Pharmacokinetics/Pharmacodynamics
Answer: B
Decreased anti-Xa activity occurs in critically ill patients
receiving several different low-molecular-weight hepa-
rins. This patient received the standard fluid bolus and
then required more fluid to raise his central venous
pressure. This suggests that the patient has redistributed
the fluids to the extravascular space. The data show-
ing that edematous patients have lower anti-Xa activity
than non-edematous patients supports the connection
between anti-Xa activity and absorption (Answer B is
correct). Given the patient’s fluid distribution, the Vd
of enoxaparin would likely be increased, not decreased
(Answer A is incorrect). Enoxaparin is not hepatically
metabolized (Answer C is incorrect). Although a patient
could have an increased anti-Xa activity secondary to
decreased renal elimination, this would require a CrCl
of less than 30 mL/minute/1.73 m2. That the patient
had a deep venous thrombosis does not correlate with
increased activity (Answer D is incorrect).
Abdominal surgery has been identified as a risk fac-
tor for ileus. Antisecretory agents such as pantoprazole
alter drug absorption. Traumatic brain injury is signifi-
cantly associated with intolerance of enteral nutrition,
as indicated by increased gastric residuals. This indi-
cates delayed gastric emptying and the risk of altered
absorption. Therefore, the combination of abdomi-
nal surgery, pantoprazole therapy, and TBI contains
the three variables identified in the literature to alter
absorption (Answer C is correct). Theoretically, intes-
tinal atrophy could cause changes in absorption, but
no data are available to confirm this theory (Answers
A and D are incorrect). Changes in cardiac output have
been correlated with changes in hepatosplanchnic blood
flow. These changes in blood flow are thought to affect
absorption, but again, no data have correlated increased
cardiac output with increased drug absorption (Answer
B is incorrect).
Answer: B
Propofol is a high extraction ratio drug that is bound
to albumin. When the albumin concentration decreases,
there is an expected increase in the free fraction of
propofol. Using the equations describing the total and
unbound concentrations of a high extraction ratio drug,
the total concentration is not affected by changes in the
free fraction, but unbound concentrations are increased
when the free fraction increases (Answer B is correct;
Answers A, C, and D are incorrect).
Answer: C
The update to the KDIGO guidelines notes that the
most important factor in determining kidney function
is having at least one estimate of GFR. The update
recommends that the GFR or the CrCl be estimated to
determine this (Answer C is correct). The BUN value can
help identify the BUN/SCr ratio indicating intravascu-
lar volume contraction and, potentially, a prerenal cause
to the patient’s AKI, but it does not help in drug dos-
ing (Answer A is incorrect). Total daily urinary output
is helpful in diagnosing AKI (oliguric vs. non-oliguric
AKI) and in staging AKI (using a urinary output of less
than 0.5 mL/kg/hour) but not in drug dosing (Answer
B is incorrect). A history of CKD can help determine a
baseline kidney function, but the GFR is still needed for
changes in drug dosing (Answer D is incorrect).
Answer: C
The ASHP (American Society of Health-System
Pharmacists) vancomycin dosing guidelines recom-
mend a 20- to 35-mg/kg loading dose of vancomycin
for serious infections. Given the patient’s sepsis, he is
likely to have more interstitial fluid, which will increase
the Vd of hydrophilic drugs like vancomycin. The
2500-mg dose is near the top end of the recommended
20- to 25-mg/kg loading dose (Answer C is correct).
The other doses are outside the recommended 20- to
25-mg/kg loading dose range (Answers A, B, and D are
incorrect).
Answer: A
Critically ill patients younger than 50 are more likely
to have augmented renal excretion. Vancomycin is
excreted unchanged in the urine. The initial dosing
would result in a therapeutic trough concentration,
given the increased (augmented) renal excretion of van-
comycin. Augmented renal excretion usually returns to
normal around day 7. An increased vancomycin trough
after a previously therapeutic trough is most likely
associated with decreased renal excretion at day 10 of
therapy (Answer A is correct). There is no indication