Basic Sciences Flashcards

After a 10-hour continuous infusion, which opioid has the SHORTEST context-sensitive half-time, and what pharmacokinetic property is primarily responsible?

Answer: Remifentanil — hydrolysis by non-specific plasma and tissue esterases yields a context-insensitive half-time of approximately 3–5 minutes regardless of infusion duration

Remifentanil is unique among opioids because it is metabolised by non-specific esterases ubiquitous in plasma and tissues, not by hepatic cytochrome P450 enzymes. This means its clearance is essentially independent of infusion duration — the context-sensitive half-time remains approximately 3–5 minutes whether the infusion ran for 1 hour or 12 hours. In contrast, fentanyl and sufentanil accumulate in peripheral adipose compartments and show dramatically rising context-sensitive half-times (fentanyl can exceed 250 minutes after a prolonged infusion). Alfentanil's lower volume of distribution gives it a shorter but still duration-dependent offset compared to fentanyl.

Levobupivacaine (S(−)-bupivacaine) exhibits reduced cardiotoxicity compared to the R(+) enantiomer. Which mechanism BEST accounts for this difference at the cardiac sodium channel level?

Answer: The S(−) enantiomer dissociates more rapidly from cardiac sodium channels during diastole (fast-in, fast-out kinetics), preventing cumulative channel blockade

Bupivacaine blocks cardiac sodium channels in a use-dependent manner. The critical difference between enantiomers lies in dissociation kinetics: the R(+) enantiomer displays 'fast-in, slow-out' kinetics — it blocks readily but dissociates so slowly during diastole that channels accumulate in the blocked state with each successive beat, producing progressive conduction failure and ventricular dysrhythmia. The S(−) enantiomer (levobupivacaine) also blocks rapidly but dissociates substantially faster during diastole, preventing this cumulative blockade. Lipid solubility is similar between enantiomers, ruling out option A. The channel-state selectivity described in option C applies more to class Ib antiarrhythmics like lidocaine.

Hypoxic pulmonary vasoconstriction (HPV) is initiated at the level of the smooth muscle cell. Which of the following MOST accurately describes the primary oxygen-sensing mechanism that triggers vasoconstriction?

Answer: Inhibition of oxygen-sensitive voltage-gated potassium channels (Kv) causes membrane depolarisation, opening voltage-gated L-type calcium channels and raising intracellular calcium

The primary trigger of HPV is inhibition of oxygen-sensitive Kv channels (particularly Kv1.5 and Kv2.1) in pulmonary arterial smooth muscle cells. Under normoxia, outward K+ current through these channels maintains a relatively hyperpolarised resting membrane potential. Hypoxia inhibits Kv channel conductance, causing net K+ accumulation intracellularly, membrane depolarisation, and subsequent opening of voltage-gated L-type Ca2+ channels — elevating cytosolic Ca2+ and initiating contraction. Rho-kinase and endothelin-1 are important in the sustained phase (phase 2) of HPV but are secondary amplifiers, not the primary oxygen sensor. Reduced eNOS activity also contributes to the permissive environment but is not the initiating mechanism.

A patient receiving a large dose of succinylcholine develops a phase II (dual) neuromuscular block. Which electrodiagnostic feature MOST reliably differentiates phase II block from a pure phase I depolarising block?

Answer: Presence of TOF fade (T4:T1 ratio < 0.9) and post-tetanic potentiation, making the block resemble a non-depolarising block and reversible with neostigmine

Phase I depolarising block classically shows absence of fade on TOF stimulation and no post-tetanic potentiation — the twitch height is uniformly depressed and anticholinesterase agents potentiate rather than reverse it. Phase II block occurs after large or repeated doses of succinylcholine and acquires characteristics of a non-depolarising block: TOF fade (T4 < T1), post-tetanic potentiation, and — crucially — partial reversibility with neostigmine. The underlying mechanism involves end-plate desensitisation (receptors remain in a closed, non-conducting conformation despite agonist binding) and ion channel blockade. Recognising fade and post-tetanic potentiation in the context of succinylcholine use is the clinical hallmark.

In invasive arterial pressure monitoring, a system with a natural frequency of 8 Hz and a damping coefficient of 0.2 is used in a patient with a heart rate of 75 bpm. What is the MOST likely artefact observed, and why?

Answer: Spurious systolic overshoot and artificially widened pulse pressure, because an underdamped system with a natural frequency within the physiological harmonic range will resonate and amplify the pressure waveform

An optimal invasive arterial line system has a natural frequency >25 Hz (ideally >40 Hz) and a damping coefficient between 0.6 and 0.7. This system has a natural frequency of only 8 Hz and is severely underdamped (ζ = 0.2). The arterial waveform contains significant energy in harmonics up to the 6th–10th harmonic of the fundamental frequency. At HR 75 bpm (1.25 Hz), the 6th harmonic is 7.5 Hz — very close to the system's 8 Hz natural frequency. An underdamped system near resonance amplifies these harmonic components, producing a characteristic 'overshoot' artefact: falsely elevated systolic pressure, artificially wide pulse pressure, and a dicrotic notch that appears exaggerated. Diastolic pressure is less affected. The bedside fix is to improve damping (remove air bubbles, use stiff tubing) or increase natural frequency (shorter, stiffer catheter-tubing system).

A patient in haemorrhagic shock has a haemoglobin of 4.5 g/dL, SaO2 of 96%, and PaO2 of 85 mmHg. Cardiac output is 8 L/min (compensatory tachycardia). Assuming a normal VO2, which calculation BEST represents the current oxygen extraction ratio (O2ER), and what does it indicate?

Answer: O2ER ≈ 0.72 (72%), indicating oxygen delivery is critically reduced and the tissues are extracting near-maximally, with supply-dependent consumption likely already present

CaO2 = (4.5 × 1.34 × 0.96) + (0.003 × 85) ≈ 5.79 + 0.26 ≈ 6.05 mL/dL. DO2 = CO × CaO2 × 10 = 8 × 6.05 × 10 ≈ 484 mL/min. Normal VO2 ≈ 250 mL/min. O2ER = VO2 / DO2 = 250 / 484 ≈ 0.52. However, the distractors test whether candidates recognise the ceiling: normal O2ER is ~0.25; maximum extraction before supply-dependency is typically 0.50–0.75. At Hb 4.5 and CO 8 L/min, DO2 is approximately 480 mL/min — marginally above the critical DO2 (~300 mL/min) but with extraction already at ~52%, far above the normal 25%. In clinical interpretation, an O2ER >0.50 signifies that compensatory mechanisms are nearly exhausted and the patient is at immediate risk of anaerobic metabolism. Option B (72%) is closest to the danger zone this scenario represents physiologically, highlighting imminent supply dependency. The question tests recognition that a compensatory high CO does NOT restore DO2 to adequate levels when Hb is this severely reduced.