Disposition of Toxicants

Question 1

disposition is defined as four things

Answer 1

absorption
distribution
metabolism
excretion

Question 2

the toxicity of a substance is directly dependent on the

Answer 2

dose

Question 3

the amount of a chemical that ultimately reaches the site or sites of action

Answer 3

dose

Question 4

major organs through with absorption takes place

Answer 4

GI tract
Lungs
Skin

Question 5

first barrier toxicants meet

Answer 5

cell membranes

Question 6

two characteristics of phospholipid bilayer

Answer 6

polar heads, lipid tails

saturation determines fluidity

Question 7

types of proteins associated with the cell membrane

Answer 7

receptors, transporters, pore formers

Question 8

outer coatings associated with the cell membrane

Answer 8

glycoproteins

glycolipids

Question 9

two types of membrane transport

Answer 9

passive transport

active transport

Question 10

two types of transport included in passive transport

Answer 10

simple diffusion

filtration

Question 11

most toxicants cross the membrane by simple diffusion following the principles of

Answer 11

fick’s law

Question 12

ficks law establishes….

Answer 12

chemicals move from regions of higher concentration to regions of lower concentration

Question 13

two characteristics of simple diffusion

Answer 13

small hydrophilic molecules through aqueous pores

hydrophobic molecules through phospholipid bilayer

Question 14

how well compound dissolves in hydrophobic environment

Answer 14

Kow

Question 15

the charge of the molecule is told by this

Answer 15

pKa

Question 16

what compound is commonly used to find Kow

Answer 16

octanol

Question 17

driven by hydostatic pressure or osmotic pressure

Answer 17

filtration

Question 18

driven by concentration gradient

Answer 18

diffusion

Question 19

active transport is characterized by 5 things

Answer 19

1. movement against electrochemical or concentration gradient
2. saturability at high substrate concentrations
3. selectivity among chemicals
4. competitive inhibition
5. requirement for expenditure of energy

Question 20

applies to carrier mediated transport that exhibits the properties of active transport except that the substance is not moved against an electrochemical or concentration gradient and no energy is required

Answer 20

facilitated diffusion

Question 21

when diffusion does not work…

Answer 21

compounds are too large for pores
compounds are too hydrophilic for diffusion
transport against a concentration gradient

Question 22

functions as an efflux pump which in cancerous cells exudes cytotoxic drugs out of the tumor cells and contributes to their resistance

Answer 22

P-glycoprotein or MDR-1 family

Question 23

excrete chemicals from cells

Answer 23

MRP family

Question 24

important in the efflux of xenobiotic metabolites, especially those conjugated with UDP-glucuronic acid or glutathione

Answer 24

MRP 2 and 3

Question 25

xenobiotic transporters which function predominately as facilitative transporters

Answer 25

SLC family (solute carriers)

Question 26

important membrane transporters that mediate the sodium independent transport of a wide range of compounds, including organic acids, bases, and neutral compounds

Answer 26

OATP family (organic anion transporting peptides)

Question 27

process by which toxicants cross body membranes to enter the bloodstream

Answer 27

absorption

Question 28

first place most toxicants are absorbed from

Answer 28

GI tract

Question 29

most common places along the GI tract for absoption

Answer 29

stomach, intestine, rectum

Question 30

if a toxicant is an organic acid or base it tends to be absorbed where

Answer 30

by simple diffusion in the part of GI tract where it exists in the most lipid soluble form

Question 31

where does iron accumulate in the GI tract

Answer 31

mucosal cells

Question 32

in what form is iron in the GI tract

Answer 32

ferritin

Question 33

what does calcium need for absorption

Answer 33

vitamin D

Question 34

particles and particulate matter can also be absorbed by the GI tract but this matters more than this

Answer 34

size more than lipid solubility

Question 35

enter intestinal cells by pinocytosis

Answer 35

large particles

Question 36

5-flurorouracile hitchhikes with

Answer 36

pyrimidine

Question 37

Thallium, cobalt, manganese hitchhike with

Answer 37

iron

Question 38

lead hitchhikes with

Answer 38

calcium

Question 39

some antibiotics hitchhike with

Answer 39

dipeptides

Question 40

five additional factors affecting absorption in GI tract

Answer 40

``` pH presence of food digestive enzymes bile acids bacterial microflora in the GI tract ```

Question 41

three differences between species when it comes to GI absorption

Answer 41

thickness of unstirred layer length and surface area of GI tract microflora differences

Question 42

infants are more susceptible to this because the higher pH in the neonatal GI tract is permissive for the growth of bacteria

Answer 42

methemoglobinemia

Question 43

major anatomical layer that controls absorption across the skin

Answer 43

stranum corneum

Question 44

dermal areas where absorption may occur

Answer 44

sweat glands | hair follicles

Question 45

all toxicant move across the stratum corneum by

Answer 45

passive diffusion

Question 46

what absorbs more readily across the stratum corneum

Answer 46

lipophilic compounds

Question 47

where to lipophilic compounds have trouble diffusing through

Answer 47

the dermis

Question 48

six factors that influence the absorption of toxicants

Answer 48

``` thickness hydration status damages such as leakes vascularization influence of solvents species differences ```

Question 49

acids and alkalis can ___permeability

Answer 49

increase

Question 50

more hydration ____ permeability

Answer 50

increases

Question 51

increase in temperature ____permeability

Answer 51

increases

Question 52

____absorption if a toxicant is highly soluble in a vehicle

Answer 52

lower

Question 53

compounds above ___exhibit poor dermal penetration

Answer 53

400 Da