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410 Toxicology > Unit 1 > Flashcards

Unit 1 Flashcards

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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
what does initial distribution depend on?
blood flow, diffusion rate from capillaries to tissue
26
what affects final distribution of toxins to tissues?
affinity of xenobiotic for tissue
27
what are the 3 ways xenobiotics can enter cells?
simple diffusion aqueous channels/pores special transport
28
how do aqueous channels/pores aid in distribution?
small/hydrophilic molecules/ions cannot readily cross cell membranes without transporters or leaky capillaries
29
what molecules need special transport to be distributed?
polar molecules large ions
30
volume of distribution
the concentration of the toxin in the tissues
31
what does it mean if Vd is low?
there is a high volume of the toxin in the blood, low volume in the tissues
32
what does it mean if Vd is high?
there is a high volume of toxin distributed to the body's tissues, low volume in the bloodstream
33
what are the 3 types of capillary porosity?
continuous, fenestrated, sinusoidal
34
continuous capillary
joined tightly with no pores BBB
35
fenestrated capillaries
have pores to allow hydrophilic substances to pass in kidney/intestines
36
sinusoidal capillaries
large diameter, discontinuous because they have spaces between cells, forming a vessel
37
what happens in restricted distribution?
xenobiotic stays in the bloodstream, does not reach tissues
38
what happens when toxin is distributed in the body?
toxin reaches tissue/organs
39
what happens when a toxin becomes accumulated in tissues/organs?
protein binding, active transport, high fat solubility
40
microcystin
liver toxicant from algae that relies on OAT to reach target site (liver)
41
what are the 3 storage depots of a toxin in distribution?
plasma protein, tissue protein, or cellular organelles
42
what are examples of plasma proteins that serve as storage depots for toxins?
albumin, melanin, or keratin
43
what is an example of a tissue protein that serves as a storage depot?
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
organelles
functional subcompartments within a cell
45
how do lysosomes trap toxins?
inside of a lysosome is acidic, so when a chemical enters, it is protonated by the cations inside, then cannot leave
46
what is ADME?
absorption distribution metabolism excretion
47
toxication
biotransformation enzymes make modifications on the poison to make a stronger toxin favors delivery
48
detoxication
biotransformation enzymes make modifications on the poison molecule to create a weaker toxin opposes delivery
49
how do hydrophobic molecules enter cells?
simple diffusion
50
how do small hydrophilic molecules molecules enter cells?
aqueous channels/pores
51
what do the kidneys do?
blood is filtered through the kidneys and excreted through urine
52
biotransformation
chemical modifications to a compound that oppose absorption/distribution but favor elimination
53
why is tylenol toxic to dogs/cats?
they cannot perform biotransformation for acetaminophon - liver toxicity in dogs - blood toxicity in cats
54
biotransformation aims to convert substances from ___ soluble to ___ soluble
lipid; water
55
where does biotransformation occur?
LIVER kidney GI tract lungs gonads (ovaries/testes)
56
how does charge affect permeation?
charged (+) molecules are repelled by their hydrophobic tails
57
how does logP/logD affect permeation?
high lipophilicity = high permeation
58
how does TPSA affect permeation?
bulkier molecules have < permeation because it's harder for them to enter greater TPSA = less permeability
59
phase 1 of biotransformation
add functional groups to molecules - increases TPSA (bulkier) - decreases logP (more hydrophilic & less likely to cross)
60
phase 2 of biotransformation
adds acid conjugate to functional group - increases TPSA (bulky) - decreases logP (even more hydrophilic)
61
what happens after a xenobiotic is blocked by biotransformation?
kidney --> urine or bile --> feces
62
NAPQI
the ultimate toxicant that reacts with proteins/nucleic acids, leading to cell death and toxicity
63
GSH (gluthathione)
allows you to metabolize toxins & rid system (hangover cure)
64
what is the drug given to replenish GSH?
N-acetylcysteine
65
explain why dogs/cats are not good at conjugating?
in most cases, they are unable to perform biotransformation (preventing toxins from entering cells), allowing a small amount of toxin to become dangerous
66
what are the 4 phenotypes of biotransformation?
1. poor metabolizers 2. intermediate metabolizers 3. extensive metabolizers 4. ultrarapid metabolizers
67
what are the 3 routes of elimination?
urinary, fecal, exhalation
68
gall bladder
stores bile to help break down food
69
urinary elimination
most effective excretory organ
70
nephron
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
what are the 3 mechanisms of urinary excretion?
glomerular filtration passive diffusion active tubular secretion
72
glomerular filtration
fenestrated capillaries filter anything smaller than albumin plasma proteins can bind and decrease excretion if filtered, xenobiotics move into lumen then urine
73
vasopresin
anti diuretic that causes body to retain h2o (hold on to urine)
74
tubular excretion via passive diffusion
lipid soluble compounds diffuse from blood into renal tubules
75
active tubular secretion
toxicants uptaken from blood into cells of renal proximal tubule, leading to efflux from the cell into the tubular fluid
76
how does urine pH affect excretion of compounds?
low pH excretes weak bases high pH excretes weak acids
77
what happens if a xenobiotic binds to albumin?
it is not filtered
78
what is the second major pathway for excretion?
fecal elimination
79
3 mechanisms of fecal elimination
direct elimination enterocyte secretion biliary excretion
80
enterocyte
cell of intestinal lining
81
direct fecal elimination
compound is not absorbed and is excreted w feces charge macromolecules
82
enterocyte secretion
enterocytes efflux xenobiotics back into lumen
83
biliary excretion
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
hepatocytes
vascularized liver cells
85
exhalation elimination
volatile (easily transform to gas) in equilibrium in alveoli dependent on gas solubility - low solubility = rapid elimination - high solubility = slow elimination
86
enterohepatic circulation
compound enters bile, where it enters the intestine and can be reabsorbed or eliminated w feces

410 Toxicology (2 decks)

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