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Flashcards in Target Concentration Intervention Deck (24):
1

What two fields of pharmacology does target concentration link?

Pharmacokinetics and pharmacodynamics

2

What is the equation for target concentration?

Target Conc =
Target effect x C50 / (Emax - target effect)

3

What does the ideal dose prediction require estimates of?

Emax
C50
V
CL

4

Of the target concentration what is the equation for the initial peak?

Initial peak = loading dose = Target concentration x Volume of distribution

5

What is the equation for average steady state with regards to target concentration?

Maintenance dose rate = Target concentration x Clearance

6

How do we find the target concentration of a drug?

Randomized concentration controlled trials = Gold standard

7

Why does PKPD vary?

Systemic (predictable)
- Body size
- Disease state (kidney, liver)
- Genotype

Random (not predictable)
- Between subject variability
- Within subject variability

8

Whats a factor that must be accounted for when finding the clearance of a subject

Age

9

What is the largest factor to affect clearance?

Individual variability

Clearance = removal or complete inhibition of agent from a system

10

What are the three methods of dosing?

Population (same for all)
Group (covariate guided, all share same characteristic i.e age)
Individual (dose determined by individual response)

11

How is renal function determined?

CLCr

Therefore can predict the clearance rate of a patient

12

What is TCI?

Target Concentration Intervention

13

How is TCI measured?

The change in disease state caused by a concentration drug as a measure of its effectiveness

14

What is the problem with using TCI?

1) usefulness is hard to measure in instances when clinical outcomes are not easily observed
i.e anti-arrhythmias (dont occur all the time)
anti-convulsants (dont happen all the time)

2) Unpredictable variability between patients
3) requires small within subject variability

15

How is TCI done?

1) Choose target concentration
2) Determine V and CL
3) Calculate LD and MDR
4) Measure response and revise TC
5) Measure concentration (revise V and CL if need be)
6) Go back to step 3 (basically repeat until desired response is achieved)

Best method for determining individual dose

16

Are all drugs cleared at the same rate?

No, depends on half life and the ability of the body to metabolize the drug

17

How is group V and Cl determined (predictable variability)?

Volume of distribution:
Size, v = Vpop x WT (patient weight)/ WTstd
- factor is body composition

Clearance
size Cl = Clpop x (WT/WTstd)3/4 (allometric observation theory)

Factors
- renal function
- Hepatic function
- concomitant drugs

18

Why do we measure blood concentration of drugs?

To determine the CL of an individual

19

When should blood concentration be measured?

Most medicines - middle of dosing interval (once)
Gentamicin - peak and trough (twice)

20

Why do most drugs measure concentration mid dosing interval?

AS this will be near the average steady state

21

Using time of sample, what is the equation for clearance?

Cl = dose rate / concentration at time

22

Why would be use TCI over therapeutic drug monitoring?

TDM is bad because if the drug is in the range then no more is given even if its at the bottom of the range and having no effect, therefore it is IMPRECISE

23

Why use TCI?

Single target not a range

Accurate

24

Why is gentamicin measured twice?

It has a half life, therefore it has a peak and a trough of activity in the body. Measuring twice tells you the half life and this can be used to calculate the clearance

Cl = V x K

T0.5 = ln (2) / K