Comparison of the vasodilator prazosin and the selective beta1 agonist prenalterol on rest and exercise haemodynamics in CHF.
Explore the source record for details and available documents.
Adrenergic beta-Agonists↗
SEARCH · Search PubMed
Results for “Practolol”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Basic pharmacological properties of prenalterol.
Explore the source record for details and available documents.
Adrenergic beta-Agonists↗
The haemodynamic effects of intravenous prenalterol and ouabain in conscious dogs.
Experiments were performed on 5 resting conscious dogs supplied with an electromagnetic flow probe on the ascending aorta and a chronic aortic catheter for pressure recording. The animals were used repeatedly in four different types of experiment involving i.v. administration of 1. saline (controls), 2. prenalterol 45 nmol/kg (approximately 10 micrograms/kg) followed by an additional dose of 135 nmol/kg 20 min later, 3. ouabain 50 nmol/kg (approximately 30 micrograms/kg) and 4. a combination of protocols 2. and 3. Ouabain and the low dose of prenalterol exerted clear-cut positive inotropic effects as reflected in increased stroke volume and max dF/dt without significant changes in heart rate or arterial pressure. The PQ interval increased with ouabain but decreased with prenalterol. The higher dose of prenalterol caused a further rise in max dF/dt, a further shortening of the PQ time, increased heart rate and reduction in systemic vascular resistance. Higher doses of ouabain could not be given due to side-effects (vomiting). The combined treatment with ouabain and prenalterol showed their inotropic responses to be additive. Arrhythmias did not occur in any of the animals at the applied dose levels of the drugs. The experiments show that prenalterol through its beta 1-adrenoceptor stimulating action exerts a positive inotropic effect which surpasses that of emetic doses of ouabain. The inotropic response at moderate doses occurs without a change in heart rate. This fact and the apparent lack of influence of prenalterol on vascular alpha- and beta 2-adrenoceptors make the substance potentially useful clinically as an inotropic agent in cardiac failure, particularly in view of its relatively long duration of action.
Adrenergic beta-Agonists↗
Inotropic, chronotropic and dromotropic effects of prenalterol, a new cardiostimulant drug.
Prenalterol (H 133/22) is an adrenergic beta-receptor stimulator which unlike isoproterenol is both orally active and has a long duration of action. The inotropic, chronotropic and dromotropic effects of prenalterol were investigated in pentobarbital anaesthetized dogs. Prenalterol was found to increase left ventricular maximum dP/dt in a dose-dependent manner up to a dose level of 50 micrograms/kg. Additional doses resulted in only small further increases in cardiac contractility. Electrophysiological studies were done to compare the effects of prenalterol and isoproterenol on sinus node and ventricular pacemaker function. Complete AV block was produced by electrocauterization of the His bundle. Prenalterol accelerated both ventricular and sinus node pacemakers at doses up to 50 micrograms/kg. The increase in ventricular rate was greater than the increase in sinus rate following supramaximal inotropic doses of prenalterol yet no ventricular extrasystoles were ever observed. Similar acceleration of the ventricular and sinus node pacemakers were observed by infusion of isoproterenol. Prenalterol and isoproterenol accelerated AV nodal conduction and ventricular conduction but had little effect upon His-Purkinje conduction. Sinus node reset time was abbreviated as was the functional and effective refractory periods of the atrium and AV nodes.
Animals↗
Prenalterol as an antidote to massive doses of metoprolol--a cardiovascular study in the dog.
Explore the source record for details and available documents.
Adrenergic beta-Agonists↗
Pharmacokinetics of prenalterol in healthy subjects and patients with congestive heart failure.
1. Prenalterol is rapidly and completely absorbed after oral administration with peak concentrations reached after 30 minutes. 2. Prenalterol is rapidly distributed to extravascular tissues after intravenous administration. 3. The extent of bioavailability after administration of prenalterol as a solution is about 25% of an intravenous dose. After administration of 20 mg prenalterol in a controlled release preparation the bioavailability is increased to about 45%. 4. The half-life of the elimination phase is close to 2 hours. 5. 60% of an intravenous dose and 15% of an oral dose is eliminated unchanged by renal excretion. The rest is mainly excreted as the sulphate ester of prenalterol.
Administration, Oral↗
Compartment model of prenalterol.
In previous pharmacokinetic studies in healthy subjects the time course of plasma concentration of prenalterol was described by a short distribution phase (alpha-phase) with a mean half-life of about 8 minutes and an elimination phase (beta-phase) with an average half- life of about two hours [1, 2]. The aim of this joint study was to check the pharmacokinetic data obtained after intravenous single dose administration with the computer program TOPFIT [3] using different compartment models and to test the predictive power of the chosen kinetic model for plasma concentration data after repetitive intravenous prenalterol dosing.
Adrenergic beta-Agonists↗
Pharmacodynamic effects of prenalterol in healthy subjects.
1. Prenalterol induces a dose-dependent effect on different variables reflecting myocardial contractility and heart rate. A clearcut effect can be demonstrated after an oral dose of 2.5 mg. The duration of the effect increases considerably when prenalterol is administered as a controlled release preparation partly due to an increased bioavailability. 2. Prenalterol induces a lipolytic effect manifested as a rise in free fatty acids and glycerol. Also a slight increase of plasma insulin is recorded while plasma potassium decreases somewhat. 3. When prenalterol is administered together with therapeutic doses of a selective or non-selective beta-adrenoceptor blocker it induces the same haemodynamic effects as before the beta-blocker but the dose has to be increased ten-fold. These results suggest that prenalterol might be a useful drug to counteract unwanted haemodynamic effects of a beta-blocker. 4. In animal studies it has been shown that prenalterol has affinity for both beta 1- and beta 2-adrenoceptors. However, it has a stimulating effect mainly on beta 1-adrenoceptors. Therefore, theoretically it might act as a beta 2-adrenoceptor antagonist. Preliminary results from studies in patients with chronic asthma indicate that prenalterol only has an insignificant beta 2-blocking effect when the drug is administered in doses which induce a significant beta 1-adrenoceptor stimulating effect.
Administration, Oral↗
Electrophysiological studies with prenalterol.
Electrophysiological studies with prenalterol in 19 patients (6 women, 13 men, 5 with sinus node disease, 4 with AV node disease, 7 with double node disease, 2 with conduction disturbance below His bundle, 1 normal) showed that sinus node function (heart rate, sinus node recovery time) is uniformly improved by this beta-stimulator. Also AV conduction is significantly and uniformly improved (shortening of AH interval and of the functional refractory period of AV conduction). There is no or little influence on intra-atrial conduction and on conduction below the His bundle. However, spontaneous depolarisation in His-Purkinje fibers--as tested in patients with complete AV block and ventricular demand pacemaker--is increased through beta-stimulation with prenalterol as reflected by shorter escape intervals and higher frequency escape rhythm. Prenalterol may be of clinical use in patients with cardiomyopathies who developed bradycardia under digitalisation or patients with severe bradyarrhythmia either with or without digitalis. It might also be useful in rare emergency situations, when complete pacemaker failure develops.
Adrenergic beta-Agonists↗
Metabolic effects of prenalterol in healthy volunteers.
The effect of the beta 1-adrenoceptor agonist prenalterol on the metabolic parameters glucose, lactate, free fatty acids and serum-insulin were studied in 8 healthy volunteers. Prenalterol was administered intravenously in geometrically increasing doses from 5 to 80 micrograms/kg. The only metabolic effect of prenalterol that could be proved was a significant dose-dependent rise in FFA-concentration. The stimulating effect of prenalterol on lipolysis was significant not only at the time points of maximal effect following each injection, but also 30 min later. Serum-insulin-concentration and glucose- and lactate-concentration failed, however, to show a significant rise after prenalterol administration. This behaviour is a strong indication of a beta 1-selectivity of prenalterol over the whole dose range given.
Adrenergic beta-Agonists↗
Metabolic effects of prenalterol in diabetic patients.
In 16 non-diabetic and 16 diabetic patients prenalterol, dobutamine and dopamine infusions (5 micrograms/kg/min for 30 min) were given. The haemodynamic and metabolic changes were similar in diabetics and non-diabetics. Prenalterol has the most pronounced haemodynamic effect on heart rate (increase 25-47%) and the heart rate-blood pressure-product (increase 54-81%). The metabolic effects were moderate. The slight lipolytic effect of prenalterol documented its functional selectivity for beta 1-adrenoceptors.
Adrenergic beta-Agonists↗
Haemodynamic effects of prenalterol in patients on dialysis.
Haemodialysis hypotension occurs with particular frequency in bilateral nephrectomised patients. This reflects the importance of the renin-angiotensin-aldosterone system for maintaining normal blood pressure. Failure of vascular access (due to clotting and thrombosis of shunts) and ischaemic necrosis of transplanted kidneys in hypotensive patients prompted us to treat them orally with a new beta 1-adrenergic agent (prenalterol). Blood pressure was normalised in 4 out of 5 patients. Because of delayed renal elimination of the drug, daily dosage must be reduced to prevent symptoms of adrenergic stimulation. A study of the pharmacokinetics of prenalterol in uraemia is in preparation.
Administration, Oral↗
Haemodynamic effects of prenalterol in patients with severe congestive heart failure--NYHA III-IV.
In 12 patients with severe congestive heart failure due to ischaemic heart disease (n = 6) and due to congestive cardiomyopathy (n = 6) the haemodynamic effects of a new beta 1-agonist, prenalterol, were studied. Left ventricular (LV) function was studied before and 20 min after infusion of 12 mg prenalterol. Heart rate was kept constant by atrial pacing at a rate of 100 min-1 unless intrinsic heart rate exceeded it. As a sign of positive inotropic support, prenalterol enhanced peak rate of LV pressure development (dP/dt) from 1160 +/- 100 mm Hg/s to 1590 +/- 190 mm Hg/s (p less than 0.005). In the mean LV end-diastolic and end-systolic volume determined by cineventriculography and two-dimensional echocardiography decreased. LV stroke work index measured with both methods increased with 4 ml/m and 5 ml/m, respectively (p less than 0.02). LV ejection fraction was improved by 6% and 8% (p less than 0.005). Increase of peak fall of left ventricular pressure (dP/dt) (1050 +/- 60 mm Hg/s to 1270 +/- 100 mm Hg/s, p less than 0.005) and shortening of time constant (T) of pressure fall from 64.5 +/- 5.0 ms to 44.5 +/- 6.0 ms (p less than 0.005) demonstrated the improved LV relaxation. Analysis of LV volume and myocardial compliance revealed decrease of left ventricular stiffness. Thus, LV filling pressure was reduced from 22.1 +/- 4 mm Hg to 14 +/- 3.5 mm Hg (p less than 0.001). Pressure volume analysis showed a significant increase of LV power and work, as well as a slight decrease of wall stress. Our study could demonstrate, even in patients with severe heart failure, a sustained positive inotropic effect of prenalterol leading to an improved left ventricular contractility, relaxation and compliance. LV power and work was enhanced. The increase of oxygen demand seemed to be counterbalanced by an improved perfusion of particularly subendocardial layers indicated by an increased transmyocardial pressure gradient.
Adrenergic beta-Agonists↗
Echocardiographic comparison between prenalterol and dobutamine.
Prenalterol, a new cardioselective beta 1-adrenoceptor agonist, was compared with the beta-stimulator dobutamine by computer-assisted echocardiography. Prenalterol decreased preload, increased heart rate and induced an increase in contractility for a longer time in comparison with dobutamine. The small influence on blood pressure and afterload indicates selective beta 1-receptor-effect by a result of slight changes in the peripheral vascular resistance.
Adolescent↗
Clinical experiences with prenalterol as an antidote to Beta-adrenoceptor blockade.
The cases presented in this paper suggest that prenalterol is useful in the treatment of myocardial depression due to beta-blockade. According to its pharmacological properties, prenalterol might even be the drug of choice in these situations. It is wellknown that massive beta-blocker overdosage may be difficult to manage and as the therapeutic guidelines in these cases have not yet been definitely stated, it is obvious that prenalterol in this context will be of utmost importance. What remains to be solved is the dosage level. So far, experience has shown that high doses, widely exceeding the recommended initial dose of 50-100 micrograms/kg, are necessary to restore normal circulation in massive beta-blocker overdosage.
Adrenergic beta-Agonists↗
Effects of prenalterol administered orally in patients with congestive heart failure.
A single-blind study of prenalterol 20-200 mg daily in a slow-release tablet preparation and a placebo was performed in 15 patients with moderate to severe congestive heart failure (NYHA II-IV) to evaluate the haemodynamic and clinical effects of oral prenalterol. Non-invasive parameters in the measurement of cardiac output, stroke volume, pre-ejection period index (PEPI), PEP/LVET ratio, ejection fraction and mean Vcf were significantly improved, indicating beneficial effects of prenalterol on cardiac contractility. Systolic blood pressure, heart rate and rate-pressure product were slightly increased at rest but were considerably lower during exercise. Arrhythmogenecity was not seen in the patients studied. Subjective improvement was noted in the majority of patients as evidenced by a decreased frequency of dyspnoea, fatigue and angina. Unwanted effects, such as palpitations and transmitted arm pulsations, were transient and disappeared with dose adjustment, while the inotropic effect of the medication was maintained. The clinical response appeared to be sustained for up to 2 weeks of treatment, indicating non-development of tachyphylaxis.
Administration, Oral↗
Haemodynamic effects of intravenously administered prenalterol in patients with severe heart failure.
The acute haemodynamic effects of prenalterol 75-225 micrograms/kg i.v. were studied at rest and during exercise in the supine position in 12 patients with chronic congestive heart failure secondary to myocardial infarction (6 pts), chronic valvular disease with valvular replacement (4 pts), ischaemic cardiomyopathy (1 pt) and post myocarditis (1 pt). In 5 of the 6 AMI patients the effect of prenalterol on myocardial oxygen consumption at rest was measured. Pulmonary artery end-diastolic pressure decreased significantly from 17 to 10 mm Hg at rest and from 31 to 21 mm Hg during exercise. Resting heart rate increased from 78 to 90 at rest but was unchanged during exercise. MVO2 in the 5 patients was unchanged or lower in 4 patients and increased in one in whom angina developed after prenalterol. In general, dyspnoea and angina during exercise were less pronounced after prenalterol. The calculated triple product was lower after prenalterol, especially during exercise, indicating lower myocardial oxygen consumption and probably less myocardial ischaemia.
Adrenergic beta-Agonists↗
Circulatory response to prenalterol in normal subjects and in patients with primary congestive cardiomyopathy.
Experimental pharmacology indicates that prenalterol is a selective beta 1-adrenoceptor activator. In 5 normal individuals, 15 minutes after the drug (infused at a dose of 15 micrograms/kg over 5 min) the following circulatory changes were seen: a) increase of cardiac index (+31%), heart rate, stroke index, systolic aortic pressure, left and right ventricular mean rate of ejection and mean rate of the pressure rise in either ventricle during the pre-ejection phase; b) reduction of systemic vascular resistance (-18%), appearance, built-up and disappearance times in the left ventricular dye dilution curves. Pulmonary systolic, diastolic and wedge pressures and vascular resistance did not vary consistently. The circulatory effects persisted almost unchanged 30 minutes after the infusion. In a group of 5 patients with heart failure due to primary congestive cardiomyopathy, refractory to conventional therapy, the haemodynamic response to prenalterol (infused at a dose of 30 micrograms/kg over 5 min) was qualitatively similar to that of normal subjects in 3 cases. In 2 other patients cardiac performance deteriorated. The reasons for this paradoxical effect were not identified. These preliminary results suggest that prenalterol is a potent selective inotropic agent in man, that may assist in the therapeutic management of refractory heart failure due to congestive cardiomyopathy. However, careful haemodynamic monitoring is advisable for its use in this dysfunction until broader clinical experience can be accumulated.
Adrenergic beta-Agonists↗