Lecture 5 - Drug Receptor Interactions Flashcards
Which amines are chiral?
Only quaternary
What are the principles of drug-receptor interactions similar to?
Drug-enzyme interactions
Does every receptor have an endogenous ligand?
Usually
What is an orphan receptor?
A receptor with an unknown endogenous ligand
Compounds with similar ______ will often bind to the same receptor
Structure
Do receptors have an infinite binding capacity?
No, binding can be saturated
Receptors are ____ specific
Tissue (they are in the tissues that need to respond to the ligand)
What does a ligand act as?
A chemical signal that produces the biological response at a specific tissue
What type of interactions do drugs use to bind to receptors and which are the most important?
- The same interactions that drugs form with solvents
- Most important - dispersion, H-bonding, ionic, ion-dipole
What are dispersion interaction referred to as for protein interactions?
Hydrophobic interactions
Is there a relationship between the number of drug-receptor complexes and the magnitude of biological response?
Yes
What is the effect of a drug related to?
The fraction of bound receptors
What is Kd and what are its units?
- Equilibrium dissociation constant; the [drug] at which you get half maximal binding
- mol/L
What is Kd a measure of?
How the equilibrium is displaced to free drug and free receptor
What does a small Kd mean?
- More drug-receptor complex, so more biological response
- Tight binding
What is the affinity constant?
1/Kd
What does a higher affinity constant mean?
Tighter binding
What do we know about a receptor that has a Kd of 1 mM?
A 1 mM [drug] will produce half maximal receptor binding
What is [Rt]?
Total receptors
What is f?
Fraction of receptors bound proportional to biological effect
What is efficacy proportional to?
The amount of drug-receptor complexes
What is intrinsic activity?
The ability of the drug to produce an effect by forming a drug receptor complex
Are intrinsic activity and affinity related?
No
Is intrinsic activity dependent on Kd?
No
When is Emax achieved?
When all receptors are bound to drug
What is ED50?
[drug] at 1/2 Emax
Can Kd and ED50 have the same value?
Yes, but they are not the same thing
What does ED50 reflect?
Potency
What does a lower ED50 mean?
Less drug needed to get the maximal response, therefore more potent
Does potency tell you anything about the effect of the drug?
No
What is potency independent of?
Intrinsic activity or efficacy
Can a drug have high potency and low intrinsic activity?
Yes
Often drugs of a similar chemical class that target the same receptor have the same _____ but differ in ______
- Maximal effect
- Potency
Why do Kd and ED50 often have the same value?
B/c we defined the effect as being directly proportional to receptor binding and we defined maximum effect as being achieved when all receptors are bound
Efficacy is the relationship between ____ and _____
Effect and amount of drug-receptor complexes
What does it mean when Kd > ED50?
Maximal effect is achieved without binding all receptors
What is spare receptor theory?
When maximal effect is achieved without binding all receptors
When does spare receptor theory usually happen?
When there are a series of biochemical events that transmit the signal of receptor binding across the cell membrane (signal amplification)
What do agonists do?
- Bind to receptors
- Have affinity for the receptor
- Have intrinsic activity
Do most receptors have an endogenous agonist?
Yes
What is a full agonist?
Binds to receptor and is capable of producing the same maximal response as endogenous agonist
What is a partial agonist?
Can bind to receptor (has affinity) but produces a smaller than maximal response and has a lower intrinsic activity than full agonist
What do antagonists do?
- Bind to receptors
- Have affinity for the receptor
- Have no intrinsic activity
What are the most important antagonists?
Competitive and non-competitive
What is the difference between competitive and non-competitive antagonists?
How they interact with the receptor and an agonist
What do competitive antagonists do?
Have similar shapes as the agonist and can fit into the agonist binding site
Can a competitive antagonist bind to the receptor if the drug is already bound?
No
What does a competitive antagonist do to Kd?
Increases Kd or decreases affinity of agonist
How can competitive antagonism be overcome?
Increasing the amount of agonist
Does a competitive antagonist change the efficacy of the agonist?
No, but the apparent ED50 for the agonist increases
Why does ED50 change in the presence of a competitive antagonist?
Because the antagonist competes with the agonist for the same receptor, which increases the dose needed to achieve the same effect (decreases potency)
Do non-competitive antagonists bind to the same site as the agonist and what does this mean?
No, so they can be structurally different
Does a non-competitive antagonist change the affinity of the agonist for the receptor when it is bound?
No
What does a non-competitive antagonist do?
Binds to or inhibits the empty receptor or the drug-receptor complexes effectively decreasing the pool of receptors
A non-competitive antagonist is characterized by _____
Decreasing the apparent number of receptors
What does a non-competitive antagonist do to Kd and potency?
Both remain unchanged
Can you overcome non-competitive antagonism by adding more agonist?
No
