14 - PDs: Time course of immediate drug effect

Question 1

Drug conc?

Answer 1

Thought to be the linking factor that explains the time course of effects after a drug dose.

Question 2

When describing the time course of drug action after a bolus dose what do you assume?

Answer 2

That there is an immediate link between concentration and effect

Question 3

Is emax visible?

Answer 3

NO - occurs at infinite drug concentration (is an asymptotic prediction)

Question 4

When does Kd = C50?

Answer 4

If it is assumed that the effect is directly proportional to binding (kd is the equilibrium binding constant - conc when FO is 50%)

Question 5

Why is a log transformation of conc effect curve misleading?

Answer 5

• misleading when assuming a linear scale
• is actually increasing rapidly at low concentrations
• allows an increasing range of concentrations to be absorbed (closer to Emax seen)

Question 6

Why doesn’t nick like dose-response curveS?

Answer 6

not the dose that causes the effect is the conc!!!

Question 7

What does the Emax model predict the change of conc needing to be to reach a 20% > 80% Emax?

Answer 7

0.25 > 4C50
= 16 fold increase in concentration

= a large change in conc is needed to get a medium change in effect

Question 8

What is the sigmoid Emax model more appropriate for

Answer 8

Specific concentration effect models like the HbO2 curve

Question 9

When the hill coefficient is 1

Answer 9

= emax model

Question 10

When the hill coefficient is very large…

Answer 10

Approx linear at C20 > C80
The concentration effect relationship is like an on off switch i.e. effect turns on at a threshold close to the C50 i.e. an action potential

Question 11

Describe the theophylline conc effect curve

Answer 11

From C50 (10mg/L) to double this, there is not much increase in effect (% peak flow change) but significant increases in adverse effects

This is due to the non-linear relationship between concentration and effect

Question 12

4 questions when considering the time course of effect?

Answer 12

1. How long does the drug effect last?
2. Is there a half life for effect?
3. What is the relevance of C50? i.e. how does it influence the time course?

Question 13

What 2 things does the time course of immediate drug effect depend on?

Answer 13

Both the initial concentration of the drug and the PKs of the drug

Question 14

Time course of action after a bolus dose of conc 10 times the C50

Answer 14

• intial effect is 90% Emax

- after one HL the conc has halved but there has only been a 10% drop in effect (conc curve steep, effect curve flat)

Question 15

What does a concentration time curve that is exponential suggest about the elimination of the drug

Answer 15

That it is eliminated by first order elimination

Question 16

Concentration peak of C50?

Answer 16

When the concentration is lower and closer to the C50 then the conc and effect curves are much similar. At lower concentrations the time course of effect is almost parallel to the time course of concentration
(BUT the effects reached are not very high i.e. max 50% emax)

I.e. after 1 hl the effects nearly halve!

Question 17

Concentration peak at 100x the C50?

Answer 17

• initial effect is close to Emax
• after 1 HL the effect decreases very little despite big changes in drug concentration
• after more then 4 HLs i.e. when most of the drug has been eliminated from the body the effect is still at 70%!! this is because the conc is still much bigger than C50
• means you can just give a drug once a day and the effects won’t drop much throughout the day, even if it has a short hl even if dose is many half lives
• often used for B blockers and ACEIs

Question 18

What 3 regions describes the time course of effect

Answer 18

• Concentration greater than C80: the curve is almost flat
• Conc between 20-80: the time course of loss of drug effect is almost a straight line (linear)
• Conc less than C20: there is an almost exponential drop in effect and the conc/effect time response curves are parallel

Question 19

Is there an effect half life?

Answer 19

NOOOO

The only time it makes sense to describe an effect half life is when the peak conc is less than C20 as the effect and conc time response curves a re very similar/parallel

Question 20

If the DOSE of a drug is doubled then the duration of response will increase by …

Answer 20

ONE HALF LIFE

Question 21

What does selecting an appropriate dosing interval depend on?

Answer 21

• half life
• target concentration and its relation to the C50!! (i.e. those graphs in order to predict the time course of effect and so when you need to dose to sustain a desired level of effect!)

Question 22

How may a drug that has a short half life still be effective for daily dosing to sustain a desired level of effect?

Answer 22

Usually this is because their concentrations are above C50! i.e. flat curve and no change in effect over many HLs

Question 23

Examples of daily dosing drugs

Answer 23

• beta blockers
• ACEIs

Higher dose = longer effects. Depends on drug i..e high conc could be toxic like theophylline!

Question 24

Does doubling the dose lead to doubling in the effect?

Answer 24

NO i.e. first coffee more important. BUT doubling the dose DOES increase the DURATION of the effect by one HL!!!