PHYL2064 Week 11: Pharmacodynamics - Agonists & Antagonists

Define an antagonist.

A substance than binds to a receptor but does not cause a response.

What is an agonist drug?

A substance that provokes a receptor-mediated biological response, often by competing with another substance for the same receptor.

What are the 4 essential components of pharmacokinetics?

Admission, distribution, metabolism, excretion

In the case of an adrenaline sympathetic, is the response inhibited or amplified? How?

Amplified. From a single adrenaline molecule binding to the GPCR, 10^8 molecules of glucose are derived from glycogen.

Define a non-competitive antagonist.

Antagonist interferes with the agonist's receptor or with the secondary effector system rather than directly competing with the agonist for the receptor.

In a log dose-response curve, 2 lines are shown. Both have the same ceiling and are virtually identical except Drug B is further to the right than Drug A. Which drug is most effective?

Both are equally effective, since effectiveness and efficacy of the drug is read on the Y axis.

In a log dose-response curve, 2 lines are shown. Drug A and Drug B peak at the same point of the X axis but A's ceiling is significantly higher than B's. Make a statement about their potency/affinity and their efficacy.

Both are equally potent. A has more efficacy than B.

What are the units of Kd?

Concentration = mol

What occurs to the curve on a dose-response graph in non-competitive antagonism and irreversible competitive antagonism?

Curve flattens, reaching maximum effect when less total binding sites are occupied.

What occurs to the curve on a dose-response graph in the case of competitive antagonism?

Curve shifts to the left, become less effective.

Give an example of a kinase-linked receptor.

Cytokine receptor in inflammation

In a log dose-response curve, 2 lines are shown. Both have the same ceiling and are virtually identical except Drug B is further to the right than Drug A. Which drug is most potent?

Drug A is more potent than Drug B (has more affinity)

What must occur for an agonist to outcompete with an antagonist?

Enough concentration of agonist must be present to overcome the effect of the antagonist.

T/F: GPCRs are slower than ion channels.

False

T/F: affinity is the attraction between 2 drug molecules.

False

T/F: efficacy is the amount of drug needed to produce an effect.

False

What type of receptor is used in an adrenaline sympathetic response?

GPCR

What is the time scale of a kinase-linked receptor?

Hours

What is the time scale of a nuclear receptor?

Hours or more

Where does the testosterone hormone acts in the cell and how?

In the DNA to stimulate the transcription of a new type of protein.

What occurs in the activation on a ligand-gated ion channel?

Ion channel is opened, allowing ions to move through channel.

The same amount of drug A, an agonist, and drug B, a competitive antagonist, are released into a tissue. What will happen to the curve of drug A compared to when it is released into the tissue without drug B?

It will shift to the left, becoming less effective.

What is the equation to find Kd?

K-1/K1

What is the equation to find drug-receptor affinity?

K1/K-1

What is the difference between Kd and EC50?

Kd = saturation of 50% of total receptors. EC50 = drug concentration that produces 50% of maximal physiological response.

Name the 4 types of receptors.

Ligand-gated ion channels, GPCRs, kinase-linked receptors, nuclear receptors

What is the time scale of a ligand-gated ion channel?

Milliseconds

Give an example of a GPCR.

Muscarinic Ach receptor

Give an example of a ligand-gated ion channel.

Nicotinic Ach receptor

Give an example of a nuclear receptor.

Oestrogen receptor.

Define R, D, K1, K-1 in the agonist affinity equation.

R = receptor, D = drug, K1 = association rate constant, K-1 = dissociation rate constant

What occurs in the activation of a GPCR?

Receptor activates G protein within the cell, setting off a cascade to inhibit or amplify intracellular response.

What is the time scale of GPCR?

Seconds

What is a drug receptor?

Site on surface or interior of cell that binds with specific agonist structures.

Define pharmacodynamics.

Study of drug action on living tissue.

Define pharmacokinetics.

Study of the processes of drug absorption, distribution, metabolism, and excretion

What is the Kd value?

The concentration at which 50% of receptors are saturated with the agonist.

Define EC50.

The drug concentration that produces 50% of maximal response.

What is Kd?

The equilibrium dissociation constant, used to quantitate and compare receptor and drug interactions.

T/F: antagonists have high affinity, but low efficacy.

True

T/F: potency is the amount of drug needed to produce an effect.

True

You are given the following linear scale and are told to find the EC50. What steps should you take?

Turn it into a log graph

In a log dose-response curve, what is read on the Y axis and what is read on the X axis?

Y axis = potency/affinity. X axis = efficacy