Receptors and Basic Pharm continued

Question 1

What is EC50?

Answer 1

• it describes the quantitative aspects of drug action (pharmacological effect)
• it refers to the dose of drug that produces 1/2 maximal effect
  - can be located on a dose response curve
• EC50 can be less than Keq

Note:
the law of mass action describes drug binding NOT action

Question 2

Define maximal pharmacological effect. When is it observed?

Answer 2

• Once drug concentration reaches a certain level, addition of more drug does not produce an additional effect.
• Observed when the drug concentration greatly exceeds EC50

[D]&raquo_space; EC50 then, max pharmacological effect is about equal to kRt

Question 3

If the drug concentration is equal to the value of EC50 then…

Answer 3

1/2 pharmacological effect = 1 / 2kRt

Note: the symbol for pharmacological effect is delta

Question 4

What equation represents pharmacological effect?

Answer 4

delta symbol = k[Rt] [D] / EC50 + [D]

k [Rt] - a function related to the total amount of receptor
[D] - concentration of drug
EC50 - the dose of drug that produces 1/2 maximal effects

Question 5

Is EC 50 the same as Keq, since EC50 produces 1/2 maximal effect and the latter produces 1/2 maximal binding to the receptor?

Answer 5

No.

Often 1/2 maximal effect are observed at less than 1/2 maximal binding. Thus EC50 can be less than or equal to Keq

Question 6

Describe the concept of partial agonists

Answer 6

• Some agonists are able to activate a higher fraction of receptors than others, independent of their relative binding affinities.
• partial agonists are so poor at activation that their best is not good enough to achieve the maximum effect that other agonists (full agonists) can achieve

Question 7

binding affinity is one factor that determines the…

Answer 7

concentration dependence of drug action
note:
the efficacy of a drug also influences the concentration dependence of drug action

Question 8

Efficacy is defined as….

Answer 8

the ability to confer a response
note:
drugs with insufficient efficacy will be partial agonists regardless of how well they bind to their receptor

Question 9

Potency refers to….

Answer 9

the relative ability of a drug to confer an effect

Question 10

What determines the potency of a drug?

Answer 10

1. ) it’s binding affinity

2. ) it’s efficacy

Question 11

Virtually, all receptors are part of a gene family. Why is this significant?

Answer 11

One drug can elicit different effects in different contexts. This (1) underscores the need for receptor specific agonists and antagonists. (2) helps explain the complexity of drug action