Receptors Flashcards
What is relative potency?
Comparing the potency of two drugs with the same method of action on a graded response curve.
What is tachyphylaxis?
A reduction in the sensitivity of a receptor to a drug
Do all tissues show tachyphylaxis?
No
How can tachyphylactic response be mitigated?
Using a discreet dose response allows for the receptor to be ‘reset’ in between doses by washing or leaving an amount of time
What is a quantal response?
All or none response
How are quantal responses measured if they don’t have a graded response?
By measuring the % of individuals that showed a response
When comparing 2 drugs EC50, what should you check?
That they have the same moa, otherwise a comparison is futile.
What can alter relative potency?
Drug interactions
If 2 drugs have the same moa, what can happen to their sensitivity?
It can decrease the sensitivity as both drugs will be competitively competing for the binding site.
What governs drug occupation of receptors?
The drugs affinity to the receptor
What governs the drug’s ability to activate a receptor?
The drugs efficacy to activate the receptor
Which type of drugs occupy but don’t activate?
Antagonists
What is the ‘Occupancy’ (Pa) of a drug?
The fraction of receptors that are occupied by the receptor
In the presence of an antagonist, what happens to the concentration response of an agonist?
The concentration required for the same response. The curve shifts to the right=> dextral shift
What is a surmountable receptor-ligand binding?
An antagonist binds to the receptor in a reversible fashion
How can binding be ‘surmounted’
Adding more agonist competitively out competes the antagonist
What is insurmountable receptor-ligand binding?
An antagonist that binds to a receptor with a permanent covalent bond
What happens to the graded response curve with a surmountable antagonist?
It shifts to the right
What happens to the graded response curve with an insurmountable antagonist?
The agonist response will show a decreased maximum response
What are spare receptors?
The excess expression of receptors in the cell membrane. A greater number of receptors are present than is required to produce a strong response.
What is the effect of spare receptors when comparing lab results to clinical trials?
Usually, a larger concentration of antagonist is required to produce a significant inhibitory response as the ‘spare’ receptors can still be used by the agonist
What is the efficacy of an agonist?
The efficacy of a drug relates to the affinity and ability to activate specific receptor states
What is the efficacy of an agonist?
It is efficacious towards receptors in the ‘off’ state; it causes them to switch to the ‘on’ state
What is the efficacy of an inverse agonist?
It is efficacious towards receptors in the ‘on’ state; it results in them turning to the ‘off’ state
Which type of cellular responses do inverse agonists have an effect on?
Constitutively active responses
What is the difference between antagonism and an antagonist?
Antagonism is the process of an agonist binding to a receptor and activating a downstream pathway that results in blocking a pathway- it does not block the receptor itself like an antagonist
What is physiological antagonism?
A drug which produces the opposite biological effect
What is pharmacokinetic antagonism?
A drug which reduces the absorption or increases the elimination of a drug which, overall, decreases its concentration in the target area
What is chemical antagonism?
A drug which binds/reacts to another drug rendering it inert/inactive
What is non-competitive antagonism?
A drug that activates a blocking pathway (inverse agonist)
Name two ways in which tachyphylaxis can occur.
1) The binding of a ligand can temporarily cause the shape of the receptor to change so that for a short period of time it is unable to bind to a ligand. This is a refractory period.
2) The cell can temporarily remove receptors from the cell membrane
What is the therapeutic index?
LD50/ED50
What can the therapeutic index show?
It demonstrates the ‘safety net’; the difference in concentration between a lethal dose and a therapeutic dose
What are silent receptors?
Silent receptors are receptors whose downstream action is unclear
What are the two primary reasons for ‘silent’ receptors?
Some have a function that is, as of yet, undiscovered and others have no use; they once formed as part of a pathway but evolution has removed the pathway but not the receptor
What do ‘silent’ and ‘spare’ receptors act as?
