6.1 Pharmacodynamics 1

Question 1

What is an i. agonist and ii. Antagonist?

Answer 1

1. Binds and activates a receptor and makes something happen
   - affinity, intrinsic efficacy and efficacy
2. Binds to receptor and blocks binding of agonist - stops something happening
   - affinity, no intrinsic efficacy and no efficacy

Question 2

What is intrinsic efficacy?

Answer 2

Ability to activate a receptor

Question 3

What is efficacy?

Answer 3

Causes a measurable response

Question 4

What is affinity?

Answer 4

Degree to which a substance combines with another e.g. Higher affinity - stronger binding

Question 5

Explain molarity and state the equation related to it.

Answer 5

Concentration - how many molecules of ‘stuff’ is in a certain amount of solution

Molecular weight x molarity = g/L

Question 6

How do we measure drug-receptor interactions?

Answer 6

1. Measure by binding of radioligand to cells/membranes

2. Conc of drug and response seen

Question 7

What graph is drawn when measuring drug-receptor interactions in relation to binding to receptors? What values can be extrapolated from this graph?

Answer 7

1. [drug] vs proportion of bound receptors
2. Kd - conc of ligand required to occupy 50% of available receptors
   - dissociation constant (index of affinity)
   - lower the value, higher the affinity
3. Bmax - highest point on graph
   - max binding capacity (info on receptor number)

Question 8

What graph is drawn when measuring drug-receptor interactions in relation to functional responses? What values can be extrapolated from this graph?

Answer 8

1. [Drug] vs Response (%)
2. EC50 - effective concentration giving 50% max response
   - potency - generating a measureable response
   - For a Ligand to have POTENCY, it requires ligand binding AFFINITY, receptor activation INTRINSIC EFFICACY and things to happen to create a measurable response EFFICACY

Note: for a response, agonist has to be used as requires efficacy

Question 9

Affinity + efficacy =

Answer 9

Potency

Question 10

What is asthma?

Answer 10

1. Reversible airflow obstruction and bronchospasm

2. Caused by constriction of airways (mechanisms)

Question 11

How are airways relaxed (opened)?

Answer 11

Circulating adrenaline
B2 adrenoreceptors activated
Relaxation

Question 12

How COULD we treat asthma? What is the problem with this and how could it be solved?

Answer 12

1. Can treat initial contraction - antagonism
2. Or use agonist to activate B2 adrenoreceptors causing relaxation
   - there are other B-adrenoreceptors elsewhere in the body e.g. In the heart
   - activating these would increase force and rate (bad news if treating asthma!)

• hence need selective/specific activation of B2 adrenoreceptors in airways

Question 13

Salbutamol Kd for B1 - 20um and B2 - 1um. Comment on affinity and efficacy.

Answer 13

Kd for B2 lower so higher affinity for airways. But small difference to B1 so this is poor.

In terms of efficacy, salbutamol causes better response for B2 than B1.

Even though small difference in affinity advantage, big difference in efficacy.

Note route of administration helps this too.

Question 14

Salmeterol Kd for B1 - 1900nM, B2 - 0.55nM. Comment on efficacy and affinity.

Answer 14

Kd for B2 lower so higher affinity

No selective efficacy therefore response depends entirely on affinity