TDM examples: Lithium, Fluoxetine, Amitriptyline MCQs With Answer

Introduction: TDM examples: Lithium, Fluoxetine, Amitriptyline MCQs With Answer — This focused quiz set is designed for M.Pharm students studying Clinical Pharmacokinetics and Therapeutic Drug Monitoring. It reviews practical TDM principles through clinically relevant multiple-choice questions on lithium (a classic drug requiring routine monitoring), fluoxetine (an SSRI with unique long‑acting metabolite considerations), and amitriptyline (a tricyclic antidepressant with narrow therapeutic index and protein-binding issues). Questions emphasize sampling timing, interpretation of concentrations, pharmacokinetic behavior, drug interactions, assay methods, and dose adjustment strategies. Use these items to test and deepen your understanding of when and how TDM informs safe, evidence‑based antidepressant and mood‑stabilizer therapy.

Q1. Which statement best describes the primary route of elimination for lithium used in TDM interpretation?

• Hepatic metabolism by CYP3A4 with biliary excretion
• Renal excretion of unchanged drug with clearance linked to glomerular filtration
• Extensive enterohepatic recirculation prolonging elimination
• Predominantly pulmonary elimination via exhalation

Correct Answer: Renal excretion of unchanged drug with clearance linked to glomerular filtration

Q2. What is the commonly accepted maintenance therapeutic plasma range for lithium in mmol/L (mEq/L) used in outpatient TDM?

• 0.2–0.6 mEq/L
• 0.6–1.2 mEq/L
• 1.5–2.5 mEq/L
• 2.5–4.0 mEq/L

Correct Answer: 0.6–1.2 mEq/L

Q3. For accurate TDM of lithium, when is the optimal time to obtain a serum concentration?

• 2 hours after oral dose (post‑dose peak)
• 12 hours after the last evening dose (trough, pre‑morning dose)
• Immediately before first dose on day 1
• Any random time is acceptable because lithium has a flat profile

Correct Answer: 12 hours after the last evening dose (trough, pre‑morning dose)

Q4. Which commonly prescribed medication class is most likely to increase serum lithium concentrations and precipitate toxicity?

• Loop diuretics (e.g., furosemide)
• Thiazide diuretics (e.g., hydrochlorothiazide)
• High‑dose corticosteroids
• Proton pump inhibitors

Correct Answer: Thiazide diuretics (e.g., hydrochlorothiazide)

Q5. Which clinical feature is most characteristic of moderate to severe lithium toxicity and therefore important for correlating with TDM results?

• Hypertension with bradycardia
• Neurological signs such as coarse tremor, ataxia, and confusion
• Isolated rash without systemic symptoms
• Persistent hypoglycemia

Correct Answer: Neurological signs such as coarse tremor, ataxia, and confusion

Q6. Which pharmacokinetic description of lithium is most helpful when interpreting levels in patients with renal impairment?

• Primarily metabolized in liver with short half‑life independent of renal function
• One‑compartment kinetics with renal clearance; half‑life ~24 hours and prolonged in renal impairment
• Predominantly cleared by intestinal secretion with negligible renal contribution
• Elimination is via enzymatic degradation to inactive metabolites

Correct Answer: One‑compartment kinetics with renal clearance; half‑life ~24 hours and prolonged in renal impairment

Q7. Why does fluoxetine require consideration of delayed steady state when TDM or clinical effects are assessed?

• Fluoxetine is rapidly cleared, reaching steady state within 24 hours
• Norfluoxetine, an active metabolite, has a long half‑life so steady state may take 4–6 weeks
• Fluoxetine is sequestered in fat and therefore never reaches steady state
• Fluoxetine is inactivated by gastric acid producing variable absorption

Correct Answer: Norfluoxetine, an active metabolite, has a long half‑life so steady state may take 4–6 weeks

Q8. Fluoxetine commonly causes clinically significant pharmacokinetic interactions by inhibiting which cytochrome P450 isoenzyme?

• CYP3A4
• CYP2C9
• CYP2D6
• CYP1A2

Correct Answer: CYP2D6

Q9. Which statement best reflects the role of therapeutic drug monitoring for fluoxetine in routine clinical practice?

• TDM is mandatory for all patients because plasma levels correlate tightly with efficacy
• TDM is rarely required but may help in adherence checks, overdose, unusual interactions, or unexpected toxicity
• TDM can replace clinical assessment of mood and side effects
• TDM is useful weekly due to very short half‑life

Correct Answer: TDM is rarely required but may help in adherence checks, overdose, unusual interactions, or unexpected toxicity

Q10. Which set of half‑life values best describes fluoxetine and its metabolite norfluoxetine, relevant to TDM timing?

• Fluoxetine 2–4 days; norfluoxetine 7–15 days
• Fluoxetine 2 hours; norfluoxetine 4 hours
• Fluoxetine 30–60 days; norfluoxetine 90–120 days
• Both fluoxetine and norfluoxetine have half‑lives <12 hours

Correct Answer: Fluoxetine 2–4 days; norfluoxetine 7–15 days

Q11. For amitriptyline, what combined therapeutic plasma concentration range (parent plus active metabolite) is commonly cited to guide efficacy and safety?

• 10–50 ng/mL
• 50–100 ng/mL
• 150–300 ng/mL
• 1000–2000 ng/mL

Correct Answer: 150–300 ng/mL

Q12. When is the appropriate time to sample plasma for amitriptyline concentration for TDM purposes?

• Random sampling within 1 hour of dosing
• Trough sample (pre‑dose) after steady state is achieved, commonly 5–7 days
• Immediately after first dose
• Only during infusion because oral dosing is unpredictable

Correct Answer: Trough sample (pre‑dose) after steady state is achieved, commonly 5–7 days

Q13. Which cytochrome enzyme contributes significantly to the N‑demethylation of amitriptyline to nortriptyline?

• CYP2C19
• CYP3A4 exclusively
• CYP2E1
• Monoamine oxidase (MAO)

Correct Answer: CYP2C19

Q14. How does hypoalbuminemia affect interpretation of total plasma amitriptyline concentration?

• Decreases free fraction and reduces toxicity risk
• Increases free fraction so patients may be toxic despite normal total concentrations
• Has no effect because amitriptyline is not protein‑bound
• Causes rapid hepatic clearance thereby lowering total levels

Correct Answer: Increases free fraction so patients may be toxic despite normal total concentrations

Q15. For which scenario is measuring free (unbound) drug concentration preferred over total concentration in TDM?

• When the drug is not protein‑bound at all
• When a highly protein‑bound drug is used in a patient with hypoalbuminemia or competing drugs for binding sites
• When immunoassays are unavailable
• When only peak concentrations are of interest

Correct Answer: When a highly protein‑bound drug is used in a patient with hypoalbuminemia or competing drugs for binding sites

Q16. Which analytical method is considered the gold standard for precise and specific measurement of antidepressants in TDM laboratories?

• Paper chromatography
• LC‑MS/MS (liquid chromatography–tandem mass spectrometry)
• Empirical colorimetric test
• Urine dipstick testing

Correct Answer: LC‑MS/MS (liquid chromatography–tandem mass spectrometry)

Q17. A patient on maintenance lithium therapy has a low measured level but poor clinical response. What is the most appropriate immediate step in interpretation?

• Immediately double the lithium dose based solely on the lab value
• Verify sample timing (trough), assess adherence, and review recent fluids/diuretics before dose adjustment
• Stop lithium and switch to an antipsychotic
• Assume lab error and ignore the level

Correct Answer: Verify sample timing (trough), assess adherence, and review recent fluids/diuretics before dose adjustment

Q18. Why are discontinuation symptoms less commonly observed after stopping fluoxetine compared with shorter‑acting SSRIs?

• Fluoxetine has no effect on serotonin transporters
• Fluoxetine and norfluoxetine have long elimination half‑lives providing a self‑tapering effect
• Fluoxetine is not psychoactive and therefore causes no withdrawal
• Fluoxetine is completely metabolized to inactive compounds within hours

Correct Answer: Fluoxetine and norfluoxetine have long elimination half‑lives providing a self‑tapering effect

Q19. A patient on fluoxetine is started on metoprolol (a CYP2D6 substrate). What TDM‑relevant effect is most likely?

• Fluoxetine will induce CYP2D6 leading to reduced metoprolol levels
• Fluoxetine inhibits CYP2D6 leading to increased metoprolol concentrations and risk of bradycardia
• No interaction because fluoxetine only affects CYP3A4
• Metoprolol will decrease fluoxetine concentrations by increasing its renal clearance

Correct Answer: Fluoxetine inhibits CYP2D6 leading to increased metoprolol concentrations and risk of bradycardia

Q20. Which of the following is NOT an appropriate goal of therapeutic drug monitoring in psychopharmacology?

• Individualize dosing to achieve a therapeutic concentration while minimizing toxicity
• Detect nonadherence and significant drug interactions
• Replace careful clinical assessment of efficacy and side effects
• Guide dose adjustments in altered pharmacokinetic states (renal/hepatic impairment)

Correct Answer: Replace careful clinical assessment of efficacy and side effects

Download