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At least 19 recordsLinked to original sources
PubMed1979

Differences in hemodynamic effects of nitroprusside and prazosin in severe chronic congestive heart failure: evidence for a direct negative chronotropic effect of prazosin.

To compare the hemodynamic effects of prazosin and nitroprusside in patients with severe congestive heart failure, nine patients with heart failure refractory to conventional therapy received oral prazosin and intravenous nitroprusside administered so as to produce a similar decrease in left ventricular filling pressure in each patient. By this comparison, both drugs produced similar decreases in mean right atrial pressure, mean pulmonary arterial pressure and systemic and pulmonary vascular resistance. However, with nitroprusside, cardiac index increased more (+0.97 versus +0.73 liters/min per m2, P less than 0.01) and mean arterial pressure decreased less (-13.7 versus -18.3 mm Hg, P less than 0.05) than with prazosin. Both drugs produced similar changes in stroke volume index (+11.7 cc/beat per m2 with nitroprusside and +12.5 with prazosin) and stroke work index (+8.1 g-m/m2 with nitroprusside and +6.6 with prazosin). Therefore, the differences in the hemodynamic responses observed with the two agents were due to the significantly greater decrease in heart rate with prazosin (-8 beats/min) than with nitroprusside (-2 beats/min, P less than 0.05). These clinical data support experimental evidence suggesting that there is a significant negative chronotropic action of prazosin independent of its peripheral vascular effects.

Administration, Oral↗
PubMed1984

Prazosin versus propranolol plus prazosin: a comparison in diuretic-treated hypertensive patients.

The antihypertensive efficacy of prazosin was compared with that of a combination of prazosin and propranolol in 14 patients with essential hypertension. All patients had sitting diastolic blood pressures greater than or equal to 95 mm Hg despite daily therapy with 50 mg of hydrochlorothiazide and 240 mg of propranolol. After a 4-week monitoring period, patients were divided randomly into 2 groups in whom either (1) propranolol was reduced to 120 mg/day (to avoid potential hypotension) and prazosin was added, starting with an initial dose of 1 mg twice daily, or (2) propranolol was tapered and discontinued as prazosin was added. The average doses of prazosin were 7.4 and 7.6 mg/day, respectively. After 12 weeks of therapy, blood pressure was reduced in both groups, and there was no significant difference in the reduction of blood pressure or dose of prazosin in the 2 groups. Mean heart rate increased significantly in both groups (p less than 0.01), but more so in the group of patients who discontinued propranolol therapy. Thus, when a combination of 50 mg/day of hydrochlorothiazide and 240 mg/day of propranolol is insufficient to control hypertension, the addition of prazosin is shown to decrease blood pressure whether or not propranolol is continued.

Aged↗
PubMed1980

Studies on the clinical pharmacology of prazosin. II: The influence of indomethacin and of propranolol on the action and disposition of prazosin.

1 The possibility of pharmacodynamic and pharmacokinetic interactions of prazosin with indomethacin and with propranolol have been studied in healthy subjects. 2 In four out of nine individuals indomethacin considerably attenuated prazosin-induced hypotension, but noradrenaline concentrations were unchanged from the day when blood pressure fell greatly. The effect of prazosin in the other five subjects was not influenced by indomethacin. 3 Indomethacin prevented the rise in plasma renin activity seen following administration of prazosin alone. 4 Propranolol did not prevent the syncope associated with the first dose of prazosin. 5 Propranolol affected neither the absorption nor elimination of prazosin. 6 It is concluded that in certain subjects indomethacin can largely prevent the hypotensive effect of parazosin, possible by increasing adrenergic receptor sensitivity. The theoretical possibility that propranolol could influence prazosin disposition or syncope was not substantiated.

Adult↗
PubMed1976

Studies with prazosin--a new effective hypotensive agent. I. Open clinical study of prazosin in combination with other antihypertensive agents.

The use of prazosin, a new antihypertensive agent, in combination with other conventional antihypertensive agents, in a hospital outpatient clinic setting, was studied in a mixed group of 104 hypertensive patients. Prazosin effectively lowered the lying and standing blood pressure in the majority of patients whose blood pressure was uncontrolled or poorly controlled before the introduction of prazosin. Blood pressure control was adequately maintained in patients who were given prazosin because of the occurrence of side effects of other antihypertensive medication. No significant change in renal function attributable to prazosin was found in patients with normal or impaired renal function.

Adult↗
PubMed1977

Open studies with prazosin in the treatment of essential hypertension. Prazosin Research Group in Japan.

The clinical usefulness of prazosin was investigated in 67 patients with mild to moderate essential hypertension for 6 to 12 weeks. The daily doses were increased from 3 to 9 mg according to the responses of the patients. The average reduction of mean arterial blood pressure by 6 weeks' prazosin treatment was 13-4 +/- 1-7 mm Hg. Thirty-three patients (49-3%) showed good or excellent responses to prazosin. Serious side effects or laboratory abnormalities did not appear in this trial, through postural dizziness was found in 6-0%. Prazosin seems to be a useful antihypertensive agent in the treatment of patients with mild or moderate essential hypertension.

Adult↗
PubMed1978

Studies with prazosin--a new effective hypotensive agent. III. An acute double-blind cross-over study comparing the effects of single doses of prazosin and hydrallazine in combination with propranolol and a diuretic.

The duration of action of a single dose of prazosin and hydrallazine on blood pressure and heart rate was studied in 16 hypertensive patients whose blood pressure was not adequately controlled by a combination of a thiazide diuretic and a beta-adrenergic blocking agent, and had required the addition of either prazosin or hydrallazine. Observations over an eight-hour period, after a single dose of either 3 mg of prazosin, or 75 mg of hydrallazine, in identical capsules, with cross-over study one week later, showed significant reductions in blood pressure within the first hour after oral administration of either agent. This reduction in blood pressure persisted for four to six hours after hydrallazine and six to seven hours after prazosin administration. Tachycardia was more pronounced and prolonged after hydrallazine administration and side effects were more common.

Adult↗
PubMed1983

Dissociation of presynaptic alpha 2-adrenoceptors following prazosin administration: presynaptic effect of prazosin.

Evidence has been obtained that prazosin possesses a presynaptic alpha 2-adrenoceptor blocking action in the rat was deferens preparation stimulated at 1 Hz. In the presence of prazosin yohimbine failed to affect the presynaptic alpha 2-adrenoceptor stimulatory effect of 1-noradrenaline while the effect of xylazine was almost completely abolished. It is therefore suggested that there are two kinetically different prejunctional alpha 2-adrenoceptor sites.

Animals↗
PubMed1989

Beneficial effects of pinacidil on blood lipids: comparisons with prazosin and placebo in patients with hypertension. Pinacidil-Prazosin and Pinacidil-Placebo Research Groups, Lilly Research Laboratories.

In two randomized, double-blind clinical trials comparing pinacidil with prazosin and with placebo in patients with hypertension, a number of statistically significant and potentially beneficial effects on blood lipids were detected in the patients taking pinacidil. Patients treated with pinacidil exhibited significant average decrements from baseline in concentrations of total and low-density lipoprotein cholesterol and triglycerides and a significant average increment in high-density lipoprotein cholesterol. The mean effects seen in the pinacidil group were significantly greater than those in the placebo group for both total cholesterol (-9.8 vs +4.2 mg/dl, p less than 0.001) and triglycerides (-21.6 vs +8.6 mg/dl, p less than 0.001). The effects seen in patients given pinacidil were also significantly greater than those seen in the patients treated with prazosin for both high-density lipoprotein cholesterol (+3.6 vs -1.0 mg/dl, p = 0.002) and triglycerides (-14.8 vs +30.3 mg/dl, p less than 0.001). Negative effects of hydrochlorothiazide and propranolol on blood lipids were not apparent in patients given pinacidil. Thus, pinacidil treatment of hypertension is associated with a beneficial effect on blood lipids, which may be of clinical significance.

Antihypertensive Agents↗
PubMed1987

[Slow elimination of a prazosin metabolite compared to prazosin kinetics after its intravenous administration to rabbits].

Serum concentration profiles of prazosin and its metabolite 2-(1-piperazinyl)-4-amine-6,7-dimethoxyquinazoline after intravenous bolus administration to rabbits (0.5 mg/kg) were shown to be biphasic. Rapid decline related to distribution was followed by a terminal slope lasting for up to 24 hours. Prazosin level in this phase decreased, its elimination half-life being about 9 hours, while the metabolite serum level was almost constant between 4 and 24 hours and averaged 0.9 mumol/l. This is in keeping with the earlier suggested extremely low elimination rate of this metabolite. Enterohepatic recirculation may account for this phenomenon, as well as a significant rise in the metabolite serum concentration I hour after the injection.

Animals↗
PubMed1981

Ambulatory prazosin treatment of chronic congestive heart failure: development of late tolerance reversible by higher dosage and interrupted substitution therapy.

To evaluate whether long-term administration of the oral vasodilator, prazosin, in the ambulatory therapy of chronic refractory congestive heart failure (CHF) results in gradual attentuation of its marked salutary peripheral circulatory relaxing actions, 16 coronary heart failure patients receiving chronic prazosin, 16 mg daily, were assessed for the development of vasodilator tolerance for 12 months. In six of these patients such tolerance was documented after 7 months which was readily surmountable, thereby allowing continuation of effective chronic prazosin therapy. Each of the six tolerance patients underwent four forearm plethysmography studies: prior to chronic prazosin (study I; 4.0 mg study dose), after 7 months prazosin (study II; 4.0 mg), repeated following 1 additional week on higher effective prazosin dose of 32 mg daily (study III; 8.4 mg), and following 2 weeks of prazosin withdrawal (study IV; 4.0 mg). The prazosin study dose increased forearm blood flow, decreased forearm vascular resistance and venous tone in studies I, III, and IV; these variables were unchanged by prazosin in study II. Despite vasodilator tolerance to the initial daily dosage at 7 months (study II), symptomatic effectiveness and improved cardiac performance were sustained throughout the entire 12 months of chronic prazosin therapy by increasing dosage (study III) and brief interruption of the vasodilator (study IV) (NYHA class IV pre-prazosin symptoms improved to class 2.7 at 3 months, class 2.4 at 6 months, and class 2.5 at 12 months chronic prazosin). This study showed that prazosin vasodilator tolerance occurred in approximately one third of CHF patients after several months of chronic prazosin therapy. More importantly, however, the present investigation demonstrated that chronic prazosin symptomatic efficacy can be maintained in such CHF patients by overcoming tolerance with higher effective prazosin dosage or brief prazosin discontinuation.

Administration, Oral↗
PubMed1988

Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats.

1. The effect of chronic prazosin pretreatment (3 days) on the ability to excrete a modest saline load (i.v. saline, 0.097 ml min-1) was studied in the anaesthetized rat. Three days before the experiment, the drinking water was replaced with 0.5% dextrose (control), 0.015 mg ml-1 prazosin in 0.5% dextrose (low dose) or 0.15 mg ml-1 prazosin in 0.5% dextrose (high dose). 2. The selectivity of the prazosin for alpha 1-adrenoceptors was evaluated in pithed rats. The pressor response to phenylephrine was partially attenuated by the low dose of prazosin and completely attenuated by the high dose of prazosin. The pressor response to clonidine was slightly decreased by the 3 day prazosin pretreatment indicating a selectivity for alpha 1-adrenoceptors. 3. In rats pretreated with the low dose of prazosin, there was a significant decrease in sodium and water, but not potassium excretion as compared to the control group. Captopril failed to alter these effects of the low dose of prazosin. Blood pressure and creatinine clearance were the same in both groups. In rats pretreated with the high dose of prazosin, there was a further decrease in sodium and water but not potassium excretion. However, this dose of prazosin also significantly decreased blood pressure and increased creatinine clearance. A decrease in renal perfusion pressure with an aortic clamp to the same level as that observed with the high prazosin dose also decreased sodium and water but not potassium excretion. The decrease in sodium and water excretion was not as great as that observed with the high dose of prazosin. 4. The results indicate that chronic a,-adrenoceptor blockade with prazosin attenuates the ability to excrete a saline load in a dose-related manner. Whether this inability to excrete a saline load is analogous to the sodium and water retention observed with the clinical use of prazosin remains to be determined.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Clinical pharmacokinetics of prazosin.

Prazosin, a quinazoline derivative, is a peripheral vasodilator used in the treatment of arterial hypertension and more recently, congestive heart failure (CHF). Prazosin is extensively metabolised by the liver and has high first-pass metabolism and low oral bioavailability. In normal healthy volunteers, the time of peak concentration occurs between 1 and 3 hours after oral administration, with wide interindividual variations. The extent of oral absorption seems to be similar for different pharmaceutical forms and is not influenced by the presence of food in the digestive tract. Oral bioavailability of prazosin ranges from 43.5 to 69.3% (mean 56.9%). Prazosin is highly (92 to 97%) bound to human plasma proteins (albumin and alpha 1-acid glycoprotein) and the extent of binding is independent of the plasma concentration of the drug in the range of 20 to 150 ng/ml. Preliminary studies in humans indicate that pathways for biotransformation of prazosin are similar to those observed in the rat and dog. Only 6% of prazosin is excreted unchanged, mainly in the urine. The two main metabolites (0-demethylated) are almost completely excreted in bile. The time course of disappearance of prazosin from plasma after intravenous injecton indicates that prazosin disposition should be described by a model containing at least 2 kinetically distinct compartments. The mean elimination half-life is about 2.5 hours. After intravenous administration, the steady-state volume of distribution has been calculated to be 42.2 +/- 8.9L and the total body clearance 12.7 +/- 1.3L/h. In hypertensive patients with normal renal function, prazosin kinetics do not differ significantly from normals. However, prazosin disposition is modified in chronic renal failure and in congestive heart failure. In both cases, the plasma free fraction of prazosin is increased and plasma elimination half-life is longer. Prazosin kinetics may be expected to be altered in patients with liver diseases. Pharmacokinetic data do not suggest a mechanism to explain the disappearance of the first-dose effect during continued administration of prazosin. Although more investigation is needed to define prazosin kinetics in congestive heart failure and chronic renal failure, the available information about prolongation of elimination half-life, decreased protein binding and increased peak plasma concentrations suggest that prazosin dosage should be titrated cautiously in such patients.

Biological Availability↗
PubMed1982

Central and peripheral prazosin binding: an in vitro autoradiographic study in the rat.

Using an in vitro autoradiographic technique the binding of [3H]prazosin to brain, spinal cord, heart and vascular tissue was studied. Histologically prepared tissue sections were incubated in 5 nM [3H]prazosin or 5 nM [3H]prazosin in the presence of 100 microM unlabelled prazosin base in order to establish sites exhibiting specific prazosin binding. Dense prazosin binding sites were found in all arterial tissue examined except mesenteric artery. Dense prazosin binding was also found in cardiac tissue. Prazosin binding to veins was present sometimes but often absent. Prazosin does not readily pass the blood brain barrier and in this in vitro study the only area, within the central nervous system, showing specific prazosin binding sites was the olfactory bulb. The selective binding of prazosin, an alpha 1-adrenoceptor antagonist, to arterial and cardiac tissue would suggest that the antihypertension induced by prazosin is mediated by a peripheral action.

Animals↗