Erythropoietin-induced hypertensive urgency in a patient with chronic renal insufficiency: case report and review of the literature.

Hypertension is a potentially dangerous side effect of erythropoietin treatment; however, extreme elevations in blood pressure are rare. A 75-year-old woman with chronic renal insufficiency was treated with subcutaneous erythropoietin. Three weeks before she started receiving erythropoietin, her hematocrit was 27.2%; after 5 weeks of treatment, it rose to 45.7%. The patient came to the emergency department and was admitted with hypertensive urgency. During her hospital stay she was treated with nitroglycerin and nitroprusside infusions, extended-release nifedipine, a variety of beta-blockers, clonidine, and furosemide. By day 3, her blood pressure was adequately controlled. Her renal insufficiency may have progressed as a result of the hypertensive episode, which probably was related to erythropoietin administration and the resultant rapid increase in her hematocrit. Erythropoietin dosing should be titrated to increase the hematocrit gradually, and blood pressure should be monitored closely to avoid serious side effects such as hypertensive emergencies.

Detriments of tPA for acute stroke in routine clinical practice.

Under optimal conditions, tissue plasminogen activator (tPA) may be a viable option for treatment of acute ischemic stroke; however, this study showed that protocol is not adhered to in practice and that these protocol deviations are associated with increased mortality and other adverse events. Based on these findings, tPA should not be used in routine clinical practice to treat acute stroke until individual hospitals develop protocols to guarantee the medication's appropriate use.

A comparison of commonly used polyethoxylated pharmaceutical excipients on their ability to inhibit P-glycoprotein activity in vitro.

P-glycoprotein (P-gp), a multidrug resistance (MDR) protein encoded by the MDR1 gene in humans, is responsible for the efflux of structurally diverse drugs. Previous studies in our laboratory have shown that excipients such as poly(ethylene)glycol (PEG)-300, Cremophor EL, and Tween 80 inhibit P-gp activity in Caco-2 cell monolayers. The objective of this study was to determine the effects of these excipients in an MDR1- transfected Madin Darby Canine Kidney (MDR1-MDCK) cell line and to compare the results with those obtained from Caco-2 cells. The results presented herein show that PEG-300 (20%, v/v) causes almost complete inhibition of P-gp activity in both Caco-2 and MDR1-MDCK cell monolayers, whereas Cremophor EL (0.1%, w/v) and Tween 80 (0.05%, w/v) only partially inhibit P-gp activity in Caco-2 cells. Cremophor EL (0.1%, w/v) and Tween 80 (0.05%, w/v) were inactive as P-gp inhibitors in MDR1-MDCK cell monolayers. This inability of Tween 80 and Cremphor EL to inhibit P-gp activity in MDR1-MDCK cells may be related to differences in the interactions of the surfactants with these different cell membranes. PEG-induced changes in P-gp activity are probably related to changes in the fluidity of the polar head group regions of cell membranes.