Receptors

Question 1

What is relative potency?

Answer 1

Comparing the potency of two drugs with the same method of action on a graded response curve.

Question 2

What is tachyphylaxis?

Answer 2

A reduction in the sensitivity of a receptor to a drug

Question 3

Do all tissues show tachyphylaxis?

Answer 3

No

Question 4

How can tachyphylactic response be mitigated?

Answer 4

Using a discreet dose response allows for the receptor to be ‘reset’ in between doses by washing or leaving an amount of time

Question 5

What is a quantal response?

Answer 5

All or none response

Question 6

How are quantal responses measured if they don’t have a graded response?

Answer 6

By measuring the % of individuals that showed a response

Question 7

When comparing 2 drugs EC50, what should you check?

Answer 7

That they have the same moa, otherwise a comparison is futile.

Question 8

What can alter relative potency?

Answer 8

Drug interactions

Question 9

If 2 drugs have the same moa, what can happen to their sensitivity?

Answer 9

It can decrease the sensitivity as both drugs will be competitively competing for the binding site.

Question 10

What governs drug occupation of receptors?

Answer 10

The drugs affinity to the receptor

Question 11

What governs the drug’s ability to activate a receptor?

Answer 11

The drugs efficacy to activate the receptor

Question 12

Which type of drugs occupy but don’t activate?

Answer 12

Antagonists

Question 13

What is the ‘Occupancy’ (Pa) of a drug?

Answer 13

The fraction of receptors that are occupied by the receptor

Question 14

In the presence of an antagonist, what happens to the concentration response of an agonist?

Answer 14

The concentration required for the same response. The curve shifts to the right=> dextral shift

Question 15

What is a surmountable receptor-ligand binding?

Answer 15

An antagonist binds to the receptor in a reversible fashion

Question 16

How can binding be ‘surmounted’

Answer 16

Adding more agonist competitively out competes the antagonist

Question 17

What is insurmountable receptor-ligand binding?

Answer 17

An antagonist that binds to a receptor with a permanent covalent bond

Question 18

What happens to the graded response curve with a surmountable antagonist?

Answer 18

It shifts to the right

Question 19

What happens to the graded response curve with an insurmountable antagonist?

Answer 19

The agonist response will show a decreased maximum response

Question 20

What are spare receptors?

Answer 20

The excess expression of receptors in the cell membrane. A greater number of receptors are present than is required to produce a strong response.

Question 21

What is the effect of spare receptors when comparing lab results to clinical trials?

Answer 21

Usually, a larger concentration of antagonist is required to produce a significant inhibitory response as the ‘spare’ receptors can still be used by the agonist

Question 22

What is the efficacy of an agonist?

Answer 22

The efficacy of a drug relates to the affinity and ability to activate specific receptor states

Question 23

What is the efficacy of an agonist?

Answer 23

It is efficacious towards receptors in the ‘off’ state; it causes them to switch to the ‘on’ state

Question 24

What is the efficacy of an inverse agonist?

Answer 24

It is efficacious towards receptors in the ‘on’ state; it results in them turning to the ‘off’ state

Question 25

Which type of cellular responses do inverse agonists have an effect on?

Answer 25

Constitutively active responses

Question 26

What is the difference between antagonism and an antagonist?

Answer 26

Antagonism is the process of an agonist binding to a receptor and activating a downstream pathway that results in blocking a pathway- it does not block the receptor itself like an antagonist

Question 27

What is physiological antagonism?

Answer 27

A drug which produces the opposite biological effect

Question 28

What is pharmacokinetic antagonism?

Answer 28

A drug which reduces the absorption or increases the elimination of a drug which, overall, decreases its concentration in the target area

Question 29

What is chemical antagonism?

Answer 29

A drug which binds/reacts to another drug rendering it inert/inactive

Question 30

What is non-competitive antagonism?

Answer 30

A drug that activates a blocking pathway (inverse agonist)

Question 31

Name two ways in which tachyphylaxis can occur.

Answer 31

1) The binding of a ligand can temporarily cause the shape of the receptor to change so that for a short period of time it is unable to bind to a ligand. This is a refractory period. 2) The cell can temporarily remove receptors from the cell membrane

Question 32

What is the therapeutic index?

Answer 32

LD50/ED50

Question 33

What can the therapeutic index show?

Answer 33

It demonstrates the 'safety net'; the difference in concentration between a lethal dose and a therapeutic dose

Question 34

What are silent receptors?

Answer 34

Silent receptors are receptors whose downstream action is unclear

Question 35

What are the two primary reasons for 'silent' receptors?

Answer 35

Some have a function that is, as of yet, undiscovered and others have no use; they once formed as part of a pathway but evolution has removed the pathway but not the receptor

Question 36

What do 'silent' and 'spare' receptors act as?