Attenuation of Prazosin Effect on Cardiac Output in Chronic Heart Failure

Abstract

The persistence of the hemodynamic effects of prazosin was studied in 12 patients with chronic congestive heart failure. Multidose evaluation involving five 5-mg doses showed the initial decrease in systemic vascular resistance and increase in cardiac index, stroke work index, and stroke volume index to be transient. Doubling the dose did not restore effect. Modest decreases in pulmonary capillary-wedge and mean arterial pressures persisted throughout the study. In six patients, plasma prazosin concentration measured at times of hemodynamic observations showed the initial hemodynamic effect of prazosin to attenuate upon further administration despite mean plasma concentrations that exceeded those measured after the first dose. In patients with chronic heart failure, resting hemodynamic studies suggest a rapid attenuation of prazosin-mediated hemodynamic effect in the presence of adequate plasma concentration. Recognizing this phenomenon, if long-term prazosin therapy for congestive heart failure is contemplated, we suggest the hemodynamic response in individual patients be monitored.

Haemodynamic Effects of a Single Low Dose of Prazosin in Patients With Chronic Congestive Cardiac Failure Correlations With Pharmacokinetics

“…With the development in this laboratory of a sensitive method for measuring prazosin , we have been able to determine the pharmacokinetics of prazosin in patients with congestive cardiac failure after a single oral dose of only 0.5 mg. Our results extend previous findings of prolongation of elimination half-life and increased area under the plasma-concentration-time curve in patients with chronic congestive heart failure (Arnold et al, 1979;Jaillon et al, 1979; Baughman ef a/., 1980) relative to normal subjects. These changes might reflect either decreased clearance or increased bioavailability of prazosin in patients with congestive cardiac failure.…”

“…In fact, comparison of the haemodynamic changes reported here with two previous acute studies using 5 mg doses (Packer et al, 1979a;Arnold et al, 1979) suggests that the haemodynamic response to the current 0.5 mg dose was not markedly less than that induced by 5 mg prazosin. Both groups of patients had similar degrees of congestive heart failure.…”

Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study.

“…Additionally, the long-term effectiveness of several of these drugs remains controversial, perhaps because patients develop a tolerance to them. [45][46][47][48][49][50] Long-term follow-up studies have presented a less optimistic picture than the initial reports.10' 51,52 Captopril is the first oral converting-enzyme inhibitor to be studied in heart failure. The initial reports documenting its acute effectiveness gained considerable attention and provided some evidence of sustained hemodynamic and clinical improvement with maintenance captopril therapy.9' 1117 Ader et al9 documented persistent hemodynamic benefit at rest in seven patients restudied after 2 months of therapy, five of whom had an accompanying increase in treadmill exercise tolerance.…”

Differential long-term intrarenal and neurohormonal effects of captopril and prazosin in patients with chronic congestive heart failure: importance of initial plasma renin activity.

“…The decrease in plasma arginine-vasopressin and in minimal urine osmolality that was observed in patients with lower renin ( figure 4) [17][18][19][20][21][22][23] Because cross-tolerance from one vasodilator to another does not always occur, mechanisms other than neurohormonal overstimulation must also be involved in the production of tachyphylaxis to vasodilators.…”