TDM Introduction Flashcards
What is the purpose of therapeutic drug monitoring?
Essentially able to link the measurement of serum drug concentrations and be able to make predictions of what likely outcome for the patient will be
Helps to devise loading and maintenance doses
Individualises drug therapy
Optimises therapeutic efficacy whilst reducing drug toxicity
For which drugs would TDM be appropriate?
For drugs with a narrow therapeutic index and therefore there is a need to monitor for a subtherapeutic or toxic response and doses can be adjusted whilst the patient is monitored closely.
For which drugs wouldn’t TDM be appropriate?
In some drugs plasma concentration may not correlate to the therapeutic effect and therefore predict a likely therapeutic outcome and therefore TDM wouldn’t be appropriate for these drugs. Might not have a concentration dependent response.
Furthermore drugs which require metabolism into their active metabolite are difficult for TDM, instead different components of each should be measured.
What are the difficulties of doing TDM for drugs such as Lithium and Phenytoin?
Display non-linear pharmacokinetics and their this makes it difficult to interpret their therapeutic effect.
Outline the drugs which have TDM.
Aminoglycoside, Gentamicin - narrow therapeutic index
Phenytoin - high risk of toxicity
Digoxin - especially if poor renal function or there are concerns regarding toxicity
Ciclosporin and Tacrolimus - want to minimise toxicity when used long term
Lithium - toxic high doses, affected by electrolytes, other meds and renal function
Theophylline - levels affected by smoking and interactions
Glycopeptide Abx, Vancomycin - again due to narrow therapeutic window
What are the specific reasons behind measuring plasma drug concentration?
For therapeutic effect - for example with Ciclosporin to ensure levels are appropriate and effective against transplant rejection
Adherence - levels can mirror with the patient is compliant with therapy or if alternative may be required. Lithium requires high adherence.
Toxicity - to assess whether symptoms a patient is presenting with could correlate to the medications
What is the importance regarding the timings of blood samples?
Firstly a number of doses is usually required before taking a drug level to ensure that it has reached a steady state concentration
Need to ensure when the drug level is taken is appropriate according to when the last dose was taken
What are the two possible drug levels you would take?
Trough level (pre dose level) - taken just before the next dose, usually an hour before
Peak level (post dose level) - when it is taken depends on how long it takes for the drug to distribute
Why should therapeutic levels not be assessed in isolation?
Ultimately because not all patients with confine within the expected responses in accordance to the therapeutic ranges. Some patients may respond at subtherapeutic levels and some get toxic effects at what would be considered a ‘normal’ level.
What is TDM based upon?
Based on population data, which although is the most informed way at predicting responses at certain drugs levels, no two patients respond to a drug in the same way and therefore shouldn’t be used in isolation.
What are the two main purposes of using population data for TDM?
Helps to calculate doses for patients yet to have the drug
Checking and compares the patient’s data at a population level
Ideally however look at the patient’s own pharmacokinetic parameters such as clearance, volume of distribution rather than the one given to us
What are the assumptions made with TDM?
That the patient is fully adherent to drug therapy or that the drug has been administered as prescribed (even the hospital may not give Gentamicin when it is due)
Assay method is reliable and accurate
Appropriate sampling time and time of last dose with both trough and peak
Ensure querying before acting on high or low levels
