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410 Toxicology > Unit 1 > Flashcards

Unit 1 Flashcards

1
Q

venom

A

poison that is injected

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2
Q

toxin

A

poison made by a living organism

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3
Q

what does toxicity depend on?

A

amount, location, duration of exposure

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4
Q

what are the 4 steps of toxicity?

A
  1. absorption
  2. distribution
  3. metabolism
  4. excretion
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5
Q

what are the 3 routes of exposure?

A

inhalation, ingestion, dermal

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6
Q

what is absorption influenced by?

A

concentration at site of exposure, vascular composition, total exposed area, and physicochemical properties of the toxicant

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7
Q

influx

A

uptake

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8
Q

efflux

A

removal/exit

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9
Q

ABC transporters

A

typically efflux
bind and hydrolyze ATP for energy
work in BBB, fetal barriers

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10
Q

SLCs

A

solute carriers
influx/bidirectional

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11
Q

simple diffusion

A

moves down concentration gradient from high –> low
lipophilic molecules can cross cell membranes, making them “unstoppable”

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12
Q

how is a toxin absorbed into the GI tract?

A

the large surface area allows for simple diffusion across the membrane

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13
Q

what are 3 examples of ABC carriers?

A

MDR1
P-GP
MRP2/3

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14
Q

what are two examples of SLCs?

A

OCT1/2
OATPs

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15
Q

what are the factors affecting absorption in the GI tract?

A

ph, fed/fasted state, digestive enzymes, bile acids, bacterial microflora, motility, permeability

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16
Q

how do the lungs absorb toxins?

A

gets in the body via inhalation
depending on the size/composition of the particle, alveolar sacs allow the toxin to penetrate into blood

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17
Q

how do gases/vapors enter the body and lead to toxicity?

A

the nose acts as a scrubber for reactive/water soluble gases
gas molecules move through the alveolar space –> blood

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18
Q

how do aerosols/particles cause toxicity?

A

smaller particles reach deeper into the body
upper resp tract- coughing, sneezing, swallowing
tracheobronchiolar- mucocilliary escalator
alveolar sacs- blood/lymphatics

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19
Q

how is a toxin absorbed dermally?

A

most absorption is blocked by the epidermis, depending on integrity, hydration, temperature, presence of solvents, and size, toxins may be able to move through barrier

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20
Q

skin

A

largest organ and barrier in body
mostly non-permeable
epidermis (outer) and dermis (inner/vascularized)

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21
Q

how do lipophilic molecules absorb through the skin?

A

they diffuse readily

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22
Q

how do hydrophilic molecules absorb through the skin?

A

limited and need appendages

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23
Q

what are the dermal appendages that aid in absorption?

A

sweat/sebaceous glands and hair follicles

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24
Q

what is distribution?

A

when the toxin moves from the blood to the tissues

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25
Q

what does initial distribution depend on?

A

blood flow, diffusion rate from capillaries to tissue

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26
Q

what affects final distribution of toxins to tissues?

A

affinity of xenobiotic for tissue

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27
Q

what are the 3 ways xenobiotics can enter cells?

A

simple diffusion
aqueous channels/pores
special transport

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28
Q

how do aqueous channels/pores aid in distribution?

A

small/hydrophilic molecules/ions cannot readily cross cell membranes without transporters or leaky capillaries

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29
Q

what molecules need special transport to be distributed?

A

polar molecules
large ions

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30
Q

volume of distribution

A

the concentration of the toxin in the tissues

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31
Q

what does it mean if Vd is low?

A

there is a high volume of the toxin in the blood, low volume in the tissues

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32
Q

what does it mean if Vd is high?

A

there is a high volume of toxin distributed to the body’s tissues, low volume in the bloodstream

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33
Q

what are the 3 types of capillary porosity?

A

continuous, fenestrated, sinusoidal

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34
Q

continuous capillary

A

joined tightly with no pores
BBB

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35
Q

fenestrated capillaries

A

have pores to allow hydrophilic substances to pass
in kidney/intestines

36
Q

sinusoidal capillaries

A

large diameter, discontinuous because they have spaces between cells, forming a vessel

37
Q

what happens in restricted distribution?

A

xenobiotic stays in the bloodstream, does not reach tissues

38
Q

what happens when toxin is distributed in the body?

A

toxin reaches tissue/organs

39
Q

what happens when a toxin becomes accumulated in tissues/organs?

A

protein binding, active transport, high fat solubility

40
Q

microcystin

A

liver toxicant from algae that relies on OAT to reach target site (liver)

41
Q

what are the 3 storage depots of a toxin in distribution?

A

plasma protein, tissue protein, or cellular organelles

42
Q

what are examples of plasma proteins that serve as storage depots for toxins?

A

albumin, melanin, or keratin

43
Q

what is an example of a tissue protein that serves as a storage depot?

A

lipophilic pollutants can collect in adipose tissue
lead can be deposited in bone in place of calcium, which may be released if bone breaks down

44
Q

organelles

A

functional subcompartments within a cell

45
Q

how do lysosomes trap toxins?

A

inside of a lysosome is acidic, so when a chemical enters, it is protonated by the cations inside, then cannot leave

46
Q

what is ADME?

A

absorption
distribution
metabolism
excretion

47
Q

toxication

A

biotransformation enzymes make modifications on the poison to make a stronger toxin
favors delivery

48
Q

detoxication

A

biotransformation enzymes make modifications on the poison molecule to create a weaker toxin
opposes delivery

49
Q

how do hydrophobic molecules enter cells?

A

simple diffusion

50
Q

how do small hydrophilic molecules molecules enter cells?

A

aqueous channels/pores

51
Q

what do the kidneys do?

A

blood is filtered through the kidneys and excreted through urine

52
Q

biotransformation

A

chemical modifications to a compound that oppose absorption/distribution but favor elimination

53
Q

why is tylenol toxic to dogs/cats?

A

they cannot perform biotransformation for acetaminophon
- liver toxicity in dogs
- blood toxicity in cats

54
Q

biotransformation aims to convert substances from ___ soluble to ___ soluble

A

lipid; water

55
Q

where does biotransformation occur?

A

LIVER
kidney
GI tract
lungs
gonads (ovaries/testes)

56
Q

how does charge affect permeation?

A

charged (+) molecules are repelled by their hydrophobic tails

57
Q

how does logP/logD affect permeation?

A

high lipophilicity = high permeation

58
Q

how does TPSA affect permeation?

A

bulkier molecules have < permeation because it’s harder for them to enter
greater TPSA = less permeability

59
Q

phase 1 of biotransformation

A

add functional groups to molecules
- increases TPSA (bulkier)
- decreases logP (more hydrophilic & less likely to cross)

60
Q

phase 2 of biotransformation

A

adds acid conjugate to functional group
- increases TPSA (bulky)
- decreases logP (even more hydrophilic)

61
Q

what happens after a xenobiotic is blocked by biotransformation?

A

kidney –> urine
or
bile –> feces

62
Q

NAPQI

A

the ultimate toxicant that reacts with proteins/nucleic acids, leading to cell death and toxicity

63
Q

GSH (gluthathione)

A

allows you to metabolize toxins & rid system (hangover cure)

64
Q

what is the drug given to replenish GSH?

A

N-acetylcysteine

65
Q

explain why dogs/cats are not good at conjugating?

A

in most cases, they are unable to perform biotransformation (preventing toxins from entering cells), allowing a small amount of toxin to become dangerous

66
Q

what are the 4 phenotypes of biotransformation?

A
  1. poor metabolizers
  2. intermediate metabolizers
  3. extensive metabolizers
  4. ultrarapid metabolizers
67
Q

what are the 3 routes of elimination?

A

urinary, fecal, exhalation

68
Q

gall bladder

A

stores bile to help break down food

69
Q

urinary elimination

A

most effective excretory organ

70
Q

nephron

A

functional unit of the kidney, containing
1. glomerulus (ball of yarn that initiates filtration)
2. tubules within the renal cortex/medulla that produce/conc urine

71
Q

what are the 3 mechanisms of urinary excretion?

A

glomerular filtration
passive diffusion
active tubular secretion

72
Q

glomerular filtration

A

fenestrated capillaries filter anything smaller than albumin
plasma proteins can bind and decrease excretion
if filtered, xenobiotics move into lumen then urine

73
Q

vasopresin

A

anti diuretic that causes body to retain h2o (hold on to urine)

74
Q

tubular excretion via passive diffusion

A

lipid soluble compounds diffuse from blood into renal tubules

75
Q

active tubular secretion

A

toxicants uptaken from blood into cells of renal proximal tubule, leading to efflux from the cell into the tubular fluid

76
Q

how does urine pH affect excretion of compounds?

A

low pH excretes weak bases
high pH excretes weak acids

77
Q

what happens if a xenobiotic binds to albumin?

A

it is not filtered

78
Q

what is the second major pathway for excretion?

A

fecal elimination

79
Q

3 mechanisms of fecal elimination

A

direct elimination
enterocyte secretion
biliary excretion

80
Q

enterocyte

A

cell of intestinal lining

81
Q

direct fecal elimination

A

compound is not absorbed and is excreted w feces
charge macromolecules

82
Q

enterocyte secretion

A

enterocytes efflux xenobiotics back into lumen

83
Q

biliary excretion

A

most significant route for fecal elimination
uptake xenobiotics into hepatocyte, efflux them into canaliculi for bile duct or efflux from hepatocyte back into blood

84
Q

hepatocytes

A

vascularized liver cells

85
Q

exhalation elimination

A

volatile (easily transform to gas) in equilibrium in alveoli
dependent on gas solubility
- low solubility = rapid elimination
- high solubility = slow elimination

86
Q

enterohepatic circulation

A

compound enters bile, where it enters the intestine and can be reabsorbed or eliminated w feces

410 Toxicology (2 decks)

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