View source for 2. Characterisation of agonist-receptor interaction. Occupancy, affinity, dose-response curve, potency, efficacy

A quick summary:

* Occupancy shows the fraction of the total number of receptors in the tissue that is occupied by the drug. It’s determined by the constant ''p.''
* A drug’s affinity to its receptor is determined by the constant Kd. When Kd is low is the affinity high. A high affinity is always good and has no drawbacks.
* Efficacy is a measure of how “effective” the drug is. It measures how large of a cellular response the drug can induce in the tissue, which roughly translates to how severe of a condition or symptom the drug can treat. The drug’s intrinsic activity determines its efficacy.
* Intrinsic activity (IA) is a measure of the efficacy of a drug compared to the most efficacious drug with the same function. IA ranges between 0 and 1.
* Agonists have an intrinsic activity of 1
* Partial agonists have an intrinsic activity of more than 0 but less than 1
* Antagonists have an intrinsic activity of 0
* Potency is a measure of how much of a drug you need to get the desired effect. It’s measured by the constant ED50. The lower the ED50, the more potent the drug is. It depends on the affinity and the intrinsic efficacy.
* A high potency is always good because when a drug is potent even a low concentration can give a satisfactory therapeutic effect. By allowing the use of low concentrations potent drugs reduce the risk for adverse effects.
* Receptor reserve is a measure of how many receptors in the tissue that are not occupied by the drug even when the drug has reached its maximum effect.
* Intrinsic efficacy is a measure of the receptor-activating ability of an agonist. It is measured by the constant ε, and it depends on the intrinsic activity and receptor reserve. A higher intrinsic efficacy is always good.

This topic is theory-heavy so hold on tight.

In this topic we study the agonist-receptor interaction, that is, what determines how an agonist affects the receptor and how can we differentiate different agonists.
[[File:Agonist-receptor interaction.png|center|thumb|450x450px|A = Agonist, R = receptor, AR = agonist bound to the receptor, AR* = the activated receptor. Effect and response are used interchangeably.]]
This figure is scary. The A is the agonist, while the R is the receptor. In order for anything to happen, the agonist must bind to the receptor to form AR. This binding is not permanent, meaning that there is an equilibrium between the number of free agonists (A) and receptors (R) and bound agonist-receptors (AR), which is why the arrow goes both ways. After A has bound R, the receptor will become activated (AR*). When the receptor is activated, it will cause an effect.

As we can see on the figure, the relationship between the agonist concentration and how many agonists are actually bound to a receptor (AR) is called the concentration-occupancy relationship. The relationship between how agonists bound to the receptor cause their effect is called the occupancy-response relationship. The sum of these two relationships, the relationship between the agonist concentration and the resulting tissue effect is called the concentration-response relationship. We’ll discuss the three separately.