Flashcards in 15. Drugs and Receptors Deck (14)
Give an example to show how spare receptors increase sensitivity.
If a full response requires 10000 activated receptors and there are no spare receptors, then a full response requires 100% occupancy. So needs more than the Kd concentration of the drug. With spare receptors, the receptors of the cell could be 20000. So only Kd concentration of agonist is needed for a full response. This is a lower concentration than without spare receptors.
How do receptor numbers adjust?
They increase with low activity, up-regulation, but decrease with high activity, down-regulation.
Why do partial agonists have lower intrinsic activity than full agonists?
They have lower efficacy.
What is the use of partial agonists?
They allow a more controlled response. They can work in the absence of ligands and can act as an antagonist if high levels of full agonist.
Compare the affinity and efficacy of morphine and buprenorphine.
Buprenorphine has a higher affinity than morphine, but is a partial agonist so has low efficacy than morphine.
How can opioid addiction be treated?
Using buprenorphine. It occupies the receptors but gives a limited response. So now, even if the addict takes heroin, there are no free receptors for it to act on so it gives no relief from withdrawal symptoms.
How can a partial agonist act as a full agonist?
If the receptor number increases enough that there is still a full response.
What are the pathways in which antagonists can act?
Reversible competitive antagonism, irreversible competitive antagonism and non-competitive antagonism.
How does reversible competitive antagonism work?
It relies on a dynamic equilibrium between ligands and receptors. If more antagonist is present, then it will bind more to the receptors than agonists, thus inhibiting agonists. This inhibition cna be overcome with high agonist concentrations though.
What is IC50?
Index of antagonist potency.
How does irreversible competitive antagonism work?
The antagonists dissociate slowly or not at all from the receptors. This is non-surmountable as no amount of agonist will displace the antagonists from the receptors.
How does non-competitive antagonism work?
The antagonist binds to an allosteric site. This can affect orthosteric ligand affinity and/ or efficacy.
What are some of the features of allosteric regulation of GPCRs?
Higher receptor subtype selectivity, non-competitive, often requires orthosteric ligand.