Pharmacodynamics - receptors Flashcards
What are drug concentrations calculated in? Why?
Molarity
Because it looks at the number of molecules per L
How is molarity calculated?
g/L
___
Mr
What are the different units of molarity?
molar, M
millimolar, mM
micromolar, muM
nanomolar, nM
picomolar, pM
How do you get from molar to millimolar?
Multiply by 1000
How do you get from millimolar to molar?
Divide by 1000
What is a ligand?
A molecule or ion that binds specifically to a receptor
How do ligands interact with receptors?
Bind to receptors
and then dissociate from the receptor
What is the proportion of ligands that bind to receptors?
Enough to reach equilibrium in the reversible reaction
ligand + receptor ligand-receptor complex
What are the effects that a ligand can have on a receptor once it’s bound to it?
Can activate it
Can just bind to it with no other effect
What are the types of ligands based on the effect they have on the receptor?
Agonists - activate the receptor
Antagonists - bind to the receptor, block it from agonists
What must a ligand have in order to bind to its receptor?
It must have affinity for the receptor
What is affinity?
The ability of the ligand to bind to its receptor
What must a ligand have in order to activate its receptor
Intrinsic efficacy
What is intrinsic efficacy?
The ability of the ligand to activate its receptor
What must a ligand have in order to bring about a cell response?
Efficacy
What is efficacy?
The ability of the ligand to bring about a larger cell response
What are the factors of efficacy?
Intrinsic efficacy
Other factors inside the cell, tissue etc.
Do agonists and antagonists have affinity?
Yes
because both bind to their receptor
Do agonists and antagonists have intrinsic efficacy?
Only agonists do, because only agonists activate the receptor
not antagonists
Do agonists and antagonists have efficacy?
Only agonists do, because only agonists activate the receptor to start off the process of bringing about the cell response
not antagonists
Why do antagonists not have efficacy?
Because they cannot activate the receptor
so it can’t interact with effector proteins
no cell response
What shape does a graph of x axis-drug concentration against y axis-receptor saturation look like?
Rectangular hyperbola
What is Bmax?
Maximum binding of receptors
What is Kd?
Drug concentration that gives half of Bmax
What does Kd measure? How?
Measures affinitiy of drug
The lower the Kd, means lower concentration of drug required to bind to half of the receptors, so drug has higher affinity for receptor
and oppositely too
What shape does a logarithmic graph of x axis-drug concentration against y axis-receptor saturation look like?
Sigmoidal curve
What is the difference between concentration and dose?
Dose - drug concentration given to patient, at site of action is unknwon
Concentration - known drug concentration at site of action
What shape does a graph of x axis-drug concentration against y axis-size of response look like?
Rectangula hyperbola
What is Emax?
Maximum size of response
What is EC50?
Drug concentration that gives half of Emax
What is EC50 a measure of?
Potency
What is potency?
The ability of a ligand to bind to its receptor, activate its receptor and bring about a cell response of a certain size
What are the factors of potency?
Affinity
Intrinsic efficacy
Efficacy
Number of receptors
What would a logarithmic graph of x axis-drug concentration against y axis-size of response look like?
Sigmoidal curve
For a ligand-receptor complex, which of the following are fixed and which are variable:
- affinity
- intrinsic efficacy
- efficacy
- potency
Affinity - fixed
Intrinsic efficacy - fixed
Efficacy - variable
Potency - variable
Do all of the receptors have to be bound by ligand in order to get the maximum response? Why?
No
because of spare receptors
What are spare receptors?
Receptors that don’t need to be bound to
to get the maximum response
Why is it possible for spare receptors to exist?
Because of signal amplification
few ligands binding to their receptors can generate a relatively massively response
Responses are limited
can’t continuously increase all the time
How does receptor number affect potency?
If have a higher number of spare receptors
lower concentration of drug needed to give bigger response
means higher drug potency
How does receptor number affect the maximum response?
Need to have enough receptors to give maximum response
if have fewer receptors, get smaller response than maximum
Can receptor number change?
Yes, not fixed
How can receptor number change? Why?
Can increase in number, with low activity
Can decrease in number, with high activity
How does drug tolerance develop?
Cells decrease their receptor number
need higher concentration of drug to bring about same-size response next time
How do the graphs for x axis-drug concentration against y axis-receptor saturation and y axis-size of response compare if there are no spare receptors?
They are the same
same percentage of receptor saturation gives same percentage of size of response
How do the graphs for x axis-drug concentration against y axis-receptor saturation and y axis-size of response compare if there are spare receptors present?
The size of response curve is to the left of the receptor saturation curve
means smaller percentage of receptor saturation gives bigger percentage of cell response
What is intrinsic activity?
The ability of the ligand to produce the maximum sized response
What are the types of agonists?
Full agonists
Partial agonists
What are full agonists?
Agonists that can bring about maximum response
What are partial agonists?
Agonists that can only bring about part of the maximum response
What are the intrinsic activities of full and partial agonists?
Full agonists have high intrinsic activity
Partial agonists have low intrinsic activity
What are the efficacies of full partial and agonists?
Full agonists have high efficacy
Partial agonists have low efficacy
How do spare receptors relate to full and partial agonists?
May or may not be spare receptors with full agonists
No spare receptors with partial agonists but still don’t give maximum response
Are partial agonists fixed?
No
can be converted into full agonists
How is a partial agonist converted into a full agonist?
By increasing receptor number
still low efficacy at each receptor but enough receptors to add up and give maximum response
What are the types of antagonism?
Competitive
- reversible
- irreversible
Non-competitive
What is the most common type of antagonism?
Reversible competitive antagonism
What is reversible competitive antagonism?
Antagonist binds to ligand-binding site on receptor
prevents agonist binding
What shape does a graph of x axis-antagonist concentration against y axis-size of response look like?
Vertically reflected sigmoidal curve
What is IC50?
Concentration of antagonist that gives inhibition of 50% of the maximum response
What is IC50 a measure of?
Antagonist potency
How are the effects of reversible competitive antagonism overcome?
By increasing the concentration of agonist
so it outcompetes the antagonist and binds to the ligand-binding site on its receptor
How do reversible competitive antagonists affect the drug concentration-size of response curve?
Cause it to shift to the right
meaning a higher drug concentration is required to give the same-size response
What is irreversible competitive antagonism?
Antagonist binds to ligand-binding site on receptor
does not dissociate
prevents agonist binding
How are the effects of irreversible competitive antagonism overcome?
They can’t be
How do irreversible competitive antagonists affect the drug concentration-size of response curve?
Shift the curve to the right as higher drug concentrations are required to bind to the spare receptors
Suppress the curve as there are not enough available receptors to produce the full response
What is non-competitive antagonism?
Antagonist binds to allosteric site
reduces effects of affinity or efficacy of agonist at orthosteric site
What is the orthosteric site?
Site where endogenous ligand binds
What is pharmacodynamics?
Study of what a drug does to the body
