Pharmacodynamics

Question 1

What are the five measurements units of mole?

Answer 1

M - molar
MM - millimolar 10-3M (0.001M)
UM - micromolar 10-6M (0.000001M)
NM - nanomolar 10-9M 
PM - picomolar - 10-12M

Question 2

What is affinity?

Answer 2

The ability for a ligand to binding to a receptor

High affinity = strong binding

Question 3

What is the difference between intrinsic efficacy and efficacy?

Answer 3

Intrinsic efficacy - how well a receptor is activated

Efficacy - ability to produce a measurable result

Question 4

What is Kd?

Answer 4

The concentration of ligand required to occupy 50% of all available receptors.

Question 5

Low Kd = X affinity

Answer 5

High

Question 6

What is Bmax?

Answer 6

The maximum binding capacity for a receptor.

Question 7

In a logarithmic scale, recording [Drug]log10M, what would be the difference between -9 and -10?

Answer 7

In a logarithmic scale, -9 would = 10-9 and -10 = 10-10
So -9 = 1nm
-10 = 0.1nm
The difference of ONE ZERO

Question 8

What is the difference between concentration and dose?

Answer 8

Concentration = concentration of drug at site of action.
Dose = Concentration of drug at site of unknown e.g. Patient.

Question 9

What is EC?

Answer 9

A measure of potency - effective concentration giving 50% of maximum response.
Dependent on affinity and intrinsic efficacy.

Question 10

For a ligand to have great potency what three things does it require?

Answer 10

1) Binding to receptor (affinity)
2) Receptor activation (intrinsic affinity)
3) Things to happen (efficacy)

Question 11

What receptors do asthma therapies target? Why can they can problematic?

Answer 11

B2-adrenoceptors

Cause relaxation of the lungs HOWEVER can also target B1 receptors in the heart, causing angina.

Question 12

How to asthma drugs such as salbutamol and salmetrol work?

Answer 12

Are selective.

Have a small Kd therefore greater affinity in B1 receptors, but high Kd and low affinity in B2 receptors.

Question 13

What are spare receptors?

Answer 13

When maximal response is achieved at less than maximal receptor occupancy, some receptors are classed as ‘spare’.
Seen when receptors are catalytically active e.g. G-protein couple receptors.

Question 14

What impact do spare receptors have?

Answer 14

They increase sensitivity and allow responses at low concentrations of agonist.

Question 15

How can the number of receptors change?

Answer 15

Increases with low activity (up-regulation)

Decreases with high activity (down-regulation)

Question 16

What’s the difference between full agonists and partial agonists?

Answer 16

Full agonists give maximal responses and indicate great intrinsic efficacy.
Partial agonists have low intrinsic efficacy, by bind to receptors but don’t always initiate a response.

Question 17

How can partial agonists be used?

Answer 17

Allow a more controlled response
Can be used with full agonists as an antagonists to reduce drug effect
Can be used with low levels of ligand

Question 18

What are receptors do opioids target and what effect do they have on the body?

Answer 18

U-opioid receptor

Pain relief, euphoria, can cause respiratory depression (hypoventilation).

Question 19

How can buprenorphine be used to slowly withdraw from heroin?

Answer 19

Buprenorphine has a higher affinity (lower Kd) and lower efficacy than morphine.
Therefore in the presence of morphine buprenorphine becomes a antagonist against heroin but will still give some of the effects.

Question 20

What are three types of antagonist?

Answer 20

Reversible competitive antagonists
Irreversible competitive antagonists
Non-competitive antagonists

Question 21

What effect does an increased concentration of reversible competitive antagonists have agonist affinity?

Answer 21

Affinity increase therefore Kd decreases

Question 22

What is IC50?

Answer 22

An index of antagonist potency.

Question 23

What is irreversible competitive antagonism?

Answer 23

Once bound with antagonist, the receptor will never bind with anything again.
In high concentrations, there will be insufficient receptors for agonists to produce a full response.

Question 24

What is a phenchromocytoma and how does the drug phenoxybenzamine help to treat it?

Answer 24

A phenochromocytoma is a rare tumour of the adrenal glands, causing too much adrenaline to by release, affecting blood pressure, metabolism and heart rate.
Phenoxybenzamine is a non selective irreversible competitive antagonist. Blocks the a-adrenoceptors, stopping adrenaline from raising blood pressure.

Question 25

What are non-competitive antagonists and what effect can they have?

Answer 25

Bind to allosteric sites of receptors.
Can enhance of reduce effect of agonists.
can work in a similar way to irreversible competitive antagonists as can block receptors.

Question 26

How is the the drug maraviroc used in HIV patients?

Answer 26

Prevents HIV from entering uninflected cells by blocking CCR5 receptors.