Drug Affinity and Efficacy Flashcards
What does a scatchard plot represent?
Affinity of a drug
How can we determine drug affinity?
By calculating the law of mass action
[Drug] + [Receptor] = [DrugReceptorconcentration]*
What is Koff?
The rate at which a drug unbinds to a receptor
What is another way to think of Bmax?
It is the point at which the specific binding curve levels off
Kd is always measured in terms of what?
Concentration (= affinity for specific drug)
* Kd only ever refers to the affinity of one drug for one receptor
What is another way to think about efficacy?
Efficacy is what the drug does when it is bound to a receptor (how big of an effect will the drug have on its receptor?)
When a receptor has a greater conformational change, what can be said in terms of efficacy?
Greater conformational change = greater efficacy
What is a conformational change?
Change in receptor shape due to the bonding of a ligand (results in the opening of a channel)
What is a cholinergic neuron?
A neuron that releases ACh as its neurotransmitter
What is an agonist?
Any substance that mimics the effect of a neurotransmitter (any ligand that binds to a receptor and activates it)
What is an antagonist?
Any substance that blocks the effects of an endogenous NT on its receptor
Do antagonists have an effect on the receptor itself? What does this mean in terms of antagonist efficacy?
No, they simply block the activation from an agonist from being carried out
- even though an agonist and an antagonist can have similar affinities, antagonists do not have any efficacy, because they themselves do not act on receptors
In what two ways can antagonists act?
- they can displace the neurotransmitter attempting to bind to the receptor by forming a covalent bond with the receptor (competitive antagonist)
- They can bind on a different receptor site and block the NT that way (non-competitive antagonist)
What is an inhibition binding curve?
It looks at how much an antagonist blocks the effect of the agonist
What does a graded dose-response curve show us?
That antagonists decrease the efficacy of a drug, because there needs to be a higher concentration of the agonist to counteract the effects of the antagonist (to achieve the same result)
What does Emax signify?
The maximum efficacy of a drug
What is EC50?
Effective concentration at 50% of the maximum
What does EC50 tell us?
It gives us information about the overall potency of a drug
- this tells us all at once about the availability of the drug, its affinity, and the efficacy of the drug
What is a competitive antagonist?
An antagonist that the agonist can outcompete (for example, when the antagonist reaches Emax, there may still be some free receptors for the agonist to bind to)
What is a non-competitive antagonist?
When the presence of the antagonist causes the Emax of an agonist to decrease (because it is not competing for the same bonding site)
What is an allosteric bonding site?
A site on the receptor away from the active site
What is ED50?
The dose at which 50% of the population responded to the drug
What is TD50?
The dose at which 50% of the population experienced negative side effects
What is LD50?
The dose at which 50% of the population ingested a lethal dose
How do we calculate the range of safety [i.e. the therapeutic index] of a drug?
Divide the LD50 by the ED50
OR
TD50/ED50 (if a lethal dose 50 is not available; usually “do not exceed” refers to the toxic dose)
What is a quantal dose response curve?
It measures the percentage of the population responding to the drug (looks at the dose for which a response occurred)
