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

Where does a drug go after an I.v bolus dose

Answer 2

1. inside blood vessels
2. Drug moves fast into well-perfused areas
3. Drug moves into poor perfused areas
4. Some of the drug will accumulate outside blood vessels (the extracellular space) therefore slowing down the removal of the drug

Question 3

What does the proportion of drug dissolving in the intracellular and extracellular space depend on

Answer 3

Depends on lipid solubility which is determined by the chemical structure of the drug

Question 4

What does chemical structure also affect

Answer 4

How readily/tightly the drug binds to plasma proteins

Question 5

What happens when a drug follows first order kinetics

Answer 5

Constant half life and constant clearance
If a constant fraction of the drug is removed , the time to remove the drug is independent of dose
No saturation of processes

Question 6

What happens when a drug follows zero order kinetics

Answer 6

Half life and clearance fluctuate with drug concentration
If a constant fraction of the drug is removed, the bigger the dose the longer the time to remove it
As the dose decreases there is no saturation so processes return to first order
e.g. Alcohol

Question 7

What is a half life

Answer 7

Time taken for the concentration of a given substance to half

Question 8

What is the apparent volume of distribution (Vd)

Answer 8

The total amount of drug / concentration of plasma

Question 9

What does the Vd indicate and why is it important

Answer 9

The extent of distribution for a drug, its clinically important for adjusting dose

Question 10

What is the Vd influenced by

Answer 10

Varies with lipid/water solubility, and the binding to plasma proteins

Question 11

What does plasma clearance =

Answer 11

Rate of elimination / concentration of drug plasma

Question 12

What is bioavailibility (F)

Answer 12

Fraction of a drug in circulation compared to the dose

Measures the extent of absorption

Question 13

What is a low bioavailability caused by

Answer 13

Poor absorption, chemical reactions at the site of delivery and first pass metabolism

Question 14

What is the choice of route guided by

Answer 14

1. Bioavailability
2. Chemical properties of a drug
3. Convenience
4. Need to control specificity of action
5. Desired onset/duration/offset of action

Question 15

What does multiple dose therapy comprise

Answer 15

1. Minimisation of drug variability

2. Simplicity

Question 16

What does a loading dose do

Answer 16

Achieves a steady state quicker for drugs with a long half life
The drug concentration is then maintained within the therapeutic range

Question 17

What are the general rules for achieving a steady state

Answer 17

1. repeated doses eventually produce a steady state concentration
2. Time to plateau is 4 to 5 drug half-lives
3. Steady state levels are not actually flat
4. Fluctuation size is inversely proportional to the number of daily doses
5. Fluctuations create the potential for sub-therapeutic treatment or toxicity