TDM examples: Phenytoin, Carbamazepine, Sodium Valproate MCQs With Answer

TDM examples: Phenytoin, Carbamazepine, Sodium Valproate MCQs With Answer

This quiz set is designed for M.Pharm students studying Clinical Pharmacokinetics and Therapeutic Drug Monitoring. It focuses on practical and conceptual aspects of TDM for three commonly monitored antiepileptics: phenytoin, carbamazepine and sodium valproate. Questions cover therapeutic ranges, protein binding and free versus total drug measurement, non‑linear kinetics and dose adjustments (including Sheiner‑Tozer correction), sampling timing, common drug interactions, clinical toxicity signs and laboratory assay considerations. The aim is to deepen understanding of when and how to apply TDM to optimize therapy, recognize toxicity, and interpret laboratory results correctly in complex clinical scenarios.

Q1. Which statement best describes phenytoin pharmacokinetics relevant to therapeutic drug monitoring?

• Phenytoin follows linear first‑order kinetics at all therapeutic concentrations
• Phenytoin exhibits Michaelis‑Menten (capacity‑limited, nonlinear) kinetics at therapeutic concentrations
• Phenytoin is eliminated primarily by renal filtration unchanged
• Phenytoin has negligible protein binding and free fraction equals total concentration

Correct Answer: Phenytoin exhibits Michaelis‑Menten (capacity‑limited, nonlinear) kinetics at therapeutic concentrations

Q2. The commonly accepted therapeutic total plasma concentration range for phenytoin is:

• 0.5–2.0 µg/mL
• 1–5 µg/mL
• 10–20 µg/mL
• 50–100 µg/mL

Correct Answer: 10–20 µg/mL

Q3. In a patient with hypoalbuminemia, which measurement is most reliable for assessing phenytoin exposure?

• Total phenytoin concentration only
• Plasma albumin concentration alone
• Carbamazepine concentration as a surrogate

Correct Answer: Free (unbound) phenytoin concentration

Q4. The Sheiner‑Tozer equation used to estimate corrected total phenytoin in hypoalbuminemia is:

• Corrected Phenytoin = Measured Phenytoin × (0.2 × Albumin + 0.1)
• Corrected Phenytoin = Measured Phenytoin / (0.2 × Albumin + 0.1)
• Corrected Phenytoin = Measured Phenytoin + (0.2 × Albumin + 0.1)
• Corrected Phenytoin = Measured Phenytoin − (0.2 × Albumin + 0.1)

Correct Answer: Corrected Phenytoin = Measured Phenytoin / (0.2 × Albumin + 0.1)

Q5. A patient has total phenytoin 8 µg/mL and albumin 2.0 g/dL. Using the Sheiner‑Tozer formula (0.2×albumin + 0.1), the corrected total phenytoin is approximately:

• 4 µg/mL
• 8 µg/mL
• 16 µg/mL
• 24 µg/mL

Correct Answer: 16 µg/mL

Q6. Which clinical signs are most characteristic of phenytoin toxicity?

• Hypotension and bradycardia
• Nystagmus, ataxia and slurred speech
• Severe hyperglycemia and polyuria
• Bronchospasm and urticaria

Correct Answer: Nystagmus, ataxia and slurred speech

Q7. Carbamazepine’s clinically relevant therapeutic plasma concentration range (total) is approximately:

• 0.5–2 µg/mL
• 4–12 µg/mL
• 20–40 µg/mL
• 50–100 µg/mL

Correct Answer: 4–12 µg/mL

Q8. Which property of carbamazepine complicates reaching steady state and dosing optimization?

• Negligible hepatic metabolism
• Autoinduction of hepatic metabolism leading to reduced half‑life over weeks
• Complete renal elimination without metabolism
• Zero protein binding

Correct Answer: Autoinduction of hepatic metabolism leading to reduced half‑life over weeks

Q9. The preferred sampling time for routine trough concentration monitoring of antiepileptic drugs (phenytoin, carbamazepine, valproate) is:

• 2 hours after dose
• At peak concentration (1 hour after dose)
• Immediately before the next scheduled dose (trough)
• Random time regardless of dose timing

Correct Answer: Immediately before the next scheduled dose (trough)

Q10. Sodium valproate therapeutic total plasma trough concentrations commonly targeted are:

• 1–5 µg/mL
• 10–20 µg/mL
• 50–100 µg/mL
• 200–400 µg/mL

Correct Answer: 50–100 µg/mL

Q11. Which adverse effect is particularly associated with valproate and should be monitored during TDM?

• Renal failure due to crystal nephropathy
• Hepatotoxicity and thrombocytopenia
• Severe hyperkalemia
• Pulmonary fibrosis

Correct Answer: Hepatotoxicity and thrombocytopenia

Q12. Valproate interacts with phenytoin primarily by which mechanism affecting phenytoin concentrations?

• Induction of phenytoin glucuronidation lowering phenytoin levels
• Inhibition of hepatic metabolism and displacement from albumin increasing free phenytoin
• Increasing renal excretion of phenytoin
• Enhancing intestinal absorption of phenytoin

Correct Answer: Inhibition of hepatic metabolism and displacement from albumin increasing free phenytoin

Q13. For which clinical situation is measuring free (unbound) carbamazepine concentration most appropriate?

• When albumin is normal and no renal disease is present
• In severe hypoalbuminemia or renal failure where protein binding is altered
• When patient is taking only a single daily dose
• Never—carbamazepine free levels are not clinically useful

Correct Answer: In severe hypoalbuminemia or renal failure where protein binding is altered

Q14. Which laboratory/assay issue is important when interpreting valproate concentrations?

• Valproate assays are unaffected by hemolysis
• Only whole blood samples are valid—plasma cannot be used
• Some immunoassays may cross‑react with metabolites; sample timing and method matter
• Valproate is measured by urine dipstick reliably

Correct Answer: Some immunoassays may cross‑react with metabolites; sample timing and method matter

Q15. Which antiepileptic is most likely to cause clinically significant hyponatremia and should prompt monitoring of serum sodium?

• Phenytoin
• Carbamazepine
• Sodium valproate
• Gabapentin

Correct Answer: Carbamazepine

Q16. When a phenytoin concentration is unexpectedly high after a small dose increase, the most likely pharmacokinetic explanation is:

• Enhanced renal clearance due to drug interaction
• Nonlinear (saturable) metabolism causing disproportionate concentration rise
• Increased protein binding lowering free fraction
• Accelerated hepatic induction decreasing levels

Correct Answer: Nonlinear (saturable) metabolism causing disproportionate concentration rise

Q17. Which of the following drug interactions is correctly paired regarding effect on carbamazepine levels?

• Carbamazepine increases levels of warfarin leading to bleeding risk
• Carbamazepine induces CYP enzymes and can decrease plasma levels of oral contraceptives
• Carbamazepine inhibits its own metabolism and causes accumulation immediately
• Carbamazepine has no interaction with other hepatic enzyme substrates

Correct Answer: Carbamazepine induces CYP enzymes and can decrease plasma levels of oral contraceptives

Q18. In which clinical scenario is immediate measurement of free phenytoin concentration most critical?

• Stable outpatient with normal albumin and renal function
• Patient with end‑stage renal disease and low albumin presenting with signs of toxicity
• Patient on once‑daily dosing with no symptoms
• Monitoring peak concentrations after a loading dose in a healthy volunteer

Correct Answer: Patient with end‑stage renal disease and low albumin presenting with signs of toxicity

Q19. Which statement about autoinduction of carbamazepine is correct?

• Autoinduction causes a progressive increase in carbamazepine half‑life over weeks
• Autoinduction usually reduces carbamazepine concentrations over 2–4 weeks after starting therapy
• Autoinduction is an immediate effect occurring within hours of first dose
• Autoinduction increases protein binding of carbamazepine

Correct Answer: Autoinduction usually reduces carbamazepine concentrations over 2–4 weeks after starting therapy

Q20. Which monitoring strategy best minimizes misinterpretation of antiepileptic drug levels?

• Collect random samples without noting dose time or clinical status
• Document exact time of last dose, clinical status, albumin/renal function and assay method when interpreting levels
• Rely only on published therapeutic ranges without considering patient factors
• Avoid repeating levels after dose changes because kinetics are predictable

Correct Answer: Document exact time of last dose, clinical status, albumin/renal function and assay method when interpreting levels

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