Receptors and the effects of drugs Flashcards
what is the Kd of a drug?
The concentration of a drug when it is bound to receptors to be 50% saturated
What is EC50?
The effective concentration to produce 50% of the maximum response
what is the patch clamp technique?
A method for looking at responses generated by individual receptors
What is the effect of a full high efficacy agonist, a partial agonist, an antagonist and an inverse agonist on a response when measuring the response of receptors?
You will get a response each time the full agonist is activated.
A partial agonist will have fewer channel openings when the agonist is stimulated and lower max response.
An antagonist will produce no response or a very little response (spontaneous opening) as all the antagonist will do is prevent the agonist form binding.
An inverse agonist will have no/decreased response.
what is the allosteric site on a GABAa receptor?
The benzodiazepine receptor or binding site
What is the effect of a ligand binding to the benzodiazepine receptor?
BZ agonists increase the affinity of the GABA site for GABA and therefore increases channel opening
Give some benzodiazepine receptor ligands
Agonists - Diazepam
Antagonist - Flumazenil
Inverse agonists - betacarbolines
What happens when there is an agonist and a positive allosteric modulator?
Increased binding to the receptor.
What are some different types of antagonism?
Competitive antagonists Irreversible antagonists Allosteric antagonists Physiological antagonist Channel blockers
What are competitive reversible antagonists?
Produce a parallel shift to the right of the agonists log D/R curve
They compete with the agonist for the same binding site
both the agonist and antagonist bind reversibly
presence of the antagonist decreases the probability of agonist binding
Give an example of a competitive reversible antagonist.
Naloxone in opiate overdose which cause a reverse of the effects of heroine
What is right-shift when there is an increasing antagonist concentration?
As the antagonist concentration increases, the agonist concentration goes down as there are fewer receptors available to bind to the agonist.
Each increase in the antagonist will cause a right-shift on the graph showing that a maximal response can still be produced at a higher agonist concentration.
How can we quantify the effect of the antagonist?
Compare the EC50 with the new EC’50 after the agonist is combined with the antagonist and then do a dose ratio (DR).
How do you calculate a DR?
EC’50 / EC50 = 100
Define the concentration ratio
The ratio of the concentration of an agonist that produces a specified response in the presence of an antagonist to the agonist that produces the same response in the absence of antagonist.
eg. EC50 agonist in presence of antagonist / EC50 agonist alone
What are irreversible antagonists?
Compete with the agonist for the same binding site
BUT antagonist binds irreversibly
presence of the antagonist will decrease the number of available receptors and hence decrease the maximal response.
How can a maximal response be produced when a irreversible antagonist is used?
The presence of spare receptors enables the agonist to still be able to produce a maximal response.
What are non-competitive antagonists?
An antagonist that binds at a different binding site and therefore prevents the effect of the agonist without effecting its binding.
The effect of a non-competitive antagonist is insurmountable. - Ie it cannot be overcome by increasing [agonist] and therefore does not change the E50 for the agonist
What is the effect of partial agonists on a response?
Partial agonists can behave as a competitive antagonist.
Increasing the concentration of partial agonists cause a depression of the maximal effect as more receptors are binding to the partial agonist out competing the full agonist.
What are allosteric antagonists?
Bind reversibly at a distinct site from the agonist and decrease agonist affinity.
They reduce likelihood of agonist binding
What is the effect of an agonist with a negative allosteric modulator?
Causes a decreased functional response
What are channel blockers?
eg. phencyclidine (PCP) at the NMDA receptor.
bind inside the channel and prevent the passage of ions.
binding of channel blockers tends to be enhance by receptor activation (use dependence)
What are physiological antagonists?
eg. Acetylcholine and adrenaline in the heart.
eg. Papaverine and acetylcholine in the ileum.
Produce opposite effects on a tissue
Produce a non-selective suppression of the response
What is desensitisation?
Prolonged or repeated exposure to an agonist reduces the response to that drug.
eg. inactivation of nicotinic receptors.
