Drug distribution

Question 1

What is drug distribution?

Answer 1

Dispersion of a drug among fluids and tissues of the body

Question 2

What is the aim of good therapeutics?

Answer 2

• Aim of good therapeutics is to deliver medicine to their site of action at effective concentrations

Question 3

What is the aim in multiple dose therapy?

Answer 3

In multiple dose therapy, aim is to keep levels as stable as possible of drug

Question 4

Where are drugs going?

Answer 4

• From I.V to inside the blood cell
○ Drug moves fast into well-perfused areas
○ Drug moving into poor perfused areas
• Can go from blood vessels to outside blood vessels

Question 5

What is the time course of the concentration of drug in circulation?

Answer 5

• Drug moves fast into well-perfused areas
• Then Drug moving into poor perfused areas
• Then Drug metabolised and eliminated from the body

Question 6

What is first order kinetics?

Answer 6

• Constant half-life
• Constant clearance
• Constant fraction of drug is removed
• Time to remove drug independent of dose
• No saturation of process

Question 7

What is zero order kinetics?

Answer 7

• Half life and clearance fluctuate with concentration of drug
• Constant amount of drug removed
• Bigger the dose the longer the time to remove it
• As dose decreases, no saturation therefore returns to 1st order kinetics

Question 8

What are pharmacokinetic parameters?

Answer 8

• Half-life
• Volume of distribution
• Clearance
Bioavailability

Question 9

Equation for apparent volume of distribution

Answer 9

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

Question 10

What does apparent volume of distribution indicate?

Answer 10

• Indicates the extent of distribution for a drug

Question 11

Why is the volume of distribution important?

Answer 11

• Clinically important for adjusting dosage

Question 12

What is the volume of distribution influenced by?

Answer 12

• Influenced by lipid/water solubility, binding to plasma proteins

Question 13

What is plasma clearance?

Answer 13

• Volume of plasma cleared of drug per time

Question 14

Equation for clearance

Answer 14

CL=Rate of elimination/[drug plasma]

Question 15

What is plasma clearance a constant for?

Answer 15

• Constant for 1st order reactions

Question 16

What happens when plasma clearance increases?

Answer 16

• As plasma clearance increases, half life decreases

Question 17

What considerations need to be taken?

Answer 17

• Most medicine not taken by i.v
• Most given as multiple doses
• Kinetics may be altered by age and disease

Question 18

What is bioavailability a measure of?

Answer 18

Measures extent of absorption

• Fraction(F) of drug in circulation compared to dose

Question 19

What is low bioavailability caused by?

Answer 19

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

Question 20

What is choice of route guided by?

Answer 20

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

Question 21

What does multiple dosing lead to?

Answer 21

• Multiple dosing:
○ Leads to steady state
○ Amount of drug absorbed equates amount of drug eliminated

Question 22

What does concentration of drug variation depend on?

Answer 22

• Concentration of drug variation depends on half life and dose interval

Question 23

What does multiple dose therapy compromise?

Answer 23

○ Minimisation of drug level variability

Simplicity

Question 24

What is the time to plateau?

Answer 24

Time to plateau is 4-5x drug half life

Question 25

How can the achievement of steady state be accelerated?

Answer 25

• Drugs with long half lives achievement of steady state can be accelerated using a loading dose

Question 26

When is maintenance dose used?

Answer 26

Maintenance dose used when concentration of drug starts to drop to ensure concentration remains in therapeutic range

Question 27

What does fluctuations create?

Answer 27

Fluctuations create potential for sub-therapeutic treatment or toxicity