EDAIC Pharmacokinetics and Pharmacodynamics 2 — Questions and Answers
Question 1: Which pharmacokinetic model best describes a drug that distributes rapidly to well-perfused tissues and more slowly to muscle and fat?
- One-compartment model
- Two-compartment model
- Three-compartment model (Correct answer)
- Non-compartmental model
Correct answer: Three-compartment model
A three-compartment model describes a central compartment (blood/highly perfused organs) plus rapid-equilibrating (muscle) and slow-equilibrating (fat) peripheral compartments.
Question 2: The context-sensitive half-time of remifentanil is unique because it:
- Increases dramatically with infusion duration due to fat accumulation
- Remains constant at approximately 3-4 minutes regardless of infusion duration (Correct answer)
- Decreases after prolonged infusion due to enzyme induction
- Is prolonged in renal failure due to active metabolite accumulation
Correct answer: Remains constant at approximately 3-4 minutes regardless of infusion duration
Remifentanil is metabolized by nonspecific plasma and tissue esterases, so its context-sensitive half-time remains ~3-4 minutes regardless of infusion duration.
Question 3: Which parameter best describes the relationship between drug concentration and effect at steady state?
- Volume of distribution
- Clearance
- EC50 (Correct answer)
- Bioavailability
Correct answer: EC50
EC50 (half-maximal effective concentration) defines the plasma concentration at which 50% of the maximum drug effect is achieved, characterizing the concentration-effect relationship.
Question 4: A patient with severe hepatic cirrhosis receives midazolam. Which pharmacokinetic change is most expected?
- Decreased volume of distribution
- Reduced protein binding increasing free fraction
- Decreased clearance prolonging elimination half-life (Correct answer)
- Increased first-pass metabolism
Correct answer: Decreased clearance prolonging elimination half-life
Severe hepatic cirrhosis reduces hepatic metabolic capacity, decreasing midazolam clearance and markedly prolonging its elimination half-life.
Question 5: Enzyme induction by chronic phenytoin use would most significantly alter the pharmacokinetics of which co-administered drug?
- Succinylcholine
- Rocuronium
- Vecuronium (Correct answer)
- Atracurium
Correct answer: Vecuronium
Vecuronium undergoes significant hepatic CYP3A4 metabolism; chronic phenytoin-induced CYP3A4 induction accelerates vecuronium clearance, reducing its duration of action.
Question 6: The Fick principle applied to hepatic drug clearance states that hepatic clearance equals:
- Hepatic blood flow multiplied by the extraction ratio (Correct answer)
- Intrinsic clearance divided by protein binding fraction
- Volume of distribution divided by elimination half-life
- Dose divided by area under the concentration-time curve
Correct answer: Hepatic blood flow multiplied by the extraction ratio
Hepatic clearance = hepatic blood flow (Q) × extraction ratio (E); this is derived from the Fick principle applied to organ drug elimination.
Question 7: During a target-controlled infusion of propofol using the Marsh model, the 'effect-site concentration' differs from the 'plasma concentration' because:
- Propofol binds irreversibly to plasma proteins
- There is a time delay for drug equilibration across the blood-brain barrier (Correct answer)
- The effect-site has a much larger volume than the central compartment
- Propofol undergoes significant first-pass pulmonary metabolism
Correct answer: There is a time delay for drug equilibration across the blood-brain barrier
The effect-site concentration accounts for the hysteresis (time lag) between plasma concentration and brain concentration due to the blood-brain barrier equilibration delay (ke0).
EDAIC Pharmacokinetics and Pharmacodynamics 2
Which pharmacokinetic model best describes a drug that distributes rapidly to well-perfused tissues and more slowly to muscle and fat?