Pharmacology Pharmacokinetics and Drug Metabolism 2 — Questions and Answers
Question 1: A drug with a high extraction ratio is administered orally. Which phenomenon most significantly reduces its systemic bioavailability?
- Renal elimination
- First-pass metabolism (Correct answer)
- Enterohepatic recirculation
- Protein binding in plasma
Correct answer: First-pass metabolism
High-extraction-ratio drugs are extensively metabolized by the liver on first pass, greatly reducing the fraction that reaches systemic circulation.
Question 2: Which cytochrome P450 isoform is responsible for metabolizing approximately 50% of all clinically used drugs?
- CYP1A2
- CYP2D6
- CYP3A4 (Correct answer)
- CYP2C9
Correct answer: CYP3A4
CYP3A4 is the most abundant hepatic CYP enzyme and metabolizes roughly half of all drugs in clinical use.
Question 3: A patient taking rifampin begins a new medication. The new drug's plasma levels are unexpectedly low. What is the most likely explanation?
- Rifampin inhibits renal tubular secretion
- Rifampin induces CYP450 enzymes (Correct answer)
- Rifampin competitively binds plasma proteins
- Rifampin increases glomerular filtration rate
Correct answer: Rifampin induces CYP450 enzymes
Rifampin is a potent CYP450 inducer that increases metabolism of co-administered drugs, lowering their plasma concentrations.
Question 4: What is the clinical significance of a drug having a large volume of distribution (Vd)?
- The drug is predominantly confined to plasma
- The drug distributes extensively into tissues (Correct answer)
- The drug is rapidly cleared by the kidneys
- The drug has high oral bioavailability
Correct answer: The drug distributes extensively into tissues
A large Vd indicates that the drug distributes widely into peripheral tissues rather than remaining in the plasma compartment.
Question 5: Which phase II metabolic reaction conjugates drugs with glucuronic acid?
- Acetylation
- Sulfation
- Glucuronidation (Correct answer)
- Methylation
Correct answer: Glucuronidation
Glucuronidation, catalyzed by UDP-glucuronosyltransferases, is the most common phase II conjugation reaction that enhances water solubility.
Question 6: A drug's half-life is 6 hours. How long does it take to reach approximately 94% of steady-state concentration during continuous infusion?
- 6 hours
- 12 hours
- 24 hours (Correct answer)
- 36 hours
Correct answer: 24 hours
Steady state is reached after approximately 4-5 half-lives; 4 half-lives (4 × 6 = 24 hours) yields about 94% of steady state.
Question 7: Which type of pharmacokinetics applies when drug-metabolizing enzymes become saturated, causing a disproportionate increase in plasma concentration with increasing dose?
- First-order kinetics
- Zero-order kinetics (Correct answer)
- Second-order kinetics
- Mixed-order kinetics
Correct answer: Zero-order kinetics
Zero-order (capacity-limited) kinetics occur when enzyme saturation causes a constant amount of drug to be eliminated per unit time regardless of concentration.
Pharmacology Pharmacokinetics and Drug Metabolism 2
A drug with a high extraction ratio is administered orally.
Which phenomenon most significantly reduces its systemic bioavailability?