Incidence and risk of potential adverse drug interactions in the emergency room.

OBJECTIVE: To determine the incidence and risk factors of potential adverse drug interactions occurring in patients in the emergency department. DESIGN: Survey of a random sample of medical records of elderly persons and other adults seeking care at an emergency department. The interactions were determined by a computer programme, reviewed using explicit criteria, and excluded if of uncertain or trivial clinical significance. SETTING: University Hospital Medical Emergency Department. PATIENTS: A total of 423 randomly selected adults seeking care at a university hospital emergency department. Attendances made by 195 persons over age 60 and 228 younger adults were evaluated. All subjects were treated on an outpatient basis. MAIN OUTCOME MEASURES: Seventy percent of attendances led to the prescription of an added medication. In 5.4% of the attendances in which at least one medication was added, the new medication introduced a potential adverse interaction. The number of medications used at attendance was the best predictor of whether a potential interaction would occur. Additional medications prescribed in the emergency department that accounted for most of the added interactions were theophylline, macrolid antibiotics, digitalis glycosides, nonsteroidal anti-inflammatory agents, angiotensin converting-enzyme inhibitors and calcium antagonists. CONCLUSIONS: Potential adverse drug interactions were more common in elderly patients because of the higher number of concurrent medications rather than age-based factors. Safeguards need to be introduced to prevent patients from receiving medications in the emergency departments that have the potential to cause adverse interactions.

Mevalonate-dependent inhibition of transendothelial migration and chemotaxis of human peripheral blood neutrophils by pravastatin.

Pravastatin, a hydrophilic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, has been reported to beneficially affect atherogenesis, plaque stability, and transient myocardial ischemia in significant coronary artery disease by influencing lipid metabolism and by intracellular signaling via mevalonate pathway products other than cholesterol. Leukocytes are implicated to play a pathophysiological role in these events. We were interested in finding out whether pravastatin could affect transendothelial migration (TEM), chemotaxis, and respiratory burst activity of the neutrophil ex vivo. In addition, effects on monocyte and T-lymphocyte chemotaxis were tested. For TEM assays, monolayers of human umbilical vein endothelial cells (HUVECs) were grown to confluence on polycarbonate filters bearing 5-microns pores in Transwell (Costar) culture plate inserts. Chemotaxis experiments were performed using modified Boyden chambers with cellulose nitrate micropore filters. Respiratory burst activity was measured fluorometrically. Treatment of neutrophils and monocytes with pravastatin at 2 to 200 mumol/L and 10 to 1000 mumol/L, respectively, significantly decreased chemotaxis triggered by fMet-Leu-Phe. This effect was abolished in the presence of mevalonic acid (500 mumol/L); no effect of pravastatin was seen on T-lymphocyte chemotaxis triggered by interleukin-8. Preincubation of neutrophils with pravastatin (200 mumol/L) also resulted in a significant reduction in the number of neutrophils that transmigrated a tumor necrosis factor-stimulated or lipopolysaccharide-stimulated HUVEC monolayer. At none of the concentrations tested (2 pmol/L to 200 mumol/L) did pravastatin affect neutrophil respiratory burst activity. We conclude that pravastatin may alter monocyte chemotaxis and neutrophil-endothelial interactions in migratory responses at concentrations obtained in vivo with cholesterol-lowering doses.