Dose Response Relationship Flashcards
Magnitude of drug effect on a cell depends on?
Receptor sensitivity to the drug.
Drug concentration at receptor site.
This two above depends on;
The dose of administered drug and
Pharmokinetic profile.(ADME)
Graded dose relationship explains what?
It explains that as the drug concentration is increased the pharmacologic effect is increased until all the receptors are occupied.
What are the important drug characteristics that can be determined with dose response curve?
Efficacy and potency.
What is potency
It’s the amount of drug required to produce an effect.
What is EC50
It’s the concentration of drug required to produce half maximum effect
How do you know drug A is more potent than drug B?
If drug A has a lesser EC50 than drug B
Example of drugs that is used to measure potency
Candersartan and Irbesartan (ARB’s)
Which is more therapeutic potent?
Candersartan or Irbesartan
Candersartan is more therapeutic potent.
Requires 4-32mg to produce effect while;
Irbesartan requires about 75-300mg
What is efficacy?
It’s the magnitude of response a drug causes when it interacts with a receptor
Factors that affect efficacy include?
Number of drug receptor complex.
Intrinsic activity of the drug(i.e ability of a drug to activate a receptor)
A drug is said to be Emax when?
All the receptors have been occupied.
Increase in concentration of the drug has no effect here.
Does an antagonist have Emax, why?
No?
Because it doesn’t have any effect, so Emax is 0
Which is more therapeutic relevant?
Potency or efficacy?
Efficacy, this is because it tells how good a drug is in producing desired effect.
What is law of mass action
Principle that the rate of chemical reaction is directly proportional to the concentration of the substance.
The quantitative relationship between drug concentration and receptor occupancy respect what law?
The law of mass action
What does affinity describe
Strength of binding between ligands and receptor
Explain what Kd(affinity) means to be lower or higher.
The higher the Kd value the weaker the interaction btw drugs and receptors.
This is because a greater strength is required for the interaction of receptor with drug.
State the vice versa.
What is the explanation to effect of drug concentration to receptor binding
As concentration of free drug increases the ratio of concentration of bound receptors to total receptors approach unity
Formula for the effect of drug concentration on receptors
DR/Rt = [D]
———
Kd + [D]
DR: drug receptor complex
Kd: equilibrium constant, measures affinity to receptor.
[D] : free drug concentration
What are the assumptions that have to be met for law of mass action to be applied to drug concentration and response;
1) The magnitude of response is proportional to the amount of receptors occupied by the drug.
2) Maximum efficacy occurs when all receptors are bound.
3) one molecule of drug binds to only one molecule of receptor.
What is the formula to this assumption;
E/Emax =. [D]
——-
Kd + [D]
Emax: maximum effect of drug
E : effect of drug at concentration [D]
What is this assumption trying to tell in summary?
It’s trying to tell that the affinity of drug binding to receptor should be related to the potency of the drug that cause the physiologic effect in a receptor
