L4: Drug Action at Receptors Flashcards
Learning Objectives: • Explain the role of receptors in cell signalling • Define the terms “specificity”, “affinity” and “efficacy” • List the main forms of antagonism produced by drugs • Describe the differences between the actions of full agonists, partial agonists and competitive antagonists on receptors - Describe the effect of a reversible competitive antagonist on the log concentration vs response curve for an agonist
What are receptors?
Protein macromolecules that are inserted across lipid bilayer of cell
2 main functions of receptors
1) Recognition/detection of extracellular molecules
2) Transduction
What is transduction?
Detect the presence of an extracellular membrane, then bring changes in cell activity
How do receptors interact with/ bind to with certain chemicals?
High degree of specificity
How are receptors named/classified?
With respect to the drugs they bind
Name given to any chemicals that bind to receptors
Ligands
Equation of binding of drug (D) to receptor (R)
D + R ⇄ DR
Whats the shape of a plot of proportion of receptors occupied vs drug concentration?
Rectangular hyperbola
What is the plot of proportion of receptors occupied (p) vs log (D)?
Symmetrical sigmoid
Define affinity of a drug for its receptor (KD)
Molar concentration of drug required to occupy 50% of the receptors at equilibrium
How is the concentration of drug given as?
KD
Is the KD high or low if a drug has a high affinity?
LOW
Equation for rate of FORWARD reaction
k+1 (D)(R)
Equation for rate of BACKWARD rate
k-1 (D)(R)
What is KD a measure of?
A measure of how tightly the receptor holds onto the drug once they come together
What is the KD?
Equilibrium Dissociation Constant
What is an agonist?
Substance that binds & active the receptor, then produce a conformational change in the shape of the receptor to lead a response in a cell/tissue
What is efficacy?
Ability of a drug to activate the receptor
What is affinity?
Strength of drug binding with receptor
What are the 2 types of agonist?
Full & Partial
What is a full agonist?
High efficacy; effective at activating receptors
What is the response of a full agonist?
Maximal response whilst activating a fraction of available receptors
What is a partial agonist?
Low efficacy; less effective at activating receptors
What is the response of a partial agonist?
Fail to produce full response despite occupying all available receptors
How is the overall response of an agonist determined by?
Affinity & Efficacy
What do we call drugs that show both affinity & efficacy at receptors?
Agonist
Why is the EC50 for an agonist drug not always the same?
Determined by affinity & efficacy
What is an antagonist?
A drug that stops the action or effect of another substance
3 forms of antagonism
Chemical, Pharmacokinetic, Physiological
What happens in chemical antagonism?
A drug combines with another to form an inactive product
What happens in pharmacokinetic antagonism?
Decrease another drug’s concentration at the site of action
What happens in physiological antagonism?
2 drugs act to produce opposing effects, so they cancel each other out
Which forms of antagonists does not act at the receptor?
Chemical, Pharmacokinetic and Physiological
Which forms of antagonists act at the receptor?
Competitive & Non-Competitive
What are competitive antagonists?
Compete with agonist for the same site on the receptor molecule, but don’t activate it
What are non-competitive antagonists?
Act at a different site on the receptor closely associated with it
What are reversible competitive antagonists?
Used to inhibit the effects of a neurotransmitter/hormone
How can reversible competitive antagonists inhibitory effects be overcome?
Increasing concentration of the AGONIST
What happens to the graph for reversible competitive antagonists?
Parallel shift to the right of the AGONIST
What are x & y axis on the reversible competitive antagonists graph?
x: log concentration of (agonist)
y: response
What happens to the line in the presence of an antagonist?
Shifts to the right
What happens to the shift in a IRREVERSIBLE competitive antagonist graph?
Shift is not parallel, inhibition they produce is not overcome by increasing agonist concentration
