Development of pharmacodynamic tolerance to prazosin in congestive heart failure

Desch, Christopher E.; Magorien, Raymond D.; Triffon, Douglas W.; Blanford, Marvin F.; Unverferth, Donald V.; Leier, Carl V.

doi:10.1016/0002-9149(79)90185-1

Cited by 59 publications

(6 citation statements)

References 9 publications

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“…The management of severe heart failure, refractory to digitalis and diuretics remains difficult. Oral vasodilators (Hindman et al, 1980;Kirkin & Pitt, 1981;Kuck et al, 1980) such as hydralazine and prazosin are useful in this setting, however many cases of tachyphylaxis (Desch et al, 1979) have been reported and they are contra-indicated in hypotensive patients. Oral ,8-adrenoceptor agonists (Bourdillon et al, 1980;Kirkin & Pitt, 1981) such as prenalterol, pirbuterol and salbutamol may also be effective but they may increase heart rate and induce ventricular arrhythmias.…”

Section: Discussionmentioning

confidence: 99%

The effective plasma concentrations of sulmazol (AR‐L 115 BS) on haemodynamics in chronic heart failure.

Renard¹,

Jacobs²,

Mols³

et al. 1983

Brit J Clinical Pharma

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1 Sulmazol (AR-L 115 BS) is a new inotropic drug which has arterial and venous vasodilating properties. We used it in seven patients with severe refractory heart failure to determine the effective plasma concentration levels and the most effective bolus dose on haemodynamics. 2 The haemodynamic monitoring included a Swan-Ganz catheter in the pulmonary artery and a radial catheter. Haemodynamic measurements and plasma concentration determinations were performed before sulmazol injection and at 5, 10 and 30 min after a bolus of 0.25, 0.50, 0.75 mg/kg. 3 We observed a gradual increase in cardiac index and decrease in pulmonary wedge pressure when plasma concentration levels rose but the beneficial effects were mainly observed for sulmazol plasma concentrations above 1 ,ug/ml. A bolus injection of 0.75 mg/kg was effective in all cases: a significant increase of cardiac index (1.9 to 2.5 1 min-' m; P < 0.001) and a significant decrease in pulmonary wedge pressure (30 to 25 mm Hg; P < 0.005) and right atrial pressure (13 to 10 mm Hg, P < 0.01) were observed. 4 In these patients sulmazol improved the severely deteriorated left ventricular function without affecting heart rate and blood pressure.

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Section: Discussionmentioning

confidence: 99%

The effective plasma concentrations of sulmazol (AR‐L 115 BS) on haemodynamics in chronic heart failure.

Renard¹,

Jacobs²,

Mols³

et al. 1983

Brit J Clinical Pharma

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“…This agent can produce marked hemodynamic effects acutely, but hemodynamic tolerance is demonstrated within several days [18]. Despite the presence of ␣-1 receptors on myocytes and in the peripheral vasculature, these drugs do not affect long-term clinical outcome, presumably due to reflex activation of neurohormonal systems that can occur with these agents or the development of pharmacologic tolerance [18]. Another case is the sympatholytic agents that are centrally acting ␣-2 adrenergic agonists.…”

Section: Interactions Between the Matrix And Neurohormones: Integratimentioning

confidence: 99%

“…Finally, not all agents that can antagonize the effects of neurohormones improve long-term outcome. ␣-1 adrenergic antagonists [18] and centrally acting ␣-2 agonists both would be expected to improve outcomes based on the neurohormonal model, but they do not (Eli Lilly press release, April 1999).…”

Section: Introductionmentioning

confidence: 99%

The myocardial matrix and the development and progression of ventricular remodeling

Sackner‐Bernstein

2000

Curr Cardiol Rep

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Our conceptual framework of chronic heart failure is based upon the neurohormonal model. In this construct, neurohormonal systems that provide short-term homeostasis remain activated after a myocardial injury, producing progressive ventricular dysfunction and worsening heart failure. However, this model fails to explain several important clinical phenomena, that can be explained by an expanded model of heart failure that focuses on myocardial matrix events as the triggers for disease progression. This model embraces the neurohormonal model and integrates the roles of the immune system and the myocardial fibroblast within the matrix to more fully describe the initiation and progression of the disease.

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“…During long term treatment of established hypertension al-adrenoceptor antagonist drugs restore the underlying elevation of peripheral vascular resistance to that found in normotensives (Taylor 1982), and there is attenuation of the baroreflex-mediated activation of the sympathetic nervous system so that heart rate returns to normal (O'Connor et al 1979). In patients with cardiac failure, short term studies with al-adrenoceptor antagonists have shown improved exercise tolerance and haemodynamic parameters (Chatterjee et al 1981;Fitchett et al 1979) but the response to repeated doses is variable, and several studies have shown marked pharmacodynamic tol- (Desch et al 1979;Jacobs et al 1979;Miles et al 1979). …”

Section: Pharmacodynamicsmentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Relationships of ??-Adrenoceptor Antagonists

Donnelly

Meredith

Elliott

1989

Clinical Pharmacokinetics

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Competitive alpha1-adrenoceptor antagonists are effective in the treatment of both hypertension and cardiac failure. Prazosin has both a short half-life and a short duration of action, but other related quinazoline derivatives, such as doxazosin and terazosin, have pharmacokinetic and pharmacodynamic profiles which make them potentially suitable for once-daily administration. Acute reductions in blood pressure have been correlated with plasma concentrations of prazosin but in most instances, particularly during long term therapy, there is no simple, direct relationship between drug concentration and the fall in blood pressure. Using integrated pharmacokinetic-pharmacodynamic analysis, correlations have been described not only for reductions in blood pressure during short and long term treatment but also for alpha1-adrenoceptor antagonist activity. Furthermore, this integrated approach defines the drug concentration-effect relationship in individual subjects and provides a mathematical description of response that is potentially useful for investigating the factors (both kinetic and dynamic) which influence the inter- and intrasubject variability in antihypertensive effect of alpha-adrenergic blockers. Preliminary data suggest that the long term response to treatment with prazosin and doxazosin is mainly dependent upon the height of the pretreatment blood pressure and the response to the first dose.

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Development of pharmacodynamic tolerance to prazosin in congestive heart failure

Cited by 59 publications

References 9 publications

The effective plasma concentrations of sulmazol (AR‐L 115 BS) on haemodynamics in chronic heart failure.

The effective plasma concentrations of sulmazol (AR‐L 115 BS) on haemodynamics in chronic heart failure.

The myocardial matrix and the development and progression of ventricular remodeling

Pharmacokinetic-Pharmacodynamic Relationships of ??-Adrenoceptor Antagonists

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