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Flashcards in Target concentration intervention Deck (11):

what is the equation for calculating loading dose? (intial peak dose)

LD = target conc x V


What is the equation for calculating maintenance dose? (to reach average steady state)

MD = target conc x CL


How is a target conc found?

The gold standard is to do a randomized concentration controlled trial. See what conc produces the desired effect and at what conc do you start to see adverse effects.


Why does the pharmacokinetics and pharmacodynamics vary among people?

Systematic/predictable variability (body size, gender, age, disease state (kidney or liver function).

Random/ non predictable variability


What is target concentration intervention?

Taking into account an individuals characteristics to specialize their drug treatment to suit them.


What are three main ways of dosing?

1. Population
- the same dose is given to everyone (this is used by most doctors and works well for those that are the average Joe Blogg.

2. Group
- the same dose is given for those in similar groups. eg grouped by weight, CLcr (creatinine clearance), genotype

3. Individual
- the dose is determined by the individuals response to the medication. (generally only used when the individuals response is easily measured)
eg give a BP lowering drug and check after a week what response it has had. If not given desired effect then give a bigger dose. If drug response/effect is too hard to measure then often conc of drug in blood is used.


Which drugs should be considered for TCI?

1. Drugs that have an effect that is hard to measure (eg cant easily measure BP) or the drug is working when the clinical outcome isnt observable such as:
Anticoagulants, anti convulsants, anti arrythmitics.
(How do you know an anti-convulsant drug is working if they only got seizures every 6 months anyway - you dont want to wait and just see if they have a seizure to know it is effective)

Therefore you can measure drug conc to get an idea that you are giving the right dose if you cant measure the effect of the drug but still want to be reassured it is working.

2. Drugs that have a big unpredictable variability (even when weight, renal function, age etc) are taken into consideration in group based dosing there is still too much unpredictable variation to be sure the medicine can be used safely and effectively. So you measure the drug conc in their blood and adjust to a concentration/level where you can be certain some of the unpredictable variation is removed/ it wont cause adverse effects.


what are the steps to achieve a perfect individual dose (target concentration strategy)?

1. Choose target concentration
2. Determine V and CL using their weight ( a generalised group V and CL without knowing what the actual values of the pharmacodynamic values are in the individual).
3. Calculate LD and MDR
4. Measure the response (eg INR - a test for warfarin to see how long it takes blood to clot) and then revise target conc
5. Measure the concentration in the blood and then revise V and CL

After all these steps go back to step 3 and repeat until the desired response and conc in the blood is achieved.

(in simple terms give patient a dose and then check to see a lil while later what the concentration is. If too high or too low then adjust accordingly).


When is the best time to measure drug concentration in order to estimate clearance?

For most medicines one measurement will suffice and the best time to take this is between doses (in the middle of a dosing interval). This is when the concentration will be closest to steady state concentration.

CL = dose rate / conc at middle of dose interval

Gentamicin is different in that it generally takes two measurements (at peak and trough conc) because its concentration varies so widely during the dosing interval.


When should Gentamicin be measured if only given once a day?

Peak measurement = directly after the dose
Trough measurement = at approx 8 hours (if you do it at 24 hours or any time close to this then the conc will be so low it will be indetectable).


What is the difference between therapeutic drug monitoring and target concentration intervention?

TDM is a traditional way of drug monitoring and more or less is guided by the idea that if a drugs concentration is within therapeutic range (not too low it is ineffective but not too high it is toxic) then it is acceptable and nothing more is done to alter the drug conc so it is getting optimum results.

TCI is a science based method of drug monitoring that uses pharmacokinetic and pharmacodynamic properties to identify how patients are different and then the drug dosing is altered to achieve a precise therapeutic target. This is cost effective and has been shown to improve clinical outcomes.