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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
    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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  • 3
    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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  • 4
    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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  • 5
    Electronic Resource
    Electronic Resource
    Haemodynamic effects and kinetics of concomitant intravenous disopyramide and atenolol in patients with ischaemic heart disease (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 161-166 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; atenolol ; pharmacodynamics ; ischaemic heart disease ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of concomitant intravenous administration of disopyramide (Norpace) and atenolol (Tenormin) were studied in a cross-over trial in 7 patients with ischaemic heart disease. Following 150 mg disopyramide i.v. the cardiac index (CI) and stroke volume index (SVI) decreased by 14% and 26%, respectively and the heart rate (HR) and preejection period index (PEPI) increased by 13% and 19%, respectively. A decrease in CI of 14% and HR of 21%, respectively were noted after intravenous administration of 7.5 mg atenolol; PEPI increased by 10% whereas SVI remained unchanged. The cardiac Index (CI) fell by 33% following the administration of both drugs. The effect on CI of the two drugs was additive. The effect of disopyramide and atenolol on HR, SVI and PEPI was not significantly modified by coadministration of the other drug. No change in blood pressure was observed after disopyramide or atenolol. A correlation (ρ) of 0.540 and 0.387 was observed between the change in PEPI and the log free and total serum concentrations of disopyramide, respectively. Combined intravenous use of the two drugs in patients with incipient or overt heart failure is not recommended, unless it is due to the arrhythmia to be treated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614295
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  • 6
    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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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 203-208 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cyclosporine ; Felodipine; dehydrofelodi-pine ; pharmacokinetics ; blood pressure ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: In a double blind, randomised, placebo-controlled, cross-over study 12 healthy male volunteers were allocated to receive felodipine + placebo, cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the interaction between the calcium channel blocker felodipine and cyclosporine as it affects the pharmacokinetics of felodipine, dehydrofelodipine, and cyclosporine, and 24-hour blood pressure measurements. Methods: Single doses of cyclosporine (capsules, 5 mg/kg body weight) and of felodipine (extended release (ER) tablets 10 mg) were given at a 1–2 week interval. Plasma drug concentrations were followed for 2 days after drug intake. Results: For cyclosporine, Cmax was increased after combined treatment (16%) compared to cyclosporine alone, but felodipine did not influence other kinetic parameters of cyclosporine. For felodipine, combined treatment with cyclosporine and felodipine increased AUC and Cmax (58% and 151%, respectively) and lowered mean residence time (24%) significantly compared to felodipine alone. For the metabolite dehydrofelodipine, too, AUC and Cmax were increased after the combined treatment (43% and 94%, respectively). Mean 24-hour systolic and diastolic blood pressures were significantly lower after felodipine, both when felodipine was given alone (121/68 mmHg) and in combination with cyclosporine (122/68 mmHg) compared to cyclosporine alone (127/73 mmHg). Conclusion: A combined single dose of cyclosporine and felodipine in healthy subjects increased the AUC and Cmax of felodipine suggesting a cyclosporine-induced decrease in the first-pass metabolism of felodipine, whereas the AUC of cyclosporine was only slightly increased by felodipine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050093
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  • 8
    Electronic Resource
    Electronic Resource
    Antipyrine metabolism is not affected by terbinafine, a new antifungal agent (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 231-233 
    Details
    ISSN: 1432-1041
    Keywords: antipyrine ; terbinafine ; drug metabolism ; drug interaction ; enzyme induction/inhibition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The potential to inhibit drug metabolism of the new antifungal agent terbinafine has been studied using antipyrine (single oral dose of 10 mg/kg) as a probe drug. In a cross-over study in 8 healthy volunteers, antipyrine was administered prior to, during and after 8 days of oral terbinafine 125 mg b.d. Antipyrine, its major metabolites 4-hydroxyantipyrine (4-OH-AP), 3-hydroxymethylantipyrine (3-OH-CH3-AP) and norantipyrine (Nor-AP) were analyzed by specific HPLC assays in multiple plasma and urine samples. During all three parts of the study, the pharmacokinetics of antipyrine viz. t1/2 (11.7 h), total plasma (38.5 ml·h−1·kg−1) and renal clearance (1.6 ml·h−1·kg−1), and its clearance rates to metabolites (CLM), eg. CLM for 4-OH-AP (12.3 ml·h−1·kg−1), CLM for 3-OH-CH3-AP (4.2 ml·h−1·kg−1) and CLM for Nor-AP (6.7 ml·h−1·kg−1) did not differ from the control values. Thus, all the cytochrome P-450-dependent isozymes involved in the metabolism of antipyrine and many other drugs should not be affected by therapeutic doses of terbinafine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00679775
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