Drug Receptor interactions Flashcards
What are the two key properties of drugs?
Affinity and Efficacy
Affinity (K_D or K_A) measures the concentration range over which a drug binds to its receptor, while Efficacy indicates the ability of the drug to generate/initiate a stimulus once bound.
What is a partial agonist?
A drug that can decrease the response to a full agonist by occupying some receptors
This results in a smaller response than if all receptors were occupied by full agonist molecules.
Define competitive antagonist.
A drug that interacts/binds reversibly with receptors, forming a complex that does not evoke a response
Only the [DR] complex gives rise to a response, while [AR] receptors are occupied but not activated.
What does the Schild equation represent?
r = ([A]/KA) + 1
‘r’ is the ratio by which [D] must be increased to overcome competition by [A].
What does the pA2 value compare?
The affinity of an antagonist
It is calculated as pA2 = -log10(KA)
What is irreversible competitive antagonism?
Binds to receptors but dissociates very slowly, if at all
It decreases the maximum response to an agonist.
What are allosteric modulators?
Substances that bind to regulatory sites on receptors, modifying affinity or efficacy
They can potentiate or inhibit the activity of a receptor’s endogenous ligand or drug.
What characterizes non-competitive antagonists?
They block access of the agonist to its binding site through steric hindrance
Non-competitive antagonism is an example of allosteric modulation.
True or False: The maximum response to an agonist remains the same with a competitive antagonist.
True
The log dose-response curves are displaced to the right but maintain the same maximum response.
Fill in the blank: The _______ is the concentration of antagonist that makes it necessary to add twice as much agonist to produce a response as would be needed in the absence of the antagonist.
K_A
What is the difference between competitive and non-competitive antagonists?
Competitive antagonists bind reversibly to the active site, while non-competitive antagonists block access to the agonist through other means
Non-competitive antagonists do not compete directly with agonists for binding.
Define a receptor in the context of drug interactions.
Specialised, localised proteins that recognise stimulants and activate the cell.
What analogy is used to describe how drugs interact with receptors?
Lock and key analogy
What is the Law of Mass Action?
The rate of a chemical reaction is proportional to the product of the concentration of the reactants.
What do the symbols [D], [R], and [DR] represent in receptor theory?
[D] = concentration of drug, [R] = concentration of receptors, [DR] = concentration of occupied receptors.
What does the equilibrium dissociation constant (K_D) represent?
The concentration of drug required to occupy 50% of the receptors at equilibrium.
How is the pD2 value calculated?
pD2 = -log10(KD)
What is meant by ‘efficacy’ in drug-receptor interactions?
The capacity of a drug to initiate a response upon receptor occupation.
What is the relationship between drug concentration and biological responses?
There is a systematic relationship between drug concentration and the magnitude of the response.
What are spare receptors?
Extra receptors that are not required to evoke a maximum response.
True or False: A maximum response can be achieved by occupying 100% of the receptors.
False
What does the response α represent in occupancy theory?
The fraction of receptors occupied.
Fill in the blank: The maximum response of a tissue can be obtained by occupying _______ of the receptors.
less than 100%
What is the role of agonists in drug-receptor interactions?
Agonists activate the receptor.
What is the role of antagonists in drug-receptor interactions?
Antagonists do not activate the receptor.
What does a powerful drug do upon receptor occupation?
Produces a large stimulus that summates until a maximum response is reached.
What is the significance of the constants K1 and K2 in receptor theory?
K1 is the rate constant for associations, K2 is the rate constant for dissociations.
What is the main aim of drug-receptor theory?
To explain the concepts of drug-receptor interactions.
What are the four regulatory protein families commonly targeted by drugs?
- Enzymes
- Carrier molecules (transporters)
- Ion channels
- Neurotransmitter, hormone or local hormone receptors
