Flashcards in Immediate Time Course of Drug Effect Deck (33):

1

## What do pharamcodynamics and pharmacokinetics describe?

### The time course of a drug

2

## What specifically in the time course of a drug does pharmacokinetics and pharmacokinetics describe?

###
Pharmacokinetics describes the change in concentration of drug over time

Pharamcodynamics describe the change in effect over time as concentration changes.

3

## What are the three ways to think of the time course of a drug?

###
1) Drug effects are immediately related to observed drug concentration (plasma con.)

2) Drug effects are delayed in relation to observed drug concentration

3) Drug effects are determined by the cumulative action of the drug

4

## What are the two parameters of pharmacokinetics relevant to time course of a drug?

###
CL = Clearance

V = Volume of distribution

5

## What are the two parameters of pharmacodynamics relevant to time course of a drug?

###
Emax

C50 (EC50)

6

## What do pharmacokinetics and pharmacodynamics determine?

###
Dose

Concentration

Effect

7

## What is half life?

### The time it takes for the concentration of drug to halve.

8

## What is Emax?

### The affect of a drug at infinite concentration, cannot be truly known

9

## What does T0.5 and effect correlate?

### When the concentration halves, the effect does not. It depends on the substance i.e may be 4 half lives before effect has halved.

10

## What is the relationship between effect and concentration?

###
Non-linear.

Hyperbolic curve as the binding to receptor and concentration follows this, therefore EC50 = kd

11

## Does the hyperbolic concentration effect curve ever reach 100%?

### No it comes close but does not

12

## What does the log transformation to the hyperbolic curve do?

### transforms it into a sigmoidal curve.

13

## What law dictates that the concentration response curve should be hyperbolic?

### The law of mass action principal

14

## What part of the sigmoidal log concentration curve is near linear?

### between 20-80% Emax

15

## What does the log concentration curve not account for?

###
That 0 concentration will have no effect, this is because log 0 is undefined

That there is a biological max, this is because mathematically emax can only occur at infinity concentration

16

## What is the Emax model?

### Fundamental description of the concentration effect relationship

17

## Write the Emax model

### E = (Emax. Conc) / (C50 + Conc)

18

## Define each parameter of the Emax model:

###
E = drug effect

Conc = Concentration at the receptor

Emax = max effect

C50 = concentration of drug at 50% receptor occupancy

19

## What are two other concentration values that are important other than C50?

###
C20 (1.4 C50)

C80 (4 times the C50)

This means from c20 to c50 this model predicts a 16 fold increase in concentration

20

## Define the sigmoid Emax model:

### E = (Emax. Conc-Hill co efficient) / (C50-Hill co efficient + Conc-Hill co efficient)

21

## What is the Hill coefficient?

### Determines the steepness of the graph, This accounts for co-operative binding in haemoglobin, as this changes depending on the amount of sites occupied.

22

## Using theophylloine as an example, describe its C50 on the concentration response curve:

###
C50 is obtained at around 10mg/L

While Emax is at 100mg/L

23

## What does the immediate effect of a drug depend on?

### The initial concentration of the drug and its pharmacodynamic properties.

24

## When the dose of drug give/ immediately following administration is C50, then what is observed regarding concentration time and effect time curves?

### Time course of effect is almost parallel with time course of concentration.

25

## When the dose of drug give/ immediately following administration is 10x C50, then what is observed regarding concentration time and effect time curves?

###
Time course of concentration is always normal because the half life is constant and unchanged.

However the time course effect is greatly elevated (as the concentration is far higher than time course concentration curve) Review page 194

26

## When the dose of drug give/ immediately following administration is 100x C50, then what is observed regarding concentration time and effect time curves?

###
Time course of concentration is always normal because the half life is constant and unchanged.

However the time course effect is greatly elevated (as the concentration is far higher than time course concentration curve)

It takes a lot of half lives to reduce the effect being produced.

27

## How can the time course effect graph be divided?

### Into three regions

28

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

###
(Flat) C80< Then the curve us almost flat (no change), little change in effect despite big changes in concentration

(Linear) C20

29

## What does the duration of a response rely on?

###
The amount of drug and its half life

i.e if the concentration of drug is doubled then the duration will increase by ONE half life

30

## Whats the most important clinical application of the Emax model?

### The prediction of target concentration to produce target effect

31

## Whats the equation for determining the target concentration for target effect?

### Conc = (C50 x Effect) / (Emax - Effect)

32

## What else is the emax model appropriate for?

###
Determining the dosing interval of a drug.

Takes into account target concentration, C50 and half life.

examples include

beta blockers

ACE inhibitors

Prednisone

33