Basic Sciences Flashcards

At very prolonged infusion durations (>10 hours), how does the context-sensitive half-time of remifentanil compare to that of fentanyl?

Answer: It remains dramatically shorter than fentanyl's context-sensitive half-time

Remifentanil is metabolized by non-specific plasma and tissue esterases independent of hepatic or renal function, giving it a context-sensitive half-time of approximately 3–4 minutes regardless of infusion duration. Fentanyl, by contrast, accumulates extensively in peripheral compartments, causing its context-sensitive half-time to increase dramatically (to >300 minutes) with prolonged infusions. This is a defining pharmacokinetic distinction between the two opioids.

A central venous catheter's effective radius is reduced by half due to partial kinking. Assuming laminar flow conditions are maintained throughout, by what factor is the flow rate reduced?

Answer: 16-fold

The Hagen-Poiseuille equation states that volumetric flow Q ∝ r⁴ (where r is the tube radius), with all other variables constant. Halving the radius (r → r/2) gives Q ∝ (r/2)⁴ = r⁴/16, a 16-fold reduction in flow. This fourth-power relationship explains why small reductions in catheter caliber — due to kinking, clot, or catheter gauge — have disproportionately large effects on flow rate.

The Haldane effect, as it applies to CO2 transport in blood, is best described as:

Answer: The increased capacity of deoxygenated hemoglobin to carry CO2 compared to oxygenated hemoglobin

The Haldane effect describes the property of deoxygenated hemoglobin (deoxy-Hb) to carry more CO2 than oxygenated Hb — both as carbaminohemoglobin (CO2 bound to globin amino groups) and by acting as a better buffer for H⁺ ions released during CO2 hydration, thereby facilitating bicarbonate formation. This is physiologically vital: as blood passes through the tissues, O2 offloading promotes CO2 uptake via the Haldane effect. The Bohr effect (options A and D) describes how CO2 and H⁺ shift the O2 dissociation curve rightward — a related but distinct phenomenon.

In the Hill equation CE/(CE + EC50E), where CE is effect-site concentration and E is the normalized drug effect, the Hill coefficient (γ) primarily determines:

Answer: The steepness of the sigmoidal concentration-effect relationship

The Hill coefficient γ (also called the sigmoidicity or cooperativity factor) governs the slope of the concentration-effect curve on a log-concentration scale. When γ = 1, the curve is a simple hyperbola (Michaelis-Menten kinetics). As γ increases above 1, the relationship becomes increasingly steep and sigmoidal, meaning small concentration changes near the EC50 produce proportionally large changes in effect. The EC50 describes the midpoint potency (option A), Emax describes the ceiling effect (option C), and ke0 governs effect-site equilibration (option D).

Using the Nernst equation at 37°C, what is the approximate equilibrium potential (E_K) for potassium in a typical neuron with intracellular [K⁺] = 140 mmol/L and extracellular [K⁺] = 4 mmol/L?

Answer: −94 mV

At 37°C, the Nernst equation for a monovalent cation is: E = (61.5 mV) × log([K⁺]o / [K⁺]i) = 61.5 × log(4/140) = 61.5 × (−1.544) ≈ −95 mV, which rounds to approximately −94 mV. This is the K⁺ equilibrium (reversal) potential — the voltage at which K⁺ has no net electrochemical driving force. It must not be confused with the resting membrane potential (≈−70 mV), which is determined by the Goldman equation integrating the conductances of all permeant ions, or with the action potential threshold (≈−55 mV).

In population pharmacokinetic modelling using NONMEM, inter-individual variability (IIV) in pharmacokinetic parameters is most commonly described using which mathematical model?

Answer: Exponential (log-normal) random effects model: θᵢ = θ_pop × exp(ηᵢ)

IIV is modelled with an exponential (log-normal) parameterisation: θᵢ = θ_pop × exp(ηᵢ), where ηᵢ ~ N(0, ω²) and ω² is the IIV variance. This is preferred because it ensures individual parameter estimates remain strictly positive (physiologically plausible for clearance, volume, etc.), and because PK parameters in populations tend to be log-normally rather than normally distributed. Additive and proportional models (options A and B) are used for residual unexplained variability (RUV) — the difference between model prediction and observed concentration — not for IIV. Fixed-effects dummy variables (option D) would destroy the ability to make predictions in new subjects.