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Toxicology > Disposition of Toxicants > Flashcards

Disposition of Toxicants Flashcards

1
Q

disposition is defined as four things

A

absorption
distribution
metabolism
excretion

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2
Q

the toxicity of a substance is directly dependent on the

A

dose

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3
Q

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

A

dose

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4
Q

major organs through with absorption takes place

A

GI tract
Lungs
Skin

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5
Q

first barrier toxicants meet

A

cell membranes

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6
Q

two characteristics of phospholipid bilayer

A

polar heads, lipid tails

saturation determines fluidity

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7
Q

types of proteins associated with the cell membrane

A

receptors, transporters, pore formers

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8
Q

outer coatings associated with the cell membrane

A

glycoproteins

glycolipids

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9
Q

two types of membrane transport

A

passive transport

active transport

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10
Q

two types of transport included in passive transport

A

simple diffusion

filtration

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11
Q

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

A

fick’s law

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12
Q

ficks law establishes….

A

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

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13
Q

two characteristics of simple diffusion

A

small hydrophilic molecules through aqueous pores

hydrophobic molecules through phospholipid bilayer

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14
Q

how well compound dissolves in hydrophobic environment

A

Kow

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15
Q

the charge of the molecule is told by this

A

pKa

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16
Q

what compound is commonly used to find Kow

A

octanol

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17
Q

driven by hydostatic pressure or osmotic pressure

A

filtration

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18
Q

driven by concentration gradient

A

diffusion

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19
Q

active transport is characterized by 5 things

A
  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
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20
Q

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

A

facilitated diffusion

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21
Q

when diffusion does not work…

A

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

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22
Q

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

A

P-glycoprotein or MDR-1 family

23
Q

excrete chemicals from cells

A

MRP family

24
Q

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

A

MRP 2 and 3

25
Q

xenobiotic transporters which function predominately as facilitative transporters

A

SLC family (solute carriers)

26
Q

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

A

OATP family (organic anion transporting peptides)

27
Q

process by which toxicants cross body membranes to enter the bloodstream

A

absorption

28
Q

first place most toxicants are absorbed from

A

GI tract

29
Q

most common places along the GI tract for absoption

A

stomach, intestine, rectum

30
Q

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

A

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

31
Q

where does iron accumulate in the GI tract

A

mucosal cells

32
Q

in what form is iron in the GI tract

A

ferritin

33
Q

what does calcium need for absorption

A

vitamin D

34
Q

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

A

size more than lipid solubility

35
Q

enter intestinal cells by pinocytosis

A

large particles

36
Q

5-flurorouracile hitchhikes with

A

pyrimidine

37
Q

Thallium, cobalt, manganese hitchhike with

A

iron

38
Q

lead hitchhikes with

A

calcium

39
Q

some antibiotics hitchhike with

A

dipeptides

40
Q

five additional factors affecting absorption in GI tract

A 
pH
presence of food
digestive enzymes
bile acids
bacterial microflora in the GI tract
41
Q

three differences between species when it comes to GI absorption

A

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

42
Q

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

A

methemoglobinemia

43
Q

major anatomical layer that controls absorption across the skin

A

stranum corneum

44
Q

dermal areas where absorption may occur

A

sweat glands

hair follicles

45
Q

all toxicant move across the stratum corneum by

A

passive diffusion

46
Q

what absorbs more readily across the stratum corneum

A

lipophilic compounds

47
Q

where to lipophilic compounds have trouble diffusing through

A

the dermis

48
Q

six factors that influence the absorption of toxicants

A 
thickness 
hydration status
damages such as leakes
vascularization
influence of solvents
species differences
49
Q

acids and alkalis can ___permeability

A

increase

50
Q

more hydration ____ permeability

A

increases

51
Q

increase in temperature ____permeability

A

increases

52
Q

____absorption if a toxicant is highly soluble in a vehicle

A

lower

53
Q

compounds above ___exhibit poor dermal penetration

A

400 Da

Toxicology (20 decks)

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