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POD > 4.1 Principles of Toxicology > Flashcards

4.1 Principles of Toxicology Flashcards

1
Q

what are the two sections of the AHL toxicology laboratory

A

organic and inorganic

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2
Q

what does the organic section of the AHL toxicology laboratory test

A
  • pesticides
  • feed additives
  • vitamin A and E in serum
  • cholinesterase
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3
Q

what does the inorganic section of the AHL toxicology laboratory test

A
  • trace minerals
  • heavy metals
  • iodine
  • nitrate/nitrite/ammonia
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4
Q

what is the definition of toxicology

A

the study of the adverse effects of chemical, physical or biological agents on living organisms and the ecosystem, including the prevention and amelioration of such adverse effects

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5
Q

what did paracelsus come up with regarding toxicology

A

the notion that the dose makes the poison

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6
Q

how does water cause death at high enough doses

A

dehydrated animals have hypertonic cytoplasm -> rapidly ingesting water leads to cellular swelling through osmotic pull -> cells swell which means that tissues and organs swell -> the brain herniates out of the foramen magnum and the respiratory centers in the medulla become compromised -> death

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7
Q

what toxic substance do apple seeds contain

A

amygdalin in apple seeds, when crushed or chewed, converts to cyanide

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8
Q

what is the normal amount of cyanide in animal blood

A

< 0.5 ppm

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9
Q

what is the minimal lethal concentration of cyanide

A

3 ppm

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10
Q

define the following:

xenobiotic

A

foreign substance taken into the body

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11
Q

define the following:

toxin

A

naturally produced toxic substance

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12
Q

define the following:

toxicant

A

man-made toxic substance

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13
Q

define the following:

toxication

A

metabolic process by which the metabolized drug or chemical is more toxic than the parent drug or chemical (ex. acetaminophen -> NAPQI)

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14
Q

define the following:

detoxication

A

reduction of the toxic properties of a substance

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15
Q

what are the 10 areas of toxicology

A
  • diagnostic
  • developmental
  • reproductive
  • mechanistic
  • toxicogenomics
  • descriptive
  • regulatory
  • forensic
  • environmental
  • clinical
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16
Q

what influences exposure and toxicity (3)

A
  • single vs multiple doses
  • local vs systemic
  • immediate vs delayed
17
Q

how does single vs multiple doses impact exposure and toxicity of benzene

A

single (acute) dose: CNS depression
multiple doses (chronic): leukemia and BM toxicity

18
Q

what is an example of species specificity to exposure/toxicity

A

bromethalin:
- cats very susceptible
- dogs less susceptible
- guinea pigs incredibly resistant (they do not metabolize bromethalin to its toxic metabolite)

19
Q

what is an example of species-specificity to toxicity that has had impacts on human food regulation

A

saccharine in sweet n low:

causes cancer in rats because it combines with a urine protein to form crystals -> chronic irritation causes neotransformation

in humans we do not have the same crystal formation, but studies on rats led to false classification of saccharine as a carcinogen

20
Q

how does susceptibility to aflatoxin differ between rats and mice

A

rats: very susceptible
mice: very resistant because they quickly metabolize it to less reactive forms and glucuronidation

21
Q

the _________ gene codes for _________, and mutations in this gene in _________ breeds results in higher susceptibility to toxicity

A

multidrug resistance; P-glycoprotein; herding

22
Q

what are the two multidrug resistance genes

A

MDR1 and ABCB1

23
Q

what is P-glycoprotein, what tissues is it in and what is its role

A

a membrane bound transporter in the BBB and several other tissues that works by exporting drugs and toxins out of cells

24
Q

what are examples of drugs that dogs with the MDR1 mutation are more susceptible to

A

sedatives (acepromazine, butorphanol), loperamide (the opioid), nad ivermectin

25
Q

T/F only dog breeds are known to have the MDR1/ABCB1 mutation

A

F; cats have been seen to have it

26
Q

what is an example of how developmental stage influences exposure and toxicity

A

thalidomide babies; severe malformations of children in utero when their mother took the drug; now used as a cancer treatment for multiple myeloma

27
Q

what is an example of selective toxicity

A

neonicotinoid pesticides -> cause overstimulation of nAChRs (by acting as an ACh agonist)

humans are less susceptible than insects because of differences in the nAChR structure

28
Q

how do we calculate therapeutic index

A

TD50/ED50 (half-toxic dose/half-effective dose)

29
Q

describe hormesis and give an example

A

a dose-response effect whereby low doses of the drug are protective and high doses are toxic; example: alcohol

30
Q

what are the sites of toxin exposure

A

skin, GI tract, respiratory tract, bite/injection site, placenta

31
Q

what are the 4 opposing mechanisms that influence delivery of a toxicant to the target site

A

1) absorption vs presystemic elimination
2) distribution towards vs away from target
3) reabsorption vs excretion
4) toxication vs detoxication

32
Q

what is toxicokinetics

A

movement and transformation of toxicants in the body

  • absorption
  • distribution
  • metabolism
  • excretion
33
Q

what is Vd

A

amount of chemical in the body/concentration in plasma at equilibrium

34
Q

metabolism makes ___________ molecules more _____________

A

hydrophobic; hydrophilic

35
Q

what is toxicodynamics

A

what the toxicant does to the body

36
Q

what are examples of toxicodynamic processes (6)

A
  • binding and activating/blocking a receptor
  • enzyme inhibition
  • uncoupling oxidative phosphorylation
  • lipid peroxidation
  • altered cell pH
  • neoantigen formation
37
Q

how do we determine risk

A

risk = hazard x exposure

38
Q

what goes into hazard identification (2)

A
  • dose-response relationship
  • association between exposure and effect

POD (18 decks)

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