Lecture 3: Drug-Receptor II

A set of flashcards covering drug-receptor interactions, affinity, efficacy, potency, and desensitization based on the provided lecture transcript.

According to the transcript, drug-receptor occupation is governed by which property?

Affinity

According to the transcript, drug-receptor activation is governed by which property?

Efficacy

In the agonist-receptor interaction model $A + R \rightleftharpoons AR \rightarrow AR^* \text{ RESPONSE}$, what does $AR^*$ represent?

The active state of the agonist-receptor complex that leads to a response.

How is drug occupation typically measured in pharmacology?

Radioligand binding

What is the efficacy value of an antagonist, and what is the resulting response?

Efficacy is $0$, and it results in no response.

What is defined as the situation where maximal response is achieved without 100% of receptors being occupied?

Receptor reserve (or spare receptors)

In the example of acetylcholine (ACh) causing contraction, what is the reported $EC_{50}$ value?

$0.3 \times 10^{-6} \text{ M}$ (or $0.3 \text{ }\boldsymbol{\text{μ}}\text{M}$)

In the example of acetylcholine (ACh) binding to receptors, what is the reported binding $K_D$ value?

$10 \times 10^{-6} \text{ M}$ (or $10 \text{ }\boldsymbol{\text{μ}}\text{M}$)

What does the term $EC_{50}$ represent?

The effective concentration of an agonist evoking 50% of the maximal response.

Identify the four key steps downstream from muscarinic receptor binding that lead to contraction in the guinea-pig ileum.

1. Activation of G-proteins, 2. Second messenger systems, 3. Rise in intracellular calcium, 4. Activation of contractile machinery.

State the formula used for fitting concentration-effect curves as provided in the transcript.

$$\text{Response} = \frac{\text{max} \times [X_a]^n}{[X_a]^n + [EC_{50}]^n}$$

In the concentration-effect curve formula, what does the variable $n$ represent?

The slope factor (often called the Hill slope).

The potency of an agonist is dependent on which three factors?

Affinity, efficacy, and spare receptors.

How is a partial agonist defined in relation to a full agonist?

Partial agonists are not able to produce the same maximum/full response as a full agonist.

What happens when a partial agonist is in the presence of a full agonist?

It behaves like an antagonist, causing a shift to the right in the concentration-response curve.

What is the specific definition of efficacy given in the notes regarding a single complex?

Efficacy is a measure of a single agonist-receptor complex’s ability to generate a response.

For a partial agonist, why does the $EC_{50}$ equal the $K_D$?

Because partial agonists require full occupancy of receptors to reach their maximal (albeit lower) response, so the halfway point of their response coincides with the halfway point of their binding.

What are the three properties that determine the effect of a drug in a living system?

Specificity, Affinity, and Efficacy.

According to the transcript, what is the efficacy of a full agonist?

$$1$$

What is the task of the UK National Board for Biological Standards Control?

Maintaining stable preparations of biological materials as reference standards.

Why does measuring the response at a single given concentration not indicate potency?

Because a valid measure of relative potency requires the comparison of equieffective doses of a standard and an unknown.

According to the pain relief comparison, what is the potency ratio of Morphine to Codeine?

$13$ (Morphine is 13 times more potent).

What is the function of inverse agonists?

They stabilize the ‘resting state of a receptor’ and decrease ‘constitutive activity’.

Between $K_D$ and $EC_{50}$, which value will remain constant across different tissues and which will vary based on spare receptors?

The $K_D$ (affinity) will not vary, while the $EC_{50}$ will vary.

List four mechanisms mentioned in the notes that cause desensitisation and tachyphylaxis.

Loss of receptors from the cell surface (internalization), phosphorylation of the receptor, decreased coupling of the receptor to effectors, and exhaustion of mediators.