Introduction Flashcards
What is vet toxicology?
The study of poisons and their actions in the body
One Health and Toxicology
-common environments shared
-things that poison animals may also poison people
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
The state of being poisoned
Toxicant
poison of man-made or synthetic origin
eg. antifreeze
Toxin
poisons that originate from a biological source
eg. from animals or plants
How can animals become poisoned?
- Humans role
-error
-poor husbandry and management
-negligence
-intentional - Environmental role
-food/feed
-water
-air
-weather
**remember natural does not always mean safe
Dosing and poison
The dose defines the poison…a substance can be safe at one dose but not at another
*the most important factor in considering poison exposure
Poison dose measurement
Amount of poison per unit body weight
**dose does not equal concentration
Median lethal dose
LD50
-estimation of lethality
-dose that kills 50% of the test species
-specific for route and species (not perfect because often determined by mice studies etc.)
Dose-response
A toxic effect is proportional to the dose of a substance
*higher dose= more severe toxic effect
What is the exception to the dose-response relationship?
Idiosyncratic reactions
*adverse drug reactions
Possible dose responses?
-lethality
-reproductive effects
-immune system effects
Categories of exposure
Acute
Sub-acute
Suc chronic
chronic
Acute duration
effects occur within 24 hrs of exposure
eg. poisons with low LD50 will be acutely toxic
Sub-acute exposure
> 24 hrs to <30days
Sub-chronic exposure
1-3mths of repeated exposure
Chronic exposures
Effects produced by prolonged exposure (>3mths)
eg. animal getting bit in water every day
**LD50 not a good estimate for chronic situations
Risk/hazard?
Toxicity + Probability of exposure
Toxicokinetics
*For an agent to cause toxicity, need to interact with its target site at a sufficient dose
- Absorption
- Distribution
- Metabolism
- Elimination
Absorption sites
-dermal
-ocular
-respiratory
-**Commonly GI (most ingested substances absorbed in small intestine)
*routes: IV, IM, SC, IP
Distribution
Factor of organ perfusion, diffusion of the toxic substance, the affinity of the toxic substance for a certain organ/tissue, binding to plasma proteins
Highly perfused organs vs. poorly perfused organs
Highly: liver, kidney, heart, lung, intestines, brain
Poorly: skin, connective tissue, fat
*depends on different affinity (ie. fat loving)
Detoxification/biotransformation
Most commonly in the liver, but some in kidney, GIT, lungs. None in neurons or fat
Phase 1: oxidation or hydrolysis by CYP 450 making them more lipophilic and more water soluble
Phase 2: conjugation to make them more water soluble
Elimination: in urine, bile, exhalation, other minor routes like sweat, milk, saliva
Bioactivation
Metabolism of a parent compound to a more toxic metabolite
Eg. Acetaminophen in cats, Ethylene glycol (antifreeze), Bromethalin (rodenticide)
Elimination through kidneys
Urine
-controlled by glomerular filtration, reabsorption, tubular secretion
*high MW compounds cannot be filtered by glomerulus
Used diagnostically!
Elimination through bile
-commonly high MW compounds
-enterohepatic re-circulation (long half lives)
-can be used for diagnostic purposes
Factors influencing toxicity
-intraspecies differences
-interspecies differences
-age
-health and physiological status
-physiochemical properties of the compound
Intraspecies differences
-most individuals fall within the bell curve for a dose response relationship
*differ in ADME
Examples: Ivermectin and ABC delta-; Bedlington terriers and Cu accumulation
Interspecies differences
Some things are toxic to one species but not another AND some species become poisoned at a lower dose than others
Poisonings can vary by species
Age and toxicity
Generally, very young and very old animals are more sensitive to toxic substances
*note ruminants vs pre ruminants
Why are young and old animals more sensitive?
-reduced ability to detoxifiy
-reduced ability to eliminate
-reduced/poor barrier function
Physiochemical properties
- The state of the toxin (gas, aqueous solution, solid (particle size))
- Size: smaller compounds are absorbed faster
- Lipophilicity: allows for passage of biological membranes easily and may partition to adipose tissue
- Acid/base character
-hederson-hasselbach- affects ionization of compound in solution= absorption
-presence or abscence of food in stomach
Health and physiological status
- liver or kidney disease= impaired ability to clear toxins
- General debilitation
- Pregnancy, lactation
- GI inflammation
Other factors affecting toxicology
- body size and body condition
2.sex differences
- concurrent medications (interactions, P-glycoprotein inhibitors, CYP450 inhibitors)
*Ketoconazole, cimetidine - Idiosyncratic rxns
Target organs
Often the site of accumulation
-knowledge helps narrow DDx
-sample submission
-some poisons target multiple organs
Mechanisms of toxicity
