Exam 1: Weeks 1 and 2

Question 1

Toxicant

Answer 1

An alternative name for poison

Question 2

Toxin

Answer 2

A poison that originates from biological processes; also called a biotoxin. Mycotoxins and zootoxins are common examples of biotoxins. Many plants are also known to be
toxic when consumed by specific types of animals.

Question 3

Toxicity

Answer 3

The quantity or amount of a poison that causes a toxic effect. Toxicity and toxicosis are often mistakenly used interchangeably.

Question 4

Toxicosis

Answer 4

A disease state that results from exposure to
a poison.

Question 5

Dose

Answer 5

Amount of toxicant received
per animal.

Question 6

Dosage

Answer 6

Amount of a toxicant per unit
animal mass or weight. Time
can also be included as a
metric.

Question 7

Route of exposure

Answer 7

How the animal is exposed to the toxicant. Orally, feed, drink, dermal, inhalation etc.

Question 8

Threshold dose

Answer 8

The highest dose of a toxicant
where no toxic effects are
observed.

Question 9

Lethal Dose (LD)

Answer 9

Acute dose resulting in death. Usually
presented as the dose resulting in
death of 50% of animals (LD50). Can
also be expressed as dose resulting in
death of 10% of animals (LD10) etc..

Question 10

Lethal concentration (LC)

Answer 10

Lowest concentration of a chemical
in a matrix (usually feed or water)
that causes death. If a concentration
in water (mg/ml) is known to kill half
of the animals it could be expressed
as LC50. LC’s are used most commonly
when expressing lethality for fish or
wildlife species.

Question 11

Median Lethal Dose

Answer 11

Used interchangeably with the LD50

Question 12

NOEL and NOAEL

Answer 12

No Observed Effect Level and No Observed Adverse Effect Level. The
NOEL is defined as the highest dose at which a significant effect
could not be detected. Similarly, a NOAEL is the highest dose where a
significant adverse effect could not be found.

Question 13

LOEL and LOAEL

Answer 13

Lowest Observed Effect Level and Lowest Observed Adverse Effect
Level. The LOEL is defined as the lowest dose at which a significant
effect could be found. The LOAEL is the lowest dose where a
significant adverse effect could be found.

Question 14

Effective dose (ED)

Answer 14

The dose of a drug or toxicant that produces some desired effect in 50%
of the population.

Question 15

Therapeutic index (TI)

Answer 15

Defined by the equation:
LD(50)/ED(50)

Question 16

Standard Safety Measure (SSM) or Margin of Safety (MoS)

Answer 16

Defined by the equation:
SSM=LD(1)/ED(99)

Question 17

Exposure Duration

define and name the four subgroups

Answer 17

The length of time an animal is exposed to a toxicant. In general, there are four subgroups:
* Acute – Exposure to single or multiple doses over a 24 hour period
* Subacute – Exposure to multiple doses of a toxicant for greater than 24 hours but for as long as 30 days.
* Subchronic – Exposure lasting from 1-3 months.
* Chronic – Exposure for 3 months or longer.

Question 18

Hazard (risk)

Answer 18

The likelihood that a toxicant will cause harm under certain conditions.
Risk assessment is a specialized area of toxicology that is of great
importance to health assessors and government regulators

Question 19

ADME

Answer 19

• Absorption
• Distribution
• Metabolism
• Excretion

Question 20

Top Pet Toxins of 2022

Answer 20

1. OTC Medications
2. Human food (xylitol)
3. Human prescription meds
4. chocolate
5. bouquets and plants
6. house toxicants (cleaning, beauty, repair)
7. veterinary products
8. rodenticide
9. insecticide
10. recreational drugs

Question 21

Why is ADME imporant on toxicology?

Answer 21

✓Absorption from different exposure routes can impact the occurrence and
scope of toxicity.
✓Distribution can affect residues in food animals as well as impact toxicity in a species and/or breed specific manner.
✓Metabolism in different species and/or breeds can impact toxicity.
✓Elimination can play an important role regarding food residues and safety as well as the duration of toxicity and treatment.

Question 22

xenobiotic

Answer 22

a foreign in our body; toxicant or drug

Question 23

Area under the curve (AUC)

Answer 23

Measure of xenobiotic exposure that
includes both concentration and time

Question 24

Bioavailability

Answer 24

the degree and rate at which a substance is absorbed into a living system or is made available at the site of physiological activity.

Question 25

Terminal/Elimination Half-Life

Answer 25

The time it takes the concentration of a
xenobiotic to decrease by half in the linear terminal phase of the concentration vs. time curve

The terminal half-life is an indicator
of how long a xenobiotic will persist
at a concentration presenting a
biological effect. This may be an
important indicator of treatment
duration or residue time.

how long does it take to get to 50%? 1 half life. Always takes 5 half lives to get under 5%

Question 26

what is volume of distribution (Vd) and its relationship to the volume of the organism?

Answer 26

A term that relates the concentration of a xenobiotic in the blood/serum/plasma to the amount of the xenobiotic in the whole body

if Vd=volume of organism, distribute sin total body water
if Vd<volume of organism, distributes in vascular system
if Vd>volume of organism, distributes in tissues

Vd=dose/c0

Remember a liter weighs ~ 1kg so…. If the Vd is 1 l/kg it would distribute in total body water.

Question 27

what are some methods of absorption?

Answer 27

inhalation (lungs): volatile agent, gases
oral (organs): food, drink, grooming, biting/playing/testing
dermal (percutaneous): applied, accidental

Question 28

Four Factors that Affect the Passage of Toxicants Through Biological Membranes:

Answer 28

1. Concentration Gradient Across the Membrane (diffusion)
2. Surface Area of the Membrane
3. Toxicant Permeability
4. Macromolecule Binding

Question 29

What is perfusion-limited distribution?

Answer 29

Drug distribution to tissues is equal to the amount of blood flow that each tissue receives

Question 30

what is diffusion-limited distribution?

Answer 30

having to cross the membrane

When the rate-limiting factor for distribution is the movement of drug from the blood to the tissue. This happens primarily with polar drugs crossing tightly knit membranes.

Question 31

What are the major physiochemical properties of a drug that dictate ease of entry into a tissue?

Answer 31

lipid to water partitioning and degree of ionization

Question 32

How are toxicants eliminated from the body?

Answer 32

Many exits but hepatic and renal elimination are generally the primary routes.

Question 33

True or false: Compounds with high liver extraction have poor oral bioavailability ?

high liver extraction is limited by blood flow

Answer 33

True

Question 34

True or false: protein binding can play a significant role in elimination for low liver extraction

Answer 34

True

Question 35

what is propofol?

Answer 35

Propofol is an intravenous anesthetic used for procedural sedation, during monitored anesthesia care, or as an induction agent for general anesthesia. It may be administered as a bolus or an infusion, or some combination of the two

bolus: a type of large pill used in veterinary medicine. In medicine, a bolus is the administration of a discrete amount of medication, drug, or other compound within a specific time, generally 1–30 minutes, to raise its concentration in blood to an effective level.

Question 36

What are some techniques for decontamination?

Answer 36

• ocular decontamination: physiologic saline, tepid water
• dermal decontamination: soap and water, clipping hair, tepid water
• inhalant decontamination: administrative oxygen
• injection contamination: gentle manipulation to emove stinger, do not suck out snake venom or use a warm press tourniquet
• GI decontamination:

Question 37

treatment principles

Five Factors to Consider Prior to Inducing Emesis

Answer 37

Time frame – If too much time has passed the toxicant may have
moved from the stomach. Emesis is indicated for most toxins
within 1-2 hours of ingestion.
* Underlying medical conditions – brachycephalic syndrome dogs
may be at greater risk for aspiration. Prior history of laryngeal
paralysis, megaesophagus, aspiration pneumonia, upper airway
disease should not have emesis performed.
* Symptomatic patients – sedate patients may have decreased gag
reflex or a lowered seizure threshold and may not be able to
protect the airway resulting in higher risk of aspiration pneumonia.
* Corrosive, caustic agents, sharp objects – emesis may cause
additional injury to the esophagus, oropharynx and GIT when
agents are expelled.
* Hydrocarbons – low-viscosity liquids can be easily aspirated into
the respiratory system resulting in severe aspiration pneumonia.

Question 38

treatment principles

What is the Effectiveness of Emesis Induction based on?

Answer 38

• Emetic agent used
• Time Elapsed
• • Within 30 minutes 49% recovery of toxicant (range 9-75%)
• • Within 60 minutes 17-62%
• • Recovery of toxicant decreases as time passes (PGO)
• Physical characteristics of the toxicant ingested
• • Agents that form large bezoars may be recovered even after 4 hours
• • Large wads of xylitol gum, large amounts of chocolate, grapes/raisins etc……
• Toxicant’s effect on gastric emptying
• • Opioids, anticholinergics, salicylates, TCA antidepressants
• Presence of gastric contents
• • Food delays gastric emptying so fed vs. fasted state can make a difference

Question 39

treatment principles

Veterinary emetic agents

Answer 39

Apomorphine (dogs, not recommended for cats)
* Acts directly on the chemoreceptor trigger zone (CTZ)
* 0.02-0.04 mg/kg IV or IM or direct application of the tablet form into the
subconjunctival sac
* If subconjunctival route is used, the subconjunctival sac must be thoroughly flushed following emesis or protracted vomiting may occur
* Emesis occurs within 4-6 minutes
* Maybe contraindicated in patients where toxicant action is sedative

Dexmedetomidine
* Selective ⍺-adrenergic agonist
* Agent of choice for use in cats
* Dose in cats is 10 mcg/kg IM
* Emesis occurs in ~10 mins
* Following emesis, sedative effects are reversed with an ⍺2-adrenergic antagonists (atipamezole)

Xylazine
* Centrally mediated ⍺2-adrenergic agonist
* Used in cats but generally not in dogs due to more effective agents
(apomorphine, hydrogen peroxide)
* Dose in cats is 0.44 mg/kg IM or SQ
* Emesis occurs in 10-20 minutes
* Can result in profound CNS and respiratory depression and cats should be
monitored
* Can be reversed with ⍺2

-adrenergic antagonists (atipamezole)

Hydromorphone
* Opioid agonist that acts directly on the chemoreceptor trigger zone (CTZ)
* Second line for dogs and cats that don’t vomit with apomorphine or
dexmedetomidine, respectively.
* Dose in cats is 0.1 mg/kg SQ
* Emesis occurs in 5-10 minutes
* Adverse effects can be reversed with naloxone following emesis.

Question 40

Gastrointestinal decontamination techniques

Answer 40

• emetics
• gastric lavage: for anesthetized or intubated patients where emesis in unproductive or contraindicated
• whole bowel irrigation: (polyethylene glycol solution) can be used for prenatal iron tablets and large
  amounts of a sustained release medication
• activated charcoal: Binds non-polar compounds well. Heavy metals and alcohols are not typically absorbed. Xylitol binds poorly to AC, aggeressive hydration needed.
• Cholestyramine: for toxicants that undergo enterohepatic
  recirculation or biliary elimination, binds with bile acids
• Osmotic cathartics – increase fluid volume of the feces
• Saccharide cathartics (e.g. sorbitol)
• Saline cathartics (e.g. magnesium citrate, magnesium sulfate,
  sodium sulfate)
  Do not use in dehydrated patient or with AC. Not thought to be beneficial for detoxification.

Question 41

Other decontamination methods (not GI)

Answer 41

• Fluid therapy: treats hypotension. Phenobarbital, Amphetamines, Salicylate, Lithium, Bromide
• Intravenous lipid emulsion (ILE): is an established, effective treatment for
  local anesthetic-induced cardiovascular collapse. dosed in a bolus. lipid emulsion has been considered a candidate for generic reversal of
  toxicity caused by overdose of any lipophilic drug