Drugs 2: Drug Distribution and Excretion

Question 1

What does drug distribution refer to/mean?

Answer 1

Reversible transfer of a drug between the blood and the extra vascular fluids and tissues of the body (e.g. fat, muscle and brain tissue)

Question 2

What proteins to drugs often bind to?

Answer 2

albumin and alpha 1-glycoprotein (e.g. phenytoin)

Question 3

Which proteins are biologically active? (bound or unbound)

Answer 3

unbound (drugs that float about free)

Question 4

Is binding to plasma proteins reversible?

Answer 4

Yes

Question 5

What factors can change bound drug concentrations? (5)

Answer 5

• . renal failure
• hypoalbuminaemia
• pregnancy
• saturability of binding
• other drugs present in system

Question 6

At what percent does the drug need to be bound to be considered to have a small tissue distribution?

Answer 6

90%

Question 7

What 3 factors need to be considered when looking at a therapeutic range of a drug?

Answer 7

1. volume of distribution
2. half-life
3. clearance

Question 8

What is the definition of volume of distribution?

Answer 8

the volume in which the amount of drug would be uniformly distributed to produce the observed blood concentration

Question 9

What is the link between Vd and drug’s ability to diffuse through membranes?

Answer 9

The greater the Vd, the greater the ability of the drug to diffuse through membranes

Question 10

In, theory what should the Vd be?

Answer 10

42L

Question 11

What is the volume of Vd if it stays in the extracellular fluid but can’t penetrate cells?

Answer 11

12L

Question 12

What is the usual Vd if it’s highly protein bound?

Answer 12

3L

Question 13

What is the definition of clearance? (measured in ml/min)

Answer 13

theoretical volume of fluid from which a drug is completely removed over a period of time

Question 14

What two organs is the clearance/elimination process dependent on?

Answer 14

1. Kidneys (urine flow rate and renal clearance)

2. liver (metabolism and biliary excretion for hepatic clearance)

Question 15

Wha is the definition of half life?

Answer 15

time taken for the drug concentration in the blood to decline to half of the current value

Question 16

What 2 factors does half life depend on?

Answer 16

1. clearance

2. volume of distribution

Question 17

What is the equation of half-life?

Answer 17

t1/2= 0.693Vd/Cl

Question 18

What will prolongation of a drug’s half-life cause?

Answer 18

Increase drug toxicity as it will take longer to break down the drug (drug concentration will remain high for longer)

Question 19

What does the formula t1/2= 0.693Vd/Cl, link together? (2)

Answer 19

1. chemical properties of the drug (lipophilicity)

2. ability of the body to metabolise and excrete the drug

Question 20

Drugs need to be given chronically. How many half-lives does a drug need to have for plasma proteins of the drug to stabilise?

Answer 20

4-5 half lives

Question 21

What does drug elimination determines?

Answer 21

The length of action of the drug

Question 22

What 2 factos make up drug elimination?

Answer 22

1. drug metabolism (usually in liver)

2. drug excretion (usually in kidneys but also in biliary system/gut)

Question 23

What 3 main mechanisms are used in drug excretion in the kidneys?

Answer 23

1. glomerular filtration
2. passive tubular reabsorption
3. active tubular secretion

Question 24

How many litres of fluid a day does glomerulus filter?

Answer 24

190L

Question 25

Will bound or unbound drugs be filtered by the glomerulus?

Answer 25

All unbound drugs (as long as their molecular size, charge and shape aren't large)

Question 26

What does passive tubular reabsorption involve?

Answer 26

Drug moves back through the tubule in the circulation along the concentration gradient.

Question 27

Where does passive tubular reabsorption occur?

Answer 27

In the distal tubule and collecting duct

Question 28

What type of drugs are reabsorbed back into the body

Answer 28

Un-ionised drugs such as weak acids

Question 29

Where does active tubular secretion occur?

Answer 29

In the proximal tubule

Question 30

What molecules does the active tubular secretion excrete/eliminate?

Answer 30

Positive and negative ions

Question 31

Where else could drugs be actively or passively excreted?

Answer 31

Into the bile (biliary secretion)

Question 32

When drugs are reabsorbed from the bile back into the circulation, what is the process called?

Answer 32

Enter-hepatic circulation

Question 33

Once a drug is absorbed in the small intestine, what are the two routes it can take from the liver?

Answer 33

1. move into systemic circulation from the liver | 2. become a conjugate in the liver and secreted into bile which is later reabsorbed back into systemic circulation

Question 34

Why does the drug become conjugated before it becomes bile?

Answer 34

So it isn't reabsorbed back in the small intestine

Question 35

What 2 factors affect the volume of distribution specifically?

Answer 35

chemical properties of the drug; 1. lipid solubility 2. ionisation

Question 36

What are some of the physiological factors which affect drug distribution and elimination in the body? (4)

Answer 36

- age - pregnancy - disease state - other drugs