Dosing in hepatic failure MCQs With Answer

Dosing in hepatic failure MCQs With Answer is a focused question bank for M.Pharm students studying Clinical Pharmacokinetics and Therapeutic Drug Monitoring. This set addresses how liver disease alters drug absorption, distribution, metabolism and elimination, and how those changes guide dose selection. Questions emphasize principles such as hepatic extraction ratio, intrinsic clearance, protein binding, portosystemic shunting, and Child–Pugh staging, and apply them to clinical examples (benzodiazepines, opioids, anticoagulants, antibiotics). Each item encourages critical thinking about when to adjust dose, when to measure free drug concentrations, and which agents are safer in advanced liver disease. Use these MCQs to test and deepen your practical dosing knowledge in hepatic impairment.

Q1. Which of the following mechanisms most directly explains reduced hepatic clearance of a low extraction drug in hepatic failure?

• Decreased hepatic blood flow
• Reduced intrinsic metabolic capacity (Clint) and altered protein binding
• Increased renal elimination
• Enhanced first-pass metabolism

Correct Answer: Reduced intrinsic metabolic capacity (Clint) and altered protein binding

Q2. For a high hepatic extraction ratio drug, which physiologic change in advanced liver disease most strongly reduces hepatic clearance?

• Decrease in plasma albumin concentration
• Decrease in hepatic blood flow
• Decrease in intrinsic hepatic enzyme activity
• Increase in volume of distribution

Correct Answer: Decrease in hepatic blood flow

Q3. Which mathematical relationship correctly describes hepatic clearance (Clh) under the well-stirred model?

• Clh = Vd × k
• Clh = Qh × EH, where EH = (fu × Clint) / (Qh + fu × Clint)
• Clh = fu × Vd
• Clh = renal clearance + biliary clearance

Correct Answer: Clh = Qh × EH, where EH = (fu × Clint) / (Qh + fu × Clint)

Q4. Portosystemic shunting in cirrhosis commonly affects oral drugs with high hepatic extraction by:

• Decreasing oral bioavailability and reducing systemic exposure
• Increasing oral bioavailability by bypassing first-pass metabolism
• Increasing renal clearance of the parent drug
• Only affecting parenteral routes of administration

Correct Answer: Increasing oral bioavailability by bypassing first-pass metabolism

Q5. Which five clinical/laboratory variables are included in the Child–Pugh classification used to grade hepatic impairment?

• Bilirubin, albumin, prothrombin time/INR, ascites, and hepatic encephalopathy
• Creatinine, bilirubin, MELD score, sodium, and age
• ALT, AST, alkaline phosphatase, bilirubin, and platelet count
• Albumin, creatinine, blood pressure, heart rate, and bilirubin

Correct Answer: Bilirubin, albumin, prothrombin time/INR, ascites, and hepatic encephalopathy

Q6. General practical dosing guidance for drugs in patients with Child–Pugh class C (severe hepatic impairment) is to:

• Use usual doses with no monitoring changes
• Avoid the drug or reduce dose substantially and monitor closely
• Increase dose to overcome reduced hepatic clearance
• Switch routinely to oral therapy to minimize exposure

Correct Answer: Avoid the drug or reduce dose substantially and monitor closely

Q7. In a patient with severe hypoalbuminemia, which drug’s total plasma concentration is most likely to be misleading and should be monitored as unbound (free) drug?

• Amoxicillin (low protein binding)
• Phenytoin (high protein binding)
• Gentamicin (renal excretion, low protein binding)
• Metformin (renal excretion)

Correct Answer: Phenytoin (high protein binding)

Q8. Which benzodiazepine is generally preferred in patients with significant hepatic impairment due to metabolism by conjugation to inactive metabolites?

• Diazepam
• Chlordiazepoxide
• Lorazepam
• Clonazepam

Correct Answer: Lorazepam

Q9. Morphine disposition in advanced liver disease is characterized by:

• Increased hepatic clearance and shortened half-life
• Reduced clearance, prolonged half-life and possible accumulation of active metabolites
• No change in pharmacokinetics because morphine is renally cleared only
• Complete shift to renal elimination with unchanged metabolism

Correct Answer: Reduced clearance, prolonged half-life and possible accumulation of active metabolites

Q10. Warfarin dosing in hepatic failure requires caution because:

• Hepatic failure increases vitamin K–dependent clotting factor synthesis
• Hypoalbuminemia and reduced clotting factor synthesis increase warfarin sensitivity and bleeding risk
• Warfarin is inactivated by renal excretion only
• Hepatic impairment makes INR measurements invalid

Correct Answer: Hypoalbuminemia and reduced clotting factor synthesis increase warfarin sensitivity and bleeding risk

Q11. Which of the following drugs is a classic example of a high hepatic extraction ratio drug (clearance highly dependent on hepatic blood flow)?

• Propranolol
• Warfarin
• Phenytoin
• Digoxin

Correct Answer: Propranolol

Q12. Which drug is typically categorized as a low extraction drug whose clearance is sensitive to changes in intrinsic hepatic enzyme activity and protein binding?

• Morphine
• Warfarin
• Propranolol
• Fentanyl

Correct Answer: Warfarin

Q13. Drugs most likely to require dose adjustment in hepatic failure share which characteristics?

• Low hepatic extraction ratio and high protein binding
• Eliminated unchanged in urine and low protein binding
• Short half-life and hydrophilic distribution
• Cleared solely by pulmonary exhalation

Correct Answer: Low hepatic extraction ratio and high protein binding

Q14. Concerning direct oral anticoagulants (DOACs) in severe hepatic impairment (Child–Pugh C), the safest general statement is:

• All DOACs are safe without dose adjustment
• DOACs should generally be avoided or used with extreme caution in Child–Pugh C
• DOAC dosing is only guided by renal function and liver disease is irrelevant
• DOACs increase protein binding in liver disease and require higher doses

Correct Answer: DOACs should generally be avoided or used with extreme caution in Child–Pugh C

Q15. When deciding the loading dose for a critically ill patient with hepatic failure, which principle is most applicable?

• Loading dose is based on clearance and should always be reduced in hepatic failure
• Loading dose depends on volume of distribution and may not need reduction solely because of reduced hepatic clearance
• Loading dose should equal half the maintenance dose in hepatic disease
• Loading dose should only be given orally in hepatic failure

Correct Answer: Loading dose depends on volume of distribution and may not need reduction solely because of reduced hepatic clearance

Q16. In hypoalbuminemia due to liver disease, interpretation of total concentrations of highly protein-bound drugs is best summarized as:

• Total concentration increases while free concentration decreases
• Total concentration decreases and free (pharmacologically active) concentration may be unchanged or increased
• Total concentration accurately predicts effect without measuring free drug
• Both total and free concentrations fall proportionally and remain clinically irrelevant

Correct Answer: Total concentration decreases and free (pharmacologically active) concentration may be unchanged or increased

Q17. For therapeutic drug monitoring (TDM) in patients with severe hepatic impairment, the recommended strategy for highly protein-bound drugs is to:

• Rely solely on total plasma concentrations
• Measure unbound (free) drug concentrations when possible
• Double the therapeutic range to compensate for hypoalbuminemia
• Use urine drug levels instead of plasma

Correct Answer: Measure unbound (free) drug concentrations when possible

Q18. Which opioid is least dependent on hepatic metabolism and therefore often preferred if opioid analgesia is required in severe hepatic failure?

• Morphine
• Fentanyl
• Remifentanil
• Codeine

Correct Answer: Remifentanil

Q19. Which antibiotic’s clearance is least likely to be affected by hepatic impairment because it is primarily renally excreted unchanged?

• Clindamycin
• Chloramphenicol
• Gentamicin
• Erythromycin

Correct Answer: Gentamicin

Q20. Which scoring system is most commonly referenced in drug dosing guidance and labeling to stratify chronic liver disease severity for dose adjustments?

• MELD (Model for End-Stage Liver Disease) only
• Child–Pugh classification
• APACHE II
• Glasgow Coma Scale

Correct Answer: Child–Pugh classification

Download