Drug Distribution

Question 1

Define Drug distribution

Answer 1

Dispersion of a drug among fluids and tissues of the body

Question 2

What is the main aim in therapeutics and in multiple-dose-therapy

Answer 2

• The aim of good therapeutics is to deliver medicines to their site of action at effective concentrations
• In multiple-dose therapy, the aim is to keep these levels as stable as possible

Question 3

What happens when a drug is injected into the body

Answer 3

On image

Question 4

What happens to the concentration of drug over time and describe the shape of the drug

Answer 4

1. Drug moves fast into well-perfused areas
2. Drug moving into poor perfused areas
3. Drug being metabolised and eliminated from the body

Question 5

Most drugs obey first-order kinetics… (5)

Answer 5

1. Constant half-life (t1/2)
2. Constant clearance - A constant fraction of drug is removed
3. The time to remove the drug is independent of dose
4. No saturation of processes
5. The body is removing the drugs either by metabolism or excretion.

Question 6

Some drugs obey zero-order kinetics

Answer 6

• “saturation kinetics”
• t1/2 and clearance fluctuate with [drug]
• A constant amount of drug is removed
• The bigger the dose the longer the time to remove it
• As dose decreases - no saturation so processes return to 1st order. For example, enzymes get saturated with the drug they are moving.

Question 7

What are the pharmacokinetic parameters?

Answer 7

• Half-life (t1/2)
• Volume of distribution (Vd)
• Clearance (CL) – volume of blood cleared of drug per unit time.
• Bioavailability (F) - the proportion of administered drug reaching the systematic circulation

Question 8

Describe Volume of Distribution

Answer 8

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Question 9

Describe the rate of clearance

Answer 9

Plasma clearance
• Volume of plasma cleared of drug per time (ml min-1)
• CL = Rate of elimination / [drug plasma]
• A constant for 1st order reactions
• t↑ CL  ↓ ½

Question 10

Describe bioavailability

Answer 10

Bioavailability
F: Fraction of drug in circulation compared to dose
Measures extent of absorption

Question 11

What is low bioavailability caused by?

Answer 11

Low bioavailability is caused by:
• Poor absorption
• Chemical reactions at site of delivery
• First-pass metabolism

Question 12

What is the choice of route guided by?

Answer 12

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

Question 13

Describe dosing regimens

Answer 13

• Multiple dosing leads to a ‘steady state’, where the amount of drug absorbed equates to the amount of drug eliminated
• Additional doses administered before [drug] falls to zero
• [Drug] variation depends on half-life and dose interval
• Multiple dose therapy compromises:
minimisation of drug level variability
simplicity