therapeutic drug monitoring

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Revision for TDM lecture PHAR2102
jenny schneider
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Frage Antworten
What is therapeutic drug monitoring (TDM)? it is measuring blood /plasma/serum levels of drug and using this to tailor dosage regimens for patient
What do we mean by therapeutic range? For some drugs we have a range of concentrations- we have a minimum effective concentration and a concentration at which we expect to see toxicity occurring- so we have a minimum and a maximum concentration and we want our levels to be in this range
What does it mean if a drug has a narrow therapeutic index? it means that the window between the minimum effective concentration and the concentration at which we see toxicity is very narrow (not much difference)
What makes a drug a good candidate for therapeutic drug monitoring? good correlation between plasma/serum drug concentration and effect narrow therapeutic index large interindividual variation in pharmacokinetics of drug desired pharmacological effect difficult to monitor
what are some factors that can cause variability in pharmacokinetcs there are many- factors that affect absorption , distribution, metabolism and excretion e.g. age, disease, smoking, genetic polymorphism, drug-drug interactions.....
How do we determine the therapeutic range? we look at drug concentration and effect in a large population of patients and cumulative plots of the percent of all patients experiencing a therapeutic effect (one plot) and toxicity (another plot) are generated. we then pick pints for minimum effective concentration where most people have effect but very few have toxicity and pick an upper point where most people have effect and only a few have toxicity
What are some assay techniques used to measure plasma/serum/blood concentrations? FPIA, RIA, EMIT and HPLC
Which of the assay techniques listed below use antibodies? RIA, HPLC, FPIA, EMIT RIA, EMIT, FPIA use antibodies
What is a disadvantage of an assay that uses antibodies? Antibodies can cross react with metabolites, other drugs or endogenous materials to give falsely elevated readings
What are advantages and disadvantages of techniques such as RIA, FPIA and EMIT compared to HPLC? Techniques using antibodies are generally easier to perform, quicker, require less blood sample than HPLC. They also require less training for the operator than HPLC. HPLC is more specific (no cross reactivity) but usually longer to perform, require more training and large sample volume
Why should an assay be validated and how do we do this? An assay needs to be validated to ensure that you can rely on the results it produces. (You re using these to determine doses in patients!) Assay validation means checking the reproducibility (does it give consistently correct results?), accuracy (if a level should read 10mg/L, does your result lie close to this value); precision (if we did 10 measurements on the same sample, would all the result lie close to each other?). we also need to know about cross reactivity and interference by other substances/drugs
When you have a result for a patient from TDM, what factors do you need to consider when interpreting the result? when was dose given (is sample a trough level?) was sample collected properly (right tube, right storage) what dose has patient been on, how long been taking and have they been adherent to dosage regimen? what other drugs is patient taking? what was reason for request (suspected ineffective or signs of toxicity) any assay considerations (e.g. cross reactivity) clinical status of patient
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