lecture 14 - pharmacodynamic principles and time course of immediate drug effects Flashcards
Emax model
- maximal effect of a drug
- asymptote (as Emax is at [drug] = ∞)
- C50 = conc. at 50% of Emax
E = drug effect conc = conc at receptor Emax = maximum drug effect C50 = conc at 50% Emax
E = slope x conc
duration of response
doubling dose of drug increases duration of effect (time
taken to drop to a specific effect) by 1 half-life
Emax model predictions
where Emax = 100 & C50 = 1:
• 0.25(C50) = 20%
• 4(C50) = 80%
• thus between 20% and 80% of Emax, there is a 16x increase in concentration
sigmoid Emax model
E = drug effect conc = conc at receptor Emax = maximum drug effect C50 = conc at 50% Emax Hill coefficient = steepness of curve
↑ coefficient gives a greater increase in effect for the same increase in concentration = “steep approach to Emax” (over the approximately-linear portion of the curve
from C20-80)
more appropriate for specific concentration/effect models (eg. HbO2 curve)
effects of doubling a dose
- does not lead to doubling of effect
- it will increase the duration of effect by 1 half-life
what does the time course of immediate drug effect depends upon
the initial concentration as well as the pharmacokinetics of the drug
what happens when the initial concentration is the same as C50
initial effect will only be 50% of Emax
at lower concentrations the the time course of effect is almost parallel to the time course of concentration
what happens when the initial concentration is 100x the C50
initial effect is close to 100% of Emax
effect changes very little despite big changes in drug concentration
(high concentration almost flat curve)
what happens when the initial concentration is 10x the C50
produces an initial effect of 90% of Emax
after one half-life the conc is halved but the effect has changed by less than 10%. As conc falls the effect disappears more quickly
