PED1003/L02 Agonists

Question 1

Define an agonist.

Answer 1

A ligand (drug, hormone or neurotransmitter) that combines with receptors to elicit a cellular response

Question 2

Describe the action of an agonist in 4 words.

Answer 2

Receptor
Agonist-receptor complex
Action
Effect

Question 3

Describe the action of salbutamol.

Answer 3

B2-adrenoceptor
Salbutamol-B2-adrenoceptor complex
Increased cAMP
Bronchodilation

Question 4

How are doses defined experimentally?

Answer 4

Through dose-response curves

Question 5

Which of the axis is plot on a logarithmic scale in a dose-response curve?

Answer 5

Agonist concentration

Question 6

What is a graded response?

Answer 6

Response of a particular (individual) system, measured against agonist concentration

Question 7

What is a quantal response?

Answer 7

Dose required to produce a specified response determines in each member of a population

Question 8

What shape is a quantal dose-response curve?

Answer 8

Upside-down ‘U’ shape

Question 9

Why are dose-response curves plotted? (4)

Answer 9

Estimate E(max)
Estimate EC50/ED50
Determine efficacy
Determine potency

Question 10

Describe the two state hypothesis.

Answer 10

Drug A + R -> AR -> activated AR -> response (reversible)

Question 11

Describe affinity.

Answer 11

The strength with which an agonist/drug binds to a receptor

Question 12

Describe efficacy.

Answer 12

The rate at which an AR complex becomes activated

Question 13

How is receptor saturation measured?

Answer 13

Maximum number of binding sites (Bmax)

Question 14

What is k1 and k-1?

Answer 14

k1 - rate of association of agonist with receptor
k-1 - rate of AR complex dissociation

Question 15

What is the equation for affinity?

Answer 15

Affinity = k1/k-1

Question 16

What is kD?

Answer 16

Physiochemical constant which is the same for a given receptor/drug combination in any species

Question 17

What does a lower kD indicate?

Answer 17

A tighter ligand-receptor interaction/ greater affinity

Question 18

What is affinity determined by?

Answer 18

Number/nature of bonds and the ‘level of fit’ between ligand and receptor

Question 19

What is potency dependent on? (4)

Answer 19

Affinity of drug
Efficacy of drug
Receptor density
Efficiency of stimulus-response mechanisms used

Question 20

What is the relationship between EC50 and potency?

Answer 20

Lower EC50 = higher potency

Question 21

When are Kd and EC50 equal?

Answer 21

When there is a linear relationship between receptor occupation and biological effect

Question 22

What are ‘spare receptors’?

Answer 22

Unoccupied receptors when a maximal response is produced from a drug

Question 23

Describe efficacy.

Answer 23

The ability of an agonist to activate a receptor

Question 24

What is a full agonist?

Answer 24

A drug with very high efficacy (very likely AR*)
Produces a maximum resopnse while occupying only a small % receptors available

Question 25

What is a partial agonist?

Answer 25

Low efficacy
Less likely AR*
Unable to produce maximum response even when occupying all available receptors

Question 26

Give 3 examples of partial agonists.

Answer 26

Varenicline
Tamoxifen
Aripipazole

Question 27

What is an inverse agonist?

Answer 27

Agonists with higher affinity for inactive AR than active, resulting in no response