M&R 8.1 - Drugs and Receptors

Question 1

What is meant by the affinity of a drug?

Answer 1

The ability of a drug to bind to its biological target e.g. a receptor

Question 2

What is meant by the efficacy of a drug?

Answer 2

The ability of a drug to generate a response upon binding

Question 3

What is meant by intrinsic efficacy?

Answer 3

The ability of an agonist to activate a receptor

Question 4

What does efficacy depend on?

Answer 4

• Efficacy

- Influential factors to the response e.g. cell-tissue dependent factors

Question 5

What is Kd?

Answer 5

• The concentration of a drug/ligand supplying 50% of the receptors (dissociation constant)
• Measurement of affinity
• Lower Kd = Higher affinity

Question 6

What is Bmax?

Answer 6

• The maximum binding capacity between a ligand and its receptors
• Indicates number of receptors

Question 7

When would radioligands be used?

Answer 7

• To obtain information about binding

- Low radioligand = low binding

Question 8

When would a concentration-response curve be used?

Answer 8

When measuring a response in cells/tissues

Question 9

When would a dose-response curve be used?

Answer 9

When measuring a response in a whole animal

Question 10

What is Emax?

Answer 10

Maximum response of a drug

Question 11

What is EC50?

Answer 11

• The effective concentration giving 50% of the maximal response
• A measure of potency

Question 12

What is potency?

Answer 12

• A combination of both affinity and efficacy

- The concentration of a drug required to give 50% of the maximal response

Question 13

What does potency depend on?

Answer 13

• Affinity
• Efficacy
• Needs to generate a MEASURABLE RESPONSE

Question 14

What is the relevance of measuring efficacy in relative terms?

Answer 14

• Agonists with different Emax = different efficacy

BUT

• Agonists with same Emax may have different efficacy as affinity could differ

Question 15

How does dose differ to concentration?

Answer 15

• Dose = concentration of the drug at a site of unknown action (mg or Mgk-1)
• Concentration = known concentration of a drug at a site of action

Question 16

What is an agonist?

Answer 16

• A molecule that activates a receptor

- Fits binding site fully

Question 17

What are the features of an agonist?

Answer 17

Have:

• Intrinsic efficacy
• Efficacy
• Affinity

Question 18

What is an antagonist?

Answer 18

A molecule that blocks the ability of an agonist by blocking the binding site without causing a conformational change

Question 19

What are the features of an antagonist?

Answer 19

• ONLY HAS AFFINITY

- Doesn’t cause a response so has no intrinsic efficacy

Question 20

How does Salbutamol compare with Salmeterol?

Answer 20

• Salbutamol has a higher affinity for Beta-2 adrenoceptors than Beta-1
• Salbutamol has a Beta-2 selective efficacy
• Salmeterol has a higher affinity for Beta-2 adrenoceptors than Beta-1
• Salmerterol has no selective efficacy (prevents side effects and Beta1 activation through affinity)

Question 21

How is the route of administration of Salbutamol significant?

Answer 21

• Gives another element of selectivity
• Limits Beta-1 activation and other side effects
• Can be given by drip to a severely ill patient but that then loses the selectivity