1-Principles of toxicology

Question 1

Paracelsus

Answer 1

Right dose differentiates poison from remedy.

Question 2

Veterinary Toxicology

Answer 2

Recognized by AVMA in the 1960s

Diplomate status (DABVT)

Question 3

Malicious poisonings

Answer 3

1-2 percent

Pesticides, drugs, aspirin, caffeine, ethylene glycol, cyanide

Question 4

polo horse deaths

Answer 4

death of 21 polo horses in Wellington

Question 5

Illicit drugs

Answer 5

Marijauna toxicosis in states legalizing marijuana

Question 6

1. Toxic (def)
2. Toxicology (def)

Answer 6

1. Causes adverse effects
2. Study of identification, treatment, assessing risks of poisons

• Clinical
• Regulatory
• Environmental

Question 7

Toxicant

Xenobiotic

Answer 7

Compound that causes toxicity, may be natural or man-made

Foreign substance

Question 8

Antidote

Answer 8

Remedy to counteract a poison

• ethanol in ethylene glycol toxicity
• Vitamin K mitigates rodenticides (Warfarin)
• Snake antivenom

Activated charcoal is not an ‘antidote’

Question 9

Manmade chemicals

Answer 9

More than 50,000 manmade chemicals

Potential toxicants include pesticides, cleaning products, pharmaceuticals, industrial chemicals

Question 10

Natural products

Answer 10

At least 800 species with millions of compounds

Microbes, vitamins, animal venoms

Question 11

Botulinum toxin

Answer 11

Exotoxin produced by clostridium botulinum

2-3 grams of this can kill the whole world

Most toxic subtance

Question 12

Level of toxicity

Botulinum:

Strychnine:

Snake vemon:

Nicotine:

Aspirin:

Foxglove:

Acetaminophen:

Grapes:

Salt:

Water:

Answer 12

Botulinum: extremely toxic

Strychnine: extremely toxic

Snake vemon: extremely to highly toxic

Nicotine: highly toxic

Aspirin: moderately toxic

Foxglove: moderately toxic

Acetaminophen: moderately toxic

Grapes: slightly toxic to practically nontoxic

Salt: Practically nontoxic (species dependent)

Water: relatively harmless

Question 13

Answer 13

Foxglove

Moderately toxic

Cardioglycosides

Something to do with digitalis…?

Question 14

Classification of chemical interactions in toxicity

Answer 14

Additive: summation

Antagonistic

Synergism: adverse effect magnified

Question 15

Factors influencing toxicity

Answer 15

1. Factors related to toxicant
2. Factors related to exposure
3. Factors related to subject
4. Factors related to environment

Question 16

Factors related to toxicant

Answer 16

chemical structure

affinity for some molecules

vehicle

Question 17

Factors related to exposure

Answer 17

dose

route of entry

• IV
• Oral
• Dermal

Question 18

Factors related to subject

Answer 18

Species

Age

Health status

Gender

• Estrogens can be protective

Question 19

Factors related to environment

Answer 19

Temperature: metabolism

pH: stomach

Question 20

Species and individual difference in metabolism

Cats

Dogs

Pigs

Answer 20

Species differency in capacity for biotransformation and sensitivity

• Cats deficient in glucuronidation
  
  • acetaminophin toxicity
• Dogs deficient in acetylation
• Pigs deficient in sulfation

Question 21

Pregnancy and metabolism

Answer 21

Parathion (pesticide) more toxic to pregnant animals

Question 22

Phase 1 vs Phase 2 enzymes

Answer 22

Phase 1

• Adds small functional groups to chemicals

Phase 2

• Adds bigger, conjugated groups to chemicals
• Solubilized and eliminated more quickly from the body

Question 23

Exposure Classifications

1. Acute
2. Sub-acute/subchronic
3. Chronic

Answer 23

Acute

• Single dose exposure or several doses within a 24 hours period
  
  • eat a bottle aspirin
  • snake envenomation
  • rat poison
  • zinc

Sub-acute/subchronic

• exposure over 7-90 days
  
  • organophosphates from pesticides sprayed on a lawn

Chronic

• Protracted exposure 6 months-lifetime
  
  • metals, lead, paint
  • arsenic from well water
  • zinc

Question 24

Dose-response relationship

Answer 24

Central concept of toxicology

• assumes a cause and effect relationship
• response is proportional to dose

Question 25

Toxicokinetics

Answer 25

Exposure and dose are NOT the same

Question 26

Most common routes exposure in vet med

Answer 26

Oral Dermal

Question 27

Bioactivation ## Footnote Metabolism Bioactivation Prodrugs

Answer 27

Metabolism usually detoxifies a compound and increases elimination. Bioactivation is when metabolism increases the toxicity of a compound * Benzo [a] pyrene * Aflatoxin * Acetaminophen Prodrugs can increase toxicity of a compound * Oxazepam-diazepam * Claritin-Clarinex

Question 28

Mechanisms of Toxicity Step 1-4

Answer 28

Step 1 * Delivery from site ofe exposure to target Step 2 * Reaction of the ultimate toxican with the target molecule Step 3 * Cellular dysfunction and resultant toxicities Step 4 * Repair: apoptosis, tissue regeneration * Disrepair: tissue necrosis, fibrosis, cancer

Question 29

Cellular Damage

Answer 29

Acetaminophen Arsenic Can result from free radical damage, inhibition of energy production, disruption of enzyme function

Question 30

Organ system dysfunction

Answer 30

Insectisides Rodenticides Not associated with specific cellular injury, but lethal to intact organism * secondary liver effects * multi-organ failure

Question 31

Top 10 toxins to dogs and cats

Answer 31

1. Prescription drugs 2. Insecticides, organophosphates 3. Over the counter drugs 4. Household products: Ajax, pinsol, toilette bowl cleaner 5. Human foods: Avocado, grapes, onions 6. Vet medications: Ivermectin 7. Rodenticides 8. Plants: sago palm toxicity, Lilies 9. Lawn products: Cocoa mulch

Question 32

10 most dangerous foods for dogs

Answer 32

1. Alcohol 2. Avocado 3. Chocolate * Theobromine 4. Coffee, caffeine * Theobromine 5. Fruit with pits/seeds 6. Grapes and raisins 7. Macadamia nuts * nuts can be high in cyanide (almonds) 8. Onions and Garlic * Hemopoeitic problems * Heinz bodies and oxidative damage 9. Xylitol (artificial sweetener) * inc insulin in small animals 10. Yeast, dough * stomach expansion * respiratory distress