Antagonist Actions - Receptors and Drug Actions Flashcards
What does a competitive antagonist do?
binds to receptor so agonist can not; it inhibits agonist from binding therefore inhibiting a response; they compete with other agents for the binding site
Key properties of competitive antagonists:
increase the concentration of agonist required to bind a give fraction of receptors; induce a given level of response, shift agonists dose curve to the right to higher the agonist concentrations
What happens to agonist curves when antagonists increase?
shifts to right; agonists can still have full-effect at high enough concentration by “out-competing”
Shift = 1 + [B]/Kb
[B] = antagonist concentration, Kb = antagonist Kd.
1xKb = agonit curve shifted by factor of 2
9xKb = shifted by factor of 10
99xKb = shifted by factor of 100x
(more B, more shift to right)
By increasing antagonist concentrations, we shift agonist dose response curve to right. What happens to the response to a fixed concentration.
Increasing antagonist concentrations DECREASES the response to a fixed concentration of agonist.
IC50 refers to what?
half-maximal inhibitory concentration
Increasing antagonist concentrations does what to the response to a fixed concentration of agonist?
DECREASES
Explain how agonist/antagonist binding can be reversible.
Which ligand is present at a higher ratio to its own Kd determines who occupies the receptor most.
What is a partial agonist?
don’t turn on receptor all the way, but active some of it, but not all (dimmer light)
What is efficacy?
how well the drug activates the receptor when it is bound;
ZERO efficacy = antagonists, 100% efficacy = agonists, in between 1%-99% = partial.; lower intrinsic activity
Differentiate between X axis and Y axis properties.
X axis: affinity and potency (related to concentration)
Y axis: efficacy (related to magnitude of maximal response when all receptors are bound)
Give potency example.
If drug works at low concentration, it has a high potency.
Give efficacy example.
If drug generate a large fractional response, it has high efficacy.
Define potency.
How much drug you have to give to get half of the maximal response.
(a drug can work at very low concentrations (be potent) but induce only a small response (low efficacy)
T/F. Many of the most effective drugs are antagonists with an efficacy of zero.
TRUE
A partial agonist has less than 100% response, even with 100% receptor occupancy.
TRUE
Explain why partial agonists are also partial antagonists.
Partial agonists reduce the full response of agonists, but won’t bring it all the way down to zero; therefore they have partial antagonists effects, too.
Endogenous activation state of receptor’s levels can tell you what?
Low endogenous activation = going to act like agonist (help with low HR, ensure adequate resting heart rate),
High endogenous activation = going to act like an antagonist (help with high HR, prevent over-stimulation of heart with exercise or stress)
Define receptor subtypes.
multiple different receptor proteins for the same endogenous ligand
Properties of subtypes:
different drug selectivity, couple to different signaling pathways and effects, expressed differently in various tissues and cell types, different regulatory properties
Example of subtype-selective drugs.
H1 vs. H2: H1 targeted anti-histamines for allergies, H2 targeted anti-histamines for ulcers
Define desensitization.
decrease in sensitivity or maximal response.
How can desensitization occur?
covalent modification, endocytosis, internalization, down-regulation.
