PSA Renal and Hepatic Prescribing 2 — Questions and Answers
Question 1: A patient with severe hepatic impairment is prescribed warfarin. What change in anticoagulant response is expected compared to a patient with normal liver function?
- INR will be lower than expected, requiring higher doses
- INR will be higher than expected, requiring lower doses (Correct answer)
- INR response will be identical to normal liver function
- INR will be unpredictably variable with no consistent trend
Correct answer: INR will be higher than expected, requiring lower doses
Hepatic impairment both reduces clotting factor synthesis and impairs warfarin metabolism, leading to enhanced anticoagulant effect and elevated INR.
Question 2: Morphine should be used with extreme caution in renal failure primarily due to accumulation of which active metabolite?
- Morphine-3-glucuronide (M3G)
- Morphine-6-glucuronide (M6G) (Correct answer)
- Normorphine
- 6-acetylmorphine
Correct answer: Morphine-6-glucuronide (M6G)
Morphine-6-glucuronide (M6G) is a potent active analgesic metabolite that accumulates in renal failure and can cause profound respiratory depression.
Question 3: Which formula is the standard method recommended for estimating creatinine clearance when adjusting drug doses in renal impairment?
- MDRD equation
- Cockcroft-Gault equation (Correct answer)
- CKD-EPI equation
- Schwartz formula
Correct answer: Cockcroft-Gault equation
The Cockcroft-Gault equation is the standard formula used for drug dosing calculations in renal impairment as it was validated using drug clearance data.
Question 4: A patient with CrCl 30 mL/min is prescribed digoxin. Compared to a patient with normal renal function, the expected pharmacokinetic change is:
- Shorter half-life, requiring more frequent dosing
- Unchanged half-life as digoxin is hepatically metabolized
- Prolonged half-life, requiring dose reduction (Correct answer)
- Reduced volume of distribution requiring a smaller loading dose
Correct answer: Prolonged half-life, requiring dose reduction
Digoxin is 70% renally excreted; in renal impairment, its half-life is prolonged significantly, requiring maintenance dose reduction to prevent toxicity.
Question 5: Which analgesic should be avoided in renal impairment due to accumulation of its neurotoxic active metabolite, norpethidine?
- Fentanyl
- Tramadol
- Pethidine (meperidine) (Correct answer)
- Hydromorphone
Correct answer: Pethidine (meperidine)
Pethidine is metabolized to norpethidine, a neuroexcitatory metabolite that accumulates in renal failure and causes CNS toxicity including seizures.
Question 6: NSAIDs cause acute kidney injury in patients with renal impairment primarily through which mechanism?
- Direct tubular epithelial toxicity
- Inhibition of prostaglandin-mediated afferent arteriolar dilation (Correct answer)
- Increased sodium reabsorption at the collecting duct
- Competitive inhibition of creatinine secretion at the proximal tubule
Correct answer: Inhibition of prostaglandin-mediated afferent arteriolar dilation
NSAIDs inhibit prostaglandins that maintain afferent arteriolar dilation in states of low renal perfusion, reducing GFR and precipitating acute kidney injury.
Question 7: A patient with Child-Pugh Class B liver disease is prescribed a drug with a high hepatic extraction ratio administered orally. The most likely pharmacokinetic consequence is:
- Reduced oral bioavailability due to compensatory enzyme induction
- Increased oral bioavailability due to reduced first-pass metabolism (Correct answer)
- No change as hepatic extraction ratio is independent of liver function
- Reduced half-life due to increased renal clearance
Correct answer: Increased oral bioavailability due to reduced first-pass metabolism
High hepatic extraction ratio drugs undergo extensive first-pass metabolism; hepatic impairment reduces this extraction, substantially increasing systemic bioavailability.
PSA Renal and Hepatic Prescribing 2
A patient with severe hepatic impairment is prescribed warfarin.
What change in anticoagulant response is expected compared to a patient with normal liver function?