L1: Principles of Vet Toxicology (Martyniuk) Flashcards Preview

Toxicology 5172 (Fall 2014) > L1: Principles of Vet Toxicology (Martyniuk) > Flashcards

Flashcards in L1: Principles of Vet Toxicology (Martyniuk) Deck (49)
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1
Q

dosimetry

A

the idea that “all substances are poisons and there is none which is not a poison. The right dose differentiates poison from remedy.” (idea of Paracelsus)

2
Q

Diclofenac

A

an anti-inflammatory used in cattle

-vultures feed on cattle treated with Diclofenac –> kidney failure

3
Q

how many manmade chemicals are potential toxins?

A

> 50,000

4
Q

how many toxic plants?

A

> 800

5
Q

toxic vs. toxicology vs. toxicant

A

toxic: poisonous
toxicology: science of poisons (concerned w/ ID, tx, and assessing risks of poisons)
toxicant: compound that causes toxicity (natural or man-made)

6
Q

xenobiotic

A

foreign substance found within an organism

7
Q

4 main factors influencing toxicity

A

1) Toxicant: structure, metabolism, elimination, size, charge (chem/biological properties)
2) Exposure: (dose, time exposed, route of exposure, conc.)
3) Subject: breed, age, health, species
4) Environment: temp, bioavailability, altitude, etc.

8
Q

3 classifications of chemical interactions in toxicity

A

additive
antagonistic
synergism

9
Q

dose-response relationship

A

central concept of toxicology; assumes a cause and effect relationship and that response is proportional to dose. Shape of curve is always sigmoidal

10
Q

NOAEL

A

No observable adverse effect level: max. dose that causes no adverse effect

11
Q

LOAEL

A

Lowest Observable Adverse Effect Level: min. dose that you can measure an effect.

12
Q

LD50:

A

dose producing death in 50% of animals

13
Q

Threshold dose:

A

min. dose to produce reaction; indicates there is “safe” dose

14
Q

acute exposure

A

single dose exposure or several doses w/n 24hr

15
Q

sub-acute/subchronic exposure

A

exposure over 7-90d

16
Q

chronic exposure

A

protracted exposure (6mo-lifetime)

17
Q

toxicokinetics

A

study of the movement and disposition of the toxicant in an organism (ADME)

  • influenced by dose, physiochemical properties of the toxin/drug, species differences in physiological and biochemical chars.
  • math. rep. of how a toxin gets into, moves about, and causes an effect on the body
18
Q

Does exposure = dose?

A

NO

19
Q

ADME

A

absorption, distribution, metabolism, excretion

20
Q

major routes of excretion:

A

renal (urine), hepatic (bile), fecal, GIT

21
Q

absorption

A

uptake of material from site of exposure; the amt. of material that enters the body

22
Q

distribution

A

from blood to tissues

23
Q

metabolism

A

enzymatic conversion
aka biotransformation: the biological conversion of a chemical compound (exogenous or endogenous) into a second compound, or metabolite
-requires enzyme catalysts (phase I or II)
-primary biochemical pathway of xenobiotic metabolism

24
Q

elimination

A

excretion from body. Can follow first or zero order kinetics

-influenced by half-life (when 50% of the compound is degraded)

25
Q

3 main routes of exposure

A

1) Lungs (pulmonary surfaces)
- uptake of vapors, gases, mists, particulates
2) Gut (dietary exp.)**
- influenced by pH of gut, rate of digestion, residence time of food, microflora of gut
3) Dermis**
- hydrophobic compounds can go through skin of animals

26
Q

Order 6 common absorption routes from fastest to slowest:

A
IV
Pulmonary
IM
IP
Oral
Cutaneous
27
Q

which is absorbed faster: aspirin or pesticide?

A

aspirin

28
Q

things that can affect drug distr.

A

solubility, protein binding, physical characteristics/health of animal, pH, charge of compound, transporters/receptors for a certain compound, etc.

29
Q

what happens between applied dose and target organ dose?

A

applied dose –> absorption –> internal dose –> distribution –> target organ dose

30
Q

central medium of distr. of chemical that target organs

A

blood

31
Q

main sites of biotransformation reactions

A

liver and kidney

  • have highest enzyme conc.
  • blood flow
  • high surface area
32
Q

phase I enzymes

A

increase hydrophilicity of compounds by adding reacting groups such as hydroxyl, thiol, carboxyl via REDOX reactions

33
Q

phase II enzymes

A

increase hydrophilicity of compounds even further by forming inactive conjugates with addition of acetate, glucoronic acid, glycine, glutathione, etc. Use PRIMARY CONJUGATION reactions.

  • have more species differences than phase I enzymes
  • bigger proteins than Phase I
34
Q

Biotransformation can lead to:

A
  • enhanced elimination (lipophylic to hydrophylic)
  • detoxification
  • sequestration
  • redistribution
  • activation
35
Q

possible adverse effects of sequestration

A

body still holding onto the toxin. If sequestration pathway randomly stops working, you can get serious acute adverse effect.

36
Q

bioactivation

A

making compound more toxic by metabolizing it
Ex: parathion (pesticide) –> oxidation –> paraoxon
*parathion is especially toxic to pregnant animals

37
Q

cats deficient in which metabolism process?

A

glucuronidation

38
Q

dogs deficient in which metabolism process?

A

acetylation

39
Q

guinea pigs/rats deficient in which metabolism process?

A

N-hydroxylation

40
Q

pigs deficient in which metabolism process?

A

sulfation

41
Q

name 3 ex. of compounds that bioactivate

A

benzopyrene
aflatoxin (a fungus)
acetaminophen

42
Q

acetaminophen metabolism

A

acetaminophen activated by cytochrome P450 (a phase I enzyme) to N-acetyl-p-Benzoquinoneimine, which causes oxidative stress in tissues and ROS formation.

43
Q

name 3 P450 inhibitors

A

cimetidine
enrofloxacin
grapefruit juice

44
Q

name a P450 inducer

A

ethanol

45
Q

2013 top 10 toxins

A

1) prescription pharmaceuticals
2) insecticides
3) OTC drugs (NSAIDs)
4) household products
5) human foods
6) vet meds (i.e. ivermectin)
7) chocolate
8) rodenticides (i.e. Warfarin)
9) toxic plants
10) lawn products

46
Q

First-order elimination

A

constant FRACTION of chemical eliminated (dose dependent). plasma drug concentration decreases linearly with time.
-most common form of elimination

47
Q

Zero-order elimination

A

constant AMOUNT of chemical eliminated; typically means that processes are saturated.

  • dose INDEPENDENT
  • acetaminophen, alcohol
48
Q

most pesticides have short/long half-lives

A

short. (ie. Fipronel). Usually present with acute exposure.

49
Q

How do toxicants cause toxicity?

A

1) Cellular damage, resulting from free radical damage, inhibiton of energy production, disruption of enzyme function
- i.e. Acetaminophen, arsenic
2) Organ system dysfunction (not assoc. with specific cellular injury, but lethal to intact organism)
- i.e. Insecticides, rodenticides