2.1.1 Clinical Pharmacokinetics and Pharmacodynamics I

Question 1

What is pharmacokinetics?

Answer 1

What effect the body has on drugs administered

Question 2

What are the 4 principles of pharmacokinetics?

Answer 2

Absorption
Distribution

Metabolism
Excretion

ADME

Question 3

What is the importance of pharmacokinetics?

Answer 3

Predicts toxicity

Allows us to predict effects of adding another drug

Question 4

In the UK what agency is responsible for pharmacokinetics?

Answer 4

MHRA
Medicines & Healthcare products Regulatory Agency

Question 5

What are the key factors when considering pharmacokinetics?

Answer 5

Bioavailability
Half-life
Drug elimination
Inter-subject variability
Drug-drug interactions

Question 6

What is the purpose of assessing pharmacokinetics?

Answer 6

Safe dose
Optimal plasma concentration
Effects the correct tissues

Question 7

What can pharmacokinetics be affected by?

Answer 7

• Renal function
• Liver function
• Cardiovascular function
• GI function
• Lifestyle factors, smoking, drugs

Question 8

What is bioavailability?

Answer 8

Measure of drug absorption, where it can be used

IV=100%
Other routes have a fraction of IV

Question 9

What is bioavailability affected by?

Answer 9

Absorption
-Formulation
-Age
-Food
-Vomiting/ malabsorption
-Previous surgery (GI disrupted)

First Pass metabolism
-Metabolism before reaching systemic circulation

Question 10

What happens to the concentration of drugs in the plasma if elimination is fast and doses are taken far apart from eachother?

Answer 10

Large fluctuations in concentration

Question 11

What can we use to prevent such large fluctuations in plasma concentartion of drugs?

Answer 11

Modified release preparations

Plasma concentration becomes dependant on rate of absorption vs rate of elimination, stays within effective therapeutic range for longer

Can help with adherence

Question 12

Why is it so important to maintain drug concentration levels in the plasma?

Answer 12

So that the drug reaches the target tissue

Question 13

What factors affect therapeutic distribution?

Answer 13

Blood flow
-Poor perfusion = less drug

Lipophilicity and hydrophilicity

Protein binding- unable to bind to receptor if bound to protein

Question 14

What do acidic drugs tend to bind to?

Answer 14

Albumin

Question 15

What do basic drugs tend to bind to?

Answer 15

Glycoproteins

Question 16

What do hormones bind to?

Answer 16

Globulins

Question 17

What is volume of distribution (Vd) ?

Answer 17

How much the drug spreads out within the body

High Vd- spread to more tissues, e.g. fats therefore lower plasma concentration

Low Vd- spread to fewer tissues, higher concentration within the plasma

Question 18

When can drugs bind to receptors?

Answer 18

When they are ‘free drugs’

Question 19

What can happen if displacement of a drug from a binding site occurs?

Answer 19

Protein binding drug interaction

Question 20

When is drug displacement from a receptor clinically important?

Answer 20

If its highly protein bound
Narrow therapeutic index
Low Vd

Question 21

If a second drug is added which displaces the first drug from binding proteins what will happen?

Answer 21

More free first drug to elicit a response

Can potentially cause harm as there could be too much of the initial drug

Question 22

When can increased initial drug concentration due to displacement from protein be more concerning?

Answer 22

Pregnancy (fluid balance) as less protein available in first place

Renal failure- acidic drugs may not bind to protein

Hypoalbuminaemia- less albumin to bind in the first palce

Question 23

What is apparent volume of distribution?

Answer 23

Proportionality factor

How much drug given to patient vs how much is actually in the plasma

Question 24

How do you work out Apparent Volume of Distribution?

Answer 24

Question 25

Example of AVd

Answer 25

Question 26

Small apparent Vd vs Large

Answer 26

Small- suggests drug confined to plasma and extracellular fluid

Large- suggests drug distributed throughout tissues

Eventually as drug is metabolised more will become free and shift to plasma

Question 27

What is the clinical relevance of Vd?

Answer 27

We can use it to work out dose sizes