MCQ Quiz: Pharmacokinetics of Valproic Acid

Valproic acid is a broad-spectrum anti-seizure and mood-stabilizing medication with a complex pharmacokinetic profile that every pharmacy student must master. The “Transcending Concept” of its pharmacokinetics, as highlighted in the Patient Care VII curriculum, emphasizes the importance of therapeutic drug monitoring, understanding its extensive protein binding, and managing its significant drug interaction potential as an enzyme inhibitor. This quiz will test your knowledge on the absorption, distribution, metabolism, and excretion of valproic acid and how these principles guide its safe and effective use in clinical practice.

1. The elimination of valproic acid at typical therapeutic concentrations follows which type of kinetics?

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

Answer: C. First-order kinetics

2. Valproic acid is a potent inhibitor of several metabolic enzymes. Its most clinically significant interaction is with which other anti-seizure medication, whose metabolism it strongly inhibits?

• A. Levetiracetam
• B. Gabapentin
• C. Lamotrigine
• D. Pregabalin

Answer: C. Lamotrigine

3. Valproic acid is highly bound (~90%) to which plasma protein?

• A. Hemoglobin
• B. Glycoproteins
• C. Globulins
• D. Albumin

Answer: D. Albumin

4. The protein binding of valproic acid is saturable. What does this mean?

• A. The percentage of bound drug remains constant at all concentrations.
• B. As the total drug concentration increases, the percentage of unbound (free) drug also increases.
• C. The drug is not bound to plasma proteins.
• D. The binding is irreversible.

Answer: B. As the total drug concentration increases, the percentage of unbound (free) drug also increases.

5. What is the generally accepted therapeutic range for total valproic acid serum concentration for the management of epilepsy?

• A. 10-20 mg/L
• B. 20-40 mg/L
• C. 50-100 mg/L
• D. 150-200 mg/L

Answer: C. 50-100 mg/L

6. A patient stabilized on phenytoin is started on valproic acid. What pharmacokinetic interaction can occur?

• A. Valproic acid will induce the metabolism of phenytoin.
• B. Valproic acid can displace phenytoin from its binding sites on albumin, initially increasing the free phenytoin level.
• C. Phenytoin will induce the metabolism of valproic acid.
• D. There is no interaction between these two drugs.

Answer: B. Valproic acid can displace phenytoin from its binding sites on albumin, initially increasing the free phenytoin level.

7. Due to its extensive hepatic metabolism, valproic acid carries a black box warning for which severe adverse effect?

• A. Nephrotoxicity
• B. Cardiotoxicity
• C. Hepatotoxicity
• D. Aplastic anemia

Answer: C. Hepatotoxicity

8. When initiating lamotrigine in a patient already taking valproic acid, the starting dose of lamotrigine must be:

• A. Higher than the standard starting dose.
• B. The same as the standard starting dose.
• C. Lower than the standard starting dose (e.g., halved).
• D. A loading dose.

Answer: C. Lower than the standard starting dose (e.g., halved).

9. The primary routes of metabolism for valproic acid are:

• A. Renal filtration and secretion.
• B. Glucuronidation and mitochondrial beta-oxidation.
• C. Only via CYP2C9.
• D. Only via CYP3A4.

Answer: B. Glucuronidation and mitochondrial beta-oxidation.

10. To properly assess a maintenance dose of valproic acid, a trough serum level should be drawn:

• A. Immediately after a dose.
• B. At a random time during the day.
• C. 1-2 hours after a dose.
• D. Just before the next scheduled dose.

Answer: D. Just before the next scheduled dose.

11. The “Transcending Concept: Pharmacokinetics” unit in the epilepsy module specifically highlights the complex kinetics of valproic acid along with which other two drugs?

• A. Levetiracetam and Lamotrigine
• B. Ethosuximide and Zonisamide
• C. Phenytoin and Phenobarbital
• D. Gabapentin and Pregabalin

Answer: C. Phenytoin and Phenobarbital

12. Different oral formulations of valproic acid have different absorption properties. Which formulation has lower bioavailability and cannot be directly converted mg-for-mg from the immediate-release form?

• A. The sprinkle capsule (Depakote Sprinkles)
• B. The delayed-release tablet (Depakote)
• C. The extended-release tablet (Depakote ER)
• D. The oral solution

Answer: C. The extended-release tablet (Depakote ER)

13. A patient taking valproic acid presents with lethargy, vomiting, and confusion. A pharmacist should suspect which potential metabolic disturbance?

• A. Hypoglycemia
• B. Hyperammonemia
• C. Hypernatremia
• D. Hypokalemia

Answer: B. Hyperammonemia

14. A patient with hypoalbuminemia (low albumin) has a total valproic acid level of 75 mg/L. Their free (active) drug level is likely:

• A. Lower than expected.
• B. Higher than expected for that total level.
• C. Unchanged.
• D. Impossible to determine.

Answer: B. Higher than expected for that total level.

15. Valproic acid is an inhibitor of which key enzyme in the urea cycle, contributing to its risk of hyperammonemia?

• A. Carbamoyl phosphate synthetase I
• B. Ornithine transcarbamylase
• C. Arginase
• D. Amylase

Answer: A. Carbamoyl phosphate synthetase I

16. The “Principles of Drug Therapy Individualization” course provides the foundation for understanding valproic acid’s:

• A. Pharmacokinetic properties and drug interaction potential.
• B. Cost and availability.
• C. Legal classification.
• D. Place in historical medicine.

Answer: A. Pharmacokinetic properties and drug interaction potential.

17. What is the typical half-life of valproic acid in adults?

• A. 1-2 hours
• B. 40-60 hours
• C. 9-16 hours
• D. >100 hours

Answer: C. 9-16 hours

18. A patient taking valproic acid should have which laboratory parameters monitored regularly?

• A. Serum creatinine and TSH
• B. Complete blood count (for thrombocytopenia) and liver function tests (LFTs)
• C. Lipid panel and blood glucose
• D. Echocardiogram

Answer: B. Complete blood count (for thrombocytopenia) and liver function tests (LFTs)

19. When valproic acid is co-administered with a highly protein-bound drug like warfarin, what potential interaction can occur?

• A. Valproic acid can induce the metabolism of warfarin.
• B. Valproic acid can displace warfarin from albumin, transiently increasing the free fraction of warfarin.
• C. Valproic acid can inhibit the absorption of warfarin.
• D. There is no interaction.

Answer: B. Valproic acid can displace warfarin from albumin, transiently increasing the free fraction of warfarin.

20. The “Assess” step of the PPCP for a patient on valproic acid would include:

• A. Formulating a plan.
• B. Reviewing recent lab results (e.g., LFTs, drug levels) and asking about potential side effects like tremor or GI upset.
• C. Educating the patient on how to take the medication.
• D. Dispensing the prescription.

Answer: B. Reviewing recent lab results (e.g., LFTs, drug levels) and asking about potential side effects like tremor or GI upset.

21. Co-administration of carbapenem antibiotics (e.g., meropenem) with valproic acid can lead to what significant pharmacokinetic interaction?

• A. A sharp increase in valproic acid levels, risking toxicity.
• B. A sharp decrease in valproic acid levels, risking subtherapeutic levels and seizures.
• C. No change in valproic acid levels.
• D. An increase in carbapenem levels.

Answer: B. A sharp decrease in valproic acid levels, risking subtherapeutic levels and seizures.

22. Valproic acid is a broad-spectrum anti-seizure medication. From a clinical pharmacology perspective, this means it is:

• A. Only effective for absence seizures.
• B. Effective against a variety of seizure types, including focal and generalized seizures.
• C. Only effective for focal seizures.
• D. A narrow-spectrum agent.

Answer: B. Effective against a variety of seizure types, including focal and generalized seizures.

23. The “drug metabolizing enzymes” and their inhibition are a major topic in which foundational course, directly relevant to valproic acid’s drug interaction profile?

• A. PHA5132 Principles of Drug Therapy Individualization
• B. PHA5703 Principles of Pharmacy Law & Ethics
• C. PHA5007 Population Health
• D. PHA5560 Pathophysiology and Patient Assessment I

Answer: A. PHA5132 Principles of Drug Therapy Individualization

24. The delayed-release and extended-release formulations of divalproex sodium were designed to:

• A. Increase the drug’s efficacy.
• B. Improve gastrointestinal tolerability compared to valproic acid syrup.
• C. Ensure a faster onset of action.
• D. Eliminate the need for therapeutic drug monitoring.

Answer: B. Improve gastrointestinal tolerability compared to valproic acid syrup.

25. A common dose-related side effect of valproic acid is:

• A. Hair growth
• B. Weight loss
• C. Thrombocytopenia
• D. Hypertension

Answer: C. Thrombocytopenia

26. The volume of distribution (Vd) of valproic acid is relatively small (0.1-0.4 L/kg). This is consistent with its:

• A. Low plasma protein binding.
• B. High lipophilicity.
• C. High plasma protein binding, which tends to confine it to the vascular space.
• D. Elimination primarily by the kidneys.

Answer: C. High plasma protein binding, which tends to confine it to the vascular space.

27. Unlike phenytoin, the saturable component of valproic acid’s pharmacokinetics is its:

• A. Metabolism
• B. Renal excretion
• C. Protein binding
• D. Absorption

Answer: C. Protein binding

28. A patient on valproic acid therapy requires a course of lorazepam. What is the potential interaction?

• A. Valproic acid induces lorazepam metabolism.
• B. Valproic acid inhibits lorazepam metabolism (via glucuronidation), potentially increasing lorazepam levels and sedation.
• C. Lorazepam induces valproic acid metabolism.
• D. There is no interaction.

Answer: B. Valproic acid inhibits lorazepam metabolism (via glucuronidation), potentially increasing lorazepam levels and sedation.

29. The “Implement” step of the PPCP for a new valproic acid prescription involves counseling the patient to:

• A. Discontinue the medication if they miss one dose.
• B. Report any signs of liver toxicity, such as abdominal pain, nausea, or jaundice.
• C. Expect the medication to work immediately.
• D. Take the medication on an empty stomach to increase absorption.

Answer: B. Report any signs of liver toxicity, such as abdominal pain, nausea, or jaundice.

30. The short half-life of valproic acid means that for the immediate-release formulation, _________ is often required to maintain stable concentrations.

• A. once-weekly dosing
• B. once-daily dosing
• C. multiple daily dosing (e.g., 2-3 times a day)
• D. as-needed dosing

Answer: C. multiple daily dosing (e.g., 2-3 times a day)

31. In therapeutic drug monitoring, “steady state” is the point where the rate of drug in equals the rate of drug out. For a drug with first-order kinetics like valproic acid, this is typically reached after how many half-lives?

• A. 1-2
• B. 4-5
• C. 7-8
• D. 10

Answer: B. 4-5

32. The “Follow-up: Monitor and Evaluate” step of the PPCP for a patient on valproic acid must include a plan for periodic monitoring of:

• A. Only seizure frequency.
• B. LFTs, CBC, and serum drug levels as clinically indicated.
• C. Only serum drug levels.
• D. Only for side effects.

Answer: B. LFTs, CBC, and serum drug levels as clinically indicated.

33. Which of the following best describes the clearance of valproic acid?

• A. It is primarily cleared by the kidneys unchanged.
• B. It is cleared by extensive hepatic metabolism.
• C. It is cleared by the lungs.
• D. It is not cleared from the body.

Answer: B. It is cleared by extensive hepatic metabolism.

34. The bioavailability of Depakote ER is about 10-15% lower than Depakote DR. This pharmacokinetic fact means that when converting a patient from DR to ER:

• A. The total daily dose should be kept the same.
• B. The total daily dose usually needs to be increased.
• C. The total daily dose usually needs to be decreased.
• D. The conversion cannot be made.

Answer: B. The total daily dose usually needs to be increased.

35. A patient on valproic acid has a total level of 110 mg/L. What is the most appropriate interpretation?

• A. The level is subtherapeutic.
• B. The level is slightly above the typical therapeutic range, and the patient should be assessed for signs of toxicity.
• C. The level is dangerously toxic.
• D. The level is therapeutic.

Answer: B. The level is slightly above the typical therapeutic range, and the patient should be assessed for signs of toxicity.

36. A key reason TDM is useful for valproic acid is:

• A. There is no relationship between concentration and effect.
• B. There is a good correlation between serum concentration and both clinical efficacy and toxicity.
• C. The drug has no side effects.
• D. All patients have the same pharmacokinetic parameters.

Answer: B. There is a good correlation between serum concentration and both clinical efficacy and toxicity.

37. Valproic acid can increase the concentration of the active metabolite of carbamazepine (the 10,11-epoxide) by inhibiting which enzyme?

• A. CYP3A4
• B. Epoxide hydrolase
• C. UGT1A4
• D. CYP2C9

Answer: B. Epoxide hydrolase

38. The use of a loading dose for valproic acid is most appropriate in which clinical setting?

• A. For the chronic management of migraines.
• B. For the initial management of bipolar depression.
• C. For the acute management of status epilepticus.
• D. It is never appropriate to use a loading dose.

Answer: C. For the acute management of status epilepticus.

39. Hair loss (alopecia) and weight gain are potential long-term side effects related to the pharmacology of which anti-seizure medication?

• A. Levetiracetam
• B. Topiramate
• C. Valproic acid
• D. Lacosamide

Answer: C. Valproic acid

40. The knowledge that valproic acid is a broad-spectrum enzyme inhibitor is a key concept from which foundational science?

• A. Pathophysiology
• B. Medicinal Chemistry
• C. Pharmacology / Pharmacokinetics
• D. Pharmaceutics

Answer: C. Pharmacology / Pharmacokinetics

41. In the context of the PPCP, assessing a patient’s lab values before dispensing valproic acid is part of which step?

• A. Plan
• B. Implement
• C. Assess
• D. Follow-up

Answer: C. Assess

42. A patient with a valproic acid level of 45 mg/L is still having seizures. Before recommending a dose increase, the pharmacist should first confirm:

• A. The patient is adherent to the current regimen.
• B. The patient’s insurance will cover a higher dose.
• C. The pharmacy has a higher strength available.
• D. The patient’s diet.

Answer: A. The patient is adherent to the current regimen.

43. A common GI side effect of valproic acid is nausea/vomiting. This can be managed by:

• A. Taking the medication on an empty stomach.
• B. Taking the medication with food or using an enteric-coated/extended-release formulation.
• C. Increasing the dose.
• D. Stopping the medication immediately.

Answer: B. Taking the medication with food or using an enteric-coated/extended-release formulation.

44. Which factor does NOT significantly alter the pharmacokinetics of valproic acid?

• A. Co-administration of enzyme inducers
• B. Co-administration of enzyme inhibitors
• C. Severe hepatic disease
• D. Mild renal impairment

Answer: D. Mild renal impairment

45. The half-life of valproic acid is generally ________ in children compared to adults.

• A. longer
• B. shorter
• C. the same
• D. unpredictable

Answer: B. shorter

46. A patient on valproic acid develops a fine tremor in their hands. This is likely:

• A. An unrelated symptom.
• B. A dose-related side effect of the medication.
• C. A sign of a subtherapeutic level.
• D. An allergic reaction.

Answer: B. A dose-related side effect of the medication.

47. The ability to perform calculations to determine appropriate doses is a core objective of the Hospital IPPE and is directly applicable to the pharmacokinetic management of:

• A. Levetiracetam
• B. Valproic acid
• C. Gabapentin
• D. Pregabalin

Answer: B. Valproic acid

48. Why is it important to monitor ammonia levels in a valproic acid-treated patient who presents with unexplained lethargy and confusion?

• A. To check for kidney function.
• B. To rule out valproate-induced hyperammonemic encephalopathy.
• C. To assess for dehydration.
• D. To confirm the diagnosis of epilepsy.

Answer: B. To rule out valproate-induced hyperammonemic encephalopathy.

49. An understanding of valproic acid pharmacokinetics is critical for a pharmacist’s role in:

• A. Preventing, identifying, and resolving medication therapy problems.
• B. Only dispensing the medication.
• C. Only billing insurance.
• D. Only managing inventory.

Answer: A. Preventing, identifying, and resolving medication therapy problems.

50. The ultimate goal of pharmacokinetic management of valproic acid is to:

• A. Achieve the highest possible serum concentration.
• B. Individualize the dose to maintain a concentration within the therapeutic range, maximizing efficacy and minimizing toxicity.
• C. Use the same dose for every patient.
• D. Avoid therapeutic drug monitoring.

Answer: B. Individualize the dose to maintain a concentration within the therapeutic range, maximizing efficacy and minimizing toxicity.