EDAIC Pharmacokinetics and Pharmacodynamics 4 — Questions and Answers
Question 1: Ketamine's dissociative anesthetic effect is mediated primarily by:
- GABAA receptor potentiation
- Non-competitive NMDA receptor antagonism (Correct answer)
- Alpha-2 adrenoceptor agonism
- Mu-opioid receptor partial agonism
Correct answer: Non-competitive NMDA receptor antagonism
Ketamine produces dissociative anesthesia by non-competitive antagonism of NMDA (N-methyl-D-aspartate) glutamate receptors, blocking the ion channel in an open-channel fashion.
Question 2: The volume of distribution (Vd) of a highly lipophilic drug is characteristically:
- Less than total body water (0.6 L/kg)
- Equal to plasma volume (0.05 L/kg)
- Much greater than total body water, often >10 L/kg (Correct answer)
- Limited to extracellular fluid volume (0.2 L/kg)
Correct answer: Much greater than total body water, often >10 L/kg
Highly lipophilic drugs distribute extensively into fat and tissue, resulting in very large apparent volumes of distribution often many times greater than actual body volume.
Question 3: Zero-order kinetics describes drug elimination where:
- A constant fraction of drug is eliminated per unit time
- A constant amount of drug is eliminated per unit time regardless of concentration (Correct answer)
- Elimination rate doubles with each doubling of concentration
- Drug half-life is independent of concentration
Correct answer: A constant amount of drug is eliminated per unit time regardless of concentration
Zero-order kinetics occurs when elimination pathways are saturated, so a fixed amount (not fraction) of drug is eliminated per unit time, as seen with ethanol and high-dose aspirin.
Question 4: Which property of local anesthetics is most responsible for their ability to cross nerve sheaths and reach the axon membrane?
- High degree of protein binding
- pKa close to physiologic pH allowing significant un-ionized fraction (Correct answer)
- Large molecular weight preventing rapid diffusion
- High water solubility facilitating aqueous diffusion
Correct answer: pKa close to physiologic pH allowing significant un-ionized fraction
Local anesthetics with pKa close to 7.4 have a larger un-ionized (lipid-soluble) fraction at physiologic pH, allowing better membrane penetration to reach the axon.
Question 5: A competitive antagonist shifts the agonist concentration-response curve:
- Downward, reducing the maximum effect (Emax)
- To the right in a parallel fashion, without reducing Emax (Correct answer)
- To the left, increasing agonist potency
- Downward and to the right, reducing both Emax and EC50
Correct answer: To the right in a parallel fashion, without reducing Emax
A competitive antagonist causes a parallel rightward shift of the agonist dose-response curve (increased EC50) without reducing Emax because its effect is surmountable by excess agonist.
Question 6: During cardiopulmonary bypass at 28°C, the pharmacokinetics of fentanyl will be most affected by:
- Increased protein binding due to hypothermia
- Reduced hepatic blood flow and metabolic enzyme activity (Correct answer)
- Enhanced renal clearance due to hemodilution
- Increased volume of distribution due to priming solution
Correct answer: Reduced hepatic blood flow and metabolic enzyme activity
Hypothermia during CPB reduces hepatic blood flow and CYP enzyme activity, significantly decreasing fentanyl clearance and prolonging its effect.
Question 7: Which neuromuscular blocking agent is most appropriate for a patient with both hepatic and renal failure?
- Vecuronium
- Rocuronium
- Pancuronium
- Cisatracurium (Correct answer)
Correct answer: Cisatracurium
Cisatracurium undergoes organ-independent Hofmann elimination and ester hydrolysis, making it the NMB of choice in combined hepatorenal failure.
EDAIC Pharmacokinetics and Pharmacodynamics 4
Ketamine's dissociative anesthetic effect is mediated primarily by: