Pathophysiologic changes in the critically ill patient: risk factors for ulceration and altered drug metabolism. Virtually all patients who are under the physiologic stress of an intensive care unit (ICU) are vulnerable to stress-related mucosal damage and ulceration. Although clinically significant hemorrhage from stress ulceration occurs in only 5-20 percent of patients in the ICU, the associated mortality is greater than 50 percent. The pathophysiologic mechanisms of stress ulcer are not well understood; however, a number of risk factors such as intraluminal gastric acidity and mucosal ischemia have been implicated. To prevent the development of stress ulcers and subsequent complications, it is important to identify and correct these underlying risk factors. Improving mucosal blood flow (i.e., fluid resuscitation and low-dose dopamine) and providing adequate nutritional support are invaluable adjuncts in minimizing the risk of stress ulcer formation. The use of pharmacologic prophylaxis controls the gastric acidity and prevents the formation of stress ulcers. The potential for drug-induced adverse effects and drug-drug interactions are of particular concern in the care of critically ill patients. Multiple organ system dysfunction or failure, malnutrition, fluid and electrolyte abnormalities, as well as the use of multiple pharmacologic agents predispose these patients to alterations in drug pharmacokinetics, drug-induced adverse effects and drug-drug interactions. These changes may alter the pharmacodynamic response to therapy and must be considered when designing drug dosage regimens for critically ill patients. 