Time course of immediate drug effect

Question 1

What are the benefits and short comings of a log transformation of a normal rectangular hyperbola of conc vs effect?

Answer 1

Benefits: Can see smaller and larger concentration

Negatives:

1) the log transformation implies that at lower concentrations, the effect increases slowly, which is not the case, it is in fact at lower concs the effect is rising the most. Is due to mathematics and the log function.
2) when drug conc is 0, effect is zero. A log scale will say negative infinity

Question 2

Don’t have to learn but what equation represents the Emax model?

What are some model predictions?**

Answer 2

Drug effect= Emax x conc/ C50 + conc

If you are to double the C50, the effect does not double. If you increase the conc by four times the C50, you only get a 30% (50-80) increase in effect. Same is if you quarter the C50, 20% of the max effect

Thus a 16 fold change in conc (from a quarter C50 to 4 times C50) is required to change 20% of max effect to 80% of max effect.

Question 3

What does the sigmoid emax model show?

Answer 3

That an extra parameter, a Hill coefficient can make a conc effect graph more steep.
Example is with a hill coefficient of 2, only a 4 fold change in conc is required to go from C20 to C80

an extreme like an off on switch is at very high hill coefficients, some anti-arrythmics are the closest we can get?

Question 4

What does the grpah showing concentration peak = 10 x the C50 show?

Answer 4

There is no half life of drug effect, due to the non exponential nature of the curve.
The effect of the drug reduces quite slowly.

Question 5

Conc peak= C50 graph

Answer 5

With a smaller dose, the effect curve is similar to that of the concentration curve.

Question 6

Conc peak= 100 x the C50 curve

practicality point

Answer 6

At these really high doses, as the concentration declines, the drug effect barely lowers. eg 48 hours later the drug effect is still at 70 of the total.

this is useful in that you can give some pills twice a day in large concentrations that will not effect us. This leads in increase in adherence

Question 7

What are the three regions of the time course of effect graphs?

Answer 7

Flat: Conc > C80
Linear: C80> conc> C20
Exponential: Conc < C20

Question 8

What is the important message to understand about the duration of response?

Answer 8

That doubling the concentration will prolong the duration of effect by one half life.

Question 9

What are some applications of the duration of response model?

Answer 9

1) Can predict target concentration by rearranging the Emax equation, from the target effect
2) Time course, selection of appropriate dosing interval depends on half life and the C50 (some drugs only have a short half life, but can be administered daily due to high concs not affecting us?)
3) doubling dose does not double effect, it increases duration of effect by one half life