Lecture 2: Basic Principles

What LD50 stand for?

Lethal Dose/Concentration that kills 50% of a test population

What does MTD stand for?

Minimum Toxic Dose

What does MLD/MLC stand for?

Minimum Lethal Dose/Concentration

Out of LD50, MTD, MLD which value is likely of most clinical use and why?

MTD to determine what values will cause toxicity

• MLD is not clinically relevant because patient will probably already be dead

Does exposure equal intoxication, why?

NO, exposure does NOT equal intoxication because of Toxicokinetics

What is Toxicokinetics? (3 steps)

1. Toxin must be absorbed

2. Toxin must reach its site of action at a high enough concentration

3. Toxin must remain at site for a sufficient amount of time to cause a toxic effect

Because of Toxicokinetics, what is the main treatment of intoxication?

Decontamination to get the toxin out before it causes damage

What are the 4 basic events in Toxicokinetics? (in order)

1. Absorption

2. Distribution

3. Metabolism

4. Excretion

Describe Toxicokinetics: Absorption

How does its get into the body?

• Orally/Ingestion

• Dermal exposure

• Injection

• Inhalation

How can we minimize absorption?
Give examples

Decontamination!

• Dermal: give a bath

• Oral: emesis

Describe Toxicokinetics: Distribution

Where does it go in the body?

• Fat or Water Soluble

• Protein binding

• pH of tissues and compartments

Describe Toxicokinetics: Metabolism

What happens to it when it gets there?

• Biotransformation

  • Metabolites are more readily excreted because converted to a more water-soluble product

Where does Metabolism often occur?

Liver

Describe Toxicokinetics: Excretion

How does it get out of the body?

What are some primary routes of excretion?

1. Urinary

2. Biliary/Fecal

3. Milk, Sweat, Saliva

What is an exception to the “typical” dose-response curve? Why?

• Give examples

Essential Nutrients

• Nutrients have a region of homeostasis

  • Too little or too much nutrients = problem

• Ex.

  • Vitamins A, D, E can cause problems because they are fat soluble vitamins

What is Therapeutic Index?

The ratio of the drug dose that causes an unwanted (toxic) effect to producing a wanted (therapeutic) effect

TI = LD50/ED50

What are 5 factors that influence toxicity?

1. Characteristics of the animal exposed

2. Route of exposure

3. Frequency of exposure

4. Characteristics of the toxicant

5. Environmental conditions

What is the biggest thing to consider for characteristics of the animal exposed?

Species

What are 7 Characteristics of the animal exposed to consider?

1. Species

2. Genetic differences

3. Age

4. Sex/Reproductive Status

5. Concurrent disease

6. Concurrent exposure to other drugs or chemicals

7. Nutritional status

What are 6 Characteristics of the Toxicant to consider?

1. Formulation

2. Valence state of metals

   1. Charge of the molecule will tell if its toxic

3. Ionization

4. Decomposition

5. Impurities

6. Stain/Subspecies

What are 3 things to consider for the Frequency of Exposure?

1. One time exposure

2. Repeated exposures

3. Cumulative effects

What are 6 things to consider for Environmental Conditions?

1. Drought

2. Time of Year

3. Growth Stage

4. Temperature

5. Photo Period

6. Winds

What is considered a WRONG question? What should be asked instead?

WRONG: Is this toxic?

• At what dosage?

• In what species?

• Under what conditions?

When are dose calculations used?

In cases involving a KNOWN exposure to a specific toxicant

Why calculate a dose of exposure?

To determine if the dose is high enough to pose a risk of intoxication or death

• Of the dose of exposure is below MTD, don’t need to treat

Why should you NOT just treat any exposure?

The risk of treatment may outweigh the risk of intoxication

ex. bleach consumption = NO emesis because they will cause more damage

If the animal ingested a possible toxicant, what is one most important thing to get from owners?

the LABEL