Chapter 6

### INTRODUCTION

From the time a fetus is viable through adolescence, the body is undergoing exponential growth and development. However, the development of organ function and body composition does not occur in a linear fashion. How the body processes nutrients and medications from birth through age 2 changes rapidly. There is also a significant change as the body begins the growth spurt through adolescence.1 Critical illness, whether in the setting of extreme prematurity, sepsis, or chronic illness, may significantly impact growth and development as well as organ function. Electrolyte abnormalities, glucose intolerance, and protein malnutrition are common in the pediatric intensive care unit (PICU) patient.2 Medications may impact these changes, and likewise the organ function disruptions that occur in critical illness may affect how the body processes medications.3 When considering drug–nutrient interactions within the PICU setting, the clinician should consider the physiologic state of the patient, as well as the pharmacokinetic, pharmacodynamic and therapeutic properties of both medications and nutrients. There is a delicate balance between maintaining nutritional and therapeutic goals in the PICU setting, but these should never be considered mutually exclusive.

Chan defines drug–nutrient interactions as “physical, chemical, physiologic, or pathophysiologic relationships between a drug and a nutrient.”4 Numerous conditions and disease states involve a countless number of medications that are used in the neonatal intensive care unit (NICU) and PICU. Various classifications of drug–nutrient interactions have been proposed, but one useful classification that is based on the drug's course through the body is as follows4:

1. Ex-vivo bioinactivation refers to the interaction between the drug and the nutritional formulation through biochemical or physical reactions. A classic example of this form of interaction is the creation of a precipitate in an enteral feeding tube by a drug that has been administered before all the enteral formula has been flushed through. This form of interaction occurs when the drug and the nutrient are in physical contact, and usually occurs in the feeding tube or the central venous catheter.

2. Interactions affecting absorption affect drugs and nutrients delivered orally or enterally. These interactions have the potential to cause either an increase or decrease in the bioavailability of the drug. A variety of medications, including carbamazepine, quinolones, phenytoin, and warfarin, have significantly impaired absorption in the presence of enteral formulas.

3. Interactions affecting systemic disposition occur after the drug and the nutrient have entered the systemic circulation. The mechanisms may involve changing the tissue distribution and/or systemic metabolism or transport. In this case, the classic example is grapefruit juice causing inhibition of the cytochrome P450 3A4 system and increasing the bioavailability of drugs like cyclosporine.

4. The final type of drug–nutrient interaction affects the elimination of drugs or nutrients, which may involve the modulation of renal or enterohepatic elimination.

This chapter will focus on the most common conditions and medications and potential nutrient interactions. Unanticipated drug–nutrient interactions may result in an adverse outcome or ...

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