Study results fuel interest in use of alpha-blockers for stone management

Results from an ex vivo study demonstrating effects of the nonselective alpha-1 receptor antagonist doxazosin (Cardura) on ureteral contractility raises questions about the role of alpha-blocker treatment in the management of ureteral stone disease, say urologists from the University of Wisconsin.

Using their established model for measuring ureteral contractility, the investigators evaluated distal, middle, and proximal segments of porcine ureter. Studies were performed under basal conditions, with the addition of epinephrine and phenylephrine, and then repeated after adding doxazosin 0.1, 1, and 10 micromolar.

The results showed that for all portions of the porcine ureter, doxazosin reduced spontaneous contractility in a dose-response fashion and reversed epinephrine- and phenylephrine-induced contractility. In addition, immunoblot analysis demonstrated the presence of alpha-1A, -1B, and -1D receptors in specimens from both normal and chronically obstructed distal ureteral segments obtained from patients who had donor nephrectomy.

"Several recent reports indicate that the alpha-1 adrenergic receptor antagonist tamsulosin [Flomax] improves ureteral distal stone passage rates," Stephen Y. Nakada, MD, associate professor and chairman of urology at the University of Wisconsin, Madison, said during a presentation here yesterday. "Do those results and our findings provide an evidence-based rationale for using alpha-blockers in patients passing ureteral stones? If so, then we might ask which alpha-blocker should be used and which stones should be treated with medical expulsive therapy."