EDAIC Pharmacokinetics and Pharmacodynamics 3 — Questions and Answers
Question 1: Which statement about the Hill equation (sigmoid Emax model) is correct?
- A Hill coefficient (γ) >1 produces a flatter concentration-response curve
- A higher γ produces a steeper sigmoid curve with a narrower dynamic range (Correct answer)
- EC50 increases as γ increases
- The maximum effect (Emax) is directly proportional to γ
Correct answer: A higher γ produces a steeper sigmoid curve with a narrower dynamic range
A larger Hill coefficient (γ) steepens the sigmoid curve, meaning a narrow concentration range spans from minimal to maximal effect.
Question 2: A drug with a narrow therapeutic index and primarily renal elimination is most dangerous in which clinical scenario?
- Mild hepatic impairment
- Acute kidney injury with oliguria (Correct answer)
- Obesity requiring dose adjustment by total body weight
- Thyroid storm with increased metabolic rate
Correct answer: Acute kidney injury with oliguria
Acute kidney injury reduces renal drug clearance, causing drug accumulation and toxicity for renally eliminated narrow therapeutic index drugs.
Question 3: The concept of 'pharmacodynamic tolerance' is best illustrated by which scenario?
- Opioid dose escalation required over time to achieve the same analgesic effect (Correct answer)
- Reduced propofol plasma concentration after prolonged infusion
- Increased morphine bioavailability after repeated oral dosing
- Decreased renal clearance of ketamine in chronic users
Correct answer: Opioid dose escalation required over time to achieve the same analgesic effect
Pharmacodynamic tolerance refers to reduced drug effect at the same concentration over time, classically seen with opioid analgesia due to receptor downregulation or desensitization.
Question 4: Which best explains why acidosis increases the free fraction of a weakly acidic, highly protein-bound drug?
- Acidosis increases hepatic metabolism of the drug
- Protonation of albumin binding sites reduces drug-protein affinity
- Competition between H+ ions and the drug for albumin binding sites displaces the drug (Correct answer)
- Acidosis increases renal tubular secretion of the drug
Correct answer: Competition between H+ ions and the drug for albumin binding sites displaces the drug
In acidosis, H+ ions compete with weakly acidic drugs for albumin binding sites, displacing the drug and increasing its free (unbound) fraction.
Question 5: When two drugs produce synergistic anesthesia, their combined isobologram shows the interaction point:
- On the line of additivity
- Above the line of additivity
- Below the line of additivity (Correct answer)
- At the origin of the isobologram
Correct answer: Below the line of additivity
Synergism means less of each drug is needed together than expected from pure additivity, so the interaction point falls below the additive isobole line.
Question 6: In a two-compartment pharmacokinetic model after IV bolus, the initial rapid decline in plasma concentration primarily represents:
- Elimination from the body via renal and hepatic routes
- Distribution from central to peripheral compartment (Correct answer)
- Protein binding saturation in plasma
- First-order metabolism in the liver
Correct answer: Distribution from central to peripheral compartment
The initial rapid alpha phase after IV bolus reflects drug redistribution from the central (plasma/highly perfused) compartment to peripheral tissues.
Question 7: Which pharmacokinetic parameter changes most significantly when a drug transitions from IV to oral administration?
- Volume of distribution
- Clearance
- Bioavailability (Correct answer)
- Elimination half-life
Correct answer: Bioavailability
Bioavailability is the fraction of administered drug reaching systemic circulation and is 100% for IV but variable (often <100%) for oral due to incomplete absorption and first-pass metabolism.
EDAIC Pharmacokinetics and Pharmacodynamics 3
Which statement about the Hill equation (sigmoid Emax model) is correct?