flashcards 2

Question 1

What is the primary purpose of Therapeutic Drug Monitoring (TDM)?

Answer 1

To measure drug concentrations in body fluids (e.g., blood, urine) to optimize treatment, ensuring efficacy while avoiding toxicity.

Question 2

Since when has TDM been routinely performed in laboratories?

Answer 2

TDM has been routine in analytical laboratories since the 1970s.

Question 3

Why might doubling a dose not necessarily improve a drug’s clinical effect?

Answer 3

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.

Question 4

What factors affect a drug’s availability at its site of action?

Answer 4

Absorption (including first-pass metabolism), distribution (lipid vs. water solubility, volume of distribution), metabolism, excretion, and plasma protein binding.

Question 5

What is meant by ‘first-pass metabolism’ in the context of TDM?

Answer 5

First-pass metabolism refers to the initial metabolism of an orally administered drug by gut and liver enzymes before reaching systemic circulation, reducing bioavailability.

Question 6

Define the terms MTD and MED in relation to the therapeutic window.

Answer 6

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).

Question 7

When is the ideal time to take a blood sample for TDM to assess steady-state concentration?

Answer 7

Immediately before the next scheduled dose (trough level), when the drug concentration is at its lowest in the dosing interval.

Question 8

What are ‘peaks’ and ‘troughs’ in a dosing regimen?

Answer 8

‘Peaks’ are maximum drug concentrations after a dose; ‘troughs’ are minimum concentrations just before the next dose.

Question 9

Why is patient compliance critically considered in TDM?

Answer 9

Because nonadherence (e.g., missed doses, incorrect timing) can lead to subtherapeutic or toxic concentrations, misleading TDM interpretation.

Question 10

How can physiological differences affect TDM outcomes?

Answer 10

Variations in body mass, organ function (hepatic/renal), age, and disease states can alter pharmacokinetics, changing drug absorption, distribution, metabolism, and excretion.

Question 11

What role do drug–drug interactions play in TDM?

Answer 11

Concomitant medications can induce or inhibit metabolic enzymes (e.g., CYP450), altering clearance and resulting in unexpectedly high or low drug levels.

Question 12

In pharmacodynamics, why is receptor status important for TDM?

Answer 12

Because the relationship between drug concentration and effect depends on drug binding to its receptor; receptor polymorphisms or disease states can modify response.

Question 13

What characterizes a drug exhibiting zero-order kinetics?

Answer 13

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.

Question 14

Which pharmacokinetic parameter describes the fraction of an administered dose that reaches systemic circulation?

Answer 14

Bioavailability (F), reflecting absorption and first-pass metabolism for non-intravenous routes.

Question 15

What is ‘volume of distribution’ (Vd)?

Answer 15

Vd is a theoretical volume representing how extensively a drug distributes into tissues versus remaining in plasma; it helps infer tissue binding and storage.

Question 16

Why is plasma protein binding relevant in TDM?

Answer 16

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.

Question 17

What is the difference between clearance and elimination rate?

Answer 17

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).

Question 18

Describe the relationship between dose and plasma concentration for most drugs.

Answer 18

Most drugs exhibit first-order kinetics, meaning plasma concentration changes proportionally with dose, as a constant fraction is eliminated per unit time.

Question 19

What is internal quality control (QC) in a TDM laboratory?

Answer 19

Procedures using known control samples to monitor day-to-day analytical performance, detect drift, and ensure reproducibility.

Question 20

What is external quality assurance (EQA) in TDM?

Answer 20

An independent program (e.g., UKNEQAS) that sends blind samples to laboratories to verify accuracy and maintain accreditation.

Question 21

What is a Levey-Jennings chart used for in QC?

Answer 21

To plot control sample results over time against the mean and ±2 standard deviation limits, identifying trends or shifts in assay performance.

Question 22

In QC terminology, what defines a ‘shift’?

Answer 22

Six or more consecutive QC results on one side of the mean, indicating a sudden change in assay accuracy.

Question 23

In QC terminology, what defines a ‘trend’?

Answer 23

Six or more consecutive QC results moving steadily upward or downward, indicating gradual drift in assay performance.

Question 24

What does ALTM stand for, and how is it calculated?

Answer 24

All Laboratory Trimmed Mean: the average QC result after removing the top and bottom 5% of values to set a target value.

Question 25

How is 'bias' defined in QC for TDM assays?

Answer 25

Bias is the percentage deviation of the laboratory’s measured value from the target (ALTM) value for a control sample.

Question 26

What is 'rolling bias' in QC parameters?

Answer 26

The mean of current and previous five QC results, indicating short-term assay accuracy trends.

Question 27

What is 'rolling variability' in QC?

Answer 27

The average deviation (ignoring direction) of the current and previous five QC results, reflecting assay precision over time.

Question 28

Define 'Bias Index Score (BIS)' in QC.

Answer 28

BIS compares each QC result’s deviation from the target to assess overall laboratory performance across multiple analytes.

Question 29

Why is TDM indicated in cases of suspected toxicity?

Answer 29

To determine if high drug or metabolite levels (due to overdose, impaired metabolism/excretion, or interactions) are causing toxicity.

Question 30

Give three examples of drugs requiring TDM due to narrow therapeutic index.

Answer 30

Digoxin (cardiac glycoside), Lithium carbonate (psychiatric), and Carbamazepine (anticonvulsant).

Question 31

What laboratory method is commonly used to measure Digoxin levels?

Answer 31

Immunoassay techniques (e.g., immunofluorescence or immunoenzymatic assays).

Question 32

Which drugs can elevate Digoxin concentrations via CYP450 interactions?

Answer 32

Amiodarone, Quinidine, and Verapamil can inhibit Digoxin clearance, raising serum levels.

Question 33

Why is TDM critical for patients with renal or hepatic impairment?

Answer 33

Because reduced metabolism (hepatic) or excretion (renal) can lead to drug/metabolite accumulation and toxicity.

Question 34

Name three patient populations for whom TDM is especially important.

Answer 34

Pediatric (especially neonates), geriatric, and patients undergoing dialysis or hemofiltration.

Question 35

Why is TDM generally not required for drugs with a broad therapeutic index?

Answer 35

Because dosage variations are less likely to cause toxicity or loss of efficacy, and clinical endpoints can often be monitored functionally.

Question 36

What defines a 'hit-and-run' drug for which TDM is not typically needed?

Answer 36

Drugs with rapid onset and offset of action, minimal toxicity risk, and easily measurable functional effects (e.g., omeprazole, MAO inhibitors).

Question 37

Which class of antibiotics often requires TDM and why?

Answer 37

Aminoglycosides (e.g., Gentamicin, Streptomycin) require TDM due to nephrotoxicity and ototoxicity risks at high concentrations.

Question 38

Describe the pharmacokinetic properties of aminoglycoside antibiotics relevant to TDM.

Answer 38

Poor oral absorption, wide distribution (Vd ≈ 0.25 L/kg), negligible plasma protein binding, renal excretion via glomerular filtration, and a half-life of ~2–3 hours.

Question 39

What toxic effects are associated with aminoglycoside accumulation?

Answer 39

Nephrotoxicity (tubular cell damage via phospholipid metabolism disruption) and reversible ototoxicity (inner ear free radical generation).

Question 40

Name two anti-epileptic drugs that require TDM and their metabolic considerations.

Answer 40

Phenytoin (zero-order kinetics near enzyme capacity) and Phenobarbital (administered as prodrug Primidone, hepatic metabolism).

Question 41

Which psychoactive drug requiring TDM is used for mood stabilization?

Answer 41

Lithium carbonate, due to its narrow therapeutic window and risk of renal toxicity.

Question 42

Why is Cyclosporine monitored in transplant patients?

Answer 42

Because Cyclosporine has a narrow therapeutic index and can cause nephrotoxicity; dosing is complicated by variable absorption and metabolism.

Question 43

What anti-neoplastic agent commonly undergoes TDM and why?

Answer 43

Methotrexate, since it inhibits DNA synthesis and can cause severe toxicity if plasma levels are too high; clearance varies with renal function.

Question 44

How long after a single marijuana use can THC metabolites be detected in urine?

Answer 44

Approximately 3–5 days, using GC/MS methods.

Question 45

Which analytical techniques are used to detect amphetamines in body fluids?

Answer 45

Liquid chromatography (LC) and gas chromatography (GC).

Question 46

Why are anabolic steroids monitored in athletes?

Answer 46

Because they can enhance muscle mass and performance; illicit use is detected via GC or GC/MS in urine.

Question 47

What are common methods to detect opioids in suspected abuse cases?

Answer 47

Gas chromatography–mass spectrometry (GC/MS) assays of urine or blood.

Question 48

In a TDM context, why is sampling time critical when measuring trough levels?

Answer 48

Because sampling immediately before the next dose ensures the lowest steady-state concentration is measured, reflecting true maintenance dosing.

Question 49

How does renal hemofiltration affect drug clearance and the need for TDM?

Answer 49

Hemofiltration can increase elimination of renally cleared drugs, necessitating dose adjustments and close TDM to maintain therapeutic levels.

Question 50

What key information must be considered to interpret Amiodarone levels correctly?

Answer 50

Patient’s dosing history, time since last dose (half-life ~50 days), concurrent medications, and liver/thyroid function, since Amiodarone distributes extensively and has complex metabolism.