MCQ Quiz-Pharmacokinetics- Phenobarbital

Patient Care and Principles of Drug Therapy Individualization courses will test your knowledge on the absorption, distribution, metabolism, and excretion of phenobarbital and the clinical implications of these properties.

1. One of the most defining pharmacokinetic characteristics of phenobarbital is its:

• A. Very short half-life
• B. Very long half-life (e.g., 50-120 hours)
• C. Non-linear, saturable metabolism
• D. Lack of hepatic metabolism

Answer: B. Very long half-life (e.g., 50-120 hours)

2. The long half-life of phenobarbital means that it will take a long time to:

• A. Be absorbed from the GI tract
• B. Reach a steady-state concentration
• Cross the blood-brain barrier
• Bind to plasma proteins

Answer: B. Reach a steady-state concentration

3. At therapeutic concentrations, phenobarbital’s elimination follows which type of kinetics?

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

Answer: B. First-order kinetics

4. Phenobarbital is a potent inducer of numerous hepatic enzymes, most notably which cytochrome P450 isoenzyme?

• A. CYP2D6
• B. CYP2C19
• C. CYP3A4
• D. CYP1A1

Answer: C. CYP3A4

5. A patient stabilized on warfarin is started on phenobarbital. What is the expected pharmacokinetic interaction?

• A. Phenobarbital will inhibit warfarin metabolism, increasing the INR.
• B. Phenobarbital will induce warfarin metabolism, decreasing the INR and therapeutic effect.
• C. There is no interaction between phenobarbital and warfarin.
• D. Phenobarbital will displace warfarin from albumin, increasing the INR.

Answer: B. Phenobarbital will induce warfarin metabolism, decreasing the INR and therapeutic effect

6. A significant portion of a phenobarbital dose is eliminated unchanged in the urine. This renal excretion can be enhanced by:

• A. Acidifying the urine
• B. Alkalinizing the urine
• Administering a diuretic
• Administering a beta-blocker

Answer: B. Alkalinizing the urine

7. Why does alkalinizing the urine increase the renal excretion of phenobarbital?

• A. It increases the glomerular filtration rate.
• B. It decreases the tubular secretion of phenobarbital.
• C. As a weak acid, phenobarbital becomes more ionized in alkaline urine, which traps it in the tubule and prevents reabsorption.
• D. It increases the hepatic metabolism of phenobarbital.

Answer: C. As a weak acid, phenobarbital becomes more ionized in alkaline urine, which traps it in the tubule and prevents reabsorption

8. What is the therapeutic serum concentration range for phenobarbital in the management of epilepsy?

• A. 1-5 mg/L
• B. 5-10 mg/L
• C. 15-40 mg/L
• D. 50-100 mg/L

Answer: C. 15-40 mg/L

9. The “Transcending Concept” lecture on the pharmacokinetics of specific ASMs in the Patient Care VII course explicitly includes which of the following?

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

Answer: B. Phenytoin, Phenobarbital, and Valproic Acid

10. To rapidly achieve a therapeutic concentration in an acute setting like status epilepticus, what type of dose is administered?

• A. A small test dose
• B. A loading dose
• A daily maintenance dose
• A tapering dose

Answer: B. A loading dose

11. The calculation of a phenobarbital loading dose is primarily based on the patient’s weight and the drug’s:

• A. Half-life
• B. Clearance
• C. Volume of distribution (Vd)
• D. Oral bioavailability

Answer: C. Volume of distribution (Vd)

12. The primary mechanism of action of phenobarbital involves:

• A. Blocking voltage-gated sodium channels.
• B. Increasing the duration of GABA-A chloride channel opening.
• C. Increasing the frequency of GABA-A chloride channel opening.
• D. Antagonizing NMDA receptors.

Answer: B. Increasing the duration of GABA-A chloride channel opening

13. A patient taking an oral contraceptive should be counseled about a potential drug interaction with phenobarbital because phenobarbital:

• A. Increases the absorption of the contraceptive.
• B. Induces the metabolism of the contraceptive, potentially leading to therapeutic failure.
• C. Inhibits the metabolism of the contraceptive.
• D. Displaces the contraceptive from protein binding sites.

Answer: B. Induces the metabolism of the contraceptive, potentially leading to therapeutic failure

14. A patient on phenobarbital reports feeling excessively drowsy and sedated. This is a predictable pharmacodynamic effect, and a serum level would likely be:

• A. Below the therapeutic range.
• B. Within the therapeutic range.
• C. Above the therapeutic range.
• D. Unrelated to the dose.

Answer: C. Above the therapeutic range

15. How long would it take for a patient to reach a steady-state concentration of phenobarbital after starting a maintenance dose?

• A. 2-3 days
• B. 1 week
• C. Several weeks (e.g., 20-25 days)
• D. 24 hours

Answer: C. Several weeks (e.g., 20-25 days)

16. The concept of “clearance” in pharmacokinetics refers to:

• A. The amount of drug in the body.
• B. The time it takes for the drug concentration to decrease by half.
• C. The volume of plasma cleared of drug per unit time.
• D. The concentration of the drug at its receptor.

Answer: C. The volume of plasma cleared of drug per unit time

17. When a patient stops taking phenobarbital after chronic use, the enzyme induction effect wears off. This means the doses of other medications they take may need to be:

• A. Increased
• B. Decreased
• C. Kept the same
• D. Discontinued

Answer: B. Decreased

18. The “Principles of Drug Therapy Individualization” course provides the foundational knowledge for understanding phenobarbital’s complex pharmacokinetic profile.

• A. True
• B. False

Answer: A. True

19. Primidone is a medication that is metabolically converted to which active compound?

• A. Phenytoin
• B. Carbamazepine
• C. Valproic acid
• D. Phenobarbital

Answer: D. Phenobarbital

20. The “Implement” step of the PPCP for a patient on phenobarbital involves:

• A. Only collecting a medication history.
• B. Educating the patient on the importance of adherence and the side effect of sedation.
• C. Diagnosing the patient’s seizure type.
• D. Formulating a problem list.

Answer: B. Educating the patient on the importance of adherence and the side effect of sedation

21. A patient with severe hepatic impairment is started on phenobarbital. What pharmacokinetic change is expected?

• A. Increased metabolism and lower drug levels.
• B. Decreased metabolism and higher drug levels, risking toxicity.
• C. No change in drug metabolism.
• D. Increased renal clearance.

Answer: B. Decreased metabolism and higher drug levels, risking toxicity

22. Therapeutic drug monitoring (TDM) for phenobarbital is essential because of its:

• A. Wide therapeutic range and lack of side effects.
• B. Narrow therapeutic range and potential for toxicity.
• C. Rapid onset of action.
• D. Low cost.

Answer: B. Narrow therapeutic range and potential for toxicity

23. The sedative and CNS depressant effects of phenobarbital are additive with which of the following substances?

• A. Caffeine
• B. Alcohol and opioids
• C. Vitamin C
• D. Water

Answer: B. Alcohol and opioids

24. A trough serum level for phenobarbital should be drawn:

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

Answer: C. Just before the next scheduled dose

25. A patient’s phenobarbital level is 55 mg/L. The pharmacist should recognize this level as:

• A. Subtherapeutic
• B. Therapeutic
• C. Toxic
• D. Within the normal range

Answer: C. Toxic

26. The half-life of phenobarbital is significantly longer in which pediatric population due to immature metabolic pathways?

• A. Adolescents
• B. School-aged children
• C. Toddlers
• D. Neonates

Answer: D. Neonates

27. The primary reason phenobarbital is no longer a first-line agent for most seizure types is its:

• A. Lack of efficacy.
• B. Unfavorable side effect profile (sedation, cognitive slowing) and extensive drug interactions.
• C. High cost.
• D. Lack of an oral formulation.

Answer: B. Unfavorable side effect profile (sedation, cognitive slowing) and extensive drug interactions

28. Phenobarbital is a weak acid. Its absorption from the GI tract after oral administration is:

• A. Poor and erratic
• B. Slow but relatively complete
• C. Dependent on active transport
• D. Negligible, requiring IV administration for all uses

Answer: B. Slow but relatively complete

29. The term “enzyme induction” means that a drug like phenobarbital:

• A. Inhibits the activity of CYP450 enzymes.
• B. Increases the synthesis of CYP450 enzymes, leading to faster metabolism of other drugs.
• C. Has no effect on metabolic enzymes.
• D. Is only metabolized by non-CYP enzymes.

Answer: B. Increases the synthesis of CYP450 enzymes, leading to faster metabolism of other drugs

30. The “Follow-up: Monitor and Evaluate” step of the PPCP for a patient on phenobarbital requires regular assessment of:

• A. Seizure frequency and side effects.
• B. Serum drug concentrations, if indicated.
• C. Adherence and potential drug interactions.
• D. All of the above.

Answer: D. All of the above

31. In a phenobarbital overdose, forced diuresis combined with urine alkalinization can be used to:

• A. Increase hepatic metabolism.
• B. Increase renal clearance of the drug.
• C. Increase protein binding.
• D. Decrease drug absorption.

Answer: B. Increase renal clearance of the drug

32. What percentage of a phenobarbital dose is typically bound to plasma proteins?

• A. <10%
• B. ~90%
• C. 40-60%
• D. 100%

Answer: C. 40-60%

33. The long half-life of phenobarbital can be an advantage in terms of:

• A. Rapid dose titration.
• B. A lower risk of seizures due to a single missed dose.
• C. A lack of side effects.
• D. Minimal drug interactions.

Answer: B. A lower risk of seizures due to a single missed dose.

34. The “drug metabolizing enzymes” and their induction/inhibition are a major topic in which foundational course?

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

Answer: A. PHA5132 Principles of Drug Therapy Individualization

35. A patient on phenobarbital develops respiratory depression. This is a severe pharmacodynamic effect resulting from:

• A. Potent CNS depression.
• B. An allergic reaction.
• C. Induction of liver enzymes.
• D. Inhibition of renal clearance.

Answer: A. Potent CNS depression

36. Because it is a potent enzyme inducer, starting phenobarbital may require ________ the dose of a co-administered drug that is a CYP3A4 substrate.

• A. halving
• B. decreasing
• C. increasing
• D. discontinuing

Answer: C. increasing

37. The volume of distribution (Vd) of phenobarbital is approximately 0.5-1 L/kg, indicating that it distributes into:

• A. Only the plasma.
• B. Total body water.
• C. Only fat tissue.
• D. Only the brain.

Answer: B. Total body water

38. The need to perform calculations to determine doses is a key objective of the Hospital IPPE, which is particularly relevant for calculating a phenobarbital _________ dose.

• A. daily
• B. maintenance
• C. loading
• D. tapered

Answer: C. loading

39. Compared to benzodiazepines, the pharmacologic action of barbiturates like phenobarbital is more dangerous in overdose because at high doses, they can:

• A. Act as a direct GABA-mimetic, opening the chloride channel without GABA.
• B. Only increase the frequency of channel opening.
• C. Be reversed by flumazenil.
• D. Be easily cleared by the kidneys.

Answer: A. Act as a direct GABA-mimetic, opening the chloride channel without GABA

40. To avoid excessive sedation, a patient starting phenobarbital should be counseled to avoid:

• A. Driving or operating heavy machinery until they know how the drug affects them.
• B. Strenuous exercise.
• C. High-protein meals.
• D. Bright lights.

Answer: A. Driving or operating heavy machinery until they know how the drug affects them

41. The primary route of metabolism for phenobarbital is:

• A. Renal filtration
• B. Biliary excretion
• C. Hepatic oxidation (primarily by CYP2C9)
• D. Glucuronidation

Answer: C. Hepatic oxidation (primarily by CYP2C9)

42. A patient on chronic phenobarbital therapy requires a shorter-acting anesthetic for a surgical procedure. The dose of the anesthetic may need to be _________ due to enzyme induction.

• A. decreased
• B. the same
• C. increased
• D. held

Answer: C. increased

43. The “Assess” step of the PPCP for a patient on phenobarbital would include:

• A. Creating a new care plan.
• B. Reviewing recent serum drug concentrations and assessing for side effects.
• C. Educating the patient.
• D. Dispensing the medication.

Answer: B. Reviewing recent serum drug concentrations and assessing for side effects

44. Which of the following best describes the oral bioavailability of phenobarbital?

• A. Low and erratic (<50%)
• B. High and reliable (>90%)
• C. Essentially zero, requiring IV use
• D. Dependent on food intake

Answer: B. High and reliable (>90%)

45. Abrupt withdrawal from chronic phenobarbital use can be life-threatening due to the risk of:

• A. Severe sedation
• B. Hypertensive crisis
• C. Status epilepticus
• D. Liver failure

Answer: C. Status epilepticus

46. Given its long half-life, a patient who misses one dose of phenobarbital is:

• A. At extremely high risk for a seizure that day.
• B. At lower risk for a seizure compared to missing a dose of a short half-life drug.
• C. Advised to double their next dose.
• D. Required to go to the emergency department.

Answer: B. At lower risk for a seizure compared to missing a dose of a short half-life drug.

47. Phenobarbital is a weak acid with a pKa of ~7.3. This means that at a physiological pH of 7.4:

• A. The drug will be almost completely ionized.
• B. The drug will be almost completely unionized.
• C. About half of the drug will be in the ionized form and half in the unionized form.
• D. The pKa is not relevant to its ionization.

Answer: C. About half of the drug will be in the ionized form and half in the unionized form

48. Why is phenobarbital TDM particularly important in polytherapy?

• A. Because other drugs do not interact with phenobarbital.
• B. To assess the impact of drug interactions (inhibition or induction) on phenobarbital levels.
• C. Because polytherapy is always safer.
• D. TDM is less important in polytherapy.

Answer: B. To assess the impact of drug interactions (inhibition or induction) on phenobarbital levels

49. An understanding of phenobarbital’s pharmacokinetics is essential for which Entrustable Professional Activity (EPA)?

• A. Identifying populations at risk for prevalent diseases.
• B. Fulfilling a medication order.
• C. Creating a care plan…to optimize pharmacologic and nonpharmacologic treatment.
• D. Performing administrative operations of a pharmacy practice site.

Answer: C. Creating a care plan…to optimize pharmacologic and nonpharmacologic treatment

50. The ultimate goal of pharmacokinetic management of phenobarbital is to:

• A. Keep the drug level as high as possible.
• B. Maintain a drug concentration within the therapeutic range to maximize efficacy while minimizing toxicity.
• C. Use the drug for the shortest possible time.
• D. Avoid all drug interactions.

Answer: B. Maintain a drug concentration within the therapeutic range to maximize efficacy while minimizing toxicity