Intro to Toxicology I

Question 1

Compared to Pharmacology, Toxicology refers to..

Answer 1

Pharmacology: Use of drugs to achieve THERAPEUTIC effect on a patient.
Toxicology: Study of toxins that produce a DETRIMENTAL effect on the patient.

Question 2

Why is toxicology like detective work?

Answer 2

It comes down to old fashioned detective work.
Focus on the basics!
Knocking on doors and answering questions.
It’s about the environment – where the patient lives — and who lives with them; what the patient has access to; and route of exposure
It’s about asking the RIGHT questions — it’s about asking ALL the questions….

Question 3

What is a toxin?

Answer 3

Poisonous substance, often a protein.
Is produced by living cells or organisms.
Is capable of causing disease when introduced into the body.

Question 4

Zootoxins

Answer 4

Animal based toxins

-Snake venom

Question 5

Mycotoxins

Answer 5

Fungal based toxins
Moldy corn
Fumonisin: produced by fusarium fungi

Question 6

What is toxicity?

Answer 6

the quantity of the amount of a toxin that causes a toxic effect

Question 7

What is toxicosis?

Answer 7

the disease state resulting from exposure to a toxin.

*The symptoms of icterus.

Question 8

*****What is dose?

Answer 8

the amount of toxin that the animal received / ingested: i.e. 250mg of acetaminophen
Patient X received a DOSE of 250 mg of acetaminophen.

Question 9

*****What is the dosage?

Answer 9

the amount of toxin per unit of animal mass or weight. May or may not include unit of time.
Think SCIENTIFIC STUDY – i.e. rats received a chemical DOSAGE of 2.5mg/kg/day of saccharin

Question 10

What is a threshold dose?

Answer 10

The HIGHEST dose at which toxic effects are NOT observed.

Question 11

What is a lethal dose?

Answer 11

A dose at which the toxin is fatal.

LD50= the dose at which 50% of the animals die during the period of observation.

Question 12

In order for a toxicosis to occur, a series of events must take place…
Step 1:

Answer 12

Step 1 is EXPOSURE.
It is more then just oral.
Inhalation (pulmonary)
Dermal (percutaneous)

Question 13

In order for a toxicosis to occur, a series of events must take place…
Step TWO:

Answer 13

ABSORPTION: How much chemical passes into the body over a period of time.

Question 14

What is absorption and what does it depend on?

Answer 14

Step two of toxicosis.
How much chemical passes into the body over a period of time.
Depends on… The route of exposure, the species, and the individual.

Question 15

What does ABSORPTION depend on?

Answer 15

The route of exposure, the species, and the individual.

Question 16

In order for a toxicosis to occur, a series of events must take place…
Step THREE:

Answer 16

DISTRIBUTION
Process by which an absorbed chemical disperses from the site of absorption to other parts of the body. Where the chemical is in the body at any given time (blood stream vs internal organs vs site of storage like bone or fat).

Question 17

In order for a toxicosis to occur, a series of events must take place…
Step FOUR:

Answer 17

METABOLISM (Biotransformation)

Process by which a substance is changed from one chemical to another by a chemical reaction in the body.

Question 18

****In order for a toxicosis to occur, a series of events must take place…
Step FIVE:

Answer 18

EXCRETION:
Process by which waste products of metabolism are excreted from the body via…
Urine, feces, milk, sweat, saliva.

Question 19

What is exposure duration?

Answer 19

The length of time an animal is exposed to a toxin.

Question 20

What is considered acute exposure duration?

Answer 20

Less then 24 hours

Question 21

What is considered subacute exposure duration?

Answer 21

24 hours up to 30 days.

Question 22

What is considered subchronic exposure duration?

Answer 22

1-3 months

Question 23

What is considered chronic exposure duration?

Answer 23

More then 3 months.

Question 24

*****What is the dose-response relationship?

Answer 24

The dose response curve.
It refers to the graphical representation of the relationship between the dose of the drug and the response elicited.
-No-effect range.
-Range of increasing effect with increasing dose.
-Maximum effect range.
Example: Dose response curve to alcohol…
No effect, giddy, sleep, deep sleep, unconscious, labored breathing, death.

Question 25

*****What can affect a dose-response curve for a particular toxin?

Answer 25

Selective toxicity.
Interspecies differences
Intraspecies differences.

Question 26

What is selective toxicity?

Answer 26

Sulfonamides.
Bacteria make their own folic acid, they cannot absorb it from their diet.
Mammals: we cannot make folic acid, so we must get it from the diet.
Sulfonamides BLOCK the production of folic acid in the bacterial cell but because mammals get what they need from their diet and not through intracellular manufacturing, normal cell processes can continue in the mammalian cell.
Therefore, sulfonamides are said to have SELECTIVE TOXICITY.

Question 27

What is interspecies differences?

Answer 27

Acetaminophen.
Cat vs Dog
The toxic dose for cats is 10-100mg/kg
Dogs can tolerate 6-12x this.
Acetaminophen is metabolized through glucuroniation, which canine livers are good at.
Cats have a limited ability to metabolize through this pathway, so they must rely heavily on other LESS EFFICENT pathways to break down the drug.
The drug essentially overwhelms the feline liver, causing hepatic necrosis sooner than in a dog.

Question 28

What is intraspecies differences?

Answer 28

Age and Maturity: Some substances are more toxic to the very young and the very old.
Gender: Since women have a larger percentage of body fat, woman may accumulate more fat-soluble toxins.
Genetic makeup: For example, people lacking in the GGPD enzyme, are more likely to suffer red blood cell damage when given aspirin or certain antibiotics than people with the normal form of the enzyme.

Question 29

How do environmental factors effect toxicity?

Answer 29

Air pollution, living conditions, workplace conditions, personal habits and previous chemical exposures may impact toxicity.

Question 30

How do chemical combinations effect toxicity?:

Answer 30

Some toxins when combined with others, cause more than an additive effect.
-Ethanol and carbon tetrachloride.
Some toxins when combined with others cause less than the predicted effect
-phosphate reduces lead absorption in the gut by forming insoluble lead phosphate.

Question 31

Even drugs that are intended to be therapeutic…

Answer 31

can become toxins depending on the dosage!

Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.

Question 32

At low doses morphine..

Answer 32

Achieves the intended therapeutic effect..
at HIGHER dosages, we see adverse effects.
Small margin of safety.

Question 33

What is an ADVERSE EFFECT?

Answer 33

Adverse event.
A suspected product induced animal injury.
-Vaccine associated fibrosarcomas (toxicity)
A suspected failure of a product to perform (i.e. a puppy that is vaccinated with D2APP-vaccinated and succumbs to parvovirus).

Question 34

*****What does the USDA regulate?

Answer 34

Evaluates the purity, safety, potency and effectiveness of all vaccines and biological products PRIOR to licensing.

Question 35

*****What does the FDA regulate?

Answer 35

Evaluates, approves, licenses and regulates all pharmaceutical products.

Question 36

****What does the EPA regulate?

Answer 36

Evaluates the safety and effectiveness of pesticides.

Flea and tick products

Question 37

What are other agencies that regulate drugs?

Answer 37

The actual drug company.
Third party reporting organizations.. US Pharmacopeia (USP) veterinary practitioners reporting program.
Pet poison helpline.
The American society for the prevention of cruelty to animals (ASPCA) animal poison control center (APCC)

Question 38

*****According to the ASPCA APCC, the 3 most common pet toxins in 2014 were..

Answer 38

1) Human prescription medications (#1)
2) Over-the-counter medications
3) Insecticides