M&R Drugs and receptors

Question 1

What is the difference between:

Drug affinity
Drug efficacy
Drug potency

Answer 1

Drug affinity is the strength that the drug binds to the receptor

Drug efficacy is the ability of the drug-receptor complex to produce maximum functional response (must be a measurable response)

Drug potency takes into account both affinity and intrinsic efficacy (ability to activate receptor). EC50 or effective concentration giving 50% of the maximal response is a measure of potency

Question 2

Define:

agonist
partial agonist
antagonist

Answer 2

An agonist activates the receptor (has affinity and efficacy)

A partial agonist produces a less than maximal response even with full receptor occupancy, due to lower intrinsic activity

An antagonist blocks the binding of an endogenous agonist (has affinity only)

Question 3

What are the benefits of using a partial agonist?

Answer 3

Can allow a more controlled response
Can act as an antagonist if there are high levels of full agonist
e.g. methadone for the management of opioid dependence (e.g. heroin)

Question 4

What are the 3 ways in which an antagonist can act?

Answer 4

1. Reversible competitive antagonism
   Most common and important in therapeutics
   Relies of dynamic equilibrium between ligands and receptors
   Can be overcome by high [agonist]
   Higher conc = greater inhibition
2. Irreversible competitive antagonism
   Occurs when antagonist dissociates slowly or not at all
   Cannot be overcome by increasing [agonist]
3. Non-competitive antagonism
   Bind to allosteric sites

Question 5

What is the purpose of spare receptors?

Answer 5

EC50

Question 6

What is intrinsic activity?

Answer 6

The ability of a drug to activate a receptor

Question 7

Give a clinical example where differences in affinity and efficacy are important

Answer 7

In asthma, treatment goal is to activate B2-adrenoreceptors to relax the airways but there are B-adrenoreceptors elsewhere in the body e.g. B1 in heart increases force and rate.

Salbutamol

• high Kd for B1 and low Kd for B2
• therefore has higher affinity for B2
• there is also selectivity for B2 through the route of administration (oral spray)

Salmeterol

• longer acting than salbutamol
• no selective efficacy so relies on prevention of B1 activation surely through differences in affinity
• 3500x greater affinity got B2