Lecture 4B: Toxicokinetic

Question 1

Physiochemical Factors

Answer 1

• Lipid Solubility/hydrophobicity
• Degree of ionization
• Size/Shape
• Charge/polarity
• Structure similarly to endogenous molecules

Question 2

Four Phases

Answer 2

– Absorption
– Distribution
– Metabolism (Biotransformation)
– Excretion

Question 3

Toxicokinetics (TK)

Answer 3

The study of how the body treats toxins/toxicants that enter and the factors that may influence the concentration of a toxin at its site of action.

Question 4

Xenobiotic

Answer 4

This is any foreign substance that is present in the body.

Question 5

Target Site/Organ

Answer 5

the site/organ on which the toxin/toxicant elicit its toxic effect.

Question 6

After absorption lead enters the blood and ___ is taken up by red blood cells (RBCs).

Answer 6

97%

Question 7

What is the half (½) life of lead?

Answer 7

2-3 weeks

Question 8

What happens during the half life?

Answer 8

there is redistribution to liver and kidney, then excretion into bile or deposition into bone.

Question 9

After an initial, reversible uptake into bone, lead in the bone will

Answer 9

become incorporated into the hydroxyapatite crystalline structure

Question 10

Past exposure to lead can be detected via _____ and ___.

Answer 10

X-ray analysis and blood and urine analysis.

Question 11

How does lead become detectable in blood & urine analysis?

Answer 11

The amount in blood representing current exposure.

Question 12

Organs and systems destroyed by lead

Answer 12

kidney, testes, bones, gastrointestinal tract and
the nervous system.

Question 13

Lead causes significant biochemical effects like

Answer 13

Being the interference with haem-synthesis giving rise to anemia

Question 14

Acute exposure to inorganic lead results to

Answer 14

renal damage particularly to the proximal tubules

Question 15

Lead adversely affects

Answer 15

reproductive function in both males and females

Question 16

Treatment/Detection of Lead

Answer 16

• X ray to detect or blood/urine test then -
• Bowel irrigation polyethylene glycol solution
• Gastric lavage
• Chelation therapy- bind to lead then excreted in urine
• Activated charcoal – bind to lead in GI then administer cathartics
• EDTA- Ethylenediaminetetracetic acid

Question 17

What is a cell membrane?

Answer 17

The structure called the phospholipid bilayer, which is amphiphilic.

Question 18

Xenobiotics pass through cells located

Answer 18

at the sites of various routes to ultimately reach the target site.

Question 19

The cell membrane contains ______ heads and ______ tails.

Answer 19

hydrophilic and hydrophobic

Question 20

The heads of the cell membrane are turned

Answer 20

outwards, facing the extracellular environment.

Question 21

The tails of the cell membrane are turned

Answer 21

inwards to the intracellular environment.

Question 22

The membrane also contains important proteins called

Answer 22

transverse proteins

Question 23

Transverse proteins aid in

Answer 23

the transport of substances

Question 24

Two modes of Transport in cell membrane

Answer 24

Passive and Special Transport

Question 25

Types of Passive Transport

Answer 25

Filtration & Simple Diffusion

Question 26

Types of Special Transport

Answer 26

Active transport & Facilitated Diffusion

Question 27

What is an ion pump?

Answer 27

An enzyme that uses ATP to move ions across the cell membrane

Question 28

What is ion gates?

Answer 28

flow of ion across cell membrane

Question 29

Passive Transport

Answer 29

The movement of substances (toxins/toxicant) across a cell membrane without the use of energy by the cell

Question 30

Filtration

Answer 30

The passage of molecules from one environment to another through a porous membrane due to osmotic pressure or hydrostatic forces.

Question 31

Simple Diffusion

Answer 31

movement of a solute from an area of high concentration to an area of low concentration

Question 32

The lipid solubility of larger compounds will determine

Answer 32

the rate of transport across the membrane.

Question 33

What factors that must be met for simple diffusion:

Answer 33

1. There most be a concentration gradient 2. Must be lipid soluble 3. Must be non-ionized

Question 34

Only _______ will go down the concentration gradient.

Answer 34

non-ionized lipid soluble compounds

Question 35

Partition Coefficient refers to

Answer 35

the solubility of a compound between two immiscible environments.

Question 36

Positive co efficient values are associated with

Answer 36

high lipid solubility

Question 37

Negative values co efficient are associated with

Answer 37

low lipid solubility

Question 38

More positive Partition Co-efficient are

Answer 38

more lipophilic

Question 39

Degree of Ionization

Answer 39

Many compounds/chemicals are weak acids or bases. This also applies to toxins/toxicants.

Question 40

The ionized form of a toxin usually has

Answer 40

low lipid solubility

Question 41

Why is degree of ionization important?

Answer 41

This determines the extent of absorption, as only the non-ionized form will be able to pass through the lipid bilayer by passive diffusion.

Question 42

Toxins/Toxicants low in lipid solubility may cross the cell membrane, but at

Answer 42

slow inefficient rates. This would aid in preventing a toxic effect.