Drug Distribution

Question 1

What is the aim of good therapeutics?

Answer 1

To deliver medicines to their site of action at effective concentrations

Question 2

What is the aim in multiple dose therapy?

Answer 2

To keep the levels as stable as possible

Question 3

What speed do drugs move at in well-perfused areas?

Answer 3

Fast

Question 4

What order kinetics do most drugs obey?

Answer 4

First order

Question 5

What is first order kinetics?

Answer 5

Rate of uptake is proportional to [drug]

Question 6

What does a first order kinetics linear graph look like?

Answer 6

Exponential decay curve

Question 7

What does a first order kinetics log graph look like?

Answer 7

Linear line

Question 8

What is constant clearance?

Answer 8

A constant fraction of the drug is removed

Question 9

What is constant half-life?

Answer 9

The time to remove the drug is independant of dose

Question 10

What is zero order kinetics?

Answer 10

A constant amount of drug is always removed (eg always 2mg)

Question 11

Name some saturable processes

Answer 11

Elimination, enzyme, transporters in the liver and kidney

Question 12

When do drugs show zero order kinetics (generally)

Answer 12

When it is saturated or something isnt working

Question 13

What are the pharmacokinetic parameters (4)?

Answer 13

Volume of distribution (vd)
Half life (t(1/2))
Clearance (Cl)
Bioavailability (F)

Question 14

What is the apparent volume of distribution?

Answer 14

Gives an idea of where the drug is in terms of vascular space

Question 15

How do you work out the apparent volume of distribution?

Answer 15

Total amount of drug/ [plasma]

Question 16

What does the apparent volume of distribution help with?

Answer 16

Dose calculation

Question 17

What is the vascular space?

Answer 17

4L

Question 18

What is extra vascular space?

Answer 18

6L

Question 19

What is the apparent volume of distribution influenced by?

Answer 19

Lipid/water solubility, binding to plasma proteins

Question 20

What does a small volume of distribution mean?

Answer 20

Drug is mostly retained in circulation, generally because they’re binding very strongly and very lightly to the plasma proteins so they’re not getting out

Question 21

What does a large volume of distribution mean?

Answer 21

Takes longer for the drug to be eliminated from the body

Question 22

What is the plasma clearance?

Answer 22

Volume of plasma cleared of drug per unit time (ml min-1)

Question 23

Give the formula for plasma clearance

Answer 23

Plasma clearance = rate of elimination / [drug plasma]

Question 24

Which type of reaction is plasma clearance a constant for?

Answer 24

First order reactions

Question 25

What does an increase in plasma clearance mean for the half life of a drug?

Answer 25

Smaller half life

Question 26

What is bioavailability?

Answer 26

Fraction of drug in circulation compared to dose

Question 27

What does bioavailability measure?

Answer 27

Extent of absorption

Question 28

What can low bioavailability be caused by(3)?

Answer 28

Poor absorption Chemical reactions at site of delivery First - pass metabolism

Question 29

What is the choice of delivery route guided by (5)?

Answer 29

``` Bioavailability Chemical properties of drug Convenience Need to control specificity of action Desired onset/ duration/ offset of action ```

Question 30

What does the [drug] variation depend on?

Answer 30

Half life and close intervals

Question 31

What does multiple dosing lead to?

Answer 31

A steady state

Question 32

When are additional doses of drug administered?

Answer 32

Before [drug] falls to zero

Question 33

What does multiple dosing compromise?

Answer 33

Minimisation of drug level variability | Simplicity

Question 34

What info do you need to accumulate drugs properly (6)?

Answer 34

``` Desired therapeutic concentration Steady state level Volume distribution Bioavailability Half life Clearance ```

Question 35

Give the formula for dosing rate

Answer 35

Dosing rate x F = CL x target conc

Question 36

How long does it take for a drug to reach its steady state?

Answer 36

4-5 x drug half-life

Question 37

What is the quickest way to reach a steady state?

Answer 37

Administration of a loading dose

Question 38

What is a loading dose?

Answer 38

Big dose to get the level up to a certain point, then a smaller maintenance dose to maintain it in the therapeutic range

Question 39

How long does it take to reach a new plateau when the dose is changed?

Answer 39

4 half lives