9 - time corse of immediate drug effect Flashcards
Definitions t1/2 Kd Emax C50
t1/2- time takes to half conc
Kd - conc at which 50% of receptors are occupied (will be same as c50 if effect is directly proportional to binding0
Emax - very hard to reach (as expodential curve of conc and effect)
-can use log to see larger range of concentrations - however log 0 is undefined so this is a problem
Emax model vs Sigmoid emax model equaiton
E = (Emax x conc) / (C50 + conc)
- conc - conc at receptor
- E - effect
- Emax - max drug effect
C20 - is 1/4 conc of c50 , c80 is 4 time C50
(model predicts a 16 time change to get from C20 to C80)
However - some drugs have steeper relationships of conc effect can be determined using sigmod emax moel
E = (Emax x Conc ^ hill) / (C50 ^ hill/ Conc ^ hill)
- hill greater than 1 - makes it steeper
- hill less than 1 - makes less steep
(not made into log)
(e.g when hill is 2 - then only takes 4 fold change in conc to go from c20 to c80)
-when hill very large -almost on off swtich to get this
Draw graphs of giving 10x cd50 conc, 100x cd50 conc or cd50 conc
- look at half lives versus CD50 conc and emax
- what do these show
- can you have a big effect with a short half life?
-Conc always follows expodential curve
10 x CD50 - at half life - the effect has only reduced a little bit, then after C50 - reduces faster
CD50 - conc and effect decrease at similar rates
100 x CD50 - Inital effect close to 100%, Conc decreases at normal rate, but effect stays high and doesnt decrease for ages (At half life, the conc is still at about 95%
These show that the time course of immediate drug effect depends upon initial concentration as well as pharmacokentics
These also show how drugs with short half-lives can have big effects even if dosing itnercal is many half lives
Draw graph of conc, effect, time and what are the 3 regions
Conc > c80
C80 > conc > C20
Conc < c20
Conc > c80 - flat (the effect is still very high and decreases at a much smaller rate than the conc)
C80 > conc > C20 - linear - effect still larger than conc and decreases at a smaller rate - effect decreasisng at about a linear rate, conc decreasing fast
Conc < c20 - almost exponential curve , and effect decreases at a greter rate than the conc . TIme course of conc and effect are almost parallel to each other (can only decribe effect as being a half life here)
Duration of response when the concentration is doubled - draw graph
- does the half life change?
- what does duration of response mean?
- does increasing duration of response make effect better?
Basically - shows that if the dose of a drug is doubled, then the duration of response will increase by one half life
- Even when the conc doubles, the half life does not change
- duration of response - time that drug effect is above a pre-defined critical value (e.g time above CD50 or anaethitised or not)
-with a low dose, the duration of effect is 20 hr, then with a doubled dose duraiton of effect will be 20hr + 1 half life
THIS IS ALL INDEPENDENT OF THE SIZE OF THE EFFECT - think of it as the time of the extent of a defined cirtical effect
Conc equation - Predicitng target conc from target effect
Conc = C50 x Effect / Emax - effect
-very important to figure out the defined clinical effect and make it into a target conc
What does selecting of a dosing interval do?
Depends on half life, also target conc and its realtion to CD50 as well
-some drugs can have short half lives and yet are still effective with oly one daily does (if you give big conc) - because normal a conc that is bigger than C50 then will last for a day
