Introduction to toxicology - common toxins: small animal focus

Question 1

What is toxicology?

Answer 1

• Toxicology is the study of toxins / poisons and their effects on living organisms
• Includes just about any substance given in sufficient quantities or by a nonconventional route
• ‘Adverse’ end of the pharmacology spectrum -> same pharmacological principles apply
• Concerned with the xenobiotic’s dose verses response at the specific receptor ->Therefore related to the xenobiotic’s pharmacokinetic and pharmacodynamic profile

Question 2

How can I make excretion occur faster?

Answer 2

• Change pH of compartment
• Give fluids

Question 3

What does LD50 mean?

Answer 3

• The term LD50 refers to an estimate of the amount of poison that, under control conditions, will be a lethal dose to 50% of a large number of test animals of a particular species.

Question 4

What is an example of a drug that might have a low LD50?

Answer 4

Chemotherapeutic drugs

Question 5

What does it mean when a drug has a high LD50?

Answer 5

A very safe drug with wide safety range

Question 6

What doesnt LD50 tell us?

Answer 6

• Doesn’t tell us the morbidity of those that survive
• Doesn’t tell us how quickly it will kill the animal

Question 7

What are the most common encountered toxicities in small animals?

Answer 7

• NSAIDS
• Rat baits
• Snail baits

Question 7

What are the most common encountered toxicities in small animals?

Answer 7

• NSAIDS
• Rat baits
• Snail baits

Question 8

Can we use information on lethal doses in laboratory animals be applied to other animals and humans?

Answer 8

• Not necessarily, but this is all we have as these tests cannot be done in humans or non laboratory animals.

Question 9

How might a cat get a permethrin toxicity?

Answer 9

If given a parasiticide intended for use on a dog

Question 10

In what situation might a dog or cat get lead toxicity? What signs might you see? How is it diagnosed?

Answer 10

• If an old house (before 1970) is renovated as lead may be in the paint
• If remnants of this paint get on coat and is groomed off
• Signs include: GIT and neurological signs and excessive vocalisation
• Diagnosis: RBCs

Question 11

What do Lilium spp. do to cats if ingested?

Answer 11

• All parts of the plant are nephrotoxic to cats

Question 12

Are peace lilies acutely toxic to cats?

Answer 12

• No, they arent accutely toxic to cats UNLESS ingested every day. They do not have severe nephrotoxic effects as Lilium spp.
• They contain calcium oxalate crystals which cause skin irritation, burning sensation in the mouth and occasionally V+ and D+

Question 13

What species do we commonly see Brunfelsia spp. toxicity in? What clinical signs would you see? How can it be treated?

Answer 13

• Dogs who ingest the berries
• Common in NSW in spring
• Toxic alkaloids in all parts of the plant
• Clinical signs: GIT (salivation, V+ and D+), CNS (ataxia, temors and seizures)
• Treatment: Decontamination and supportive therapy

Question 14

What samples can be taken from a live animal to detect toxins?

Answer 14

• Urine (toxin or its metabolites) - can be frozen
• Serum / plasma (toxin or metabolites) - can be frozen
• Red blood cells – only useful 3 weeks - can be frozen
• Vomitus – may be useful
• Faeces of little value other than for Brunfelsia spp.

Question 15

What samples can be collected from a dead animal to detect toxins?

Answer 15

• collect all urine from bladder
• Examine/collect stomach contents for unusual material (Plants, chemical granules, foreign matter)
• Fat may be useful if suspect lipophilic toxin e.g. organophosphate
• Samples of organs placed in fixative (for histopathology) as well as frozen (for toxicological analysis)

Question 16

What wouldnt you do with necropsy samples when youre trying to detect toxins?

Answer 16

You wouldnt put it in formaldyhde, instead freeze

Question 17

Can you request a broad tox screen from the lab?

Answer 17

No there is no such thing, you need to be specific on what you want tested

Question 18

What toxins and drug assays are available?

Answer 18

Question 19

What is an antidote for a cholinesterase inhibitor?

Answer 19

Pralidoxime OR for short term relief a muscarinic receptor antagonist (atropine)

Question 20

What is an antidote for Alpha 2 adrenoreceptor agonist (sedative)?

Answer 20

Alpha 2 adrenoreceptor antagonist

Question 21

What is an antidote for a Mu opioid receptor agonist?

Answer 21

Mu opioid receptor antagonist

Question 22

What is an antidote for benzodiazepines?

Answer 22

Flumazenil (not usually required in veterinary practice)

Question 23

Generally speaking, how would you treat a toxicity?

Answer 23

• Minimisation of absorption
• Limit toxin distribution
• Manipulation of toxin metabolism
• Expedite toxin excretion
• Supportive therapy for patient

Question 24

Which rodenticide is widely available?

Answer 24

• Vit K1 antagonists

Question 25

Out of warfarin (ratsak) and brodifacoum, which is more problematic if ingested by a dog?

Answer 25

• Brodifacoum is more problematic - longer half life and more potent. LD50 = 1.7g
• Warfarin (ratsak) - half life = 14.5 hours. LD50 = 40g

Question 26

What are the sources of anticoagulent toxicity?

Answer 26

• Eat the poison & the box (most common)
• Dogs eat baits (easy to obtain as on ground level)
• A dog eating a liver of an intoxicated rodent is not a significant risk

Question 27

Explain the mechanism of action of rodenticides (warfarin)?

Answer 27

• Concerned about clotting factors 2, 7, 9 and 10  needs to become activated
  o Most important is 7 as it has the shortest half live  runs out first
   18 hours after blockage of this enzyme  no longer getting tissue clotting. Usually bleeding into body cavities. Wont generally see blood coming out externally.
   Other clotting factors (2, 5, 9 and 10) follow this
  o How are they activated?
   Reduced vit K  trigger that allows them to be activated
   Oxidised Vit k needs to go back to the reduced vit k form  Warfarin BLOCKS vit K epoxide which stops this process

Question 28

How is rodenticide toxicity diagnosed?

Answer 28

• History of exposure – evidence
• clinical signs ->Key clue is not clotting following injection or sampling  do a coagulation profile
• Increased clotting indices (OSPT, APTT, ACT, +ve PIVKA etc)
• Response to therapy, once Vit K therapy commences OSPT and PIVKA give false negative results
• Detection of poison in stomach, or toxin concentrations in liver or serum

Question 29

How can rodenticide toxicity be treated?

Answer 29

• Decontamination ONLY within 3 hours. Pointless once clinical signs begin
• Supportive therapy: cage rest, fresh whole blood and fresh frozen plasma (contains clotting factors), transfusion
• Replace reduce form of Vit K1 (phytomenadione). Oral (preferable) but SC injections available - 1st gen at least 14 days, 2nd to 3rd gen at least 3-4 weeks

Question 30

What is the likely patient outcome of rodenticide toxicity?

Answer 30

o If minimise patients blood loss & treat with Vitamin K1 patient can survive.
o Patients die if severe internal bleeding is not detected

Question 31

Which coagulation test would we do if we suspect rodenticide toxicity?

Answer 31

Coagulation test - OSPT. We do this as it is specific for factor 7 which is the clotting factor with the shortest half life.

Question 32

What are the clotting tests?

Answer 32

• OSPT (one stage prothrombin time) - specific for CF 7
• ACT (activated clotting time)
• APTT (activated partial thromboplastin time