A 58-year-old man is admitted to the cardiac care unit for the management of recurrent, su… — USMLE Step 3

A 58-year-old man is admitted to the cardiac care unit for the management of recurrent, sustained ventricular tachycardia. An intravenous infusion of lidocaine is initiated at a constant maintenance rate. Forty-eight hours later, the patient develops cardiogenic shock due to an acute myocardial infarction, resulting in severely reduced cardiac output and diminished tissue perfusion. Pharmacokinetic analysis in this low-flow state indicates that both the systemic clearance ( $CL$ ) and the apparent volume of distribution ( $V_d$ ) of lidocaine have decreased by approximately 50%. Assuming the intravenous infusion rate remains constant, which of the following best describes the expected changes in the drug's elimination half-life and steady-state plasma concentration compared to his baseline?

Elimination half-life remains unchanged; steady-state concentration increasesCevap
B
Elimination half-life increases; steady-state concentration increases
C
Elimination half-life increases; steady-state concentration remains unchanged
D
Elimination half-life remains unchanged; steady-state concentration remains unchanged
E
Elimination half-life decreases; steady-state concentration increases

Cevap

Elimination half-life remains unchanged; steady-state concentration increases

The elimination half-life (

t_{1/2}

) is defined by the equation

t_{1/2} = \frac{0.693 \times V_d}{CL}

. In cardiogenic shock, poor tissue perfusion reduces the apparent volume of distribution (

V_d

), and poor hepatic perfusion reduces systemic clearance (

CL

). Because both parameters decrease by 50%, their ratio remains constant, resulting in an unchanged elimination half-life. Conversely, the steady-state concentration (

C_{ss}

) during a continuous infusion is determined by the equation

C_{ss} = \frac{\text{Infusion Rate}}{CL}

. Since the infusion rate is constant and clearance is halved, the steady-state concentration will double.

Adım Adım Çözüm

Identify the formula for elimination half-life.

t_{1/2} = \frac{0.693 \times V_d}{CL}

This establishes the relationship between half-life, volume of distribution, and clearance.

Apply the given physiological changes to the half-life formula.

t_{1/2} = \frac{0.693 \times (0.5 \times V_d)}{(0.5 \times CL)}

. The

0.5

factors cancel out, meaning

t_{1/2}

remains unchanged.

Cardiogenic shock reduces both tissue perfusion (lowering

V_d

) and hepatic blood flow (lowering

CL

) proportionally for certain drugs.

Identify the formula for steady-state plasma concentration.

C_{ss} = \frac{R_0}{CL}

, where

R_0

is the constant infusion rate.

This formula determines how drug levels respond to continuous administration.

Determine the effect of the physiological changes on steady-state concentration.

Since

R_0

is unchanged and

CL

is reduced by 50%,

C_{ss} = \frac{R_0}{0.5 \times CL} = 2 \times C_{ss}

. The steady-state concentration increases.

Clearance is the sole pharmacokinetic determinant of steady-state concentration during a constant-rate infusion.

Anahtar Kavram

The elimination half-life depends on both the volume of distribution and clearance. If both decrease proportionally, half-life remains constant. Steady-state concentration depends solely on the infusion rate and clearance.

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