1 – Fundamentals of Vet Toxicology Flashcards
1
Q
What is the difference between toxin and toxicant?
A
- Toxin: poisons that originate form a biological source
- Toxicant: poison of man-made or synthetic origin
2
Q
What is poison?
A
- Non-infectious substance that causes pathophysiological effects by chemically interfering with normal biological processes
3
Q
Toxic
A
- Describes the effect of a poison
4
Q
Toxicity
A
- Amount or dose that produces a toxic effect
5
Q
Toxicosis
A
- State of being poisoned
6
Q
What are 2 main ways that animals become poisoned?
A
- Humans
a. Error
b. Poor husbandry and management
c. Negligence
d. Intentional - Environment
a. Food
b. Water
c. Air
d. Weather
e. Natural doesn’t not mean safer
7
Q
What is the most important factor in considering exposure to poisons?
A
- DOSE
o Does NOT equal concentration
o “dose defines the poison” - Ex. LD50
8
Q
What is a toxic effect proportional to?
A
- Dose of a substance
- Higher dose=more severe toxic effect
- *exception: idiosyncratic reactions (adverse drug reactions)
9
Q
What are some of the most toxic substances?
A
- Cyanide (ex. rodenticides)
- Botulinum
- Monesin to horses
10
Q
Duration of exposure
A
- Acute, sub-acute, sub-chronic, chronic
- *poisons with low LD50 tend to be acutely toxin
- Chronic toxicity results from prolonged, repeated exposure
o LD50 is NOT a good estimate of chronic toxicity
11
Q
What contributes to risk?
A
- Toxicity + probability of exposure
- Ex. Yew=toxic plant
o Cardiotoxic
o But animals do NOT get into it=loss probability of exposure - Ex. ibuprofen: highly toxic to dogs and cats and in most peoples household
12
Q
Toxicokinetics: ADME
A
- Absorption: poison from route of exposure to bloodstream
- Distribution: from bloodstream to organs/tissues
- Metabolism: detoxification or activation of a poison
- Elimination: removal of poison from body
13
Q
Absorption
A
- Most ingested substances are absorbed in small intestine
- Vet med: ORAL (GI)
14
Q
What is distribution a factor of?
A
- Organ perfusion
o Highly perfused=liver, kidney, heart lung brains
Tend to get highest exposure to poisons
o Poorly perfused=skin, connective tissue, fat
affinity - Diffusion of toxic substance
- Affinity of toxic substance for a certain organ/tissue
- Binding to plasma proteins
15
Q
What are the 3 steps of detoxification/biotransformation?
A
- Phase I: oxidation, hydrolysis, reduction: lipophilic to more water soluble
o *cytochrome p450 monooxygenases - Phase 2: conjugation: addition of polar functional groups (glucuronidation, glutathione, sulfonation, methylation)
- Elimination: urine, bile, exhalation, other minor routes
16
Q
What is the main site of detoxification/biotransformation?
A
- *Liver
- Kidney, GIT, lungs
17
Q
What is bioactivation?
A
- Metabolism of parent compound to a more toxic metabolite
18
Q
What are some toxic substances that undergo bioactivation?
A
- Acetaminophen
o Can kill cats (do NOT give them Tylenol) - Ethylene glycol (ex. antifreeze)
- Bromethalin (rodenticide)
19
Q
Elimination: kidney (urine)
A
- Controlled by glomerular filtration, reabsorption, and tubular secretion
- High MW molecules=cannot be filtered by glomerulus
- *can be a useful diagnostic tool
20
Q
Elimination: bile (feces)
A
- High MW compounds
- Enterohepatic circulation (ex. Naproxen in dogs=can become toxin and be a poison again and longer half life)
- Can be used for diagnostic purposes
21
Q
What are some factors that influence toxicity?
A
- Intraspecies differences
- *Interspecies differences
- Age
- Health and physiological status
- Physiochemical properties of compound (state, size, lipophilicity, acid/base character)
22
Q
Intraspecies difference in toxicity
A
- “treat the patient, NOT the poison”
- Ex. ivermectin and delta-1
- Ex. Bedlington Terriers and Cu accumulation
23
Q
Interspecies differences in toxicity
A
- Different toxins or different doses
24
Q
Why is it that very young and very old animals are more sensitive to toxic substances?
A
- Reduced ability to detoxify
- Reduced ability to eliminate
- Reduced/poor barrier function
25
Ruminants vs. pre-ruminants and toxicity
- Pre-ruminants=more sensitive to lead poisoning
o But NOT poisoned by urea, cyanide or nitrate (NO rumen yet)
- *more later in course
26
Health and physiological status
- Liver and/or kidney disease
- General debilitation
- Pregnancy, lactation
- GI inflammation
27
What are other factors that can influence toxicity?
- Body size and condition
- Sex differences (usually minimal)
- Concurrent medications
- Idiosyncratic reactions
28
Target organs
- Often the site of accumulation
o Some target multiple organs (ex. certain plants)
- Knowledge of them helps NARROW DDx
- Helpful for sample submission
29
What targets the liver?
- Alfatoxins
- Microcystin
- Amanita mushrooms
30
What targets the kidney?
- Raisins/grapes
- Lilies
- Cadmium
- Ethylene glycol (anti-freeze)
31
What targets the blood?
- Nitrate
- Red maple (ex. horses, NAVLE QUESTION)
- CO
32
What targets the CNS?
- Strychnine
- OP/carbamate insecticides
33
What targets the lungs?
- 3-methylindole (‘fog fever’)
- Paraquat
34
What targets the heart?
- Ionophores
- Yew
- Oleander
35
What are some different mechanisms of toxicity?
- Enzyme inhibition
- Receptor agonist
- Receptor antagonist
- Direct cytotoxicity
- Oxidative stress/free radical damage
- Impaired macromolecule synthesis
- Impaired neurotransmitter release
36
What is something that does enzyme inhibition?
- Organophosphate/carbamates
37
What is something that does receptor agonist?
- Ergot alkaloid mycotoxins
38
What is something that does receptor antagonist?
- Strychnine
39
What is something that does direct cytotoxicity?
- Bleach
40
What is something that does oxidative stress?
- Acetaminophen
41
What is something that impairs macromolecule synthesis?
- Microcystin
42
How many ppm is 1%?
- 10,000ppm
- 1ppm=mg/kg (concentration NOT dose)
- *sample calculations
