Pharmacokinetics/Pharmacodynamics
Phase II enzymatic activity may also be enhanced in patients with TBI, as evidenced by increased
lorazepam clearance. Similar data for lorazepam were noted in thermally injured patients. These
data suggest that phase II metabolism can be affected by critical illness.
the Hepatic Failure/GI/Endocrine Emergencies chapter for more information regarding drug dosing in
hepatic failure.
Patient Cases
A.P. is a 35-year-old woman admitted to the ICU for an acute asthma exacerbation. She was intubated and
required mechanical ventilation. She is prescribed morphine for pain control. Which best describes the
effect of mechanical ventilation on morphine unbound concentrations?
J.M. is a 34-year-old woman admitted to the ICU with new-onset sepsis. She was continued on her home
medication, diazepam, for anxiety. She is empirically initiated on vancomycin
1 g intravenously every 12 hours, piperacillin/tazobactam 3.375 g intravenously every 6 hours, and flucon-
azole 400 mg intravenously every 24 hours. Which PD response would you most expect in J.M.?
P.M. is receiving phenytoin for the treatment of posttraumatic seizures. The measured total phenytoin
concentration is 8 mcg/mL. You calculate the adjusted concentration according to P.M.’s hypoalbuminemia
(albumin of 2.5 g/dL) and determine the concentration to be approximately 13 mcg/mL. Which of the
following relationships best describes why an adjusted total phenytoin concentration must be calculated?
C.P. is a 50-year-old man admitted to the medical ICU for management of diabetic ketoacidosis. His medi-
cal history is significant for hypertension, type 1 diabetes, and a myocardial infarction 2 years ago. He quit
smoking last year and drinks alcohol occasionally. His vital signs are significant for heart rate 125 beats/
minute, blood pressure 95/65 mm Hg, and respiratory rate 22 breaths/minute. His significant hypovolemia
contributed to the development of AKI. His current SCr is 2.8 mg/dL. His blood glucose is significantly
elevated at 350 mg/dL. He will be initiated on a continuous intravenous infusion of insulin to correct his
blood glucose. Which factor is most important to consider when dosing insulin in C.P.?