into thrombin.

Question 4

Typical clinical presentation of anticoagulant toxicity

Answer 4

• Clinical signs generally reflect some manifestation of hemorrhage, including anemia, hematomas, melena, hemothorax, hyphema, epistaxis, hemoptysis, and hematuria, any of which may lead to weakness, ataxia, colic, polypnea, etc.
• Petechiae rarely develop until after repeated small bleeds have consumed too many platelets.

Sudden death with no obvious clinical signs is also possible! That’s a scenario where a postmortem examination can bring the owner a lot of closure!

Question 5

how can we diagnose anticoagulant toxicity?

Answer 5

 History, clinical signs, physical exam
 Lab evaluation: Prothrombin time (PT), useful as occurs early, also activated partial thromboplastin time (aPTT)
 Chemical detection in fluids, vomitus, baits
 PM Lesions: blood-filled cavities and GI tract

Question 6

what are the best samples to send for an anticogulant screen?

Answer 6

Turn around time - 7-10 d > in a live animal, treat presumptively!

Liver and serum are the best samples

Question 7

how can we treat animals exposed to anticoagulant rodenticides?

Answer 7

Recent exposure: Decontamination; induce vomiting, AC or lavage

Monitor PT, aPTT; if normal no further tx
Vit K therapy: if high PT or toxic dose ingested, given orally with food
Dose and length of treatment of vitamin K based on dose and type of anticoagulant (see duration of action – up to 30 days)
Check PT 48 h after last vitamin K tx
If symptomatic: give whole blood, high dose injectable vitamin K, cage rest, serial coagulation profiles, restrict exercise

Question 8

prognosis for animals that ingest anticoagulant rodenticide? how can we prevent ingestion?

Answer 8

Prognosis:
Animals with mild clinical signs recover in 1-2 weeks
If severe clinical signs including coma, paralysis are present – poor prognosis

Prevention: restrict access to bait; educate clients

Question 9

what are the toxicokinetics of cholecalciferol rodenticides? where are they stored in the body?

Answer 9

Toxicokinetics:
 Well absorbed orally
 Clinical signs in 12-36 h
 Fat soluble; stored in adipose tissue
 Bound to plasma proteins

Question 10

what is cholecalciferol? what does it do?

Answer 10

vitamin d3, helps body absorb calcium

Question 11

mechanism of toxicity of cholecalciferol. what are early clinical effects? what can lead to end-stage signs?

Answer 11

Vit D and metabolites increases Ca and P absorption from GIT
Osteoclastic resorption and Ca mobilization from bone > >SO MUCH CALCIUM!!!

Early clinical effects (48h) due to effect of increased plasma Ca on cells:
Altered cell membrane permeability
Altered Ca pump activity
Decreased cellular energy production
Cellular necrosis

 Mineralization in kidneys, GI tract, cardiac and skeletal muscle, blood vessels and ligaments leading to loss of function & end-stage signs

Question 12

clinical signs of cholecalciferol toxicity

Answer 12

 Seen at 0.5 mg/kg = 1⁄2 tablespoon of pellets for 12 kg dog
 Vomiting & diarrhea
 Anorexia and depression
 Fulminant acute renal failure (in 24-48 h)
 Survivors have renal, cardiac and musculoskeletal loss of function

Question 13

how can we diagnose cholecalciferol toxicity? PM lesions?

Answer 13

 Increased plasma Ca and P (Ca X P may = 130)
 Increased BUN and creatinine, urine SG = isothenuria
 PM lesions: diffuse soft tissue mineralization
> Oral and gastric mineralization, ulceration and hemorrhage
> Renal tubular mineralization; casts
> Cardiac necrosis; mineralized myocytes

Question 14

how can we treat cholecalciferol toxicity?

Answer 14

Decontamination: induce vomiting, activated charcoal, gastric lavage; repeat if necessary
 Monitor serum Ca, P, BUN, creatinine for 4 days; if normal no further tx
 If symptomatic, diuresis with 0.9% saline, furosemide ➝ increases renal Ca excretion Oral prednisone decreases serum Ca
 If severe, use bisphosphonate to decrease bone resorption of Ca

Question 15

cholecalciferol toxicity prognosis? prevention?

Answer 15

Prognosis:
Good if treated promptly before tissue mineralization Prognosis varies with length and severity of increases
Ca:P

Prevention: restrict access to bait; educate clients

Question 16

bromethalin rodenticides toxikokinetics? stored where?

Answer 16

Well absorbed orally
Metabolized in liver to toxic N-demethylated metabolite
 Fat soluble; stored in adipose tissue and brain
 Excreted slowly in bile (t1/2= 5 d)

Question 17

bromethalin rodenticides mechanism of toxicity

Answer 17

• Uncouples oxidative phosphorylation ➝ decr ion channel pump activity ➝ decr osmotic gradients ➝ incr pressure on axon, cerebral edema, decr nerve impulse conduction, paralysis

Question 18

bromethalin rodenticides clinical signs of toxicity

Answer 18

– Onset of clinical signs (hours to days) is dose-dependent
– High dose: tremors, hyperthermia, hyperexcitability, seizures
– Low dose: slower onset (days), hind limb ataxia, paresis, paralysis, CNS depression ➝ coma

Question 19

bromethalin rodenticide toxicity diagnosis

Answer 19

• History of exposure
• Increased CSF pressure (CSF otherwise normal)
• Cerebral edema, spongy degeneration of CNS white matter
• Bromethalin residues in fat and brain

Question 20

bromethalin rodenticide toxicity treatment

Answer 20

Decontamination: induce vomiting, gastric lavage, activated charcoal; repeat if necessary
 Use of mannitol and corticosteroids has been suggested to treat clinical signs, because they may help manage cerebral edema due to other causes.
> However, this has not been shown to be very helpful, likely because of the presence of intra-myelin edema.
Phenobarbital or diazepam for seizures

Question 21

bromethalin rodenticide toxicity prognosis

Answer 21

Good if treated promptly
Mild clinical signs, prolonged recovery (1-2 wks) Severe signs, poor prognosis

Question 22

zinc phosphide rodenticide toxicokinetics

Answer 22

 Zinc phosphide forms phosphine gas in acidic gastric
conditions
Distinctive rotten fish/garlicky odour
Inhaled, absorbed through skin, ingested

Question 23

zinc phosphide rodenticide mechanisms of toxicity

Answer 23

• Phosphine gas blocks cytochrome oxidase
• Inhibition of oxidative phosphorylation ➝ decreased energy production in mitochondria ➝ cell death

Question 24

zinc phosphide rodenticide clinical signs

Answer 24

– Onset of clinical signs is dose-dependent
– Large dose: death in 3-5 h
– No specific signs
– Initially: diarrhea, abdominal pain, vomiting, anorexia and depression
– Then: rapid, wheezy respirations, vomiting, bloat in large animals
– Terminally: ataxia, weakness, recumbency and struggling, coma and death

Question 25

zinc phosphide rodenticide diagnosis - what organs are most likely to be damaged? where do we look for signs? what should we do with tissue samples?

Answer 25

• No specific lesions
• Organs with high O2 demand most sensitive (brain, kidneys, liver, heart)
• Renal tubular degeneration & necrosis, hepatocyte degeneration
• Detection of zinc phosphide in stomach
• Submit frozen samples to prevent loss of phosphine gas
  IMPORTANT NOTE - vets at risk of inhaling phosphine gas! Protect yourself at PM! Ventilate area!

Question 26

zinc phosphide rodenticide treatment

Answer 26

 Early decontamination: induce vomiting, use antacid to increase gastric pH, lavage with 5% NaOH,
activated charcoal; MgSO4 cathartic
 No specific antidote
 Correct acidosis, O2 for respiratory problems, corticosteroids for shock, B vitamins, low protein diets for liver failure

Question 27

zinc phosphide rodenticide prognosis

Answer 27

Guarded-to-poor if showing clinical signs
Better if recent ingestion (within last 1-2 hours)

Question 28

strychnine toxicokinetics

Answer 28

 Rapid absorption in GI tract
 Wide distribution so only small amounts (<4 ppm) stay in blood
 Metabolized by hepatic enzymes, excreted in urine

Question 29

strychnine mechanisms of toxicity

Answer 29

• Decreased inhibitory action of glycine on cells of anterior horn of spinal cord;
  > Decreased neurotransmitter release from Renshaw cells
  => Excessive excitatory activity, severe muscle spasms, tetanic convulsions, and exaggerated reflex arcs

Question 30

strychnine clinical signs?

Answer 30

– Highly toxic; dogs most frequently poisoned
– Rapid onset of CS; within 10-120 min – no vomiting seen
– Severity is dose-dependent (e.g. mild ataxia ➝ convulsions)
– Anxiety, respiratory rate, salivation, then ataxia, muscle spasms, stiffness
– Terminally: convulsions with opisthotonus, hyperthermia
– Impaired respiration ➝ death

Question 31

posture expected due to strychnine poisoning

Answer 31

Opisthotonos: hyperextension of the neck, trunk, limbs and tail

Question 32

strychnine toxicity diagnosis

Answer 32

• No specific blood and serum chemistry findings
• No specific gross or histologic lesions
• Necrosis of cerebral cortex and brainstem
• Presence of strychnine in tissues (stomach contents are best)

Question 33

strychnine treatment

Answer 33

 Reduce GI absorption, symptomatic and supportive care
 Induce vomiting, activated charcoal
 Pentobarbital, diazepam to control convulsions
 Methocarbamol for muscle relaxation
 IV fluids (LR, saline); keep in dark quiet areas