Sesh 6: Pharmacodynamics

Question 1

Define a ligand.

Answer 1

A molecule that binds specifically to a receptor.

Question 2

What is an antagonist?

Answer 2

A molecule that prevents receptor activation by an agonist.

Question 3

Both agonists and antagonists have _________.

Answer 3

Affinity.

Question 4

Only agonists have ________ and _________.

Answer 4

1. Affinity

2. Efficacy

Question 5

What govern’s an agonist’s ability to activate a receptor?

Answer 5

The agonist’s intrinsic efficacy.

Question 6

What governs an agonist’s ability to cause a measurable biological response?

Answer 6

Its overall efficacy- determined by its intrinsic efficacy, and cell/tissue-specific factors such as receptor number.

Question 7

What is Bmax?

Answer 7

The max binding capacity (100% receptor occupancy). Indicates receptor number.

Question 8

What is Kd?

Answer 8

It is the dissociation constant-the concentration of drug required to occupy 50% of available receptors. Indication of affinity.

Question 9

If drug A has a lower Kd at a specific receptor than drug B, what does this tell you about drug A?

Answer 9

Drug A has a higher affinity for that receptor than drug B.

Question 10

What is EC50?

Answer 10

The concentration of drug needed to produce 50% of the maximal response (Emax). Indicates agonist potency.

Question 11

What is potency?

Answer 11

The ability of a drug to cause a measurable response. Is a combination of affinity and efficacy.

Question 12

What is functional antagonism?

Answer 12

Antagonising an effect via a mechanism distinct from the one causing the effect.

Question 13

What type of compounds are used to reverse airflow obstruction and bronchospasm in asthmatics?

Answer 13

Beta-2 adrenoceptor agonists e.g. Salbutamol

Question 14

Name a tissue/cell-specific factor that can alter a drug’s potency.

Answer 14

Receptor number.

Question 15

What type of receptors often have ‘spare receptors’ within a tissue?

Answer 15

Catalytically active receptors e.g. Tyrosine kinase or GPCRs, due to amplification in signal transduction

Question 16

Why do tissues have spare receptors?

Answer 16

They increase sensitivity…still get a response at low agonist concentrations.

Question 17

How do cells alter their receptor number in response to over-stimulation?

Answer 17

They down-regulate those receptors, lowering their sensitivity for the agonist.
Contributes to drug tolerance…need higher dose to get same response.

Question 18

If an agonist’s EC50< Kd, what does this indicate?

Answer 18

It’s a full agonist, and there are spare receptors.

Question 19

What does maximal response indicate about an agonist?

Answer 19

Its intrinsic activity e.g. Partial agonists cannot elicit a max response, so have low intrinsic activity-usually due to low intrinsic efficacy (ability to activate a R to the active conformation).

Question 20

In what circumstance can a partial agonist act as an antagonist?

Answer 20

If there are high levels of the full agonist.

Question 21

What is buprenorphine, and how can it be used?

Answer 21

A partial agonist at the u-opioid receptor…but can act as a mixed agonist/antagonist.
Can be used for gradual opiate withdrawal in addicts, as has higher affinity, but lower efficacy than morphine and heroin for the receptor.

Question 22

Partial agonism is dependent on what 2 things?

Answer 22

1. Compound

2. System

Question 23

What is the IC50?

Answer 23

Concentration of antagonist resulting in 50% inhibition of response. Indicates antagonist potency.

Question 24

What type of antagonism is surmountable?

Answer 24

Reversible, competitive antagonism.

Question 25

How can naloxone be used clinically?

Answer 25

It is a high-affinity, competitive antagonist at the u-opioid R, so can be used to reverse opioid-mediated respiratory depression by effectively competing with heroin.

Question 26

What type of antagonism is non-surmountable?

Answer 26

Irreversible competitive antagonism.

Question 27

Non-competitive antagonists bind to an ___________ site on the receptor.

Answer 27

Allosteric.