Therapeutic Drug Monitoring Flashcards
What is therapeutic drug monitoring (TDM)? What is the main goal?
clinical practice of measuring the plasma levels of specific drugs to optimize individual dosage regimens
achievement of the desired therapeutic effect while minimizing adverse effects in each individual patient
What are the main 2 reasons to undertake therapeutic drug monitoring (TDM)?
- avoid drug toxicity
- improve therapeutic efficacy
TDM is most useful when what 4 criteria are met?
- drug has a narrow therapeutic range
- therapeutic effect can not be readily assessed by clinical observation
- a direct relationship between the drug levels in plasma and toxic effects
- availability of cost-effective drug assays
In what 4 special populations is TDM most useful?
- patients at the extremes of age
- patients with dosing problems
- patients taking multiple medications
- patients who have unusual pharmacokinetics as a result of physiological, environmental, disease, or genetic factors
What are 4 advantages to using TDM?
- maximizing drug efficacy
- avoiding toxicity
- identifying therapeutic failure
- cost-effectiveness
What 6 criteria are required for TDM? Why?
- history of drug administration
- present and previous plasma drug concentrations
- clinical status of patient
- time of sampling
- physiological data
- concurrent drug therapy
helps estimate the patient’s current pharmacokinetic parameters and allows for the design of a new dosage regiment to more closely achieve the target values
What 3 PK variables are needed for TDM? 2 PD variables?
PK - absorption, clearance, volume of distribution
PD - maximum efficacy in target tissue, potency
How can compliance failure (over- or under-dosing) be detected?
absorption amount of the drug can be measured using drug measurements (blood/serum test)
What is the most important factor determining drug fate? What are 2 major factors that influence this?
clearance
- dose
- intrinsic function of liver and kidneys
What relationship does volume of distribution have with drug binding?
high Vd = tissue binding
low Vd = plasma protein binding
How does the age of a patient affect volume of distribution? Edema/ascites in a patient?
older patients have decreased muscle mass, which leads to less binding and a lower Vd
accumulation of fluid increases Vd of hydrophilic drugs that normally have a small Vd
How does drug clearance affect half-life? When is TDM measured?
low drug clearance = high half-life
measurement of drug levels at steady state, when the rate of the drug administration is balanced by drug elimination
What happens when drug concentrations are much greater than the ED50? What should be done next to the patient if this happens?
pharmacological responses are saturated
avoid further administration that can lead to ineffective and possibly toxic doses
What is the target concentration (TC) strategy? What are the 4 steps?
multi-step process for optimizing drug dosage in an individual on the basis of PK, PD, and pharmacogenetic properties
- chose target concentration (TC)
- predict Vd and clearance from standard population values
- measure patient’s response and drug concentration
- revise Vd and/or clearance based on the measured drug concentration
How can doses be modified in patients that have drug concentrations outside of the therapeutic range?
If the plasma concentration for a drug is found to be 400 ng/mL and the target concentration is 700 ng/mL, a dose of 300 mg/day should be adjusted to…..?
