FPGEE Pharmacokinetics 4 — Questions and Answers
Question 1: A drug has a hepatic extraction ratio of 0.9. Hepatic blood flow decreases by 50% due to heart failure. What is the expected effect on systemic clearance of this drug?
- Clearance is unchanged because metabolism is unaffected
- Clearance decreases by approximately 50% (Correct answer)
- Clearance increases due to compensatory mechanisms
- Clearance decreases by 90%
Correct answer: Clearance decreases by approximately 50%
For high-extraction drugs, clearance ≈ hepatic blood flow; a 50% reduction in flow causes an approximately 50% reduction in clearance.
Question 2: The renal clearance of a drug is found to be greater than GFR (125 mL/min). This indicates which renal mechanism?
- Net tubular reabsorption
- Net tubular secretion (Correct answer)
- Glomerular filtration only
- Protein-bound fraction being filtered
Correct answer: Net tubular secretion
Renal clearance exceeding GFR means additional drug is being added to tubular fluid via active secretion beyond what filtration alone can account for.
Question 3: What is the time to reach steady state primarily dependent upon?
- Dose size
- Dosing frequency
- Drug half-life (Correct answer)
- Route of administration
Correct answer: Drug half-life
Steady state is reached in approximately 4–5 half-lives regardless of dose size or frequency; half-life is the primary determinant.
Question 4: A drug's bioavailability is 30% by oral route. To achieve the same AUC as a 50 mg IV dose, the oral dose should be:
- 15 mg
- 50 mg
- 167 mg (Correct answer)
- 500 mg
Correct answer: 167 mg
Oral dose = IV dose / F = 50 mg / 0.30 ≈ 167 mg to compensate for the 70% lost to incomplete absorption and first-pass.
Question 5: Which plasma protein primarily binds basic (cationic) drugs such as lidocaine and propranolol?
- Albumin
- Alpha-1-acid glycoprotein (AAG) (Correct answer)
- Beta-globulin
- Transferrin
Correct answer: Alpha-1-acid glycoprotein (AAG)
Alpha-1-acid glycoprotein preferentially binds basic drugs, while albumin primarily binds acidic drugs and some neutral drugs.
Question 6: A drug exhibits non-linear (dose-dependent) pharmacokinetics. Which clinical implication is most important?
- Dose adjustments cause predictable proportional changes in drug levels
- Small dose increases can cause disproportionately large toxicity risk (Correct answer)
- Half-life remains constant regardless of dose
- Monitoring drug levels is unnecessary
Correct answer: Small dose increases can cause disproportionately large toxicity risk
Non-linear kinetics means plasma levels rise disproportionately with dose increases, creating unpredictable toxicity risk requiring careful therapeutic monitoring.
Question 7: Henderson-Hasselbalch equation predicts that a weak acid (pKa 4.0) will be predominantly ionized at which pH?
- pH 2.0
- pH 3.5
- pH 4.0
- pH 7.4 (Correct answer)
Correct answer: pH 7.4
A weak acid with pKa 4.0 is predominantly ionized (>99.99%) at physiological pH 7.4 because pH >> pKa favors the ionized form.
FPGEE Pharmacokinetics 4
A drug has a hepatic extraction ratio of 0.9.
Hepatic blood flow decreases by 50% due to heart failure.
What is the expected effect on systemic clearance of this drug?