Receptors: A Pharmacological Perspective Flashcards
What is the shape of a graph showing proportion of receptors occupied (Y) against drug concentration (X)
Rectangular hyperbola
What is the shape of a graph showing proportion of receptors occupied (Y) against log of drug concentration (X)
Symmetrical sigmoid (s-shaped)
What is Kd?
It is the concentration of the drug required to occupy 50% of the receptors at equilibrium.
Drugs with a low Kd have a high affinity for their receptor.
Define Efficacy.
The efficacy of a drug is its ability to activate the receptor. Drugs may have a high affinity (so easily bind to the receptor) but have a low efficacy.
What is the difference between partial agonists and full agonists?
Although they both have affinity, their efficacy differs.
Partial agonists have low efficacy and despite occupying all the available e receptors, they fail to produce the maximal response.
Full agonists have high efficacy so are able to produce the maximal response by activating fewer of the receptors. As a result there are many spare receptors.
Can you determine agonist affinity from response vs log [agonist] (symmetrical sigmoid) graphs?
No because response is dependent on both affinity and efficacy.
What is chemical antagonism?
Using one drug to chemically inactivate another e.g dimercaprol in arsenic poisoning
What is pharmacokinetic antagonism?
Using one drug to alter the way the body handles another e.g antacids prevent absorption of phenytoin from the gut.
What is physiological antagonism?
Two drugs act to produce opposing effects - glucagon and insulin in the regulation of blood glucose.
What is the difference between competitive and non-competitive antagonists?
Competitive antagonists compete with the agonist for the same binding site on the receptor molecule but DON’T activate the receptor.
- High affinity, zero efficacy and can be reversible or irreversible
Non-competitive antagonists act at a different site on the receptor or another molecule closely associated with the receptor.
How can the effects of competitive antagonists be reversed?
By increasing the concentration of agonist.
How does the the presence of a competitive antagonist alter the drug response vs log [agonist] graph?
The competitive antagonist causes a parallel shift to the right.
The size of the shift can be measured using the dose-ratio, which is the ratio of concentration of agonist producing the same response in the presence and absence of the antagonist.
The size of the shift is a measure of the affinity of the antagonist for the receptor - pA2
What is pA2 in terms of antagonism?
It is the negative logarithm of the molar concentration of antagonist that necessitates that you double the agonist concentration to produce the same response.
The affinity of an antagonist is quantified using its pA2.
How does the the presence of an irreversible competitive antagonist alter the drug response vs log [agonist] graph?
The height of the sigmoid curve is reduced and there is a non-parallel shift to the right.
Define potency.
A potent drug is effective in very small amounts.
Both agonists and antagonists have potency.
Quantified using EC50 - The effective concentration that produces 50% of the maximal response.
