FFICM Pharmacology Fundamentals 3 — Questions and Answers
Question 1: Which mechanism best explains the tachyphylaxis seen with repeated doses of ephedrine?
- Downregulation of adrenoceptors
- Depletion of noradrenaline from presynaptic vesicles (Correct answer)
- Increased renal clearance
- Competitive inhibition of monoamine oxidase
Correct answer: Depletion of noradrenaline from presynaptic vesicles
Ephedrine acts indirectly by displacing noradrenaline from presynaptic terminals; repeated dosing depletes these stores, reducing each subsequent response.
Question 2: Rocuronium's neuromuscular blockade is antagonised by sugammadex via which mechanism?
- Cholinesterase inhibition increasing acetylcholine at the synapse
- Encapsulation of rocuronium molecules reducing free plasma concentration (Correct answer)
- Competitive displacement of rocuronium from nicotinic receptors
- Alkalinisation of plasma shifting rocuronium to inactive form
Correct answer: Encapsulation of rocuronium molecules reducing free plasma concentration
Sugammadex is a modified gamma-cyclodextrin that encapsulates rocuronium (and vecuronium) in a tight complex, removing it from plasma and reversing blockade.
Question 3: A therapeutic drug monitoring level is taken 6 hours after an IV dose of vancomycin. The result is best described as:
- Peak level representing maximum efficacy
- A trough level used to guide dosing interval
- An area-under-the-curve surrogate correlating with bactericidal activity (Correct answer)
- Neither peak nor trough — timing is too variable to interpret
Correct answer: An area-under-the-curve surrogate correlating with bactericidal activity
Modern vancomycin monitoring uses AUC/MIC ratio as the pharmacodynamic target; a mid-interval level can be used to estimate AUC when combined with another sample.
Question 4: Which pharmacodynamic parameter is most predictive of beta-lactam antibiotic efficacy?
- Peak concentration / MIC ratio (Cmax/MIC)
- Area under the concentration–time curve / MIC (AUC/MIC)
- Time above MIC (%T>MIC) (Correct answer)
- Total daily dose administered
Correct answer: Time above MIC (%T>MIC)
Beta-lactams exhibit time-dependent bactericidal activity; efficacy correlates with the proportion of the dosing interval during which free drug concentration exceeds the MIC.
Question 5: A critically ill patient develops prolonged paralysis after a single intubating dose of suxamethonium. The most likely cause is:
- High hepatic extraction ratio leading to drug accumulation
- Pseudocholinesterase deficiency reducing hydrolysis of suxamethonium (Correct answer)
- Upregulation of acetylcholine receptors increasing sensitivity
- Renal failure preventing tubular secretion
Correct answer: Pseudocholinesterase deficiency reducing hydrolysis of suxamethonium
Suxamethonium is hydrolysed by plasma pseudocholinesterase (butyrylcholinesterase); deficiency — genetic or acquired — prolongs the duration of blockade from minutes to hours.
Question 6: Which statement about propofol pharmacokinetics in critically ill patients is correct?
- Clearance is primarily renal and unaffected by hepatic dysfunction
- Its large volume of distribution means context-sensitive half-time rises markedly with prolonged infusions (Correct answer)
- Propofol has a narrow therapeutic window with predictable plasma concentrations
- Albumin binding is minimal, making free fraction stable in critical illness
Correct answer: Its large volume of distribution means context-sensitive half-time rises markedly with prolonged infusions
Propofol's high lipophilicity and large Vd cause redistribution from deep tissue compartments after prolonged infusions, markedly increasing context-sensitive half-time.
Question 7: Non-depolarising neuromuscular blocking agents are monitored at the adductor pollicis. Which train-of-four (TOF) ratio confirms adequate reversal before extubation?
- TOF ratio ≥ 0.7
- TOF ratio ≥ 0.9 (Correct answer)
- Presence of at least 2 twitches
- Sustained tetanus at 50 Hz for 5 seconds
Correct answer: TOF ratio ≥ 0.9
A TOF ratio ≥ 0.9 at the adductor pollicis is the current standard for confirming adequate neuromuscular recovery before extubation.
FFICM Pharmacology Fundamentals 3
Which mechanism best explains the tachyphylaxis seen with repeated doses of ephedrine?