Pharmacokinetic dosing in patients with hepatic dysfunction is one of the most intellectually challenging yet clinically vital responsibilities of a pharmacist. Unlike renal dosing, there is no single equation that can precisely guide adjustments. Instead, pharmacists must rely on a deep understanding of pharmacokinetic principles—a “transcending concept” explored in courses like Patient Care 4 and built upon the foundations of Drug Therapy Individualization. This involves assessing how liver disease impacts drug metabolism, protein binding, and bioavailability to ensure patient safety. This quiz will test your ability to apply these complex principles to make sound clinical judgments for patients with impaired liver function.
1. Which of the following best describes the primary pharmacokinetic challenge in patients with hepatic dysfunction?
- a. Increased renal clearance of all drugs.
- b. Decreased metabolic capacity of the liver, leading to reduced drug clearance.
- c. Enhanced first-pass metabolism for all oral drugs.
- d. Unpredictable changes in drug absorption only.
Answer: b. Decreased metabolic capacity of the liver, leading to reduced drug clearance.
2. In a patient with cirrhosis and hypoalbuminemia, what happens to the free fraction of a highly protein-bound drug like phenytoin?
- a. The free fraction decreases.
- b. The free fraction remains unchanged.
- c. The free fraction increases, potentially leading to increased pharmacologic effect and toxicity.
- d. The total drug concentration increases.
Answer: c. The free fraction increases, potentially leading to increased pharmacologic effect and toxicity.
3. For a drug with a high hepatic extraction ratio (ER > 0.7), its clearance is primarily dependent on:
- a. The intrinsic activity of liver enzymes.
- b. The fraction of unbound drug in the blood.
- c. Hepatic blood flow.
- d. The patient’s serum creatinine.
Answer: c. Hepatic blood flow.
4. How does severe cirrhosis affect the oral bioavailability of a high extraction ratio drug like labetalol?
- a. It decreases bioavailability due to poor absorption.
- b. It has no effect on bioavailability.
- c. It significantly increases bioavailability due to reduced first-pass metabolism.
- d. It makes the bioavailability unpredictable.
Answer: c. It significantly increases bioavailability due to reduced first-pass metabolism.
5. The Child-Pugh score is a clinical tool used to assess the severity of cirrhosis. Which of the following is NOT a component of the score?
- a. Serum albumin
- b. Prothrombin time (or INR)
- c. Serum creatinine
- d. Presence of ascites
Answer: c. Serum creatinine
6. “PK Dosing in hepatic dysfunction” is a specific “Transcending Concept” in which course?
- a. PHA5784C Patient Care 4
- b. PHA5104 Sterile Compounding
- c. PHA5703 Pharmacy Law and Ethics
- d. PHA5878C Patient Care 3
Answer: a. PHA5784C Patient Care 4
7. For a drug with a low hepatic extraction ratio (ER < 0.3), its clearance is primarily dependent on:
- a. Hepatic blood flow only.
- b. The drug’s pKa.
- c. The fraction of unbound drug and intrinsic enzymatic activity.
- d. The patient’s heart rate.
Answer: c. The fraction of unbound drug and intrinsic enzymatic activity.
8. Phase I drug metabolism, which is often impaired in liver disease, typically involves what type of reactions?
- a. Conjugation reactions like glucuronidation.
- b. Oxidation, reduction, and hydrolysis via CYP450 enzymes.
- c. Acetylation.
- d. Sulfation.
Answer: b. Oxidation, reduction, and hydrolysis via CYP450 enzymes.
9. In a patient with cirrhosis and ascites, the volume of distribution (Vd) for a hydrophilic drug would be expected to:
- a. Decrease
- b. Remain the same
- c. Increase
- d. Become zero
Answer: c. Increase
10. Which statement about dosing adjustments in liver disease is most accurate?
- a. A simple formula can be used for all drugs.
- b. All drugs require a 50% dose reduction.
- c. There is no single reliable marker of hepatic function, so dosing must be individualized with caution.
- d. Dose adjustments are only necessary for IV medications.
Answer: c. There is no single reliable marker of hepatic function, so dosing must be individualized with caution.
11. The principles of hepatic clearance are a major topic in which foundational course?
- a. PHA5132 Principles of Drug Therapy Individualization
- b. PHA5781 Patient Care I
- c. PHA5163L Professional Skills Lab 3
- d. PHA5021C Personal and Professional Development 1
Answer: a. PHA5132 Principles of Drug Therapy Individualization
12. A patient with a Child-Pugh score of 12 would be classified as having:
- a. Child-Pugh Class A (well-compensated)
- b. Child-Pugh Class B (significant functional compromise)
- c. Child-Pugh Class C (decompensated)
- d. Normal liver function
Answer: c. Child-Pugh Class C (decompensated)
13. Why might Phase II metabolic reactions (e.g., glucuronidation) be better preserved in liver disease compared to Phase I reactions?
- a. They occur outside of the liver.
- b. They are less dependent on hepatic blood flow and oxygen delivery, which are often compromised in cirrhosis.
- c. They are not enzymatic reactions.
- d. They are not important for drug clearance.
Answer: b. They are less dependent on hepatic blood flow and oxygen delivery, which are often compromised in cirrhosis.
14. A patient with cirrhosis has a low serum albumin of 2.1 g/dL. For a highly bound drug, the pharmacist should be aware that:
- a. The total drug concentration may be low, but the pharmacologically active free concentration could be high or normal.
- b. The total drug concentration will be very high.
- c. The free drug concentration will be very low.
- d. Protein binding does not affect drug activity.
Answer: a. The total drug concentration may be low, but the pharmacologically active free concentration could be high or normal.
15. A patient with cirrhosis should be advised to avoid which over-the-counter pain reliever due to its potential for hepatotoxicity?
- a. Ibuprofen
- b. Naproxen
- c. Acetaminophen (or use with extreme caution at reduced doses).
- d. Aspirin
Answer: c. Acetaminophen (or use with extreme caution at reduced doses).
16. Predicting the effects of protein binding on drug clearance is a key objective in the Drug Therapy Individualization course.
- a. True
- b. False
Answer: a. True
17. Shunting of blood away from the liver in severe cirrhosis reduces the clearance of which type of drugs the most?
- a. Drugs with low hepatic extraction ratios.
- b. Drugs eliminated only by the kidneys.
- c. Drugs with high hepatic extraction ratios.
- d. Drugs administered topically.
Answer: c. Drugs with high hepatic extraction ratios.
18. For which of the following drugs would you need to be most concerned about increased oral bioavailability in a patient with severe cirrhosis?
- a. Atenolol (low first-pass metabolism)
- b. Propranolol (high first-pass metabolism)
- c. Digoxin (renally cleared)
- d. Lisinopril (renally cleared)
Answer: b. Propranolol (high first-pass metabolism)
19. A patient with hepatic encephalopathy should avoid which class of medications?
- a. Stool softeners
- b. Benzodiazepines
- c. Non-selective beta-blockers
- d. Diuretics
Answer: b. Benzodiazepines
20. A general guideline for initiating a new, hepatically metabolized drug in a patient with Child-Pugh Class B or C cirrhosis is to:
- a. Start with a higher-than-normal dose.
- b. Use the standard dose.
- c. Start with a lower dose (e.g., 25-50% of the usual dose) and titrate slowly.
- d. Avoid all new medications.
Answer: c. Start with a lower dose (e.g., 25-50% of the usual dose) and titrate slowly.
21. Drug biotransformation (metabolism) is a major topic within the Medicinal Chemistry curriculum.
- a. True
- b. False
Answer: a. True
22. A patient with cholestatic liver injury would have a predominant elevation in which lab values?
- a. AST and ALT
- b. Alkaline phosphatase (Alk Phos) and bilirubin
- c. Albumin and INR
- d. Serum creatinine and BUN
Answer: b. Alkaline phosphatase (Alk Phos) and bilirubin
23. Which of the following is NOT a good reason to reduce a drug dose in a patient with liver disease?
- a. The drug is known to be hepatotoxic.
- b. The drug is primarily cleared by the liver and has a narrow therapeutic index.
- c. The patient has a low albumin and the drug is highly protein-bound.
- d. The drug is primarily cleared by the kidneys and the patient has normal renal function.
Answer: d. The drug is primarily cleared by the kidneys and the patient has normal renal function.
24. The presence of ascites in a cirrhotic patient can:
- a. Decrease the volume of distribution for hydrophilic drugs.
- b. Have no effect on drug distribution.
- c. Increase the volume of distribution for hydrophilic drugs, potentially requiring a higher loading dose.
- d. Increase the volume of distribution for lipophilic drugs only.
Answer: c. Increase the volume of distribution for hydrophilic drugs, potentially requiring a higher loading dose.
25. A patient with cirrhosis has an INR of 1.8. They need anticoagulation for a new DVT. Which statement is correct?
- a. The elevated baseline INR is protective, so no anticoagulation is needed.
- b. Despite the elevated INR, these patients can still have thrombotic events and require careful anticoagulation.
- c. Warfarin is the safest anticoagulant in this patient.
- d. The INR goal should be 4.0-5.0.
Answer: b. Despite the elevated INR, these patients can still have thrombotic events and require careful anticoagulation.
26. The term “intrinsic clearance” refers to:
- a. The liver’s blood flow rate.
- b. The inherent metabolic capacity of the liver enzymes, independent of blood flow.
- c. The rate of biliary excretion.
- d. The amount of drug bound to albumin.
Answer: b. The inherent metabolic capacity of the liver enzymes, independent of blood flow.
27. For a low extraction ratio, highly protein-bound drug, a decrease in protein binding will:
- a. Decrease the free concentration of the drug.
- b. Increase the total clearance of the drug.
- c. Decrease the total clearance of the drug.
- d. Have no effect on clearance.
Answer: b. Increase the total clearance of the drug.
28. Why must NSAIDs be used with extreme caution in patients with cirrhosis?
- a. They can precipitate hepatorenal syndrome and increase the risk of GI bleeding.
- b. They are the leading cause of cirrhosis.
- c. They inhibit CYP450 enzymes.
- d. They cause severe constipation.
Answer: a. They can precipitate hepatorenal syndrome and increase the risk of GI bleeding.
29. A patient’s MELD (Model for End-Stage Liver Disease) score is primarily used to:
- a. Guide routine drug dosing.
- b. Prioritize patients on the liver transplant list.
- c. Diagnose hepatitis C.
- d. Assess for ascites.
Answer: b. Prioritize patients on the liver transplant list.
30. The “PK Dosing in hepatic dysfunction” active learning session is part of which course?
- a. PHA5784C Patient Care 4
- b. PHA5163L Professional Skills Lab 3
- c. PHA5781 Patient Care I
- d. PHA5782C Patient Care 2
Answer: a. PHA5784C Patient Care 4
31. A patient with a Child-Pugh Class A score has:
- a. Decompensated cirrhosis
- b. The most severe form of liver disease
- c. Well-compensated cirrhosis
- d. A need for immediate transplant
Answer: c. Well-compensated cirrhosis
32. The half-life of a hepatically cleared drug is expected to be prolonged in cirrhosis. This means:
- a. The drug will reach steady state faster.
- b. The drug will take longer to be eliminated from the body.
- c. The dosing interval should be shortened.
- d. The dose should be increased.
Answer: b. The drug will take longer to be eliminated from the body.
33. Which of the following drugs undergoes extensive first-pass metabolism?
- a. Lithium
- b. Gentamicin
- c. Nitroglycerin
- d. Atenolol
Answer: c. Nitroglycerin
34. The best approach for a pharmacist when a provider asks for a dose recommendation for a new drug in a patient with severe cirrhosis is to:
- a. Give the standard dose.
- b. Refuse to make a recommendation.
- c. Consult drug information resources, consider the drug’s PK properties (clearance, ER, protein binding), and recommend a cautious starting dose with close monitoring.
- d. Tell the provider to choose a different drug.
Answer: c. Consult drug information resources, consider the drug’s PK properties (clearance, ER, protein binding), and recommend a cautious starting dose with close monitoring.
35. An elevated AST and ALT are markers of:
- a. Liver synthetic function
- b. Cholestasis
- c. Hepatocellular injury
- d. Renal function
Answer: c. Hepatocellular injury
36. For a low extraction ratio drug that is not highly protein-bound, clearance is mainly dependent on:
- a. Hepatic blood flow
- b. Intrinsic clearance (enzyme activity)
- c. The patient’s weight
- d. The patient’s age
Answer: b. Intrinsic clearance (enzyme activity)
37. Which statement is true regarding drug dosing based on the Child-Pugh score?
- a. It can be used to calculate a precise dose for any medication.
- b. It provides a general guide for dose reduction for some, but not all, medications.
- c. A Class A score always requires a 50% dose reduction.
- d. It is primarily used for renally cleared drugs.
Answer: b. It provides a general guide for dose reduction for some, but not all, medications.
38. The liver’s role in synthesizing clotting factors means that in severe liver disease, patients are at an increased risk of:
- a. Bleeding
- b. Thrombosis
- c. Both bleeding and thrombosis
- d. Neither bleeding nor thrombosis
Answer: c. Both bleeding and thrombosis
39. Understanding hepatic clearance is a module in the Principles of Drug Therapy Individualization course.
- a. True
- b. False
Answer: a. True
40. Why is morphine used cautiously in patients with severe liver disease?
- a. It undergoes extensive glucuronidation, and while this Phase II reaction is preserved, accumulation of metabolites can occur.
- b. It can precipitate hepatic encephalopathy.
- c. Both a and b are correct.
- d. It is not used in liver disease.
Answer: c. Both a and b are correct.
41. If a patient with cirrhosis needs a benzodiazepine for alcohol withdrawal, which agents are preferred due to their metabolism primarily by conjugation?
- a. Diazepam and chlordiazepoxide
- b. Lorazepam, oxazepam, and temazepam (“LOT”)
- c. Alprazolam and clonazepam
- d. Midazolam
Answer: b. Lorazepam, oxazepam, and temazepam (“LOT”)
42. Drug-induced liver injury (DILI) is:
- a. Always predictable and dose-dependent.
- b. A potential adverse effect of many drugs, including herbals and supplements.
- c. Easy to diagnose with a single lab test.
- d. Never serious.
Answer: b. A potential adverse effect of many drugs, including herbals and supplements.
43. A drug’s extraction ratio (ER) is:
- a. The fraction of drug entering the liver that is removed in a single pass.
- b. The percentage of drug bound to protein.
- c. The drug’s half-life.
- d. The drug’s volume of distribution.
Answer: a. The fraction of drug entering the liver that is removed in a single pass.
44. A patient has Child-Pugh Class B cirrhosis. What general dose adjustment might be considered for a hepatically cleared drug?
- a. No adjustment needed.
- b. A 25-50% reduction in the initial dose.
- c. A 75% reduction in the initial dose.
- d. A 100% increase in the dose.
Answer: b. A 25-50% reduction in the initial dose.
45. The most important principle of dosing in hepatic dysfunction is:
- a. Using a complex formula.
- b. Close clinical monitoring for efficacy and toxicity.
- c. Always choosing the lowest possible dose.
- d. Avoiding all medications.
Answer: b. Close clinical monitoring for efficacy and toxicity.
46. Which of these labs would be most indicative of cholestasis (impaired bile flow)?
- a. A low albumin
- b. An elevated INR
- c. A markedly elevated alkaline phosphatase
- d. An elevated AST that is twice the ALT
Answer: c. A markedly elevated alkaline phosphatase
47. The pharmacokinetic principle of “first-pass metabolism” is most relevant for which route of administration?
- a. Intravenous
- b. Transdermal
- c. Oral
- d. Subcutaneous
Answer: c. Oral
48. An active learning session covering PK dosing in hepatic dysfunction is part of which course?
- a. PHA5784C Patient Care 4
- b. PHA5163L Professional Skills Lab 3
- c. PHA5781 Patient Care I
- d. PHA5782C Patient Care 2
Answer: a. PHA5784C Patient Care 4
49. For a high extraction ratio drug administered IV, what is the main determinant of its clearance?
- a. Intrinsic enzyme activity
- b. Protein binding
- c. Hepatic blood flow
- d. Biliary secretion
Answer: c. Hepatic blood flow
50. The ultimate goal of pharmacokinetic dosing in hepatic dysfunction is to:
- a. Use the most expensive drugs available.
- b. Avoid using the liver for drug metabolism.
- c. Achieve therapeutic drug concentrations that are both effective and non-toxic, despite the patient’s compromised liver function.
- d. Standardize dosing for all patients regardless of liver function.
Answer: c. Achieve therapeutic drug concentrations that are both effective and non-toxic, despite the patient’s compromised liver function.