Absorption and Toxicokinetics Flashcards
(45 cards)
1
Q
Functional antagonism
A
2 toxicants produce opposite effects on a physiological function
2
Q
chemical antagonism
A
chemical reaction between the compounds leads to an inactivation that produces a less toxic effect
3
Q
dispositional antagonism
A
alters the absorption, biotransformation, distribution or elimination of the toxicants
4
Q
receptor antagonist
A
2 toxicants bind to the same receptor and interfere with the response
5
Q
disposition
A
- composite of its absorption, distribution, biotransformation, elimination
- depend on the properties of the toxicant
- depends on the dose
6
Q
absorption
A
- when toxicants cross cell membranes and enter the bloodstream or lymph system
- effects may be local or systemic
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
8
Q
cell types are often
A
- stratified epithelium (skin)
- thin cell layers of epithelium of the lungs and gastrointestinal tract
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
10
Q
passive transport
A
- diffusion
- filtration
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
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
13
Q
paracellular diffusion
A
diffusion of toxicants in-between cells
14
Q
filtration
A
- water flows across a porous membrane, small molecules can move with it
- important in renal glomeruli in the kidneys
15
Q
carrier mediated transport
A
- active transport
- facilitated diffusion
- xenobiotic transporters
16
Q
active transport
A
- movement against gradients
- saturated
- competitive inhibition
17
Q
facilitated diffusion
A
carrier mediated transport that does not require energy
18
Q
xenobiotic transporters
A
- ATP-binding cassette (ABC) transporters=largely function through active transport
- Solute carriers=largely function through facilitative diffusion
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
parental administration
-injection
26
GI
- 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
liver
- 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
small intestine
- ph 6 to 7.5
| - major area of nutrient uptake
29
large intestine
- ph 6
- major area of water uptake
- natural gut bacteria can convert toxicants to different forms
30
stomach
- ph 2
- may degrade toxicants
- low ph will help the absorption of weak acids
31
MDR and MRP
- multidrug-resistant
- multi-resistant drug proteins
- move xenobiotics out of cells
32
gases and vapours
- 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
aerosols
- 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
aerosol definition
-small droplet of liquid
35
particulate
- small chunk of solid matter
- swept out by cilia
- some particles hang around for months to years
36
skin absorption
- 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
absorption through the skin can increase by..
- damage to the stratum corneum
- increased hydration
- increased blood flow
- size of toxicant
38
toxicant storage through the body
- bound in different storage sites in the body
- aren't always the target of the toxicant
- blood, liver and kidney, fat
39
blood
- albumin protein in the blood, can bind toxicants
- transport fat, hormones, and hydrophobic compounds
- reversible process
40
live and kidney
- metabolism and excretion of toxicants
| - site of storage
41
fat
- 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
blood brain barrier keeps many toxicants out of the brain because..
- 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
toxicokinetics
- 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
one compartment model
-linear relationship when the log plasma concentration is plotted over time
45
two compartment model
- central tissues and peripheral tissues
| - curved line when the log plasma concentration is plotted over time
