Drug Distribution

Question 1

What is drug distribution?

Answer 1

Dispersion of a drug among fluids and tissues of the body

Question 2

Where can the drug actually go?

Answer 2

From the dose, it will enter circulation/blood vessels and can then go to outside blood vessels or into well perfused areas and then poor-perfused areas.

There is an equilibrium between:
[drug] in blood <—> [drug] at site of aciton

Question 3

What are examples of extravacular space?

Answer 3

Adipocytes, skeletal muscle

Question 4

What are some pharmacokinetic parameters?

Answer 4

• Drug half-life
• Volume of distribution
• Bioavailability
• Elimination process / Clearance

Question 5

What happens in first-order kinetics?

Answer 5

• Exponential decay in rate
• Constant half-life
• Constant fraction of drug being removed
• No saturation point of transporters involved in elimination

Question 6

If the dosage of the drug is increased, what happens with first-order kinetics?

Answer 6

Nothing changes - the same constant fraction is removed, and constant half life remains same.

Question 7

Do most drugs obey first-order or zero-order kinetics?

Answer 7

First-order

Question 8

What happens in zero-order kinetics?

Answer 8

• There is a fixed rate, so absorption/distribution/elimination processes are saturated
• Constant AMOUNT of drug is removed
• The bigger the dose the longer the time to remove it
• Unpredictable kinetics and can lead to toxicity eg. alcohol

Question 9

What is the volume of distribution (Vd)?

Answer 9

Total amount of drug / [plasma] = Apparent volume of distribution

Tells you how much of the drug is in vascular space/indicates distribution, if Vd high then some drug outside vascular space.

Clinically important for adjusting dosage

Question 10

What is meant by plasma clearance?

Answer 10

It is how quickly our body removes the drug - the volume of plasma cleared of drug per time (ml min^-1).

It’s a constant for 1^st order reactions

Question 11

What is bioavailability?

Answer 11

F = The fraction of drug in circulation compared to dose (measures extent of absorption).

For IV, F = 1 always.

Oral, F = 0.1 (10% bioavailability) so need to increase dose by x10

Question 12

Give reasons for low bioavailability

Answer 12

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

Question 13

What is the point of multiple dosing?

Answer 13

• Achieve a ‘steady state’
• More doses before [drug] falling to zero - to allow buildup
• [drug] variation depends on half-life + dose interval

Question 14

What does the dosage regime balance?

Answer 14

Dosing rate = rate of elimination

Question 15

What is the equation for dosing rate and target concentration?

Answer 15

Dosing rate x F = CF x Target concentration (Css)

(example calculation on powerpoint)

Question 16

Repeated doses of drug eventually produce a steady state concentration, true or false?

Answer 16

Tru

Question 17

How long is the time to plateau (steady state)?

Answer 17

4-5 x drug half life

Question 18

Steady state levels are flat, true or false?

Answer 18

False

Question 19

Why are fluctuations bad?

Answer 19

Create potential for sub-therepeautic treatment or toxcitity

Question 20

Will increasing the number of daily doses decrease or increase fluctuations?

Answer 20

Decrease

Question 21

For drugs with long half lives, achievement of steady stte can be accelerated by a loading dose. What is a loading dose?

Answer 21

Loading dose is a much bigger initial dose to bring concentration up to steady state, then smaller maintenance dose is given to maintain the desired level in the long run.

Question 22

Will changing the rate of drug infusion change the time required to reach steady-state?

Answer 22

No - Time required to reach steady state is independent of the dose. Only the concentration of steady state changes, but time/rate remains same (4-5 half life).