L1-6 ***Need to look through L1-4 to make sure nothing missed***

Poison

a substance that is capable of causing illness or death of a living organism when introduced or absorbed

Poisonous

substance causing or capable of causing death or illness if taken into the body

Toxin

a poisonous substance that is a specific product of the metabolic activities of a living organism, is notability toc when introduced into tissues of another organism

What is a toxin capable of inducing?

antibody formation

Toxic

substance containing or being poisonous material especially when capable of causing death or serous debilitation

Toxicant

any toxic substance

Toxicants can be ___

poisonous either synthetic or naturally occuring

Where can different toxicants be found

in air, soil, water, food

Venom

a toxic substance produced by some animals that is injected into prey or an enemy chiefly by biting or stinging and has an injurious or lethal effect broadly

If YOU bite it and die it is _______

poison

If IT bites you and you die its ____

venom

Toxicosis

a pathological condition caused by the action of a poison/toxin

Intoxication

the state of being intoxicated

Should you specify the type of intoxication?

yes

Poisoning

the action of administering poison to a living organism

Toxicity

the quality of being toxic or poisonous

Does "natural", "organic", "non-artificial" tells you anything about safety?

NO

What are the seven most deadly (to humans) chemical substances?

botulinum toxin A, tetanus toxin A, diphtheria toxin, dioxin, muscarine, bufotoxin, sarin

Where does botulinum toxin A come from?

Clostridium botulinum

Where does tetanus toxin A come from?

Clostridium tetani

Where does diphtheria toxin come from

corynebacterium diphtheriae

Where does dioxin come from?

its manufactured

Where does muscarine come from?

mushrooms

Where does bufotoxin come from?

toad, bufo

Where does sarin come from?

manufactured

Hazard

something that has the potential to cause harm

What does hazard include?

element of magnitude

What can a hazard be?

physical trauma, chemical effect, infection, neoplasia

Risk

the likelihood / probability that a hazard will cause harm

What does risk include?

element of probability

What is the calculation for risk?

hazard x probability

Risk assessment

the systematic process of identifying, analyzing and evaluating potential hazards or risks that could cause harm, determining the risk, and what can be done to reduce or eliminate it

Hazard is something that has the ___ to harm you

POTENTIAL

Risk is the _____ of hazard causing harm

LIKELIHOOD

Without context, hazard is ___

meaningless

What are the steps to toxicology analysis?

list toxicological differentials, obtain appropriate samples w/ appropriate extraction technique, determine appropriate analysis, interpret results

What are toxicological differential based on?

signalment, history, clinical signs, other diagnostics

If toxic etiology on the differential list is that ALWAYS the cause?

no

What are many toxicological diagnosis based on?

HISTORY and analysis is confirmatory

What things should you not assume in animal history?

that what you are told is the truth, that the owner will volunteer all info, and the case is cut and dry

What makes up the examination?

physical exam and postmortem exam

What are the things you collect in antemortem sampling

blood (whole and serum), urine, feces, vomit/gastric lavage, hair in topical exposure

Why is serum separation important?

prevents sample degradation and allows better testing

What organs do you collect for postmorem sampling

liver, kidney, brain, heart, skeletal muscle, fat, etc

What fluids should you collect postmortem?

urine, blood from heart, aqueous fluid

What GI contents should you sample postmortem?

stomach or rumen contents, cecal or intestinal contents, feces, crop or gizzard contents

What do you collect if you expect topical exposure

skin and hair

Dog presenting with vomiting, diarrhea, tremors, salivation, fever (107°F). What's the approach of the case?

history, exam, baseline diagnostics, environmental exam, toxicology analysis

What body temp do you start worrying about brain denaturation

108

What diagnostic framework can be used for toxicology differential lists

DAMNIT V

What is the D in DAMNIT V

degenerative, developmental

What is the A in DAMNIT V

anatomic

What is the M in DAMNIT V

metabolic

What is the N in DAMNIT V

neoplastic, nutritional

What is the I in DAMNIT V

infectious, inflammatory, immune-mediated, idiopathic, iatrogenic

What is the T in DAMNIT V

traumatic, toxic

What laboratory methods are used to confirm toxin exposure

gas chromatography, liquid chromatography, mass spectrometry

What are toxicological rule-outs based on

History, Physical or postmortem exam, Baseline diagnostics, Environmental exam, Toxicological analyses

What is the difference between signs and symptoms

Symptoms are how patient describes so our patients have NONE

Who is the grandfather of toxicology

Paracelsus

What makes the posion

the DOSE

Toxicology is to ___

pharmacology

What is a dose response

increase dose can cause toxic effect

Increasing dose past the therapeutic effect can cause

a toxic effect

____ is toxic at the right dose

EVERYTHING

What is NOAEL

no observed adverse effect level

What is LD50 or LC50

lethal dose/concentration that kills 50% of a test population

What it MTD

minimum toxic dose

What is MLD or MLC

minimum lethal dose/concentration

What toxicity parameter is used most clinically

MTD because shows dose where we have problems in our patients

Why does exposure NOT EQUAL intoxication

intoxication requires absorption, sufficient dose and affect on body systems

What are the 4 steps of toxicokinetics

ADME

What does ADME stand for

absorption, distribution, metabolism, excretion

What are the ways toxins are absorbed

oral/ingestion, dermal exposure, injection, inhalation

How can we minimize absorption

decontamination

What things influence distribution

fat solubility vs water solubility, protein binding, pH of tissues and compartments

Where does metabolism normally occur

in the liver but can be in other organs

What happens in metabolism

biotransformation to a more water-soluable product

What happens in metbaolism

coverting into a more water soluble product

What are the primary routes of excretion

urinary, biliary/fecal (milk, sweat, saliva)

Why are species differences important in metabolism

Some species produce less toxic metabolites, others produce more toxic ones

Describe acute

generally 24 hours or less (hours)

Describe subacute

less than 24 hrs but less than a month (days to weeks)

Describe subchronic

several months, less than a year (months)

Describe chronic

signifcant portion of life (years)

Describe dose response curve

What are exceptions to dose response curves

essential nutrients, hormesis

Describe essential nutrients in dose response curves

toxic at high doses, deficiency at low doses

Describe hormesis in dose response curves

small exposures are protective, large are dangerous

What is therapeutic index?

the ratio of the dose of the drug that produces toxic effect to therapeutic effect in 50% of patients (TI = TD₅₀ / ED₅₀)

How do you calculate therapeutic index TI

TD50 / ED50

How do you calculate safety margin

TD1 / ED99

What does a small TI mean

narrow safety margin

What does a large TI mean

large safety margin

What are the factors influence toxicity

characteristic of animals exposed, route of exposure, frequency of exposure, characteristics of the toxicant, environmental conditions

List animal characteristics that influence toxicity

species, genetic differences, age, sex, concurrent disease, nutritional status, concurrent exposure to other drugs

What are the toxicant-related factors that influence toxicity.

formulation, vehicle, valence of metals, ionization, decomposition, impurities, strain

What are the frequency of exposure factors that influence toxicity.

one time exposure, repeated exposure, cumulative effects

What are the enviornmental condition that influence toxicity.

drought, time of year, growth stage, temperature, photo period, winds

Why do you calculate dose of exposure

to determine if the dose is toxic or lethal and help with treatment