MCQ Quiz: Pharmacokinetics of Phenytoin

The pharmacokinetic properties of phenytoin are a classic and critical topic in pharmacy education, representing a cornerstone of therapeutic drug monitoring and the principles of drug therapy individualization. As covered in the Patient Care VII: Brain and Behavior course, the “Transcending Concept” of phenytoin pharmacokinetics is essential for safe and effective management of epilepsy. This quiz will test your knowledge of phenytoin’s non-linear metabolism, high protein binding, therapeutic range, and the calculations required to manage this effective but challenging anti-seizure medication.

1. Phenytoin is well-known for exhibiting non-linear, or Michaelis-Menten, pharmacokinetics. This means that:

• A. The rate of drug elimination is directly proportional to the drug concentration at all doses.
• B. The drug’s half-life is constant regardless of the serum concentration.
• C. The enzymatic pathway for its metabolism becomes saturated at therapeutic concentrations.
• D. The drug is not metabolized by the liver.

Answer: C. The enzymatic pathway for its metabolism becomes saturated at therapeutic concentrations.

2. A key clinical implication of phenytoin’s non-linear kinetics is that:

• A. Dose adjustments can be made in large increments without risk.
• B. A small increase in the maintenance dose can lead to a disproportionately large increase in the steady-state serum concentration.
• C. Therapeutic drug monitoring is not necessary.
• D. The drug has a very wide therapeutic index.

Answer: B. A small increase in the maintenance dose can lead to a disproportionately large increase in the steady-state serum concentration.

3. In the context of Michaelis-Menten kinetics, “Vmax” represents the:

• A. Serum concentration of the drug.
• B. Maximum rate of drug metabolism.
• C. The drug concentration at which the rate of metabolism is half of the maximum.
• D. The volume of distribution.

Answer: B. The maximum rate of drug metabolism.

4. What is the generally accepted therapeutic range for total phenytoin serum concentration?

• A. 1-5 mg/L
• B. 50-100 mg/L
• C. 5-10 mg/L
• D. 10-20 mg/L

Answer: D. 10-20 mg/L

5. Phenytoin is highly bound to which plasma protein?

• A. Hemoglobin
• B. Alpha-1 acid glycoprotein
• C. Albumin
• D. Transferrin

Answer: C. Albumin

6. It is necessary to calculate a “corrected” phenytoin level in a patient with:

• A. High serum albumin.
• B. Low serum albumin (hypoalbuminemia).
• C. Normal renal and hepatic function.
• D. High blood pressure.

Answer: B. Low serum albumin (hypoalbuminemia).

7. Only the ________ fraction of phenytoin is pharmacologically active and able to cross the blood-brain barrier.

• A. protein-bound
• B. ionized
• C. unbound (free)
• D. metabolized

Answer: C. unbound (free)

8. A patient has a total phenytoin level of 12 mg/L and a serum albumin of 2.5 g/dL (normal ~4 g/dL). Their corrected phenytoin level will be:

• A. Lower than 12 mg/L.
• B. Higher than 12 mg/L.
• C. Equal to 12 mg/L.
• D. Impossible to determine without the creatinine clearance.

Answer: B. Higher than 12 mg/L.

9. What is the primary purpose of administering a loading dose of phenytoin?

• A. To minimize the risk of adverse effects.
• B. To quickly achieve a therapeutic serum concentration in an acute setting.
• C. To test for an allergic reaction.
• D. To saturate metabolic enzymes immediately.

Answer: B. To quickly achieve a therapeutic serum concentration in an acute setting.

10. The calculation for a phenytoin loading dose is primarily based on the patient’s weight and which other pharmacokinetic parameter?

• A. Clearance (Cl)
• B. Half-life (t½)
• C. Michaelis-Menten constant (Km)
• D. Volume of distribution (Vd)

Answer: D. Volume of distribution (Vd)

11. Which two CYP450 enzymes are primarily responsible for the metabolism of phenytoin?

• A. CYP1A2 and CYP3A4
• B. CYP2D6 and CYP2C19
• C. CYP2C9 and CYP2C19
• D. CYP2E1 and CYP2A6

Answer: C. CYP2C9 and CYP2C19

12. Nystagmus (involuntary eye movement) is an early sign of phenytoin toxicity and typically appears at serum concentrations:

• A. Below 10 mg/L
• B. Between 10-20 mg/L
• C. Above 20 mg/L
• D. Above 40 mg/L

Answer: C. Above 20 mg/L

13. Ataxia, slurred speech, and confusion are signs of more severe phenytoin toxicity, typically seen at serum concentrations:

• A. Between 10-15 mg/L
• B. Between 15-20 mg/L
• C. Above 30 mg/L
• D. Below 10 mg/L

Answer: C. Above 30 mg/L

14. Phenytoin is a potent inducer of several CYP enzymes, including CYP3A4. This means it can _______ the concentration of other drugs metabolized by these enzymes.

• A. increase
• B. decrease
• C. have no effect on
• D. double

Answer: B. decrease

15. A patient stabilized on phenytoin is started on amiodarone, a known inhibitor of CYP2C9. What is the likely effect on the phenytoin level?

• A. The phenytoin level will decrease.
• B. The phenytoin level will increase, risking toxicity.
• C. There will be no change in the phenytoin level.
• D. The amiodarone level will decrease.

Answer: B. The phenytoin level will increase, risking toxicity.

16. The concept of applying mathematical principles to calculate drug doses is a core objective of which foundational course?

• A. Principles of Law & Ethics
• B. Principles of Drug Therapy Individualization.
• C. Population Health
• D. Pathophysiology and Patient Assessment

Answer: B. Principles of Drug Therapy Individualization.

17. Fosphenytoin is a prodrug that is converted to phenytoin in the body. Its primary pharmacokinetic advantage for IV use is:

• A. It is more potent than phenytoin.
• B. It is highly water-soluble, allowing for safer and faster infusion.
• C. It has a much longer half-life.
• D. It bypasses liver metabolism.

Answer: B. It is highly water-soluble, allowing for safer and faster infusion.

18. When interpreting a phenytoin level, it is crucial to know:

• A. The patient’s favorite food.
• B. The time the level was drawn in relation to the dose and whether the patient is at steady state.
• C. The color of the phenytoin capsule.
• D. The brand name of the medication only.

Answer: B. The time the level was drawn in relation to the dose and whether the patient is at steady state.

19. At very low concentrations, phenytoin follows first-order kinetics. As concentrations rise and enzymes become saturated, its elimination kinetics shift toward:

• A. Second-order kinetics
• B. Fractional-order kinetics
• C. Zero-order kinetics
• D. First-order kinetics still

Answer: C. Zero-order kinetics

20. A patient’s phenytoin dose is increased from 300 mg/day to 340 mg/day. A pharmacist would recognize this small dose increase is appropriate due to:

• A. The drug’s linear pharmacokinetics.
• B. The drug’s saturable, non-linear metabolism.
• C. The need to avoid side effects.
• D. The high cost of the medication.

Answer: B. The drug’s saturable, non-linear metabolism.

21. The Sheiner-Tozer equation is used to calculate:

• A. A loading dose of phenytoin.
• B. The half-life of phenytoin.
• C. A corrected phenytoin concentration in patients with low albumin.
• D. The Vmax of phenytoin metabolism.

Answer: C. A corrected phenytoin concentration in patients with low albumin.

22. Which of the following conditions, besides hypoalbuminemia, would require calculation of a corrected phenytoin level due to altered protein binding?

• A. Hypertension
• B. Gout
• C. Severe renal impairment (CrCl < 25 mL/min)
• D. Migraines

Answer: C. Severe renal impairment (CrCl < 25 mL/min)

23. The pharmacokinetic principle of “steady state” is defined as the point where:

• A. The drug is completely eliminated.
• B. The rate of drug administration equals the rate of elimination.
• C. The peak concentration is reached after a single dose.
• D. The patient experiences the most side effects.

Answer: B. The rate of drug administration equals the rate of elimination.

24. Due to its non-linear kinetics, how long does it take phenytoin to reach steady state?

• A. A predictable 3-5 half-lives.
• B. Always less than 24 hours.
• C. It is unpredictable and can take much longer than expected, especially as concentrations approach saturation.
• D. Always exactly 7 days.

Answer: C. It is unpredictable and can take much longer than expected, especially as concentrations approach saturation.

25. A patient on chronic phenytoin therapy has a therapeutic level but is still having seizures. Before increasing the dose, what is the first pharmacokinetic consideration to assess?

• A. Medication adherence
• B. The patient’s Vmax
• C. The patient’s Km
• D. The brand of the medication

Answer: A. Medication adherence

26. The pharmacokinetic focus on phenytoin, phenobarbital, and valproic acid is a specific “Transcending Concept” in the Patient Care VII curriculum because:

• A. These drugs are new and have simple kinetics.
• B. These drugs are older and have complex kinetics that require careful management by pharmacists.
• C. These drugs have no side effects.
• D. These drugs are rarely used today.

Answer: B. These drugs are older and have complex kinetics that require careful management by pharmacists.

27. What is the impact of phenytoin’s high protein binding on its volume of distribution (Vd)?

• A. It causes a very small Vd.
• B. It has no impact on Vd.
• C. The Vd is moderate, as the drug is largely confined to the vascular space and tissues where albumin is present.
• D. It causes an extremely large Vd because it is sequestered in fat.

Answer: C. The Vd is moderate, as the drug is largely confined to the vascular space and tissues where albumin is present.

28. An interaction that involves one drug displacing another from its binding site on albumin is a type of:

• A. Pharmacodynamic interaction.
• B. Pharmaceutical interaction.
• C. Pharmacokinetic interaction at the level of distribution.
• D. Pharmacokinetic interaction at the level of excretion.

Answer: C. Pharmacokinetic interaction at the level of distribution.

29. The administration of IV phenytoin requires an in-line filter. This is due to what pharmacokinetic/pharmaceutical property?

• A. The drug’s high water solubility.
• B. The drug’s low water solubility and potential to precipitate in solution.
• C. The need to remove toxic metabolites.
• D. The drug’s viscosity.

Answer: B. The drug’s low water solubility and potential to precipitate in solution.

30. The “Implement” step of the PPCP for a patient on phenytoin involves:

• A. Only dispensing the medication.
• B. Counseling the patient on the importance of adherence and signs of toxicity.
• C. Diagnosing the patient’s seizure type.
• D. Assessing the patient’s phenytoin level.

Answer: B. Counseling the patient on the importance of adherence and signs of toxicity.

31. At concentrations well below the Km, phenytoin’s elimination approximates:

• A. Zero-order kinetics
• B. First-order kinetics
• C. Second-order kinetics
• D. Michaelis-Menten kinetics

Answer: B. First-order kinetics

32. At concentrations well above the Km, phenytoin’s elimination approximates:

• A. Zero-order kinetics
• B. First-order kinetics
• C. Michaelis-Menten kinetics
• D. Fractional-order kinetics

Answer: A. Zero-order kinetics

33. What is the standard loading dose of phenytoin for an adult in status epilepticus?

• A. 5-10 mg/kg
• B. 15-20 mg/kg
• C. 25-30 mg/kg
• D. A fixed dose of 1000 mg for all patients.

Answer: B. 15-20 mg/kg

34. A patient taking oral contraceptives requires treatment with phenytoin. What is the pharmacokinetic concern?

• A. Phenytoin will increase the contraceptive level, risking side effects.
• B. Phenytoin will induce the metabolism of the contraceptive, risking therapeutic failure.
• C. The oral contraceptive will inhibit the metabolism of phenytoin.
• D. There is no interaction.

Answer: B. Phenytoin will induce the metabolism of the contraceptive, risking therapeutic failure.

35. A key learning objective in the PHA5132 course is to understand how pharmacogenetics contributes to variability in drug metabolism. A patient who is a CYP2C9 poor metabolizer would require a _________ maintenance dose of phenytoin.

• A. higher
• B. lower
• C. standard
• D. weight-based

Answer: B. lower

36. The free (unbound) fraction of phenytoin is typically what percentage of the total concentration?

• A. 1%
• B. 10%
• C. 50%
• D. 90%

Answer: B. 10%

37. The maximum rate of IV phenytoin infusion is limited to prevent:

• A. Hepatotoxicity.
• B. Severe skin rashes.
• C. Cardiovascular collapse and hypotension.
• D. Nephrotoxicity.

Answer: C. Cardiovascular collapse and hypotension.

38. The pharmacist’s role in phenytoin management is a classic example of applying:

• A. Clinical pharmacokinetics to individualize therapy.
• B. Basic compounding skills.
• C. Pharmacy law.
• D. Population health principles.

Answer: A. Clinical pharmacokinetics to individualize therapy.

39. A patient’s phenytoin level comes back as 8 mg/L. This is considered:

• A. Therapeutic
• B. Toxic
• C. Supratherapeutic
• D. Subtherapeutic

Answer: D. Subtherapeutic

40. If a patient’s maintenance dose of phenytoin is equal to their Vmax, what will happen to their serum concentration over time?

• A. It will remain stable.
• B. It will decrease.
• C. It will accumulate indefinitely, leading to toxicity.
• D. It will fluctuate but remain in the therapeutic range.

Answer: C. It will accumulate indefinitely, leading to toxicity.

41. The use of fosphenytoin allows for which route of administration that is not possible with phenytoin?

• A. Oral
• B. Sublingual
• C. Intramuscular (IM)
• D. Topical

Answer: C. Intramuscular (IM)

42. When should a trough phenytoin level be drawn to assess a maintenance dose at steady state?

• A. Immediately after a dose.
• B. Just before the next scheduled dose.
• C. At any random time during the day.
• D. 2 hours after a dose.

Answer: B. Just before the next scheduled dose.

43. A patient’s phenytoin level is 25 mg/L, and they complain of dizziness and difficulty walking. This clinical presentation is consistent with the drug’s:

• A. Therapeutic effect.
• B. Dose-related CNS toxicity.
• C. An allergic reaction.
• D. An idiosyncratic reaction.

Answer: B. Dose-related CNS toxicity.

44. What is the significance of the Km in Michaelis-Menten kinetics?

• A. It represents the maximum rate of metabolism.
• B. It represents the concentration at which the rate of metabolism is half of the maximum.
• C. It represents the drug’s half-life.
• D. It represents the volume of distribution.

Answer: B. It represents the concentration at which the rate of metabolism is half of the maximum.

45. Which of the following is a long-term side effect of chronic phenytoin therapy?

• A. Weight loss
• B. Hypertension
• C. Bone demineralization (osteoporosis/osteomalacia)
• D. Improved memory

Answer: C. Bone demineralization (osteoporosis/osteomalacia)

46. A patient’s phenytoin dose should be held, and a physician notified, if a level comes back at:

• A. 12 mg/L
• B. 18 mg/L
• C. 35 mg/L
• D. 8 mg/L

Answer: C. 35 mg/L

47. The pharmacokinetic reason that some ASMs, like phenytoin, are not first-line choices for new-onset epilepsy despite being effective is:

• A. Their high cost.
• B. Their complex, non-linear kinetics and high potential for drug interactions.
• C. Their lack of oral formulations.
• D. Their narrow spectrum of activity.

Answer: B. Their complex, non-linear kinetics and high potential for drug interactions.

48. Why can’t phenytoin be administered in a dextrose solution?

• A. It will form a precipitate.
• B. It will lose its potency.
• C. It will cause a chemical burn.
• D. It will be rapidly inactivated.

Answer: A. It will form a precipitate.

49. The “Follow-up: Monitor and Evaluate” step of the PPCP for a patient on phenytoin must include:

• A. Only asking about seizure frequency.
• B. A plan for periodic therapeutic drug monitoring.
• C. Only checking for side effects.
• D. A one-time assessment at initiation.

Answer: B. A plan for periodic therapeutic drug monitoring.

50. Understanding phenytoin pharmacokinetics is a critical skill emphasized in the pharmacy curriculum because:

• A. It is a simple drug to manage.
• B. It exemplifies many complex but important pharmacokinetic principles that pharmacists must manage to ensure patient safety.
• C. It is a new drug with an unknown profile.
• D. It has no drug interactions.

Answer: B. It exemplifies many complex but important pharmacokinetic principles that pharmacists must manage to ensure patient safety.