Rapid development of tachyphylaxis to prazosin mediated preload and afterload reduction in refractory congestive heart failure

Initial doses of prazosin (PZ) have been reported to increase markedly cardiac index (CI) and reduce left ventricular filling pressure (LVFP) in patients with severe congestive heart failure (CHF), but the effectiveness of repeated doses has not been demonstrated. To do so, we administered three serial doses of 5 mg. of oral PZ (mean 86 μg/kg) at 12- to 24-hour intervals to each of eight patients with CHF, followed by a 10 mg dose in five patients. Six of eight patients demonstrated no significant hemodynamic or clinical improvement at any dose level of PZ (up to 45 mg daily) after the first two doses. Only two patients had persistent vasodilator effects sufficient to justify chronic ambulatory therapy. In conclusion, previous reports of the beneficial hemodynamic effects of PZ in patients with CHF largely represent a 'first dose phenomenon' which is not sustained with repeated administration of the drug by either hemodynamic or clinical evaluation.