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Tox 300 midterm 1 > Absorption > Flashcards

Absorption Flashcards

1
Q

what are the ways that xenobiotics can get absorbed or past the cell membrane?

A
  1. Passive (simple) diffusion
  2. Filtration
  3. Active Transport system
  4. Facilitated diffusion
  5. Phagocytosis
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2
Q

what are the three barriers that seperate higher organisms from an environment containing a large number of chemicals?

A
  1. the skin 2. lungs 3. alimentary canal
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3
Q

only the —————– form of a drug can readily penetrate cell membranes!

A

non-ionized

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4
Q

there are three places in the body where absorption is pretty big? what are those 3?

A
  1. GI tract
  2. / Lungs
  3. Skin/dermal
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5
Q

what equation is used to solve for the ratio of the 2 forms of the a drug?

A

log (protonated)/(non-protonated)=pka-pH

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6
Q

describe phagocytosis and pinocytosis:

A

basically when you have a cell and the cell membrane forms around the xeno and shoots it out.

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7
Q

how does very small hydrophillic chemicals do passive diffusion? provide an example

A

the pores in cell membranes have a certain gap and so very small molecules, like water, can just slip right through, no problem! This is called paracellular diffusion. ex.) ethanol. It can just slip on by and enter blod stream very quickly and that is how you can get drunk quickly.

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8
Q

particles 1um and smaller penetrate where in the lungs?

A

aveolar sacs.

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9
Q

Absorption can take place anywhere along the GI tract (even the mouth and the rectum) but where is it very important?

A

the small intestine, this is because it is surrounded by mesentery that can absorb lots of important stuff

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10
Q

what is the main difference between pinocytosis and phagocytosis?

A

Pinocytosis also works as phagocytosis; the only difference is that phagocytosis is specific in the substances it transports. Phagocytosis engulfs whole particles, which are later broken down by enzymes, such as cathepsins, and absorbed into the cells.

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11
Q

how is the lung different than the GI tract?

A

when you inhale something like a gas theres an equilibrium between the alveoli and the blood and the blood and the tissue.

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12
Q

the key to absorption is what?

A

to get to the systemic circulation

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13
Q

what are examples of types of chemicals for passive diffusion?

A
  1. very small hydrophilic chemicals
  2. Lipophillic organic chemicals
  3. weak organic acids and bases
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14
Q

Toxicokinetics:

A

determination of the time course of disposition (ADME) of xenobiotics in the body

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15
Q

define passive diffusion:

A

most toxicants cross membranes by simple diffusion which establishes that chemicals move from regions of higher concentration to regions of lower concentration without any energy expenditure.

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16
Q

In addition to the characteristics of the compounds themselves, there are numerous additional factors relating to the GI itself that influence the absorption of xenobitoics which are:

A
  1. pH
  2. the presence of food
  3. digestive enzymes
  4. bile acids
  5. bacterial microflora
  6. motility and permeability of the GI tract
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17
Q

where are MDRS expressed?

A

expressed on the inner cell membrane. They are super expressed on the inner surface of blood brain barrier.

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18
Q

what happen when we breathe in fine particles that are less than 2.5 um

A

deposited mainly in the tracheobronchiolar regions of the lungs from which they may be cleared by retrograde movement of the mucus layer in the cilitated portions of the respiratory tract.

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19
Q

if only the non ionized form of a drug can readily penetrate the cell membranes what is the difference between bases and acids?

A

only the non protonated forms for bases and protonated form of acids.

20
Q

weak base and acids are ionized according to what?

A

arrehnius theory

21
Q

what are ‘targets”

A

these are things xenobitoics have an infinity for. these can be genes, receptors, structural proteins in cells, organs!

22
Q

do metabolic poisons interfere with facilitated diffusion?

A

no

23
Q

Most cells have around 4nm cell junctions. But what are two exceptions?

A

our kidney in the glomerulus the filtration apparatus of our nephorn where our blood gets filteed in the glomerulus is way bigger at 70nm. It will filter all the solutes and water.

Also the blood brain barrier. Essentially there are no gaps between the cells that line our central nervous system.

24
Q

Define dose:

A

the amount that ultimately reaches the site or sites of action

25
Q

define filtration:

A

xenobiotics are moving with water through the gapes between cells called cell junctions.

26
Q

describe active transport

A

energy dependent process that requires ATP and the key with active transport is they get pumped against their concentration gradient.

27
Q

the absorption of gases and vapors by inhalation is determined by what?

A

the partitioning of the compound between the blood and the gas phase along with its solubility and tissue reactivity.

28
Q

an organiz acid with a low pKa is a relatively ——— acid and one with a high pKa is a ——- acid. The —— is true for bases

A

strong, weak and opposite

29
Q

what type of membrane are animal cells?

A

phospholipid bilayers

30
Q

what are two different types of facilitated proteins or molecules?

A
  1. Organic cation transporters
  2. The most important in toxicology is organic anion transporters (OAT)
31
Q

how is the term modifying factors applicable to the human skin and absorption?

A

the skin is a very affective barrier to most xenobitoics. however there is always exception to the rules! For the vast majority of humans the skin is good and can prevent xenobiotics from getting in but some have dermal conditions that can make them more or less susceptible to toxilogical substances.

32
Q

examples of active transport systems:

A
  1. MDRS (multi-drug resistance proteins)
  2. MRPs (Multi-drug resistance associated proteins)
  3. BCRP (breast cancer resistant protein)
33
Q

what does the henderson hasselbach equation determine?

A

the fraction of a toxicant that is in the non-ionized (lipid-soluble) form and estimates the rate of absorption from the stomach or intestine.

34
Q

how do liophillic organic chemicals do passive diffusion? and real world example

A

they basically passive diffuse across cell membrane and the text refers to this as transcellular diffusion! they are basically just totally soluble and follow their concentration from outside the cell to inside the cell. POP’s are like this, and very hard to get rid of from our bodies. Very lipid soluble

35
Q

when a gas in inhaled into the lungs what happens first?

A

the gas molecule diffuse from the alveolar space into the blood and then dissolve.

36
Q

what are 7 various routes of exposure?

A
  1. ingestion 2. inhalation 3. dermal 4. intravenous 5. subcutaneous 6. intramsucykar 7. intraperitoneal
37
Q

target organ concentrations is not the only factor that can influence the susceptibility of organs to toxicants and is not necessarily the site where toxicity is observed. what is a classic example of this?

A

DDT where it acheives high concentrations in fat deposits but is not toxic to that tissue.

38
Q

define facilitated diffusion:

A

with the concentration gradient. There is a protein or molecule that facilitates diffusion, gives it an oof to get across the membrane!

39
Q

active transport is more important in ————— than in absorption

A

excretion

40
Q

what is the most important factor allowing a xenobiotic to diffuse across the cell membrane?

A

the lipophilicity

41
Q

in terms of passive diffusion the smaller a molecule is the more readily it will….

A

it traverses membranes by simple diffusion through aqueous pores.

42
Q

what is a major determinant in absorption within the GI tract?

A

particle size whereas factors such as lipid solubility or ionization are less important.

Absorption increases with decreasing particle size.

43
Q

the number of toxicants that are actively absorbed by the GI tract is ——.

A

low

44
Q

in contrast to gases, what are the important characteristics that affect absorption after exposure to aerosals?

A

the aerosals size and water solubility of any chemical present in the aerosol.

45
Q

the lung is a major what?

A

target organ

46
Q

what are P2.5?

A

these are fine particles that are less than 2.5 microns that are super toxic because we breathe these particles in that cannot be filtered out through our nose hairs! They go right down to the deepest places in our lungs and can cause toxic responses.

Tox 300 midterm 1 (5 decks)

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