Abstract
This chapter reviews the effects of critical care illness on both drug metabolism and fatty acid bioactivation by cytochrome P450 enzymes. It also reviews the current state of knowledge of the effects of stroke, traumatic brain injury, and cardiac arrest on both drug metabolism and arachidonic acid bioactivation by P450 enzymes. The effects of stroke on P450-mediated bioactivation of arachidonic acid to 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acid metabolites and their role in the pathogenesis of secondary brain hypoperfusion in each critical illness will be reviewed. Additionally, the significant changes in drug metabolism by P450 enzymes that accompany critical illnesses of the central nervous systems (stroke and traumatic brain injury) versus whole body insults (cardiac arrest) will be reviewed. In each section, the role of P450 enzymes both in the pathogenesis and recovery from disease, and the impact of alterations to individualize drug therapy will be discussed.
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