4 Flashcards
(20 cards)
What is the primary purpose of Therapeutic Drug Monitoring (TDM)?
To measure drug concentrations in body fluids (e.g., blood, urine) to optimize treatment, ensuring efficacy while avoiding toxicity.
Since when has TDM been routinely performed in laboratories?
TDM has been routine in analytical laboratories since the 1970s.
Why might doubling a dose not necessarily improve a drug’s clinical effect?
Because the clinical response is proportional to the drug concentration at the site of action, not simply the administered dose; exceeding the therapeutic window can cause toxicity.
What factors affect a drug’s availability at its site of action?
Absorption (including first-pass metabolism), distribution (lipid vs. water solubility, volume of distribution), metabolism, excretion, and plasma protein binding.
What is meant by ‘first-pass metabolism’ in the context of TDM?
First-pass metabolism refers to the initial metabolism of an orally administered drug by gut and liver enzymes before reaching systemic circulation, reducing bioavailability.
Define the terms MTD and MED in relation to the therapeutic window.
MTD is the Maximum Tolerated Dose (threshold above which toxicity occurs), and MED is the Minimum Effective Dose (threshold below which therapeutic effect is inadequate).
When is the ideal time to take a blood sample for TDM to assess steady-state concentration?
Immediately before the next scheduled dose (trough level), when the drug concentration is at its lowest in the dosing interval.
What are ‘peaks’ and ‘troughs’ in a dosing regimen?
‘Peaks’ are maximum drug concentrations after a dose; ‘troughs’ are minimum concentrations just before the next dose.
Why is patient compliance critically considered in TDM?
Because nonadherence (e.g., missed doses, incorrect timing) can lead to subtherapeutic or toxic concentrations, misleading TDM interpretation.
How can physiological differences affect TDM outcomes?
Variations in body mass, organ function (hepatic/renal), age, and disease states can alter pharmacokinetics, changing drug absorption, distribution, metabolism, and excretion.
What role do drug–drug interactions play in TDM?
Concomitant medications can induce or inhibit metabolic enzymes (e.g., CYP450), altering clearance and resulting in unexpectedly high or low drug levels.
In pharmacodynamics, why is receptor status important for TDM?
Because the relationship between drug concentration and effect depends on drug binding to its receptor; receptor polymorphisms or disease states can modify response.
What characterizes a drug exhibiting zero-order kinetics?
Zero-order kinetics occurs when the metabolism rate is at or near enzyme capacity (e.g., phenytoin, ethanol), so a constant amount—not a constant fraction—is metabolized per unit time.
Which pharmacokinetic parameter describes the fraction of an administered dose that reaches systemic circulation?
Bioavailability (F), reflecting absorption and first-pass metabolism for non-intravenous routes.
What is ‘volume of distribution’ (Vd)?
Vd is a theoretical volume representing how extensively a drug distributes into tissues versus remaining in plasma; it helps infer tissue binding and storage.
Why is plasma protein binding relevant in TDM?
Highly protein-bound drugs have less free (active) concentration; changes in binding (e.g., due to hypoalbuminemia) can alter the free fraction and require dose adjustments.
What is the difference between clearance and elimination rate?
Clearance is the volume of plasma cleared of drug per unit time (mL/min or L/hr), while elimination rate describes the change in drug concentration over time (e.g., half-life).
Describe the relationship between dose and plasma concentration for most drugs.
Most drugs exhibit first-order kinetics, meaning plasma concentration changes proportionally with dose, as a constant fraction is eliminated per unit time.
What is internal quality control (QC) in a TDM laboratory?
Procedures using known control samples to monitor day-to-day analytical performance, detect drift, and ensure reproducibility.
What is external quality assurance (EQA) in TDM?
An independent program (e.g., UKNEQAS) that sends blind samples to laboratories to verify accuracy and maintain accreditation.
