Receptors and the effects of drugs

Question 1

what is the Kd of a drug?

Answer 1

The concentration of a drug when it is bound to receptors to be 50% saturated

Question 2

What is EC50?

Answer 2

The effective concentration to produce 50% of the maximum response

Question 3

what is the patch clamp technique?

Answer 3

A method for looking at responses generated by individual receptors

Question 4

What is the effect of a full high efficacy agonist, a partial agonist, an antagonist and an inverse agonist on a response when measuring the response of receptors?

Answer 4

You will get a response each time the full agonist is activated.
A partial agonist will have fewer channel openings when the agonist is stimulated and lower max response.
An antagonist will produce no response or a very little response (spontaneous opening) as all the antagonist will do is prevent the agonist form binding.
An inverse agonist will have no/decreased response.

Question 5

what is the allosteric site on a GABAa receptor?

Answer 5

The benzodiazepine receptor or binding site

Question 6

What is the effect of a ligand binding to the benzodiazepine receptor?

Answer 6

BZ agonists increase the affinity of the GABA site for GABA and therefore increases channel opening

Question 7

Give some benzodiazepine receptor ligands

Answer 7

Agonists - Diazepam
Antagonist - Flumazenil
Inverse agonists - betacarbolines

Question 8

What happens when there is an agonist and a positive allosteric modulator?

Answer 8

Increased binding to the receptor.

Question 9

What are some different types of antagonism?

Answer 9

Competitive antagonists 
Irreversible antagonists
Allosteric antagonists 
Physiological antagonist 
Channel blockers

Question 10

What are competitive reversible antagonists?

Answer 10

Produce a parallel shift to the right of the agonists log D/R curve
They compete with the agonist for the same binding site
both the agonist and antagonist bind reversibly
presence of the antagonist decreases the probability of agonist binding

Question 11

Give an example of a competitive reversible antagonist.

Answer 11

Naloxone in opiate overdose which cause a reverse of the effects of heroine

Question 12

What is right-shift when there is an increasing antagonist concentration?

Answer 12

As the antagonist concentration increases, the agonist concentration goes down as there are fewer receptors available to bind to the agonist.
Each increase in the antagonist will cause a right-shift on the graph showing that a maximal response can still be produced at a higher agonist concentration.

Question 13

How can we quantify the effect of the antagonist?

Answer 13

Compare the EC50 with the new EC’50 after the agonist is combined with the antagonist and then do a dose ratio (DR).

Question 14

How do you calculate a DR?

Answer 14

EC’50 / EC50 = 100

Question 15

Define the concentration ratio

Answer 15

The ratio of the concentration of an agonist that produces a specified response in the presence of an antagonist to the agonist that produces the same response in the absence of antagonist.

eg. EC50 agonist in presence of antagonist / EC50 agonist alone

Question 16

What are irreversible antagonists?

Answer 16

Compete with the agonist for the same binding site
BUT antagonist binds irreversibly
presence of the antagonist will decrease the number of available receptors and hence decrease the maximal response.

Question 17

How can a maximal response be produced when a irreversible antagonist is used?

Answer 17

The presence of spare receptors enables the agonist to still be able to produce a maximal response.

Question 18

What are non-competitive antagonists?

Answer 18

An antagonist that binds at a different binding site and therefore prevents the effect of the agonist without effecting its binding.
The effect of a non-competitive antagonist is insurmountable. - Ie it cannot be overcome by increasing [agonist] and therefore does not change the E50 for the agonist

Question 19

What is the effect of partial agonists on a response?

Answer 19

Partial agonists can behave as a competitive antagonist.
Increasing the concentration of partial agonists cause a depression of the maximal effect as more receptors are binding to the partial agonist out competing the full agonist.

Question 20

What are allosteric antagonists?

Answer 20

Bind reversibly at a distinct site from the agonist and decrease agonist affinity.
They reduce likelihood of agonist binding

Question 21

What is the effect of an agonist with a negative allosteric modulator?

Answer 21

Causes a decreased functional response

Question 22

What are channel blockers?

Answer 22

eg. phencyclidine (PCP) at the NMDA receptor.
bind inside the channel and prevent the passage of ions.
binding of channel blockers tends to be enhance by receptor activation (use dependence)

Question 23

What are physiological antagonists?

Answer 23

eg. Acetylcholine and adrenaline in the heart.
eg. Papaverine and acetylcholine in the ileum.
Produce opposite effects on a tissue
Produce a non-selective suppression of the response

Question 24

What is desensitisation?

Answer 24

Prolonged or repeated exposure to an agonist reduces the response to that drug.
eg. inactivation of nicotinic receptors.