Lecture 14: Time Course of Immediate drug effects

Question 1

Emax model of drug action?

Answer 1

Parabolic curve

Kd and C50 are the same if the effect is directly proportional to the binding.

NB: emax can NEVER be directly observed.

Question 2

Log tranformtion of the Emax model?

3 issues with this model?

Answer 2

• The concertrations values able to be expressed are of a much larger range.
• A sigmoid graph is formed where very high concertrations can be seen to reach close to Emax
• Between 20-80% of Emax the grah is apporx proportional (straight line)

1. Doesn’t account for 0 effect at 0 conc.
2. Doesn’t recognise that in a biological system it will only appraoch a maximum but never theoretically reach it.
3. slope isn’t reflective of rate

Question 3

Effect equation

Answer 3

E = (Emax x Conc) / (C₅₀ x conc)

Question 4

Kd and C50 are what?

C20 and C80? implications?

Answer 4

Kd = the affinity constant where 50% or receptors are bound

C50 = is the concentration of drug producing 50% of Emax

C20 = 1/4 of C50

C80 = 4x of C50

This means that the Emax model shows a 16x increase in conc needed for the effect to change from 20% to 80%

Question 5

The sigmoid Emax model? Different from Emax model?

Different co-efficient values?

Answer 5

This model is the same except that it includes the Hill Coeffiencent above the concentration.

Hill < 1 = (eg EPO) as more is bound the slope decreses so a much larger conc. increases is needed to go C20 to C80

Hill 1 = same as Emax

Hill 2 = takes a 4x increase in conc to go C20 to C80

Hill >10 = acts more like an on/off switch

Question 6

Time course of drug action after a bolus dose

Conc peak = 10 x C50

Answer 6

• Initial effect is 90%
• After one half life the conc is halved but effect has changed <10%.
• As conc falls the effect disappears more quickly

Question 7

The time course of a drug after a bolus dose

concentration peak = C50

Answer 7

• Initial effect is only 50% of Emax
• Time course of effect and concentration are almost parallel to one another (i.e. effect is almost directly proportional to conc.)
• Here we can talk about an “effect half-life” sort of but not commonly done.

Question 8

The time course of a drug after a bolus dose

Concentration peak = C50 x 100

Answer 8

• Initial effect is close to 100% of Emax
• Effect changes very little despite big changes in drug conc.
• After >5 half-lives the drug has nearly been eliminated the effect is 70% Emax
• SO drugs with short half-lives (2-3 hours) can have big effects even if dosing interval is many half-lives
• Quite common for receptor antagonists (e.g. beta blockers = propanolol and ACE inhibitors)
• provided that this high concentration doesnt have edverse effects one dose a day can be given for ease

Question 9

The time course of effect in the three regions

1. Conc > C80
2. C80 > Conc > C20
3. C20 > Conc

Answer 9

1. flat
2. linear
3. exponential

ALMOST

Question 10

The duration of response changes with changing dose?

Answer 10

If the dose of a drug is doubbled then the duration of response is increased by one half life of the drug.

ie. The time at which the drug effet will be the same will be exctly one half life longer from the bolus dose.

Question 11

Applications of knowing the duration of response

Answer 11

1. we can select an appropriate dosing interval, as this depends on not just half-life but also the target concentration and it’s relationship to C50
2. We can also predict the target concentration if there is a known taget effect.

Question 12

If you drink a double shot cappuccino with cinamon and a squirt of caramel in the morning instead of a single shot will the effect double?

Answer 12

No, doubling the dose will increase the duration by one half-life NOT lead to a doubling of effect.