Unit 2 - Biological barriers & ADME 2

Question 1

What is the approximate volume of total body fluid?

Answer 1

42 litres

Question 2

What is the approximate volume of intracellular fluid?

Answer 2

28 litres

Question 3

What is the approximate volume of extracellular fluid?

Answer 3

14 litres

Question 4

What is the approximate volume of interstitial fluid?

Answer 4

10 litres

Question 5

What is the approximate volume of plasma?

Answer 5

5 litres

Question 6

what are the categories body fluids are distributed into ?

Answer 6

body is 60% fluid

intracellular fluid - 40% body weight

Extracellular fluid - 20% body weight
(Plasma & interstitial fluid)

Question 7

How can drug sequestration take place?

Answer 7

Lipid sequestration
- drug in plasm
Binding to a host of tissue components
- plasma proteins
- tissue proteins

Question 8

What percentage of the blood is plasma?

Answer 8

55%

Question 9

What percentage of the blood is red blood cells?

Answer 9

45%

Question 10

What percentage of the blood is white blood cells and platelets?

Answer 10

1%

Question 11

What are the major drug-binding plasma proteins?

Answer 11

Plasma is protein rich

Albumin
Alpha1-acid glycoprotein
Lipoproteins
- variable

Question 12

What is able to cross cellular barriers to access tissues, intracellular targets and bind to receptors?

Answer 12

Unbound drug

- free drug

Question 13

What does drug binding have an effect on?

Answer 13

Distribution and Elimination of drug

Pharmacologic response

Question 14

What is Fu?

Answer 14

Fraction of total mass of drug in plasma (blood) that is unbound

Question 15

How can fraction unbound be calculated?

Answer 15

Fu = drug concentration [free] / drug concentration plasma [total]

[Total] = free + bound

Question 16

Describe the concept of reversible equilibrium

Answer 16

Drug enters the plasma

Equilibrium between free drug in plasma and bound drug in plasma
Equilibrium between free drug in plasma and free drug in tissue compartment
Equilibrium between free drug in tissue and bound drug in tissue

Question 17

How much albumin is produced a day by hepatocytes?

Answer 17

9 - 12g/day

Question 18

What is the concentration of albumin in plasma?

Answer 18

40 g/L

Question 19

How many binding sites does albumin have?

Answer 19

Two

Question 20

Which type of molecules bind to albumin in plasma?

Answer 20

Hydrophobic

Negative charge or electronegative feature

Question 21

How can the affinity for a drug to albumin be increased?

Answer 21

More acidic (pKa < 6)
More hydrophobic

Question 22

What is alpha1-acid glycoprotein?

Answer 22

Heavily glycosylated plasma protein synthesised in the liver

Question 23

How many binding sites does alpha 1-acid glycoprotein have?

Answer 23

One

Question 24

Which type of molecules bind to alpha 1-acid glycoprotein in plasma?

Answer 24

Hydrophobic

Positive charge or electropositive feature

Question 25

Give examples of plasma lipoproteins

Answer 25

Triglycerides and cholesterol esters Phospholipids Cholesterol Proteins

Question 26

Give examples of plasma lipoprotein particles

Answer 26

``` High-density lipoprotein - HDL Low-density lipoprotein - LDL Intermediate density lipoprotein - IDL Very low density lipoprotein - VLDL Chylomicrons - CM ```

Question 27

What is the function of plasma lipoproteins?

Answer 27

To transport various fat molecules around body to tissues

Question 28

How do plasma lipoproteins sequest drugs?

Answer 28

``` Lipid solubilisation of drug into core Lipid interaction with surface phospholipids - non-restrictive - non-saturable Binding to surface apoproteins ```

Question 29

What is the structure of a plasma lipoprotein?

Answer 29

``` Surface monolayer - phospholipids - free cholesterol - protein Hydrophobic core - triglyceride - cholesteryl esters ```

Question 30

What might cause albumin levels to decrease?

Answer 30

``` Burns Liver damage - synthesises albumin Renal disease - eliminates albumin Malnutrition - can't synthesise albumin ```

Question 31

What might cause alpha 1-acid glycoprotein levels to increase?

Answer 31

``` Inflammatory disease - rheumatic arthritis - Crohn's disease Cancer Trauma ```

Question 32

What might cause alpha 1-acid glycoprotein levels to decrease?

Answer 32

Liver disease | - synthesises alpha1-acid glycoprotein