Pharmacodynamics I - The concept of agonism

Question 1

What are the 2 functions of receptors?

Answer 1

Binding to and recognizing signalling molecules

Initiating signalling pathways

Question 2

What kind of bonds are typical of receptor/ligand interactions?

Answer 2

Weak bonds such as hydrogen bonds, ionic bonds, and van der waals forces.

Question 3

What influences affinity of a drug to bind to its target?

Answer 3

Complementary attractive forces of attraction

3d shape of drug and target

Question 4

What key factors affect strength of chemical forces between receptor and ligand?

Answer 4

Type of bond

Distance between the receptor and ligand

Total number of bonds

Question 5

What 2 factors affect how much of a drug is bound to receptors?

Answer 5

Affinity

Drug concentration

Question 6

Is drug binding reversible?

Answer 6

Yes, reaction between drug binding and separation is in equilibrium

Question 7

Fraction of target bound by drug=

Answer 7

[Drug]/([drug]+Ka) this is a rectangular hyperbolic function

Ka=[drug] where 50% of receptors ate bound

Question 8

What phenomena cause the shape of the rectangular hypolic function seen in receptor binding vs [drug] graph?

Answer 8

Initially, no drugs bound to target.

At the plateau all receptors are bound by drug.

Until the point of saturation there is an increase in number of ligands bound to receptors but this increase slows down as the receptors are filling up.

Question 9

What is Ka?

Answer 9

The [drug] at which 50% of receptors are bound

Question 10

What information does Ka provide us with?

Answer 10

The affinity

Question 11

What does a low Ka value indicate?

Answer 11

Low concentration for 50% of receptors to be bound by drug. This means the affinity is high. (relationship is inversely proportional)

Question 12

What is drug selectivity?

Answer 12

A drug can have a higher affinity for certain molecules compared to others.

Question 13

What are drugs that bind to and activate receptors that alter activity of downstream signalling pathways called?

Answer 13

Agonists

Question 14

What is efficacy of an agonist?

Answer 14

The ability to activate a receptor after binding.

Question 15

How does beta2 adrenoceptor get activated?

Answer 15

Adrenaline binds to it and movesone of the 7 transmembrane helices into a conformation that opens up for G protein to bind to it and to activate downstream signals.

Question 16

What is the difference between full and partial agonists?

Answer 16

Full agonists have high efficacy and a high level of receptor activation with large effect.

Partial agonists have lower efficacy, less receptor activation and a smaller effect.

Question 17

What do antagonists do?

Answer 17

Bind to receptors but have no efficacy so they don’t activate signals.

Question 18

What drug-dependent factors affect agonist-induced changes?

Answer 18

Concentration

Affinity

Efficacy

Question 19

What happens to drug effect if we decrease number of receptors in the cell?

Answer 19

We decrease overall effect

Question 20

What can trigger a decrease in receptor density?

Answer 20

Disease (eg myasthenia gravis)

Drugs (irreversible antagonists)

Gene silencing techniques

Question 21

What is the plot of [D] vs effect called?

Answer 21

Dose-response curve which is a measure of agonist potency

Question 22

What is agonist potency?

Answer 22

Describes relationship between [agonist] and effect

Question 23

What is EC50?

Answer 23

[agonist] that produced 50% of maximum possible effect

Question 24

The lower the EC50 the more ____ the agonist.

Answer 24

Potent

Question 25

Which common drug is an agonist?

Answer 25

Salbutamol

Question 26

True or False?

Most widely-used drugs work as agonists.

Answer 26

False, most drugs work by binding to and inhibiting the function of the target.