1 – Fundamentals of Vet Toxicology Flashcards
What is the difference between toxin and toxicant?
- Toxin: poisons that originate form a biological source
- Toxicant: poison of man-made or synthetic origin
What is poison?
- Non-infectious substance that causes pathophysiological effects by chemically interfering with normal biological processes
Toxic
- Describes the effect of a poison
Toxicity
- Amount or dose that produces a toxic effect
Toxicosis
- State of being poisoned
What are 2 main ways that animals become poisoned?
- 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
What is the most important factor in considering exposure to poisons?
- DOSE
o Does NOT equal concentration
o “dose defines the poison” - Ex. LD50
What is a toxic effect proportional to?
- Dose of a substance
- Higher dose=more severe toxic effect
- *exception: idiosyncratic reactions (adverse drug reactions)
What are some of the most toxic substances?
- Cyanide (ex. rodenticides)
- Botulinum
- Monesin to horses
Duration of exposure
- 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
What contributes to risk?
- 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
Toxicokinetics: ADME
- 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
Absorption
- Most ingested substances are absorbed in small intestine
- Vet med: ORAL (GI)
What is distribution a factor of?
- 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
What are the 3 steps of detoxification/biotransformation?
- 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
What is the main site of detoxification/biotransformation?
- *Liver
- Kidney, GIT, lungs
What is bioactivation?
- Metabolism of parent compound to a more toxic metabolite
What are some toxic substances that undergo bioactivation?
- Acetaminophen
o Can kill cats (do NOT give them Tylenol) - Ethylene glycol (ex. antifreeze)
- Bromethalin (rodenticide)
Elimination: kidney (urine)
- Controlled by glomerular filtration, reabsorption, and tubular secretion
- High MW molecules=cannot be filtered by glomerulus
- *can be a useful diagnostic tool
Elimination: bile (feces)
- 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
What are some factors that influence toxicity?
- Intraspecies differences
- *Interspecies differences
- Age
- Health and physiological status
- Physiochemical properties of compound (state, size, lipophilicity, acid/base character)
Intraspecies difference in toxicity
- “treat the patient, NOT the poison”
- Ex. ivermectin and delta-1
- Ex. Bedlington Terriers and Cu accumulation
Interspecies differences in toxicity
- Different toxins or different doses
Why is it that very young and very old animals are more sensitive to toxic substances?
- Reduced ability to detoxify
- Reduced ability to eliminate
- Reduced/poor barrier function
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
Health and physiological status
- Liver and/or kidney disease
- General debilitation
- Pregnancy, lactation
- GI inflammation
What are other factors that can influence toxicity?
- Body size and condition
- Sex differences (usually minimal)
- Concurrent medications
- Idiosyncratic reactions
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
What targets the liver?
- Alfatoxins
- Microcystin
- Amanita mushrooms
What targets the kidney?
- Raisins/grapes
- Lilies
- Cadmium
- Ethylene glycol (anti-freeze)
What targets the blood?
- Nitrate
- Red maple (ex. horses, NAVLE QUESTION)
- CO
What targets the CNS?
- Strychnine
- OP/carbamate insecticides
What targets the lungs?
- 3-methylindole (‘fog fever’)
- Paraquat
What targets the heart?
- Ionophores
- Yew
- Oleander
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
What is something that does enzyme inhibition?
- Organophosphate/carbamates
What is something that does receptor agonist?
- Ergot alkaloid mycotoxins
What is something that does receptor antagonist?
- Strychnine
What is something that does direct cytotoxicity?
- Bleach
What is something that does oxidative stress?
- Acetaminophen
What is something that impairs macromolecule synthesis?
- Microcystin
How many ppm is 1%?
- 10,000ppm
- 1ppm=mg/kg (concentration NOT dose)
- *sample calculations
