Hemodynamic and clinical tachyphylaxis to prazosin-mediated afterload reduction in severe chronic congestive heart failure.

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Abstract
Sequential doses of 5 mg of oral prazosin hydrochloride were administered to 8 patients with severe chronic congestive heart failure refractory to conventional therapy. Initial doses of the drug produced marked increases in cardiac index (+ 0.87 l/min per m2) associated with substantial decreases in left ventricular filling pressure (-10.7 mm Hg), total systemic vascular resistance (2118-1154 dyn-s-cm-5), and heart rate (89 to 76 beats/min). Serial administration of the same dose at 12-24-h intervals was accompanied by the rapid development of tachyphylaxis, such that the magnitude of hemodynamic effects with second doses was less than 50% of the magnitude of effects seen with 1st doses (P < 0.01), and third doses produced no overall significant hemodynamic responses. Diuresis with furosemide failed to restore the circulatory effects of prazosin, and the use of 10-mg doses improved cardiovascular performance to only a small extent. Only 2 of 8 patients had sustained hemodynamic responses large enough to justify chronic oral ambulatory therapy. Administration of oral hydralazine caused hemodynamic improvement superior to even high-dose prazosin therapy (P < 0.02).