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Toxicology > Absorption and Toxicokinetics > Flashcards

Absorption and Toxicokinetics Flashcards

1
Q

Functional antagonism

A

2 toxicants produce opposite effects on a physiological function

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2
Q

chemical antagonism

A

chemical reaction between the compounds leads to an inactivation that produces a less toxic effect

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3
Q

dispositional antagonism

A

alters the absorption, biotransformation, distribution or elimination of the toxicants

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4
Q

receptor antagonist

A

2 toxicants bind to the same receptor and interfere with the response

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5
Q

disposition

A
  • composite of its absorption, distribution, biotransformation, elimination
  • depend on the properties of the toxicant
  • depends on the dose
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6
Q

absorption

A
  • when toxicants cross cell membranes and enter the bloodstream or lymph system
  • effects may be local or systemic
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7
Q

Toxicants to targets

A
  • pass through many cell types and membranes to reach their targets
  • exchange of gases and other materials occurs in blood capillaries located below the basement membrane
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8
Q

cell types are often

A
  • stratified epithelium (skin)

- thin cell layers of epithelium of the lungs and gastrointestinal tract

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9
Q

cell membranes

A
  • semipermeable
  • phospholipid bilayer
  • transmembrane proteins
  • lipophilic compounds diffuse through the lipid layer
  • proteins can form pores and transporters to move other larger compounds or hydrophilic compounds
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10
Q

passive transport

A
  • diffusion

- filtration

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11
Q

diffusion

A
  • net movement of molecules from an area of high concentration to low concentration
  • small hydrophobic toxicants move through aqueous pores
  • small hydrophobic diffuse across membranes correlates with their lipid solubility
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12
Q

transcellular diffusion

A
  • diffusion of toxicants through cells, passing through cell membranes
  • occurs if the cells are packed tightly with little space between them
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13
Q

paracellular diffusion

A

diffusion of toxicants in-between cells

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14
Q

filtration

A
  • water flows across a porous membrane, small molecules can move with it
  • important in renal glomeruli in the kidneys
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15
Q

carrier mediated transport

A
  • active transport
  • facilitated diffusion
  • xenobiotic transporters
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16
Q

active transport

A
  • movement against gradients
  • saturated
  • competitive inhibition
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17
Q

facilitated diffusion

A

carrier mediated transport that does not require energy

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18
Q

xenobiotic transporters

A
  • ATP-binding cassette (ABC) transporters=largely function through active transport
  • Solute carriers=largely function through facilitative diffusion
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19
Q

endocytosis

A
  • larger toxicants can enter cells

- large molecules

20
Q

receptor-mediated endocytosis

A

-cells have receptors that recognize these proteins and pinch off some of the cell membrane to form a vesicle that contains proteins

21
Q

protein toxins

A

-heterodimers made of the toxin and multiple beta subunits

22
Q

beta subunits

A

-binds to membrane components and tricks the cell into taking in the toxin

23
Q

main sites of absorption

A
  • gastrointestinal tract
  • lungs
  • skin
24
Q

enteral administration

A
  • all routes involving the alimentary canal

- sublingual, oral, rectal

25
Q

parental administration

A

-injection

26
Q

GI

A
  • absorbs nutrients from gut into the bloodstream
  • absorbed via diffusion
  • many transporters and electrolytes used to move xenobiotics from the intestine to the bloodstream
  • rate of absorbance of a toxicant increases the longer it stays in the intestine
27
Q

liver

A
  • chemicals first go through the livers via the hepatic portal
  • major site of metabolism
  • target organ for many toxicants
  • can extract toxicants and excrete them into bile
28
Q

small intestine

A
  • ph 6 to 7.5

- major area of nutrient uptake

29
Q

large intestine

A
  • ph 6
  • major area of water uptake
  • natural gut bacteria can convert toxicants to different forms
30
Q

stomach

A
  • ph 2
  • may degrade toxicants
  • low ph will help the absorption of weak acids
31
Q

MDR and MRP

A
  • multidrug-resistant
  • multi-resistant drug proteins
  • move xenobiotics out of cells
32
Q

gases and vapours

A
  • gas molecules diffuse from the alveoli space into the blood until at equilibrium
  • blood distributes the gases throughout the body and where they can be transferred to target tissues
  • blood pick up more gas at the lungs
  • keep happening until the gas is in equilibrium in the lungs, blood and target tissue
33
Q

aerosols

A
  • deposition of aerosols depends on the size
  • greater then 5 micro meters=nasopharyngeal region
  • 2.5 micro meters=lungs
  • less then 1 micro meter=alveolar sacs, potentially enter the blood
34
Q

aerosol definition

A

-small droplet of liquid

35
Q

particulate

A
  • small chunk of solid matter
  • swept out by cilia
  • some particles hang around for months to years
36
Q

skin absorption

A
  • minor route
  • passively diffuse through the stratum corneum, rate determining barrier
  • must pass through several cell layers in the upper epidermis to get to the blood stream
37
Q

absorption through the skin can increase by..

A
  • damage to the stratum corneum
  • increased hydration
  • increased blood flow
  • size of toxicant
38
Q

toxicant storage through the body

A
  • bound in different storage sites in the body
  • aren’t always the target of the toxicant
  • blood, liver and kidney, fat
39
Q

blood

A
  • albumin protein in the blood, can bind toxicants
  • transport fat, hormones, and hydrophobic compounds
  • reversible process
40
Q

live and kidney

A
  • metabolism and excretion of toxicants

- site of storage

41
Q

fat

A
  • organic toxicants are hydrophobic, so accumulate in the adipose tissue
  • release from fat deposits can be a significant source of toxicants in the blood
42
Q

blood brain barrier keeps many toxicants out of the brain because..

A
  • capillaries in the brain have few pores, limiting diffusion
  • capillary endothelial cells have MDR transporters that can pump unwanted chemicals back into the bloodstream
  • paracellular transport limited
  • evolved to keep natural toxins out of our brains
  • hydrophobic non-ionic chemicals can readily pass through
  • poorly developed in infants
43
Q

toxicokinetics

A
  • compound move through the body as if there were only 1 or 2 compartments
  • represent a series of mass balance equations that describe each tissue
44
Q

one compartment model

A

-linear relationship when the log plasma concentration is plotted over time

45
Q

two compartment model

A
  • central tissues and peripheral tissues

- curved line when the log plasma concentration is plotted over time

Toxicology (14 decks)

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