EDAIC Pharmacokinetics and Pharmacodynamics 5 — Questions and Answers
Question 1: The minimum alveolar concentration (MAC) of a volatile anesthetic is best described as the concentration that:
- Prevents movement in 50% of patients in response to a surgical skin incision (Correct answer)
- Causes unconsciousness in 95% of unpremedicated patients
- Prevents cardiovascular response to laryngoscopy in 50% of patients
- Blocks memory formation in 99% of patients
Correct answer: Prevents movement in 50% of patients in response to a surgical skin incision
MAC is defined as the alveolar concentration of volatile anesthetic at 1 atm that prevents purposeful movement in response to a surgical skin incision in 50% of patients.
Question 2: Drug protein binding primarily affects pharmacokinetics by influencing:
- Intrinsic hepatic clearance only
- The free (unbound) fraction available for distribution, metabolism, and effect (Correct answer)
- Renal tubular secretion rate
- Gut wall metabolism
Correct answer: The free (unbound) fraction available for distribution, metabolism, and effect
Only the free (unbound) fraction of a drug can cross membranes, interact with receptors, undergo metabolism, and be filtered by the glomerulus.
Question 3: A pharmacokinetic-pharmacodynamic (PK-PD) model incorporating an 'effect compartment' (Ce) is necessary because:
- All drugs undergo significant first-pass metabolism
- There is a time lag between plasma concentration and pharmacological effect (Correct answer)
- Plasma concentration always overestimates brain concentration
- Drug elimination always begins at the effect site
Correct answer: There is a time lag between plasma concentration and pharmacological effect
The effect compartment model accounts for hysteresis (the clockwise delay loop) between plasma drug concentrations and observed pharmacological effects.
Question 4: Which statement about the oil:gas partition coefficient of volatile anesthetics is correct?
- Higher oil:gas coefficient correlates with lower potency (higher MAC)
- The oil:gas coefficient predicts hepatic metabolism rate
- Higher oil:gas coefficient indicates greater lipid solubility and lower MAC (Correct answer)
- Oil:gas coefficient determines speed of onset more than blood:gas coefficient
Correct answer: Higher oil:gas coefficient indicates greater lipid solubility and lower MAC
Higher oil:gas partition coefficient indicates greater lipid solubility and thus higher potency, corresponding with a lower MAC value (Meyer-Overton correlation).
Question 5: Morphine-6-glucuronide (M6G) is clinically significant because it:
- Is pharmacologically inactive and excreted unchanged in bile
- Is a more potent mu-opioid agonist than morphine and accumulates in renal failure (Correct answer)
- Inhibits morphine metabolism by competitive glucuronidation
- Undergoes enterohepatic recirculation causing delayed sedation after oral dosing
Correct answer: Is a more potent mu-opioid agonist than morphine and accumulates in renal failure
M6G is an active metabolite with greater mu-opioid receptor affinity than morphine, and it accumulates to toxic levels in renal failure due to impaired renal excretion.
Question 6: The principle of 'pharmacological antagonism' used to reverse neuromuscular blockade with sugammadex differs from neostigmine because sugammadex:
- Inhibits acetylcholinesterase to increase ACh at the neuromuscular junction
- Directly encapsulates rocuronium/vecuronium molecules, reducing free drug concentration (Correct answer)
- Competes with rocuronium for nicotinic receptor binding sites
- Stimulates acetylcholine release from motor nerve terminals
Correct answer: Directly encapsulates rocuronium/vecuronium molecules, reducing free drug concentration
Sugammadex is a modified cyclodextrin that encapsulates (chelates) aminosteroid NMBAs (rocuronium, vecuronium) with high affinity, creating a gradient that draws drug away from the NMJ.
Question 7: In a patient receiving a continuous propofol infusion who suddenly develops metabolic acidosis, high anion gap, and cardiac failure, which pharmacodynamic mechanism is most likely?
- Propofol-induced GABAA receptor desensitization
- Inhibition of mitochondrial electron transport chain complex I and II (Correct answer)
- Propofol-induced catecholamine release causing vasoconstriction
- Competitive antagonism of adenosine receptors causing dysrhythmia
Correct answer: Inhibition of mitochondrial electron transport chain complex I and II
Propofol infusion syndrome is caused by propofol inhibiting mitochondrial electron transport chain complexes I and II, impairing oxidative phosphorylation and causing lactic acidosis and cardiac failure.
EDAIC Pharmacokinetics and Pharmacodynamics 5
The minimum alveolar concentration (MAC) of a volatile anesthetic is best described as the concentration that: