Receptor theory III Flashcards

1
Q

How is the response of a drug measured?

A

In a bioassay

  • Apply different concentrations of drugs and measure the outcome
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2
Q

What does a response curve look like?

A
  • Similar to an affinity curve

- Sigmoidal shape which reaches a maximum

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3
Q

What is measured in response curves and what is this?

A

Ec50

The concentration of the drug which gives 50% of the maximal response

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4
Q

What is the difference between Ec50 and Kd for a FULL AGONIST?

A
  • Ec50 is a measure of the concentration of the drug which gives 50% the maximal response
  • In a concentration- response curve
  • Kd is the concentration of drug at which 50% of the receptors are occupied
  • In a concentration- binding curve (Langmuir plot)
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5
Q

What is the relationship between Ec50 and Kd of a FULL AGONIST?

A
  • Ec50 is shifted to the left of Kd for that particular concentration (NOT EQUAL)
  • NOT 50% occupancy with 50% response!!!
  • Less occupancy needed for more response
  • Shifted to the left due to amplification through secondary messengers
  • Smaller concentration to produce 50% response
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6
Q

What is a receptor reserve and why is this important?

A

Spare receptors in a tissue, which are more than is needed to produce a maximum response

Can afford to lose receptors in tissues without impacting the function of the tissues

If increase partial agonist concentration - can bind to the receptors in the receptor reserve and produce a closer o maximum response

If increase full agonist concentration - no change in the maximum response

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7
Q

How does the response curve not match the binding curve and why is this?

A

The response curve is shifted to the left of the binding curve (Ec50 is lower than KD)

Because there is AMPLIFICATION in the system through secondary messengers

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8
Q

What is the maximum response determined by?

A

Efficacy

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9
Q

What does the dose-response curve location on the graph depend upon? (left to right)

A

The POTENCY of the drug, which is dependant on:

  • Affinity
  • Efficacy
  • Receptor reserve
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10
Q

What does the hill equation describe?

A

The relationship between the SIZE of the response and the CONCENTRATION of the agonist added

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11
Q

What does the hill coefficient tell you and what is this related to?

A

How steep the slope is

Related to:
How many molecules of agonist is needed to bind to a receptor to generate a response

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12
Q

How many molecules of agonist is needed to bind to a receptor to generate a response and what is the exception?

A

Normally 1

But can be 2, for example, for ligand gates ion channels

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13
Q

What can be used to predict the response for any concentration of drug?

A

The hill equation

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14
Q

Why can’t a low Ec50 be used to conclude that that drug has the highest affinity for a certain receptor?

A
  • Ec50 determines the potency
  • The lower the Ec50, the higher the potency

But potency is determined by:

  • Affinity
  • Efficacy
  • Spare receptors
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15
Q

What does increasing the spare receptors in a tissue do to the response curve and why?

A
  • Shifts it to the left
  • Higher the probability of the receptor to encounter a ligand
  • Increase potency
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16
Q

What can drawing up many dose-response curves show when testing them in different tissues (with the same ligand/receptor pair)

WHY this and not the other factors that are determined by potency?

A

Which tissue has the most spare receptors

Cant be affinity as it is the ‘same receptor-ligand pair’ - Kd (and affinity) is CONSTANT in this case

17
Q

What are partial agonists?

A

Agonists which cannot produce the maximum response

18
Q

What do agonists with different efficacies produce?

A

Different maximal responses

19
Q

Does a partial agonist have a higher or lower efficacy than a full agonist?

A

A lower efficacy - produces less than maximum response

20
Q

What is the relationship between efficacy and affinity?

A

No relationship

An agonist with a high affinity can have a low efficacy

21
Q

What is the relationship between EC50 and Kd for a partial agonist and why?

A

They are equal

Why:
- For a partial agonist to make a max response, need 100% occupancy

  • So, conc of drug producing 50% of response is the same as 50% occupancy
22
Q

What is the ‘potency’ of a drug?

A

The concentration of a drug needed to produce a specific intensity of response

23
Q

Describe the dose-response curve

A

Sigmoidal graph

Concentration of AGONIST vs % of maximum response

24
Q

Which graph is the dose-response curve similar to?

A

Affinity (langmuir)

25
Q

What can the dose-response curve be used to work out?

A

EC50 (concentration of agonist where there is 50% of maximum response)

26
Q

Why are antagonists not referred to as ‘full’ or ‘partial’

A

Because is refers to the level of response in the tissue (is it maximal or not)

Antagonists do not cause a response in the tissue

27
Q

Does potency refer to antagonists?

Why?

A

No - they do not produce a response in the tissue