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33 Cards in this Set
- Front
- Back
What is KD? |
The molar concentration of drug require to occupy 50% of receptors at equilibrium |
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How can we measure the affinity of a new drug e.g relaxin at cannabinoid receptors in the brain? |
Label the drug with a radioactive isotope We can gain information on the number of specific binding sites (cannabinoid receptors) in our tissue (brain) and the affinity of the drug (relaxin) for these receptors |
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How can we do a radioactive binding assay? |
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What is "hot relaxin"? |
Radioactive relaxin |
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What will occupy specific receptor sites and what will occupy non specific receptor sites? |
Specific receptor sites occupied by "cold" relaxin Non specific binding sites occupied by "hot" relaxin |
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For the first set of tubes, the amount of binding is plotting against the concentration of labelled relaxin. What will this give a plot of? |
"Total binding" and will include both "specific" (to receptors) and "non specific" (elsewhere) binding |
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How can we tell from this curve that the drug isn't just binding to receptors? |
If drug is just binding to receptors, line should eventually level off as there are a limited number of receptors. |
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For the second set oftubes plot the amount ofbinding against theconcentration of thelabelled relaxin. What will this give a plot of? |
Non-specific binding since all the receptor sites willhave been occupied by the“cold” relaxin and thus nothave been free to bind theradioactive drug |
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How can we get a measure of specific relaxin binding? |
Subtract non-specific binding from the total binding |
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What kind of plot is this called and why? |
A saturation plot as the specific binding saturates as the receptor sites become full |
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What can we calculate from data such as this? |
The maximum number of receptors per tissue (B max) The affinity of (KD) of the radioactively labelled drug |
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The extent to which the agonist curve is shifted by the antagonist is a measure of what? |
The affinity of the antagonist for the receptor |
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What is meant by the "dose ratio"? |
The ratio of concentration of agonist producing the same response in the presence and absence of the antagonist |
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Under control conditions, you may need 1mM of agonist to get a response, but then you use a reversible competitive antagonist and you now need 20mM to get the same response. What is the dose ratio? |
20 You have had to increase the concentration of drug by 20 times to get the same response |
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The extent to which you have to increase the concentration of agonist is a measure of what? |
The antagonists affinity to the receptor |
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For a reversible competitive antagonist, how should the does ratio increase with the concentration of agonist? |
Linearly |
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How is the affinity of a reversible competitive antagonist measured? |
Using its pA2. |
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What is |
The negative logarithm of the concentration of antagonist that necessitates that you double the agonist concentration to produce the same response (i.e dose ratio =2) |
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The presence of 6.3 x10-9 M propranololnecessitates that you need to double theconcentration of noradrenaline to producethe same increase in heart rate. What is the pA2 for propranolol? |
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A lower drug concentration gives a higher pA2. Do you want a drug to have a high or low pA2? |
High This means it is effective in low concentrations so less of the drug needs to be present to produce the blocking action |
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The pA2 can be obtained by experiment. A log [concentration] vs response curve for the agonist is plotted in the presence of several concentrations of antagonist. This allows the pA2 to be calculated by "Schild analysis". What else does it allow? |
Allows the experimenter to determine whether the antagonism is competitive. Schild analysis cannot be carried out on non competitive antagonists. |
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What is the Schild equation? |
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What is KB? |
The dissociation equilibrium constant (similar to KD) for the antagonist |
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For a reversible competitive antagonist a plot of log(dose ratio-1) vs log [antagonist] (aSchild plot) should have a slope of what and where does it intercept the x axis? |
Slope of 1 Intercept x axis at (log KB) |
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For a reversible competitive antagonist, what is pA2 equal to? |
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What is the first step in producing a Schild plot? |
Construct (log) [agonist] vs-response curves to the agonist in the presence of several concentrations of antagonist From the curves read the log EC 50 values for the agonist in the absence of presence of different concentrations of antagonist. Calculate the EC50 values for the agonist in the absence and presence of the different concentrations of antagonist |
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What is the second step in producing a Schild plot? |
Calculate the dose ratio for the concentration of each antagonist Plot Log (dose ratio -1) vs log [agonist] |
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The X-axis intercept occurs when Y=0 so what is the does ratio here? |
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If the slope of the Schild plot is not equal to 1.0 ( or at least fall in the range 0.8-1.2) them way does this suggest? |
The antagonism is either NOT competitive or NOT reversible |
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Is the pA2 obtained for the antagonist dependent or independent of the agonist used? |
Independent as it is a measure of the antagonists affinity for the receptor |
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2 different experiments with different agonists but with same antagonist should have different pA2s. True or False. |
False. Should have same pA2 because pA2 is nothing to do with agonist. |
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What does it suggest if the same drug has a different PA2 in the heart compared to the lungs? |
Receptors must be different. |
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What is B max? |
The maximum number of receptors per tissue |