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  • 1
    Electronic Resource
    Electronic Resource
    Immediate haemodynamic effects of propranolol, practolol, pindolol, atenolol and ICI 89,406 in healthy volunteers (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 223-228 
    Details
    ISSN: 1432-1041
    Keywords: betablocker ; haemodynamics ; cardioselectivity ; impedance cardiography ; intrinsic sympathomimetic activity ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Changes in cardiac output, heart rate and arterial blood pressure were determined in 31 healthy volunteers after i. v. administration of equipotent doses of five different adrenergic betareceptor blocking drugs. Propranolol was given to seven subjects, atenolol to five, practolol to seven, pindolol to five, and (a new drug) ICI 89,406 to seven. Each drug was given in six logarithmically spaced doses. Propranolol is non-cardioselective and lacks intrinsic sympathomimetic activity. Atenolol, practolol, and ICI 89,406 are cardioselective. Practolol, pindolol, and ICI 89,406 have intrinsic sympathomimetic activity. Cardiac output was determined by impedance cardiography at supine rest. The dose-response curves for cardiac output and heart rate were of three different types: one obtained after administration of drugs without intrinsic activity, represented by propranolol and atenolol, both of which caused a maximal decrease in cardiac output of about 27%, and in heart rate of about 21%. A second type, obtained after drugs with moderate intrinsic sympathomimetic activity, represented by practolol, showed small but significant decreases in cardiac output of 12%, and in heart rate of 11 per cent. A third type, after drugs with marked intrinsic sympathomimetic activity, was represented by pindolol and ICI 89,406, which did not significantly reduce cardiac output or heart rate. The blood pressure was essentially unchanged in all subjects, even after the largest dose of any of the drugs. It was concluded that the degree of intrinsic sympathomimetic activity possessed by an adrenergic betareceptor blocking agent is responsible for acute changes in heart rate and cardiac output, and cardioselectivity is of no importance in this respect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00618509
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of adrenergic beta receptor blockade on ethanol elimination and on ethanol-induced changes in carbohydrate and lipid metabolism in man (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 91-95 
    Details
    ISSN: 1432-1041
    Keywords: Propranolol ; ethanol ; drug interaction ; lipid metabolism ; carbohydrate metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of adrenergic beta receptor blockade on the elimination rate of ethanol was studied in seven healthy young men. The studies were performed before and after 14 days of propranolol 240 mg/day: the ethanol was given perorally — 0.8 mg/kg b.w. The blood concentration of ethanol, glucose, lactate and glycerol, and the plasma concentration of free fatty acids and triglycerides were followed in samples from the superior vena cava taken every 20 min for four hours. The splanchnic hepatic blood flow was estimated with a single i.v. injection of indocyanine green. The absorption rate, absorption fraction and elimination rate of ethanol were not changed by propranolol. The splanchnic hepatic blood flow was significantly reduced (mean 19 per cent) during beta receptor blockade. The ethanol-induced change in the concentration of glucose, lactate and free fatty acids was affected by propranolol, the time-concentration curves for glucose and lactate being significantly elevated and that for free fatty acids being significantly reduced. The time-concentration curves for glycerol and triglycerides did not differ in the two studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609751
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  • 3
    Electronic Resource
    Electronic Resource
    Acute and long-term effects of labetalol on systemic and pulmonary haemodynamics in hypertensive patients (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 5-11 
    Details
    ISSN: 1432-1041
    Keywords: labetalol ; essential hypertension ; thermodilution ; pulmonary circulation ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of the combined adrenergic alpha- and beta-receptor blocking compound labetalol on the systemic and pulmonary circulation were studied after its acute and long-term administration to patients with essential hypertension (WHO grade I–II). Nine men and one woman (mean age 46 years) participated in the acute study. Cardiac index, systemic blood pressure, pulmonary artery pressure and heart rate were measured at rest in the supine and upright positions, and during supine exercise at two work loads (50 and 100 watt), before and after intravenous administration of labetalol 50 mg. Eight of the men were re-examined after three months oral treatment with labetalol 600–900 mg daily. In the acute study cardiac index was unchanged by labetalol, except at the work load of 100 watt, when it decreased by 18.7%. The mean blood pressure decreased under all conditions; 11.6 mm Hg at supine rest, 22.3 mm Hg in the upright position, and by 15.9 mm Hg and 16.9 mm Hg at the two work loads. Heart rate was unchanged at supine rest, but was reduced in the upright position 9,0% and during exercise — at 50 watt by 9.3%, and at 100 watt by 10.3%. Systemic vascular resistance decreased at rest in the supine and upright positions, but not during exercise. The pulmonary artery pressure remained unchanged both at rest and during exercise. In the long-term study cardiac index was unchanged except at the heavy work load, when it decreased by 11.4%. Mean blood pressure was reduced significantly under all circumstances, by 14.6 mm Hg at supine rest, 16.8 mm Hg in the upright positions, and by 13.9 mm and 13.4 mm, respectively, at the two work loads. Heart rate was reduced both at rest 13.6% and during exercise at the two work loads 9.6% and 12.4%. Systemic vascular resistance decreased at rest, but not during exercise. The pulmonary artery pressure were unchanged. Thus, the haemodynamic patterns after acute and long-term administration of labetalol were essentially similar, which suggests that the agent is suitable both for acute and long-term treatment of hypertension, at least from a haemodynamic point of view.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561670
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  • 4
    Electronic Resource
    Electronic Resource
    Immediate central and regional haemodynamic effects of a new beta1-adrenergic stimulating drug, xamoterol (Corwin) in healthy volunteers (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 155-158 
    Details
    ISSN: 1432-1041
    Keywords: xamoterol ; beta-adrenoceptor agonist ; intrinsic sympathomimetic activity ; forearm blood flow ; systolic time intervals ; haemadynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dose-response curves for heart rate, arterial blood pressure, cardiac output, total peripheral resistance, systolic time intervals, forearm blood flow and forearm vascular resistance were obtained after i.v. administration of seven logarithmically increasing doses of xamoterol to 8 healthy volunteers. The total cumulative dose was 0.2 mg/kg b.w. At rest after the seventh dose of xamoterol heart rate, systolic blood, pressure, cardiac output and forearm blood flow were increased by 10%, 20%, 23% and 41%, respectively. Diastolic blood pressure was unchanged. Forearm vascular resistance was reduced by 21% and total peripheral resistance by 10%. Systolic time intervals were reduced: total electromechanical systole index (QS2I), left ventricular ejection time index (LVETI), pre ejection period index (PEPI) and PEP/LVET ratio by 4%, 2%, 12% and 14%, respectively. No side-effects were observed. During upright exercise after the seventh dose of xamoterol heart rate was reduced by 11% and systolic BP by 6%. Diastolic blood pressure was unchanged. Thus xamoterol increased the contractility of the heart with only a small increase in heart rate, increased systolic blood pressure and caused vasodilatation in resting skeletal muscle. During exercise the reduction in heart rate and blood pressure suggests beta-adrenoceptor blocking activity of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547414
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of labetalol on plasma noradrenaline and adrenaline in hypertensive man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 227-230 
    Details
    ISSN: 1432-1041
    Keywords: Plasma adrenaline ; adrenergic alpha- and beta blockade ; blood glucose ; blood pressure ; heart rate ; labetalol ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Injection i. v. of labetalol, a new adrenergic alpha- and beta-blocking agent, decreased arterial blood pressure in 9 hypertensive subjects resting in the supine position, when standing and during supine exercise. Heart rate after labetalol was unchanged in the resting supine position, and it fell in the latter two conditions. Plasma noradrenaline concentration was higher after labetalol in all three experiments as compared to a control study. Plasma adrenaline after labetalol was increased only in the standing position, when the highest plasma noradrenaline concentrations were observed. Blood glucose concentration tended to increase after labetalol, but the difference was not statistically significant. The changes in plasma noradrenaline and blood glucose after labetalol mimic findings observed after alpha-adrenergic receptor blockade. The beta-adrenergic receptor blocking property of labetalol is responsible for the reduced heart rate and it is likely to contribute to the higher plasma noradrenaline concentration observed when standing and during supine exercise.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00560454
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  • 6
    Electronic Resource
    Electronic Resource
    Immediate haemodynamic effects of prenalterol, a new adrenergic beta-1-receptor agonist, in healthy volunteers (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 219-223 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; metoprolol ; beta-receptors ; cardiac output ; impedance cardiography ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute haemodynamic effects of prenalterol, a selective adrenergic beta-1-receptor agonist, were studied in eight healthy male volunteers. Prenalterol was administered i.v. in five increasing doses to a cumulative dose of 5.55 mg. After the last dose of prenalterol, three doses of the selective adrenergic beta-1-receptor antagonist metoprolol were administered i.v. to a cumulative dose of 17.5 mg. After each dose, cardiac output (CO), stroke volume (SV), blood pressure (BP), heart rate (HR), systolic time intervals (STI) and forearm blood flow (FBF) were determined. Prenalterol had the following effects: CO was significantly increased by 21.0% after the fourth dose, but the fifth dose did not further change CO. SV was unchanged after the first four doses, but after the fifth dose a significant decrease in SV of 7.0% was seen. Mean BP was increased significantly by 7.7%, but diastolic BP remained unchanged. HR was increased by 28.4%. Total peripheral resistance was reduced by 8.8%. STI were reduced significantly after the second dose, which indicates that prenalterol has a positive inotropic action. FBF was increased significantly after the fourth dose. After the third dose of metoprolol, the CO, SV, mean BP, HR, STI and FBF had returned to their control values. It is concluded that prenalterol has positive inotropic and chronotropic effects on the myocardium, and that metoprolol is a specific antidote.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563002
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  • 7
    Electronic Resource
    Electronic Resource
    Haemodynamic effects of atenolol, pindolol and propranolol during adrenaline infusion in man (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 659-663 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; pindolol ; propranolol ; beta-receptor blocking drugs ; beta1-selectivity ; intrinsic sympathomimetic activity ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind, cross over study the haemodynamic effects of an i.v. infusion of adrenaline during concomitant administration of atenolol, pindolol, propranolol or placebo were examined in 7 healthy volunteers. During coadministration with placebo, adrenaline caused an increase in systolic blood pressure (SBP) of 26 mm Hg and a decrease in diastolic blood pressure (DBP) of 20 mm Hg. Heart rate (HR) and stroke volume (SV) were increased by about 20–30%. Total peripheral resistance (TPR) fell significantly. When the subjects were pretreated with atenolol, the adrenaline increased SBP by 16 mm Hg, the DBP did not change, HR and SV increased by 19 and 30%, and TPR fell. During concomitant administration of the non-selective betablocker pindolol, which has strong intrinsic sympathomimetic activity (ISA), adrenaline increased SBP by 11 mm Hg and DBP by 17 mm Hg. This pure pressor response led to a significant reduction in HR and SV and an increase in TPR, probably mediated through the baroreceptors. The haemodynamic response to adrenaline during coadministration of propranolol was very similar to that seen after pindolol. It is concluded that a beta1-selective blocker interferes very little with the haemodynamic response to adrenaline, whereas it is changed to a pure pressor response during coadministration of a non-selective betablockers. ISA did not significantly modify the pressor response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608212
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  • 8
    Electronic Resource
    Electronic Resource
    Haemodynamic and metabolic effects of diazoxide during rest and forearm exercise (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 111-116 
    Details
    ISSN: 1432-1041
    Keywords: diazoxide ; arterial blood pressure ; exercise ; muscle blood flow ; free fatty acids ; glucose ; heart rate ; triglycerides ; oxygen uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The immediate haemodynamic and metabolic effects of acute dose of diazoxide 300 mg i.v. were studied in six healthy subjects at rest and during dynamic forearm exercise. Control periods of rest, exercise and recovery were compared with corresponding periods after drug administration. Resting forearm blood flow was almost doubled after diazoxide, and during forearm exercise it increased by about 24%. Systolic blood pressure did not change significantly, but diastolic blood pressure was moderately decreased (5–10 mm Hg). The mean heart rate increased from 57 to 92 beats/min immediately after diazoxide administration, and remained about 20% higher throughout the study. There was a sustained increase in arterial blood glucose of almost 1 mmol/l. The arterial concentration of free fatty acids increased transiently just after diazoxide and then returned to the pre-drug level. The arterial concentration of triglycerides after diazoxide was decreased by about 15% throughout the study. Arterial blood lactate remained unchanged. Forearm uptake of oxygen and glucose tended to increase during the exercise and recovery periods, whereas lactate release remained unchanged.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542454
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  • 9
    Electronic Resource
    Electronic Resource
    Pinacidil, a new vasodilator: Pharmacokinetics and pharmacodynamics of a new retarded release tablet in essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 557-561 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I–II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p〈0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p〈0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the changes in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p〈0.05); four patients complained of oedema. Therapy was discontinued in one patient after a fainting episode following an increase in the dose. Thus, pinacidil was able to lower blood pressure during monotherapy for 4 weeks provided that an adequate serum concentration was achieved. The present retarded tablet formulation is not suitable for b. d. dosing. The tendency towards fluid-retention suggests that pinacidil should be used in combination with a diuretic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542128
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of three beta-blockers with different pharmacodynamic properties on platelet aggregation and platelet and plasma cyclic AMP (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 17-20 
    Details
    ISSN: 1432-1041
    Keywords: beta-adrenoceptor blockade ; platelet aggregation ; intrinsic sympathomimetic activity ; plasma cyclic AMP ; mild hypertension ; platelet cAMP ; pindolol ; metoprolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of three different types of beta-adrenoceptor blocking agents on platelet aggregation and on platelet and plasma cyclic AMP content have been studied in 14 patients with mild hypertension given each drug in turn for two weeks. The drugs were a non-selective blocking agent with high intrinsic sympathomimetic activity, pindolol, the nonspecific blocking agent propranolol, and the beta1-selective metoprolol. The threshold values of ADP and adrenaline for irreversible platelet aggregation were significantly higher for pindolol and metoprolol than for propranolol. The cyclic AMP content of platelets was higher during pindolol and metoprolol than during propranolol treatment. Pindolol produced a substantial increase in plasma cyclic AMP relative to the other two drugs. Thus, platelet aggregation and cyclic AMP formation are influenced by beta-adrenoceptor blockade in proportion to intrinsic sympathomimetic activity and affinity for different beta-adrenoceptor subtypes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555501
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