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  • hypertension  (276)
  • Springer  (276)
  • American Chemical Society
  • 1985-1989  (146)
  • 1980-1984  (130)
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  • Springer  (276)
  • American Chemical Society
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 43 (1987), S. 403-405 
    ISSN: 1420-9071
    Keywords: SHR ; cyclosporin ; immune mechanisms ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In spontaneously hypertensive rats the effect of the T-cell inhibitor cyclosporin was studied at different ages. If treatment was started at the age of 2 weeks the development of hypertension was delayed, but the ultimate level of blood pressure was not affected. These results indicate the involvement of immune mechanisms in the early development of hypertension in spontaneously hypertensive rats.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 42 (1986), S. 1238-1239 
    ISSN: 1420-9071
    Keywords: Kinins ; bradykinin ; kallidin ; cerebrospinal fluid ; HPLC ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Rat cerebrospinal fluid contains peptides which displace radiolabeled bradykinin from its specific antibodies. Two peptides which showed the same retention time as kallidin and bradykinin in a reverse phase high pressure liquid chromatography system were detected in cerebrospinal fluid of rats. The concentration of radioimmunologically detected kinins in the cerebrospinal fluid of spontaneously hypertensive rats of the Okamoto strain was lower than that of the Wistar Kyoto control rats.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 34 (1988), S. 513-515 
    ISSN: 1432-1041
    Keywords: methyldopa ; prolactin ; hypertension ; sustained release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a group of ten hypertensive patients, the effects of methyldopa administration in two different formulations on serum prolactin (PRL) were studied. A single oral dose of normal release methyldopa significantly increased serum prolactin levels, peak concentrations occurring 3 to 6 h after drug administration. On the contrary, administration of sustained release methyldopa at the same dose was only followed by slight and not significant fluctuations in prolactin plasma levels. Both formulations produced a significant decrease of systolic and diastolic blood pressures, without significant differences between sustained and normal release methyldopa effects.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 34 (1988), S. 605-611 
    ISSN: 1432-1041
    Keywords: oxprenolol ; hypertension ; osmotic delivery system ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two oxprenolol oral osmotic (OROS) delivery systems on heart rate and blood pressure before and during recovery from exercise at a predetermined load were examined in twelve patients with hypertension previously responding to beta-blocker monotherapy. Haemodynamic responses were attenuated during the 24 h after single and repeated (15 days') once daily administrations of 10/170 and 16/260 oxprenolol OROS. At 24 h after repeated doses, compared to placebo there were significant reductions in resting blood pressure and in heart rate immediately following exercise. Attenuation of heart rate after exercise was dose related but differences between the systems with respect to resting heart rate and blood pressure were inconsistent. Antihypertensive responses after repeated doses were greater than those after single doses. However, reductions in resting and exercise heart rates were consistently less on chronic therapy. This may reflect enhanced expression of the partial agonist activity of oxprenolol due to altered receptor sensitivity after prolonged beta-blockade. The plasma oxprenolol profiles after both systems indicated slow absorption and substantial concentrations were apparent 24 h after drug administration. These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise.
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  • 5
    ISSN: 1432-1041
    Keywords: nicardipine ; propranolol ; hypertension ; concomitant administration ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A twelve-week parallel study was conducted to compare the efficacy and safety of nicardipine plus propranolol with that of propranolol alone in 67 patients with mild to moderate essential hypertension. Efficacy data was analysed for 50 patients. The regimens used were 90 mg · day−1 of nicardipine and 120 mg · day−1 of propranolol. Both treatments significantly reduced supine and standing systolic and diastolic blood pressure from baseline values at all visits. At all visits, concomitant administration of nicardipine and propranolol produced a greater reduction in systolic and diastolic pressures than did propranolol alone, although the difference between treatments did not always reach statistical significance. Few adverse events were reported, and none was clinically important. We conclude that nicardipine taken concomitantly with propranolol is more effective than propranolol alone in treating patients with hypertension and that the combined regimen is well tolerated.
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  • 6
    Electronic Resource
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    Springer
    European journal of clinical pharmacology 33 (1987), S. 423-426 
    ISSN: 1432-1041
    Keywords: Ketanserin ; pharmacokinetics ; hypertension ; ketanserinol ; predicted plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of ketanserin in 6 hypertensive patients after a single oral 40 mg dose and at steady-state after 4 weeks treatment with 20 mg and then 40 mg 12-hourly. Pharmacokinetic variables after a single dose were similar to those reported in healthy volunteers, with median values for Cmax 112 ng·ml−1, tmax 1 h, and t1/2 19 h. The corresponding values for the metabolite ketanserinol were Cmax 155 ng·ml−1, tmax 2 h, and t1/2 25 h. The median AUC was 3.3 times greater for ketanserinol than for the parent drug. These results were used to predict the mean steady-state plasma concentrations of ketanserin and ketanserinol. Predicted values were on average similar to those observed after four weeks treatment with 40 mg 12-hourly, although there were marked differences between the observed and predicted values in some patients. There was no evidence of time- or dose-dependent kinetics for ketanserin, but the study had insufficient power to exclude the occurrence of these phenomena entirely.
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  • 7
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; controlled-release metoprolol ; systolic and diastolic blood pressure ; heart rate ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups 195 hypertensive patients were randomly allocated to treatment with either conventional tablets of metoprolol, 100 mg once daily, or a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily. The dose was doubled if the patient's diastolic blood pressure remained ≥95 mmHg after six weeks on 100 mg, whereas well-controlled patients continued on 100 mg once daily for a further six-week period. In the metoprolol tablet group the 200 mg dose was administered in the form of Durules. There was a significant reduction from the placebo baseline in systolic and diastolic blood pressure and heart rate at 24 h after both six weeks and 12 weeks of active treatment; no significant difference in the mean reduction from baseline between the two groups was demonstrated. However, significantly more patients responded to treatment with metoprolol CR when compared with those patients taking metoprolol tablets. After six weeks of active treatment 61% of the metoprolol CR group and 56% of the conventional metoprolol tablet group had a diastolic blood pressure 〈95 mmHg. After another six weeks the corresponding figures were 83% and 69% respectively. Between week 6 and 12, 36% of patients in the metoprolol CR group and 42% of patients in the conventional metoprolol tablet group were receiving a 200 mg dose. All formulations of metoprolol were well-tolerated. Fewer subjective symptoms were reported during active treatment than during the placebo phase. There were no differences between the groups with regard to changes in laboratory variables from baseline, changes in all combined symptoms, or changes in any one symptom.
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  • 8
    ISSN: 1432-1041
    Keywords: felodipine ; propranolol ; hydrochlorothiazide ; hypertension ; general practice ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighty one patients with uncomplicated hypertension who required additional antihypertensive medication (diastolic Phase V [dBP]≧95 mm Hg) after 4 weeks treatment with hydrochlorothiazide (HCTZ) 25 mg o.m. were randomized to receive felodipine 5 mg b.i.d. (n=40) or propranolol (n=41) 80 mg b.i.d. in addition to HCTZ 25 mg o.m. If the dBP measured about 12 h post-dose was not ≦90 mm Hg after 4 weeks, the dose of felodipine or propranolol was doubled. The double blind trial period was 8 weeks for all patients. Over the 8 week period, felodipine reduced the seated dBP from 100 to 83 mm Hg and propranolol from 101 to 86 mm Hg. The attained seated dBPs were significantly different in the two groups. About one third of patients in each group received the high dose of second-line therapy. After 8 weeks 91% of patients receiving HCTZ+felodipine and 84% receiving HCTZ+propranolol had a dBP ≦ 90 mm Hg. Both regimens were well-tolerated with an equal incidence but different pattern of adverse events (felodipine: flushing, headache and peripheral oedema; propranolol: dyspepsia, fatigue and vasospasm). In this 8-week study, felodipine and propranolol were safe and effective second-line antihypertensive drugs when added to hydrochlorothiazide. At the doses selected, felodipine was at least as effective as propranolol.
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  • 9
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    Springer
    European journal of clinical pharmacology 34 (1988), S. 411-413 
    ISSN: 1432-1041
    Keywords: bopindolol ; hypertension ; beta-adrenoceptor blocker ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients (mean age 53 years) with essential hypertension have been studied at rest and during exercise following oral treatment for 6 weeks with a new beta-adrenoceptor blocking agent, bopindolol. The treatment caused a significant decrease in systolic and diastolic arterial blood pressure and heart rate, both at rest and during exercise. Stroke volume fell, too, and therefore so did cardiac output, whereas the systemic vascular resistance was increased. Left ventricular filling pressure was elevated both at rest and during exercise following bopindolol therapy. However, a different haemodynamic pattern was noted in patients with elevated total peripheral resistance prior to therapy (Group 1) compared to patients with normal or subnormal peripheral resistance (Group 2). A decrease in systemic vascular resistance seemed to be the cause of the fall in blood pressure in Group 1, as the expected increase in vascular resistance did not occur, whereas a reduction in cardiac output was of greater importance in Group 2. During exercise the lowering of arterial blood pressure in both groups was mediated by a reduction in cardiac output.
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  • 10
    ISSN: 1432-1041
    Keywords: atenolol ; nifedipine ; hypertension ; adverse effects ; fixed combination ; drug efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this randomized, double-blind, crossover study we investigated the haemodynamic effects of a beta-blocker (atenolol 50 mg) and a calcium antagonist (nifedipine SR 20 mg) given either separately or in combination in three groups of hypertensive patients. Each treatment was administered twice daily. The fixed combination given twice daily for four weeks produced reductions in blood pressure which lasted for at least 12 h after administration of the last dose. The control of blood pressure by the combination was superior to that achieved by its individual components. Adverse effects normally associated with nifedipine were less frequent when it was given with atenolol. Compliance with treatment was good, but best when the drugs were given together rather than separately. A fixed combination of atenolol and nifedipine may prove useful in treating hypertensive patients inadequately controlled on beta-blocker therapy alone.
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  • 11
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    European journal of clinical pharmacology 35 (1988), S. 21-24 
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha-adrenergic blockade ; bioavailability ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mm Hg in the supine and 13/18 mm Hg in the standing position. Adverse effects were generally mild and of brief duration.
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  • 12
    ISSN: 1432-1041
    Keywords: metoprolol ; hydralazine ; hypertension ; pregnancy ; pharmacokinetics ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the plasma concentrations levels of metoprolol after its twice daily administration in a dose of 50 mg for 4 days in ten, hypertensive pregnant women to the during monotherapy and in combination with 25 mg of hydralazine given twice daily. Hydralazine increased the median AUC and Cmax of metoprolol by 38% and 88% respectively, and decreased the tmax from 1.5 h to 1.0 h. Hydralazine had no effect on the plasma concentrations of alpha-OH-metoprolol. These results suggest that the effect of hydralazine on metoprolol plasma concentrations is primarily due to a reduction in first-pass elimination.
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  • 13
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    European journal of clinical pharmacology 35 (1988), S. 431-432 
    ISSN: 1432-1041
    Keywords: rifampicin ; enalapril ; hypertension ; drug interaction ; case report
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary When a 35-year-old man with essential hypertension was treated with antibiotics for brucellosis his blood pressure rose significantly. While all other treatment was kept constant rifampicin was discontinued. On rechallenge rifampicin did not alter serum concentrations of enalapril or the area under the curve (AUC) between 0 and 7 h, but it did reduce the AUC of the active metabolite enalaprilat by 31%. These observations suggest that there may be an interaction between rifampicin and enalapril, causing reduced hypotensive efficacy of enalapril. The mechanism of such an interaction merits further study, but it could be due to enhanced renal clearance of enalaprilat.
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  • 14
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    European journal of clinical pharmacology 33 (1987), S. 119-126 
    ISSN: 1432-1041
    Keywords: hypertension ; nicardipine ; propranolol ; serum lipids ; electrocardiogram ; side-effects ; ECG changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind controlled trial 22 patients with mild or moderate essential hypertension were treated with nicardipine 30 mg t.d.s. and 19 patients with propranolol 80 mg t.d.s. as monotherapy for 24 weeks. Blood pressure in both groups at the end of trial was equally and significantly reduced; systolic pressure 22.2 mmHg and diastolic pressure 15.5 mmHg in the supine position, and 24.4 mmHg and 18.4 mmHg, respectively, in the standing position in those on nicardipine, and by 23.7 and 16.2 mmHg and 28.0 and 19.2 mmHg, respectively, in the propranolol group. There was an initial increase in heart rate in the nicardipine group, but the rise was only moderate (3 beats/min supine p=0.3219, and 7 beats/min standing, p=0.0203) at the end of the 24 weeks. In the propranolol group heart rate was reduced markedly. Adverse effects occurred in 77% of patients on nicardipine and in 63% of those on propranolol, and there were no unexpected findings. The effects were mild in both groups and did not lead any patient to stop medication. One patient on propranolol was withdrawn from the trial because of poor blood pressure control and suspected angina pectoris after 5 weeks on active medication. There were no significant changes in blood chemistry, including lipoprotein classes. Overall, in comparison with propranolol, nicardipine was effective, well-tolerated and safe to use in the monotherapy of mild or moderate essential hypertension.
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  • 15
    ISSN: 1432-1041
    Keywords: muzolimine ; chlorthalidone ; hypertension ; serum electrolytes ; potassium ; ion transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous short-term studies of muzolimine (a diuretic with frusemide-like activity) had shown that it did not induce a significant change in the serum potassium concentration. In the present study sodium and potassium handling and other metabolic variables have been compared during 16 weeks of therapy with muzolimine and chlorthalidone, a thiazide-like diuretic. During muzolimine treatment, plasma and red cell potassium concentrations remained unchanged, while a significant fall in potassium occured with chlorthalidone. Neither drug affected the activity of sodium-potassium cotransport or sodium-lithium countertransport in red cells in vitro. Muzolimine and chlorthalidone had similar effects on arterial pressure and on the other metabolic variables tested.
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  • 16
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    European journal of clinical pharmacology 33 (1988), S. 549-555 
    ISSN: 1432-1041
    Keywords: verapamil ; sustained release formulation ; hypertension ; renal disease ; kidney function ; angiotensin II ; aldosterone ; arginine vasopressin ; atrial natriuretic peptide ; lipids and lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory and casual blood pressure readings plasma, angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, creatinine clearance, plasma lipids and lipoproteins, and body weight were determined after consecutive 3-week periods on placebo and sustained release verapamil 240 mg/day. Verapamil reduced the mean 24-h ambulatory blood pressure from 152/104 to 142/97 mm Hg. Blood pressure was significantly reduced during the daytime and the evening, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were found in the hormones, creatinine clearance, plasma lipids and lipoproteins, heart rate or body weight. The atrial natriuretic peptide level was significantly correlated with the calculated creatinine clearance (r=−0.797). Thus, sustained release verapamil 240 mg as a single daily dose had a moderate hypotensive effect in patients with chronic renal disease without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increasing body weight, and without altering renal function and plasma lipids and lipoproteins. The negative correlation between atrial natriuretic peptide and glomerular filtration rate supports the hypothesis that the extracellular volume increases during progression of renal disease.
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  • 17
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; hydrochlorothiazide ; hypertension ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained ≥95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective ‘calcium antagonist’ felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metroprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if ‘control’ of BP (dBP 〈90 mmHg) was not achieved on the initial doses. Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose. Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.
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  • 18
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    European journal of clinical pharmacology 34 (1988), S. 61-65 
    ISSN: 1432-1041
    Keywords: lisinopril ; renal failure ; half-life ; drug dose ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of lisinopril was studied after administration of single and multiple doses of 5 mg to hypertensive patients with normal and impaired renal function. In patients with severe renal failure the peak concentrations were higher, the decline in serum concentration was slower and the time to peak concentration was extended. Accumulation of lisinopril was highly correlated with the creatinine clearance. The effective half-life was doubled and tripled in patients with mild and severe renal impairment, respectively, as compared to patients with a normal renal function. Lisinopril lowered blood pressure in all three groups over 24 h. It is suggested that smaller doses of lisinopril should be administered to patients with severe renal failure.
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  • 19
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; elderly patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The α1-adrenoceptor antagonist doxazosin has been compared with placebo in 40 elderly hypertensive patients (mean age 71.4 years). At the end of 10 weeks once daily treatment with doxazosin the mean 24-h post-dose changes in standing and supine blood pressure compared with placebo were −6.9/−5.6 mmHg (systolic/diastolic) and −6.2/−5.5 mmHg respectively. The reductions in standing and supine diastolic blood pressures were statistically significant compared with placebo. At the end of treatment steady-state pharmacokinetics were evaluated in 18 patients. The plasma elimination half-life during the dose interval in these patients was 16.1 h (range 10.1–27.1 h) and the median time to peak plasma concentration was 3 h (range 1–4 h). One patient was withdrawn because of adverse effects (headache, weakness, and sweating) during doxazosin treatment. Once daily doxazosin reduced diastolic blood pressure and was well tolerated in these elderly hypertensive patients.
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  • 20
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    European journal of clinical pharmacology 35 (1988), S. 571-572 
    ISSN: 1432-1041
    Keywords: cadralazine ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 21
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; combination therapy ; diuretic ; beta-adrenergic blocker ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of ketanserin 40 mg b.d. in combination with a beta-adrenergic blocking agent or a diuretic was assessed in an open study in 35 patients with essential hypertension, who had not responded to treatment with beta-blockers, diuretics or their combination. The ketanserin/beta-blocker combination decreased mean sitting systolic/diastolic blood pressure (SBP/DBP) from 169/107 mm Hg to 156/91 mm Hg at the end of the 12-week active treatment period. The decrease in systolic blood pressure was significant only at Week 8, while the decrease in diastolic blood pressure was highly significant at all times. A significant reduction in heart rate by 10 beats·min−1 was observed with the ketanserin + β-blocker combination. The ketanserin/diuretic combination led to a significant reduction in mean SBP/DBP from 164/106 mm Hg to 146/92 mm Hg after 12 weeks, with no significant change in heart rate. Body weight slightly increased in both groups. There were significantly fewer adverse reactions with the ketanserin/diuretic combination than with the ketanserin/beta-blocker combination. The results indicate a potentially useful therapeutic role for ketanserin in combination with beta-blockers or diuretics.
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  • 22
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; tolerability ; exercise ; once-daily dosing ; controlled-release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily, was compared with conventional metoprolol tablets, 100 mg once daily, in 27 patients with primary hypertension. Exercise tests on a bicycle ergometer were undertaken 24 h after intake of the last dose of the drug following a four-week placebo run-in period and after four weeks of active treatment. Heart rate, measured in the supine position and during exercise at the highest comparable workload, was reduced significantly more by metoprolol CR (p〈0.05), thus indicating a higher degree of β1-blockade at the end of the dose interval with metoprolol CR. There was a greater reduction in supine systolic pressure (p〈0.05) but not in supine diastolic pressure after metoprolol CR than after conventional tablets at 24 h. There was no significant difference between the two groups with respect to reduction in systolic blood pressure during exercise. The 24-h plasma concentrations of metoprolol CR and conventional tablets correlated with the effects on heart rate, but not with blood pressure. The tolerability of metoprolol CR was comparable with that of metoprolol administered as conventional tablets. In conclusion, there was significantly greater β1-blockade 24 h after the intake of drug after metoprolol CR compared with conventional tablets.
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  • 23
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    European journal of clinical pharmacology 34 (1988), S. 125-128 
    ISSN: 1432-1041
    Keywords: celiprolol ; acebutolol ; hypertension ; beta-blockers ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of the new cardioselective beta-blocker celiprolol and acebutolol have been compared. Thirty patients with arterial hypertension WHO Grade I–II were treated in a double-blind fashion with celiprolol or acebutolol. Before starting the treatment and on Days 15 and 29, before the morning dose, blood samples were taken for measurement of the plasma level of celiprolol. At the same times physical examinations, and clinical and urine chemistry analyses were performed. At the 99% probability level both drugs had significantly lowered the systolic and diastolic blood pressures to normal values at the end of the second and fourth weeks. There was no significant difference between their antihypertensive efficacy. The decrease in diastolic blood pressure at the end of the second week was significantly correlated with the reciprocal of the plasma celiprolol concentration at steady-state at the end of the dosage interval.
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  • 24
    ISSN: 1432-1041
    Keywords: dilevalol ; hypertension ; labetolol R-R-isomer ; renal function ; plasma renin activity ; plasma aldosterone ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of oral dilevalol (an R, R-isomer of labetalol), a new β-adrenoceptor blocker with β2-receptor stimulating and α-recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks. Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study. Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA. The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects.
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  • 25
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    European journal of clinical pharmacology 35 (1988), S. 25-30 
    ISSN: 1432-1041
    Keywords: alfuzosin ; alpha1-adrenoceptor blockers ; hypertension ; adverse reactions ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week runin placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was 〉90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypothensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml. Nine of the 11 patients reached the end-point (supine diastolic BP≤90 mm Hg) at the end of 28 days: 1 at the dose of 5 mg b.d., 6 at 10 mg b.d. and 2 at 20 mg q.i.d. At the high dose they both complained of palpitations. Two other patients complained of mild and transient palpitations at lower doses.
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  • 26
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; obesity ; betaendorphin ; ACTH ; cortisol ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of alpha2-adrenoceptor stimulation by clonidine on the secretion of beta-endorphin, ACTH, and cortisol in essential hypertension and obesity was studied in 45 subjects: 15 non-obese hypertensives, 10 obese hypertensives, 11 obese normotensives, and 9 healthy subjects. The circadian rhythm of plasma beta-endorphin, ACTH, and cortisol was determined after placebo and after three days on clonidine 0.45 mg daily. Clonidine lowered the blood pressure and blood ACTH and cortisol levels in all the subjects. A significant decrease in beta-endorphin after clonidine occurred in the healthy subjects. In obese normotensives basal beta-endorphin concentrations were significantly higher than in healthy subjects and did not change after clonidine. In about 50% of non-obese and obese hypertensives a significant increase in beta-endorphin secretion after clonidine was noted (responders). In the subgroup of non-obese hypertensive responders no circadian rhythm of beta-endorphin was observed. The results suggest that adrenergic regulation of beta-endorphin secretion is altered in obesity and in certain patients with essential hypertension.
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  • 27
    ISSN: 1432-1041
    Keywords: ritanserin ; hypertension ; serotonin ; (5 HT) ; blood pressure ; platelet aggregation ; QT interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have given the selective 5 HT2 antagonist ritanserin in a dose of 10 mg twice daily for 4 weeks in a double-blind, randomized, placebocontrolled, parallel group study of 18 patients with untreated essential hypertension. The fall in single platelet count due to 5 HT-induced platelet aggregation was significantly reduced by ritanserin compared with placebo (p〈0.05). There were no significant changes in supine or erect blood pressure or heart rate after ritanserin compared to placebo. Forearm blood flow, measured by mercury-in-strain gauge venous occlusion plethysmography, was not significantly altered by ritanserin. Ritanserin caused prolongation of the QTc interval by 41 (SEM 11) ms (p〈0.05 compared to placebo) but had no detectable effect on QRS duration, features suggestive of Class III antiarrhythmic activity. These findings do not support an independent role of the 5 HT2 receptor in maintaining raised arterial pressure in essential hypertension.
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  • 28
    ISSN: 1432-1041
    Keywords: aldosterone ; DA2-receptor ; co-dergocrine ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study we have investigated the effect of co-dergocrine, a selective DA2-agonist, on plasma aldosterone concentrations (PAC) in twelve patients with essential hypertension both in basal conditions and during sodium depletion. Sodium depletion resulted in an increase of PAC from 38 (13) pg/ml to 297 (21) pg/ml. The PAC response to sodium depletion was reduced to 155 (29) pg/ml by co-dergocrine. No significant PAC changes were found in patients maintained on a normal sodium intake. In addition the drug did not significantly modify plasma renin activity (PRA) in either experimental group. These results suggest that the dopaminergic inhibition of aldosterone secretion in man is mediated by DA2-receptors in the adrenal cortex.
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  • 29
    ISSN: 1432-1041
    Keywords: ramipril ; renal insufficiency ; hypertension ; pharmacokinetics ; ramiprilat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1–2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5–15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15–40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40–80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex. The study indicates that in patients with severe renal insufficiency (creatinine clearance below 30 ml/min) smaller doses of ramipril are required than in patients with normal or borderline renal function.
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  • 30
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    European journal of clinical pharmacology 36 (1989), S. 575-578 
    ISSN: 1432-1041
    Keywords: bunazosin ; hypertension ; alpha1-adrenoceptor blocker ; blood pressure ; renal blood flow ; renal function ; renin ; aldosterone ; atrial natriuretic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal and hormonal effects of the α1-adrenoceptor blocker bunazosin were examined in 6 patients with essential hypertension. Oral bunazosin for 4 to 12 weeks significantly decreased mean blood pressure by 10%, increased effective renal blood flow and creatinine clearance by 34% and 37%, respectively, the plasma norepinephrine concentration was elevated by 60%, and the plasma atrial natriuretic peptide level was lowered by 22%. The plasma renin activity and aldosterone concentration were unchanged. Thus, a moderate reduction in blood pressure was produced by bunazosin treatment while maintaining renal perfusion.
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  • 31
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; atenolol ; hypertension ; exercise ; pharmacokinetics ; adverse effects ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure ≥95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.
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  • 32
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    European journal of clinical pharmacology 31 (1986), S. 155-163 
    ISSN: 1432-1041
    Keywords: hypertension ; verapamil ; norverapamil ; pharmacokinetics ; dosing frequency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve hypertensive patients (WHO Stage I-II) were given oral verapamil (Isoptin) b.d. or t.d.s. as long-term treatment. The pharmacokinetics of verapamil and norverapamil were studied both after single and b.d. and t.d.s. doses of verapamil 240, 360 or 480 mg daily adjusted according to the blood pressure response. The apparent oral clearance of verapamil was decreased after both the twice and thrice daily dosage regimens (1.38 and 1.841/min, respectively) as compared to the single dose (4.39 l/min). The plasma half-life of verapamil was increased from 3.34 h (single dose) to 4.65 h (b.i.d.). Decreased elimination of norverapamil was also found after multiple doses of verapamil, as shown by an increase in the adjusted AUC of norverapamil (adjusted to a verapamil dose of 80 mg), namely from 574.9 h·ng·ml−1 (single dose) to 1172 h·ng·ml−1 (b.d.) and to 841 h·ng·ml−1 (t.d.s.). The plasma half-life of norverapamil increase from 5.68 h to 7.34 h during twice daily dosing. During thrice daily verapamil, no increase in plasma half-life was found either for verapamil or norverapamil, probably due to the relatively short sampling time (6 h). The plasma concentration of verapamil and the reduction in supine systolic and diastolic blood pressure were correlated. The mean decrease in supine systolic blood pressure was 5.8 mm Hg per 100 ng verapamil/ml plasma, and for diastolic pressure 2.9 mm Hg per 100 ng verapamil/ml plasma. The mean steadystate plasma concentrations of verapamil were similar after twice and thrice daily dosing regimens, which agrees with the clinical observation that blood pressure control in hypertensive patients is as good after verapamil b.d. and t.d.s.
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  • 33
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    European journal of clinical pharmacology 31 (1986), S. 227-229 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; hypotensive therapy ; hypertensive emergency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-eight severely hypertensive patients were treated with oral clonidine. Each patient received a “loading” dose of 0.2 mg clonidine, followed by 0.1 mg hourly until the blood pressure was substantially reduced, or until a total dose of 0.8 mg has been administered. Thirty-five (82.1%) patients responded favourably, with a reduction in the systolic blood pressure in the supine position from 210±20 to 145±20 and to 98±15 mmHg diastolic after 6 hours. The average dose of clonidine was 0.5 mg. Side-effects were minimal. The study has shown that oral clonidine given in a “loading” dose is safe and effective in the management of patients with hypertensive emergencies, and it may have an advantage over other antihypertensive drugs administered parenterally.
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  • 34
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    European journal of clinical pharmacology 18 (1980), S. 321-326 
    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
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  • 35
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    European journal of clinical pharmacology 19 (1981), S. 19-24 
    ISSN: 1432-1041
    Keywords: hypertension ; guanfacine ; central antihypertensives ; withdrawal ; catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1. Guanfacine (2–6 mg/day) a centrally acting antihypertensive drug, was effective in controlling blood pressure in 5 essential hypertensives and lowered plasma noradrenaline and urinary catecholamine excretion. 2. Withdrawal of guanfacine by blind substitution of identical placebo tablets under observation in hospital led to a gradual recovery of blood pressure over 2–4 days. 3. Salivary flow, which was reduced on guanfacine, returned to pretreatment levels by 2 days after withdrawal and significantly exceeded control for the next two days. 4. Urinary catecholamine excretion returned to pretreatment levels by 3 days but did not exceed control levels during the period of study. 5. Plasma noradrenaline returned gradually to pretreatment levels, and by day 4 significantly exceeded them. 6. No patient experienced symptoms suggesting catecholamine excess although four out of five reported a headache from the second day onwards. 7. Guanfacine, a centrally acting drug which pharmacologically resembles clonidine, has a slow offset of hypotensive effect over 2–3 days. Symptoms or biochemical evidence of catecholamine excess were not encountered within 48 h of withdrawal, possibly reflecting the longer duration of action and plasma half-life of guanfacine.
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  • 36
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    European journal of clinical pharmacology 18 (1980), S. 225-229 
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; slow-release preparations ; maximal exercise power ; fatigue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The treatment of hypertension with a single daily-dose of a beta-blocker gives rise to high peak-plasma concentrations 1.5 h after ingestion. After slow release-preparations of beta-blockers, the peak concentrations are half those produced by the conventional preparation at the same oral dose. A frequently occurring side-effect of beta-blocker therapy is fatigue. In this study the effect of a single dose of metoprolol 300 mg, 200 mg, 200 mg slow-release and a placebo on maximal exercise power was tested in 6 healthy subjects, 1.5 h and 24 h after ingestion. Maximal exercise power was significantly reduced 1.5 h after ingestion of metoprolol 300 mg and 200 mg. No change was found 1.5 h after 200 mg of a slow-release preparation. The possible reasons for reduced maximal exercise power are discussed. It is concluded that use of a beta-blocker for the treatment of hypertension in a single daily-dose regimen may be a reason to prefer a slow-release preparation.
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  • 37
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    European journal of clinical pharmacology 18 (1980), S. 399-401 
    ISSN: 1432-1041
    Keywords: prazosin ; hypertension ; central monoaminergic neurons ; monoamine metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six hypertensive patients were treated with prazosin up to a final dose of 3–4.5 mg/day. There was a significant reduction of blood pressure. The cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline, dopamine and serotonin were unchanged. This indicates that the antihypertensive effect is not mediated via central monoaminergic neurons as suggested by animal studies.
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  • 38
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    European journal of clinical pharmacology 18 (1980), S. 105-108 
    ISSN: 1432-1041
    Keywords: renin ; angiotensin ; aldosterone ; hypertension ; hypoaldosteronism ; pseudohypoaldosteronism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is increased activity of the renin, angiotensin, aldosterone (RAA) system in infancy and childhood. An inverse relationship between plasma renin, aldosterone and age has been demonstrated. In childhood hypertension due to renovascular disease or pyelonephritic scarring peripheral plasma renin is increased. Renal vein renin measurements in children with renal hypertension have proved valuable in predicting surgical curability of the underlying lesion. The upper limit of normal for the renal venous renin ratio in normotensive children without renal disease is 1.5. Pharmacological blockade of the RAA system has a place in diagnosis and treatment of hypertensive children. The plasma renin aldosterone profile is diagnostically useful in the investigation of salt-wasting disease and can easily distinguish between aldosterone biosynthetic defects and pseudohypoaldosteronism.
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  • 39
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    European journal of clinical pharmacology 18 (1980), S. 135-139 
    ISSN: 1432-1041
    Keywords: hypertension ; labetalol ; propranolol ; renal haemodynamics ; glomerular filtration rate ; blood pressure ; exercise ; renal blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of exercise on renal haemodynamics was examined in young patients with mild essential hypertension. Four groups of subjects were studied: 13 normotensive, healthy control subjects, and 15 untreated, 11 propranolol-treated, and 6 labetalol-treated patients. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during four consecutive periods, a pre-exercise control period, two exercise periods with loads of 450 kpm/min and 600 kpm/min, respectively, and a post-exercise control period. In the untreated patients RPF and GFR were lower during exercise than in the normotensive control subjects, whereas no significant differences were found at rest. In the propranolol-treated patients the reduction in RPF and GFR during exercise was more pronounced than in the untreated hypertensives. In the labetalol-treated patients however, RPF and GFR were reduced only to the same degree as in the untreated hypertensives. The reduced renal blood flow in propranolol-treated patients may be attributed to a compensatory increase in sympathetic activity caused by an impaired cardiac response to exercise. The lack of reduction in renal blood flow during labetalol therapy could partly be related to alpha-adrenergic blockade in the renal vascular bed induced by labetalol, and partly to the smaller reduction in cardiac output during labetalol than during propranolol therapy.
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  • 40
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    European journal of clinical pharmacology 18 (1980), S. 231-235 
    ISSN: 1432-1041
    Keywords: molsidomine ; hypertension ; hypotension ; angina pectoris
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Molsidomine (M), a new long-lasting antianginal compound, was studied in 38 hypertensive patients to assess its antihypertensive properties. Six patients were selected for an acute, single dose comparative trial with placebo over 8 h after treatment. The remaining 32 patients were used in a 1 month trial to study the effect on BP of more prolonged treatment. Systolic, diastolic and mean BP were significantly reduced after a single dose of M 4 mg, and the effect lasted for about 8 h. M also inhibited the hypertensive response to isometric exercise in handgrip tests performed 1 and 8 h after M ingestion. A dose-related decrease in systolic and diastolic BP in the one month trial was also observed. In addition to its antianginal properties, M appears to possess an interesting effect on BP in mildly to moderately hypertensive patients. A fall in BP is also a valuable effect in coronary patients with augmented metabolic demands of the heart.
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  • 41
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; beta-adrenoceptor blockade ; hypotensive action ; adverse effects ; combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of nifedipine (10–20 mg t.i.d.) given alone, or in combination with a beta-adrenoceptor blocking drug, was related to the observed plasma concentration during one dosage interval at steady-state (Pl-Nifss). The study was carried out as a within-patient comparison of treatment with nifedipine or placebo for 4 weeks. A highly significant reduction in blood pressure was obtained during monotherapy, as well as during combined treatment. The blood pressure reduction when nifedipine was added to beta-adrenoceptor blockade was of the same magnitude as that observed on nifedipine monotherapy. A considerable variation in Pl-Nifss was noted (range: 2–70 ng/ml). No significant correlation was found between the percentage reduction in blood pressure and Pl-Nifss in either of the two groups. There was a close relationship between Pl-Nifss and the concentration found 4 h after the morning dose. Side-effects were common during nifedipine monotherapy and were the reason for discontinuation of treatment in 4 of 18 patients. In contrast, none of the 9 patients on combined treatment dropped-out. In neither of the treatment groups was there any evidence for sodium retention and volume expansion during the first 4 weeks expressed as weight gain or signs of cardiac insufficiency. However, in 13 patients who continued on long-term treatment for 3–14 months, a definite need for concomitant diuretic therapy was found. The results indicate that nifedipine is effective in lowering blood pressure in patients with mild to moderate essential hypertension, either when given alone or in addition to beta-adrenoceptor blockade. It appears best tolerated as combination therapy. Long-term treatment requires addition of a diuretic. Pl-Nifss did not seem to be a major determinant of the magnitude of the hypotensive response.
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  • 42
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    European journal of clinical pharmacology 18 (1980), S. 375-382 
    ISSN: 1432-1041
    Keywords: calcium antagonist ; verapamil ; hypertension ; vasodilators ; plasma renin activity ; mode of action ; sodium balance ; fluid balance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 12 in-patients with moderate uncomplicated hypertension, maintained on constant sodium intake for 15 days, single-blind oral administration of verapamil 80–160 mg t. i. d. for 10 days had a significant antihypertensive effect: in the supine position systolic blood pressure decreased from 177±5 to 150±3 mmHg, and diastolic pressure from 111±3 to 96±2 mmHg; standing values were similarly lowered from 171±7 to 143±4 mmHg, systolic, and from 118±4 to 97±2 mmHg, diastolic. The heart rate did not show any significant change (from 79±3 to 77±2 beats/min, supine, and from 92±3 to 87±3 beats/min, upright). The antihypertensive effect was uniform throughout the day, being similar 2, 3, 6 and 8 h after administration of a dose. Dynamic exercise (75–100 watts on a cycle-ergometer) caused identical increases in arterial pressure and heart rate on the last day of placebo and again on the last day with verapamil, but the peak levels of systolic pressure reached during exercise were lower after verapamil than with placebo, because of the lower blood pressure before exercise. Reduction of arterial pressure by verapamil was not accompanied by increased plasma renin activity, or by renal retention of sodium and water: there was a small increase in sodium excretion, at least during the first days of verapamil administration (from 107±15 to 113±15 mEq Na+/day), and a slight significant reduction in body weight (from 74.2±3.7 to 73.5±3.7 kg). It is concluded that oral administration of verapamil significantly lowers blood pressure without simultaneously inducing cardiac stimulation, renin secretion or salt and water retention.
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  • 43
    ISSN: 1432-1041
    Keywords: guanfacine ; methyldopa ; hypertension ; rebound hypertension ; withdrawal symptoms ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine patients with essential hypertension completed a clinical trial designed to study the effects and side effects of administration and withdrawal of guanfacine (2 mg tds) and methyldopa (250 mg tds) on blood pressure, heart rate, and plasma noradrenaline. The study was of randomised doubleblind crossover design with two active therapy phases of eight weeks each, preceded by an initial 4 week placebo phase, separated by an intermediate 2 week placebo phase, and followed by a final 2 week placebo phase. Patients took bendrofluazide 5 mgs daily throughout the entire trial, during both active and placebo periods. Each patient was admitted to hospital at the end of the 8 week active treatment phases, so that the effects of drug withdrawal on blood pressure, heart rate, plasma noradrenaline and side reactions, could be closely observed and monitored. The main conclusions from analysis of the results were that: 1. The hypotensive efficacy of guanfacine and methyldopa was very similar in the doses used, each of the two drugs lowering the supine mean arterial pressure by about 15 mm Hg and the supine diastolic pressure by about 10 mm Hg. 2. The frequency of side effects was greater with guanfacine than with methyldopa. 3. There was no signficant early rebound phenomenon after withdrawal of either methyldopa or guanfacine. 4. There was tendency for the blood pressure to rise slowly and marginally above initial placebo values, 2 weeks after cessation of guanfacine treatment though this was not significant. It was however, accompanied by a significant increase in plasma noradrenaline at 2 weeks. This was not seen 2 weeks after cessation of methyldopa. There was no single incidence of worrying rebound hypertension or withdrawal symptoms either early or late in any patient following cessation of methyldopa or guanfacine.
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  • 44
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    European journal of clinical pharmacology 21 (1982), S. 287-291 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
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  • 45
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    European journal of clinical pharmacology 21 (1982), S. 363-367 
    ISSN: 1432-1041
    Keywords: labetalol ; clonidine ; hypertension ; dose titration ; bendrofluazide ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B (5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits until normotension was achieved, or intolerable side-effects occurred. The treatment with B and L or C was then continued in a cross-over fashion for two 6-week periods, with 3 week diuretic washouts and subsequent dose-titration periods between the treatment periods. At the end of B, the supine blood pressure (BP) was 156/101, and at the end of B + L and B + C it was 136/91 (p〈0.001) and 137/91 (p〈0.001), respectively, pooling the data from both periods. At the end of B, the standing BP was 155/115, and at the end of B + L and B + C 134/100 (p〈0.001) and 139/106 (p〈0.001), respectively. The mean daily doses required were L 476mg and C 0.335 mg. On a weight basis, labetalol had about 1/1400 of the potency of clonidine. 12 patients complained of tiredness and dry mouth on clonidine and 2 patients of unsteadiness on labetalol. Labetalol caused a psoriasiform rash on the hands in one patient and limb weakness in one patient.
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  • 46
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    European journal of clinical pharmacology 22 (1982), S. 7-14 
    ISSN: 1432-1041
    Keywords: prazosin ; baroreflexes ; hypertension ; reflex tachycardia ; alpha adrenergic blockade ; dopamine-beta-hydroxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prazosin is a post synaptic alpha adrenergic blocker effective in hypertension, whose hypotensive effect is unaccompanied by reflex tachycardia or hyperreninemia, nor by other evidence of increased sympathetic activity. We studied the baroreceptor reflex arc as a potential mediator of these effects. Twenty-two essential hypertensive men were treated with prazosin alone versus placebo, and experienced a blood pressure fall (from 114.8±3.6 down to 101.1±2.5 mm Hg,p〈0.005) unaccompanied by any change in heart rate, plasma renin activity, or several other indices of sympathetic nervous system activity (plasma dopamine-β-hydroxylase activity; urinary excretion of free catecholamines and vanillyl mandelic acid; allp〉0.1). Concomitant with the blood pressure fall, there was a significant depression of baroreflex arc sensitivity, from 11.4±2.0 ms/mmHg down to 6.6±1.9 ms/mmHg (p〈0.05), without an associated change in cardiac vagal inhibition (291.2±46.2 versus 300.3±19.2 ms,p〉0.1). Baroreflex arc sensitivity depression may in part explain the lack of reflex sympathetic outflow noted during prazosin treatment of hypertension.
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  • 47
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    European journal of clinical pharmacology 22 (1982), S. 197-201 
    ISSN: 1432-1041
    Keywords: hypertension ; oxprenolol ; indomethacin ; drug interaction ; hypotensive effect
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double-blind, cross-over study in 16 patients with essential hypertension was carried out, to evaluate any possible interference by indomethacin, a known prostaglandin-synthetase inhibitor, with the antihypertensive effect of oxprenolol, a non-selective beta-adrenoceptor blocking agent. Both indomethacin and oxprenolol, as well as the two drugs combined, inhibited plasma renin activity; no change was found in urinary sodium excretion or body weight. Oxprenolol alone caused a highly significant decrease in the systolic (−10.4 mmHg,p〈0.001), diastolic (−7.4 mmHg,p〈0.001) and mean (−7.7 mmHg,p〈0.01) blood pressures, whereas indomethacin did not influence blood pressure. When the two drugs were given in combination, blood pressure decreased (systolic: −5.9 mmHg; diastolic: −4.0 mmHg; mean: −4.6 mmHg), but the changes induced in blood pressure were reduced by about 50% when compared with those in the oxprenolol alone period. The data show that indomethacin seems to interfere with the antihypertensive effect of oxprenolol, by an action which may be due to the inhibition of prostaglandin synthesis.
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  • 48
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    European journal of clinical pharmacology 20 (1981), S. 163-168 
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; cardiac output ; extracellular fluid volume ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril 450 mg/day for 4 weeks on blood pressure, heart rate, cardiac output and extracellular fluid volume were compared in severe, often drug-resistant hypertension (n=23), mild to moderate hypertension associated with renal artery stenosis (n=10) and mild to moderate essential hypertension (n=20). Plasma renin in the three groups was 52±19, 58±17 and 20±4 µU/ml (mean ± SEM), respectively. Blood pressure fell by 18±4%, 21±2% and 18±1%. The pressure drop was mainly due to a fall in peripheral vascular resistance. Addition of the diuretic hydrochlorothiazide (25–100 mg/day) caused a further fall in resistance. Despite the vasodilator effect of captopril, reflex cardiostimulation and reactive fluid retention were not observed. In severe hypertension, captopril alone was more effective in lowering blood pressure than combined diuretic-betablocker-vasodilator therapy. Moreover, cardiac output in these patients was higher and resistance was lower after captopril than during combined treatment. Thus, captopril was capable of normalising the abnormal haemodynamic state in patients with essential hypertension, and in hypertension associated with renal artery stenosis. Despite marked differences in pre-treatment plasma renin, the effects of captopril on systemic haemodynamics were similar in all the patients.
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  • 49
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; haemodynamic effects ; renal plasma flow ; renal tubular function ; plasma renin activity ; aldosterone ; Ro 12-4713
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Selected cardiovascular and endocrine effects of the new oral vasodilator Ro 12-4713 have been evaluated in an acute single dose study. In five patients with essential hypertension, Ro 12-4713 caused a dose-dependent decrease in supine and upright blood pressure and an increase in heart rate. Initial effects occurred one to 2 h after drug ingestion and maximal effects were noted after five hours and persisted for at least 8 h. Blood pressure was normalized, and the antihypertensive and chronotropic effects persisted for 24 h after a dose of about 300 mg/1.73 m2. Plasma and urinary norepinephrine and plasma renin levels tended to be raised, whereas plasma and urinary epinephrine and plasma aldosterone did not change. Changes in supine heart rate were inversely correlated with changes in mean blood pressure (r=−0.60; P〈0.02), and positively with those in plasma norepinephrine (r=0.55; P〈0.05) and renin (r=0.62, P〈0.01); changes in supine plasma renin level were also inversely correlated with those in mean blood pressure (r=−0.65; P〈0.01), and positively with those in plasma norepinephrine (r=0.58; P〈0.05). 24 h-urinary sodium excretion was significantly (P〈0.001) decreased; it was positively correlated with mean blood pressure (r=0.51; P〈0.05) and inversely with supine plasma renin activity (r=−0.63; P〈0.01). In six normal subjects and six patients with essential hypertension, effective renal plasma flow and the renal clearance of sodium, potassium, calcium and uric acid were not significantly altered five hours after a dose of Ro 12-4713 of about 250 mg/1.73 m2; glomerular filtration rate tended to be slightly decreased, and filtration fraction was significantly (P〈0.05) reduced in the hypertensive patients. At the same time blood pressure was decreased and plasma norepinephrine (P〈0.01) and renin (ns) were slightly increased in both groups. Ro 12-4713 in a single oral dose of about 300 mg appeared to be a potent, long acting, hypotensive vasodilator.
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  • 50
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    European journal of clinical pharmacology 22 (1982), S. 495-499 
    ISSN: 1432-1041
    Keywords: hypertension ; cyclothiazide ; hydrochlorthiazide ; thiazide diuretics ; potassium-sparing diuretics ; saluretic effect ; hypokalaemia ; hyperuricaemia ; amiloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive, saluretic and hypokalaemic effects of a small dose of cyclothiazide (2.5 mg daily) were compared with those of a conventional dose of an hydrochlorthiazide-amiloride hydrochloride combination (50+5 mg daily). Both preparations were given to 13 patients with mild (WHO I) hypertension in a cross-over manner for six weeks, with an intervening wash-out phase of three weeks. The antihypertensive efficacy of cyclothiazide was well comparable to that of the hydrochlorthiazide-amiloride combination, although cyclothiazide tended to inhibit renal sodium reabsorption less than the combination. Cyclothiazide tended to cause hypokalaemia, apparently due to increased potassium loss, but with the present dosage none of the 13 patients developed marked hypokalaemia (serum potassium less than 3.3 mmol/l). Both drugs led to a comparable increase in serum urate concentration. Neither of the preparations affected creatinine or free-water clearance. The results suggest that even in relatively small doses thiazides effectively decrease blood pressure, and combining thiazides with potassium-sparing diuretics is advantageous only in patients with marked hypokalaemia and its associated risks.
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  • 51
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    European journal of clinical pharmacology 24 (1983), S. 157-161 
    ISSN: 1432-1041
    Keywords: hypertension ; cadralazine ; single dose ; dose response curve ; hypotensive action ; prolonged effect ; side effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cadralazine (ISF 2469) was administered to 24 hypertensive patients in single oral doses of 7.5, 10, 15, 20 and 30 mg, according to a single-blind, placebo-controlled, within-patient change-over design. The study was done in 2 stages: in the first a range including the upper and lower doses was studied (7.5, 15, 30 mg and placebo), and in the second the range of doses was restricted (10, 15, 20 mg and placebo). The drug produced a significant decrease in blood pressure in the supine and standing positions. The decrease became clinically important starting from the 15 mg dose. Its action was still significant 12 h after administration. A significant increase in heart rate was also observed. All the effects were correlated with the dose. Side effects occurred mainly after the 30 mg dose. Thus, cadralazine, in a single oral dose in man, showed good antihypertensive activity starting from the 15 mg dose, and its effect was dose-related, slow in onset and long-lasting.
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  • 52
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    European journal of clinical pharmacology 24 (1983), S. 217-220 
    ISSN: 1432-1041
    Keywords: metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
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  • 53
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    European journal of clinical pharmacology 24 (1983), S. 307-314 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; blood pressure ; heart rate ; renal clearance ; plasma renin activity ; plasma aldosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of endralazine, a new antihypertensive hydrazinopyridazine derivative, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), effective renal plasma flow (CPAH), urine volume (V), the clearance of Na, K, urea (Ur) and uric acid (UA), plasma renin activity (PRA) and plasma aldosterone (PA) were studied in hypertensive patients after a single oral dose of 10–15 mg, and after 8–17 days of treatment with daily doses of 15–90 mg. In the acute experiments, heart rate increased by 27%, mBP decreased on average by 17% and GFR by 33% and CPAH fell by only 5%. Urine volume and electrolyte clearance were also depressed. There was a significant increase in PRA and PA. The fall in GFR correlated directly with mBP, CPAH and the product (mBP×CPAH). The logarithms of the Na clearance and V were correlated with GFR and mBP. The logarithms of the fractional excretion of Na and water also correlated with mBP, suggesting that tubular reabsorption of sodium and water may be affected by change in mBP. The fractional potassium excretion correlated directly with CPAH and ln PA. In contrast, on sustained daily treatment, mBP was less depressed (9%), but GFR increased strikingly by 27% and CPAH by 46%. The body weight increased by 4.5% as a consequence of salt and water retention. GFR was correlated with CPAH, the product (mBP×CPAH) and the increase in body weight. Thus, the improvement in GFR and effective renal plasma flow observed under these conditions may be due, in part, to volume expansion. However, a direct renal vasodilating effect of the drug appears to be the more important determinant.
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  • 54
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    European journal of clinical pharmacology 24 (1983), S. 579-583 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; baroreflex ; vascular reactivity ; heart rate ; blood pressure change
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic treatment with indapamide on blood pressure (BP), baroreceptor sensitivity (BRS) and vascular reactivity (VR) were investigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135±6 to 112±2 mmHg (p〈0.001); the heart rate (HR) had not changed, VR had decreased from 6.1±1.2 to 4.8±1.8 (pg·min·kg)−1 (p〈0.05), and BRS had increased from 8.3±3.7 to 12.2±5.3 ms/mmHg (p〈0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r=0.59; p〈0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations.
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  • 55
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    European journal of clinical pharmacology 25 (1983), S. 143-144 
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; plasma concentration ; blood pressure response
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  • 56
    ISSN: 1432-1041
    Keywords: furosemide ; hypertension ; plasma renin activity ; plasma adrenaline ; plasma noradrenaline ; body fluid loss ; diuretic response
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and ∼65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.
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  • 57
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    European journal of clinical pharmacology 25 (1983), S. 307-312 
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
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  • 58
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    European journal of clinical pharmacology 25 (1983), S. 571-575 
    ISSN: 1432-1041
    Keywords: beta-blocker ; felodipine ; calcium antagonist ; hypertension ; vasodilator ; side effects ; plasma levels ; metoprolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, cross-over trial, 10 men with primary hypertension, not adequately controlled with a β-blocker alone, were also given felodipine or placebo for periods of one week. Placebo was administered single-blind for 2 weeks and 1 week, respectively, before randomization and between treatments. The dose of felodipine ranged from 6.25 mg to 25 mg. The addition of felodipine resulted in a pronounced (20%), statistically significant reduction in blood pressure (BP) and a small but significant increase in heart rate (HR). The effects were seen within 1–2 h and were maximal after 3–4 h. During steady state treatment the duration of BP reduction was at least 12 h. No orthostatic reaction was seen. There was a significant correlation between the plasma concentration of felodipine and change in BP. The most frequently reported side-effects were headache and ankle oedema, the latter probably being due to pronounced pre-capillary vasodilatation. There was no weight increase and thus no indication of general water retention. No clinically significant change in laboratory variables and no influence on the P-Q time were seen. Thus, felodipine in combination with a β-blocker seems to be a useful addition to the treatment of hypertensive patients whose BP is not adequately controlled with a β-blocker alone.
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  • 59
    ISSN: 1432-1041
    Keywords: prizidilol ; hypertension ; exercise test ; beta-blockade ; vasodilatation ; haemodynamic effects ; vascular tone ; muscle blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fourteen men with moderately severe essential hypertension were treated with prizidilol hydrochloride 400–700 mg once daily (mean±S.D. 612±56 mg/day). The study was open and ambulatory, with an initial placebo period followed by dose titration of prizidilol. Prior to treatment and during optimal control of blood pressure cardiovascular adaptation was examined in a submaximal exercise test. Plethysomographic assessment of vascular flow, resistance and tone in the calf musculature during supine rest and during maximal vasodilatation was also performed. A highly significant reduction in systolic (from 164±4.5 to 141±2.7 mmHg; p〈0.001) and diastolic blood pressure (from 105±1.6 to 87±1.3 mmHg; p〈0.001) at supine rest was noted during therapy with prizidilol. There was no significant change in heart rate. Systolic pressure in the standing position was reduced (from 159±4.2 to 139±2.9 mmHg; p〈0.001) and so was the diastolic pressure (from 111±2.5 to 95±1.9 mmHg; p〈0.001). The heart rate in the standing position was significantly increased compared to supine rest in the placebo period and during optimal treatment with prizidilol. The β-adrenoceptor blocking properties of prizidilol were apparent as a reduction in the exercise-induced heart rate response at even the lowest work load. During prizidilol therapy an increase in resting calf muscle blood flow was found from 3.1±1.5 ml/min·100 ml to 4.3±2.1 ml/min·100 ml (p〈0.025). Vascular resistance and vascular tone were significantly reduced. No change regarding blood flow or resistance during maximal vasodilatation was noted. It is considered that prizidilol has a clear antihypertensive effect combining β-receptor blocking and vasodilator properties.
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  • 60
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    European journal of clinical pharmacology 26 (1984), S. 309-313 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 µg/kg to patients with essential hypertension (n=6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time — plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the antihypertensive effect was established. At a plasma clonidine concentration of 0.65±0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
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  • 61
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    European journal of clinical pharmacology 26 (1984), S. 331-334 
    ISSN: 1432-1041
    Keywords: metoprolol ; oxprenolol ; hypertension ; beta-blockers ; HDL-cholesterol ; intrinsic sympathomimetic activity ; cardioselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present study was to evaluate whether a reduction in HDL-cholesterol is peculiar to non cardioselective beta blockers or whether it is also produced by cardioselective beta1-blockers. 16 patients with primary arterial hypertension on a balanced isocaloric diet were given oxprenolol 120 to 240 mg/day or metoprolol 100 to 200 mg/day in a random cross-over study. No significant change was observed after either treatment in fasting blood glucose, serum total cholesterol and triglycerides. HDL-cholesterol concentration was significantly decreased on metoprolol, from 41 to 36 mg/dl (p〈0.05), while oxprenolol did not affect it at all. The difference might depend on intrinsic sympathomimetic activity which is possessed by oxprenolol and which metoprolol lacks.
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  • 62
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    European journal of clinical pharmacology 26 (1984), S. 549-553 
    ISSN: 1432-1041
    Keywords: pafenolol ; hypertension ; antihypertensive therapy ; beta1-blocking agent ; exercise tests ; plasma levels
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pafenolol, a new selective adrenergic beta1-blocking agent, has been tested for the first time in 6 hypertensive patients. After single oral doses of pafenolol 25 to 100 mg, there was a marked reduction in heart rate and systolic blood pressure during exercise tests. These effects were dose dependent. A significant positive correlation was found between the reduction in heart rate during exercise and the plasma level of pafenolol 5 hours after drug intake (correlation coefficient r=0.94). Side effects were mild and seemed to be dose dependent. It is concluded that this new beta1-blocking agent was effective in reducing blood pressure and was well tolerated.
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  • 63
    ISSN: 1432-1041
    Keywords: etozolin ; ozolinone ; furosemide ; hypertension ; renin ; catecholamines ; chronic renal failure ; steady state kinetics ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on urinary electrolyte excretion, renin release and plasma norepinephrine of single oral doses of 400 mg etozolin (E) and of 40 mg furosemide (F) were studied in hypertensive patients with normal (n=6) and impaired kidney function (n=6). E caused a marked saluresis up to 24 hours, showing its long duration of action. F, however, displayed a brief, brisk peak diuresis, followed by a rebound from the 4th to the 24th hours. The brisk peak diuresis induced by F was associated with pronounced release of renin, almost twice that induced by E. In chronic renal failure the renin release in relation to the magnitude of the diuresis was increased, i.e. the sensitivity of these patients to changes in water homeostasis was increased. E and F stimulated the sympathetic system to roughly the same extent. Patients with essential hypertension had higher plasma levels of norepinephrine than hypertensive patients with chronic renal failure. In addition, hypertensive patients with normal renal function (n=4) and varying degrees of renal impairment (n=11) were also given 400 mg daily for 2 weeks. Effects on blood pressure and electrolyte homeostasis were monitored, as well as the plasma kinetics of metabolite I, ozolinone. At the end of the 2 week treatment E had significantly lowered systolic (−12 mm Hg) and diastolic (−9 mm Hg) blood pressure, and had produced a significant loss of body weight, without altering plasma electrolytes or blood chemistry. There was no accumulation of the effective metabolite ozolinone under conditions of severe impairment of kidney function. It is concluded that E can effectively control high blood pressure in patients with normal and impaired kidney function. Its effective metabolite ozolinone did not accumulate in chronic renal failure.
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  • 64
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    European journal of clinical pharmacology 27 (1984), S. 397-405 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; cardiovascular reflexes ; diuretic effect ; blood pressure variability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.
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  • 65
    ISSN: 1432-1041
    Keywords: amiloride ; hydrochlorothiazide ; hypertension ; total body potassium ; plasma potassium ; renin-angiotensin-aldosterone system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After a run-in period of 8 weeks on a regimen of hydrochlorothiazide (HCT, median dosage 75 mg/day), patients with essential hypertension were randomly allocated to continued hydrochlorothiazide therapy (Group I) or additional treatment with amiloride (Group II, median dosage 15 mg/day, or 5 mg per 25 mg hydrochlorothiazide) for the following 12 weeks. Thereafter all the patients were changed to treatment with a fixed combination tablet containing 5 mg amiloride and 50 mg hydrochlorothiazide (Moduretic), keeping the thiazide dosage unchanged for an additional 12 weeks. In Group I patients there was no change in plasma potassium, total body potassium content or the renin-angiotensin-aldosterone system during the 12 weeks on HCT. When the treatment was changed to Moduretic, significant increases were found of 10% in plasma potassium and 3% in total body potassium content. No important stimulation of the renin-angiotensin-aldosterone system was found. In Group II patients addition of an average of 15 mg amiloride to the hydrochlorothiazide treatment led to significant increases in plasma potassium and total body potassium content of approximately 15% and 4%, respectively. There was also a significant increase in the plasma concentrations of renin, angiotensin II and aldosterone. Reducing the average dose of amiloride to 7.5 mg/day by use of Moduretic did not lead to decrease in plasma potassium or total body potassium content. Plasma concentrations of renin, angiotensin II, and aldosterone were decreased, but the individual changes varied markedly and no significant overall change was found.
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  • 66
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    European journal of clinical pharmacology 29 (1985), S. 207-210 
    ISSN: 1432-1041
    Keywords: metoclopramide ; enalapril ; aldosterone secretion ; dopamine receptors ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess if dopaminergic control of aldosterone secretion is mediated by the renin-angiotensin system, the effect of chronic angiotensin converting enzyme inhibition by enalapril on the aldosterone response to metoclopramide has been studied in 10 patients with mild to moderate essential hypertension. Enalapril reduced supine blood pressure and increased the heart rate significantly. Plasma renin activity and urinary sodium excretion rose significantly. PRA was not changed by metoclopramide, neither during placebo nor during enalapril treatment. Metoclopramide induced a two-fold increase in plasma aldosterone, the peak response being reached within 15 min. Enalapril treatment did not alter the aldosterone response to metoclopramide. Dopaminergic control of aldosterone secretion appears to be independent of the renin-angiotensin system.
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  • 67
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    European journal of clinical pharmacology 29 (1985), S. 215-219 
    ISSN: 1432-1041
    Keywords: penbutolol ; renal impairment ; beta-adrenoceptor blocking agents ; metabolism ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of penbutolol, its 4-hydroxylated metabolite and of their conjugates was studied in hypertensive patients with various degrees of renal impairment. A single oral dose of penbutolol 40 mg, was rapidly absorbed after a lag-time of 0.34 h. Its plasma concentration reached a maximum after 0.84 h and then declined bi-exponentially, with an apparent elimination half-life of 21.8 h. The hydroxylation of penbutolol was negligible and conjugation was of major importance for its elimination. Consequently, the kinetics of unchanged penbutolol were not altered by renal impairment. The 48 h-urinary excretion of penbutolol and its metabolites reached 13–14% of the administered dose, which is consistent with extensive metabolism of the drug. After treatment for 30 days with penbutolol 40 mg/d there was no accumulation of the parent drug but the concentration of its conjugates was increased. It is concluded that the dose of penbutolol need not be changed in patients with mild renal insufficiency, 4-hydroxypenbutolol is unlikely to participate in the anti-hypertensive effect of the drug, due to its low concentrations, and biotransformation of penbutolol may be enhanced during chronic treatment.
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  • 68
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    European journal of clinical pharmacology 30 (1986), S. 541-547 
    ISSN: 1432-1041
    Keywords: ramipril (HOE 498) ; hypertension ; angiotensin converting inhibition ; dose-response relationship ; time course
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of the blood pressure lowering effect and the dose-response relationship of the new angiotensin converting enzyme inhibitor ramipril (HOE 498) were studied in 8 patients with essential hypertension. As compared with placebo, a single oral dose of 2.5 mg ramipril lowered systolic and diastolic blood pressure. The antihypertensive action of single oral doses of 5, 7.5 and 10 mg ramipril was more pronounced. No change in heart rate occurred. Angiotensin converting enzyme activity was suppressed after all doses of ramipril studied. Plasma renin activity increased after 2.5 mg and 5 mg ramipril. Plasma aldosterone was not affected by 2.5 mg, but it fell after 5 mg ramipril. Thus, ramipril produced prolonged inhibition (more than 12 hours) of angiotensin converting enzyme activity and lowered blood pressure in patients with essential hypertension.
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  • 69
    ISSN: 1432-1041
    Keywords: hypertension ; hypertensive therapy ; drug utilization ; therapeutic traditions ; international differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A questionnaire survey based on hypertension case histories was performed among a representative sample of 400 GP's and hospital doctors in Northern Ireland, Norway and Sweden, countries having markedly different utilization of antihypertensive drugs. We found a greater propensity to start antihypertensive drug treatment in Northern Ireland than in Norway and Sweden. This was true both in mild diastolic and isolated systolic hypertension. Yet the utilization of antihypertensive drugs in Sweden is about 60% higher than in Northern Ireland and 30% higher than in Norway. Swedish physicians preferred beta-blockers as their first choice to a greater extent than physicians in Northern Ireland and Norway who selected thiazides more often. In general, the choice of drugs agreed with the sales and prescribing patterns in the three countries. Besides providing more insight in therapeutic traditions the study indicates that the lower prescribing of antihypertensive drugs in Northern Ireland, and to some extent in Norway, compared to Sweden, might be due to differences in true or apparent morbidity.
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  • 70
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    European journal of clinical pharmacology 29 (1985), S. 383-389 
    ISSN: 1432-1041
    Keywords: felodipine ; hypertension ; calcium antagonist ; vasodilator ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Felodipine, a selective arteriolar dilator, was given to 13 hypertensive patients to assess its hypotensive effects and duration of action. Nine patients were treated with 5 mg three times a day and 4 with 10 mg three times a day. Mean blood pressures fell with both treatment regimens: 5 mg placebo 170/103 mmHg; 5 mg felodipine 148/91 mmHg; 10 mg placebo 154/93 mmHg; 10 mg felodipine 137/82 mmHg. Heart rates increased as blood pressures fell with both treatments. However, in the patients given 5 mg three times a day this effect was less noticeable after successive doses. Plasma concentrations of noradrenaline, both resting and tilted, increased after felodipine. There was a negative correlation between the fall in blood pressure and the increase in noradrenaline, suggesting that those patients with good baroreceptor reflexes were better able to counteract the effects of vasodilatation. Four of the nine patients treated with 5 mg felodipine three times a day experienced mild and transient adverse effects. Of the four patients treated with 10 mg three times a day, three experienced moderate to severe headache, and for this reason recruitment into this group was stopped. Felodipine at a divided daily dose of 15 mg effectively lowered blood pressure.
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  • 71
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    European journal of clinical pharmacology 29 (1985), S. 395-399 
    ISSN: 1432-1041
    Keywords: Ro 31-1118 ; cardioselectivity ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with mild hypertension were given single oral doses of Ro 31-1118 (10, 20, 40, and 80 mg) and placebo in a randomized, double-blind, within-patient study. Plasma concentrations of Ro 31-1118 and supine, standing, exercise, and post-exercise heart rates and blood pressures were measured before and at regular intervals after drug administration. The pharmacokinetic data were consistent with a one-compartment model with first-order absorption and a variable time lag. Peak plasma concentrations and area under curve were linearly related to dose, whereas time to peak concentration, half-time, clearance and apparent volume of distribution were dose-independent. There was a reduction in exercise and post-exercise heart rate of approximately 10% after 10 mg and 20 mg Ro 31-1118, and of approximately 15% after 40 mg and 80 mg. At all doses standing systolic blood pressure was reduced by approximately 5%. A similar fall was seen in exercise and post-exercise systolic blood pressures. There was no substantial effect of Ro 31-1118 on supine or standing heart rates nor on diastolic blood pressure. No adverse effects were reported. It is concluded that Ro 31-1118 has linear pharmacokinetics over the dose range 10–80 mg, and has a weak antihypertensive effect when administered in single doses to patients with mild hypertension.
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  • 72
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    European journal of clinical pharmacology 29 (1985), S. 401-403 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; once daily dosing ; atenolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We report the first placebo controlled parallel group study of once daily endralazine (5–20 mg) in hypertension uncontrolled by a beta-blocker plus a diuretic. Following a 4-week run-in period 22 patients with a sitting mean arterial pressure (MAP) greater than 110 mm Hg were entered into the study and received either endralazine 5 mg or placebo. Blood pressure was measured 2 h and 24 h after dosing and the drug dose doubled at 2 and 4 weeks if the 24-h MAP remained 〉110 mg Hg. The final blood pressure assessment was made after 6 weeks treatment in the 19 patients who completed the study. Three patients withdrew from the study because of side effects. The hypotensive effect (sitting) was in excess of placebo at 2 h by 15.8 mm Hg systolic (NS), 15.4 mm Hg diastolic (p〈0.01), 15.5 mm Hg MAP (p〈0.02) and at 24 hours by 7.7 mm Hg systolic (NS), 8.9 mm Hg diastolic (p〈0.02) and 11.1 mm Hg MAP (p〈0.02). This study suggests that endralazine should be prescribed twice daily.
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  • 73
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    European journal of clinical pharmacology 30 (1986), S. 641-647 
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; vasodilators ; renal function and — haemodynamics ; beta-blockers ; guanidines ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and chronic effects of pinacidil on blood pressure (BP) and renal function were investigated in 10 patients with moderate arterial hypertension insufficiently controlled by chronic beta-blockade. Acute i. v. administration of pinacidil caused a significant fall in BP of 29.9/18.3 mm Hg and, despite beta-blockade, a concomitant rise in heart rate (HR) of 21%. Renal vascular resistance (RVR) showed a marked reduction as a consequence of the fall in BP, and a transient rise in renal plasma flow (RPF). Diuresis and renal clearance of sodium and uric acid showed a parallel fall. The excretion rates of albumin and β2-microglobulin were also significantly reduced. Pharmacokinetic studies indicated that glomerular filtration was responsible for elimination of the parent drug, and that proximal tubular secretion was the pathway of excretion of the main metabolite, pinacidil pyridine-N-oxide. During therapy for 4 months there was no further significant reduction in BP, despite increases in the daily dose of pinacidil. The effects on HR were less conspicious after 4 months; renal haemodynamic parameters and body weight were not significantly changed. The initial level of RVR and the initial acute reduction in this parameter appeared to be major determinants of the long-term BP response. The drug was well tolerated apart from one patient who developed slight fluid retention. However, concomitant administration of a diuretic will probably be necessary during routine use of this therapeutic combination.
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  • 74
    ISSN: 1432-1041
    Keywords: pinacidil ; hydralazine ; ambulatory blood pressure monitoring ; vasodilation ; hypertension ; diastolic blood pressure decrease ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Forty-three patients with mild essential hypertension were randomized into two double-blind studies: pinacidil vs. placebo or pinacidil vs. hydralazine. Pinacidil (62±18 mg/day) decreased office systolic and diastolic blood pressures from 145 to 137 mm Hg and from 98 to 89 mm Hg, respectively, after 6 weeks of therapy. Similarly, hydralazine (128±28 mg/day) reduced supine systolic blood pressure from 140 to 134 mm Hg and supine diastolic blood pressure from 93 mm Hg to 84 mm Hg. Significant tachycardia was not noted with either drug. Ambulatory blood pressure was monitored for 24 h during the placebo-washout and efficacy phases with both pinacidil and hydralazine. Mean 24-h blood pressure was 128 systolic and 81 diastolic with pinacidil and 121 systolic and 76 diastolic with hydralazine. Reduction in awake hypertensive diastolic blood pressure was significant for both pinacidil and hydralazine. Normal sleep diastolic blood pressure was not reduced by pinacidil but was reduced by hydralazine. Side-effects with both drugs included edema, headache, and palpitations. These data demonstrate that pinacidil is as effective an antihypertensive agent as hydralazine.
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  • 75
    ISSN: 1432-1041
    Keywords: milrinone ; renal impairment ; hypertension ; pharmacokinetics ; healthy subjects ; antihypertensive effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30–63 ml/min) and 7 patients with severe renal impairment (CRI II, creatinine clearance 9–29 ml/min). All except one of the patients with renal impairment had hypertension. The mean urinary recovery of milrinone was 82% in healthy subjects, the renal clearance was 288 ml/min and the plasma half-life (t1/2) was 0.94 h. In CRI the mean plasma t1/2 was prolonged (CRI I 1.78 h, CRI II 3.24 h). There was a significant linear relationship between creatinine clearance and the elimination rate constant, and between creatinine clearance and the renal clearance of milrinone. During the study day there was a tendency to a decrease in supine BP from 1 to 6–8 h after dosing, with the maximal decrease at 2–3 h (healthy subjects 118/71→107/56, CRI 159/95→136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2–6 h after dosing. Changes in BP and HR are difficult to evaluate since the study was not placebo-controlled. The plasma elimination rate of milrinone was decreased in CRI and dose adjustment may be necessary. Placebo-controlled studies of milrinone in hypertensive patients would be required to validate its possible antihypertensive effect.
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  • 76
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    European journal of clinical pharmacology 31 (1986), S. 505-506 
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; orthostatic hypotension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 77
    ISSN: 1432-1041
    Keywords: perindopril ; hypertension ; angiotensin converting enzyme inhibition ; renin-angiotensin system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the effects of treatment for one month with perindopril, 4 or 8 mg once daily, in seven hypertensive patients. Blood pressure was lowered from 164/93 mm Hg to 145/84 mm Hg by 4 mg of perindopril and after one month remained at 142/82 mm Hg. Neither postural hypotension nor tachycardia occurred. Inhibition of plasma angiotensin converting enzyme (ACE) lasting for over 24 h was achieved and there was a significant increase in plasma renin activity (PRA). Maximum plasma concentrations of the active metabolite of perindopril, S-9780, were detected four h after oral administration. After treatment for one month there was evidence of reduced sensitivity of plasma ACE to the action of the inhibitor. The plasma concentration of S-9780 required to produce 50% inhibition of plasma ACE rose from 2.4 ng · ml−1 following the first dose to 5.5 ng · ml−1 after one month.
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  • 78
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    European journal of clinical pharmacology 31 (1987), S. 553-557 
    ISSN: 1432-1041
    Keywords: ibuprofen ; diclofenac ; sulindac ; anti-inflammatory drugs ; hypertension ; NSAIDs ; hydrochlorothiazide ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open triple crossover study in 8 patients with essential hypertension, the possibility has been investigated of whether the blood pressure lowering effect of hydrochlorothiazide 50 mg once daily was attenuated by co-administration for 4 weeks of ibuprofen 400 mg t.i.d., diclofenac 25 mg t.i.d. or sulindac 200 mg b.i.d. Only a slight, statistically non-significant change was found, with the exception of a significant increase in systolic blood pressure after 4 weeks treatment with ibuprofen. There was considerable variation in the blood pressure response during treatment with all three NSAIDs, with slight rises in blood pressure in 13 out of 24 periods. Body weight increased significantly on treatment both with ibuprofen and diclofenac, whereas the increase on sulindac was less and was transient. No significant change was found in various biochemical parameters, including plasma electrolytes, plasma renin activity (PRA), aldosterone, albumin and creatinine, in haematocrit or in the 24-h urinary excretion of sodium and potassium. The sole exception was a decrease in PRA during ibuprofen treatment. From these observations it is concluded that ibuprofen and diclofenac differ from sulindac in their interaction with the diuretic action of hydrochlorothiazide. It appears that all three NSAIDs can safely be combined with hydrochlorothiazide in hypertensive patients, but blood pressure should be monitored carefully when an NSAID are added.
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  • 79
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    European journal of clinical pharmacology 29 (1986), S. 645-650 
    ISSN: 1432-1041
    Keywords: moxonidine ; prazosin ; hypertension ; intraindividual comparison ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty hypertensive outpatients were treated with moxonidine for 4 weeks in an intraindividual comparison study. After a wash-out period of at least 2 weeks the same patients were given prazosin for 4 weeks. The initial daily doses were 0.2 mg moxonidine and 1 mg prazosin. The antihypertensive dose was titrated individually until the diastolic blood pressure (BP) fell below 95 mm Hg. Within 3 days of dose titration, a mean dose of 0.37 mg moxonidine produced a significant decrease in BP from a mean of 184/100 to 155/90 mm Hg, while in prazosin treated patients 5 to 8 days were necessary to reduce the BP from 180/100 to 149/89 mm Hg; the mean prazosin dose was 2.8 mg. In addition to the lower dose of moxonidine compared to prazosin, it was found that in 67% of patients moxonidine was given once daily whilst prazosin was administered three-time daily in 73%. Within the first week of moxonidine treatment 14/30 patients experienced dryness of the mouth, but it was so mild that the patients did not want to discontinue the trial. In contrast, 3/30 patients discontinued therapy with prazosin because of side effects. The most frequent adverse effects of prazosin were orthostatic dysregulation in 6 patients, pain in the chest in 5, giddiness and tachycardia in 4 and nervousness in 3 patients; no patient had these complaints whilst on moxonidine. In intraindividual comparisons with moxonidine, efficacy, tolerance and the well-being of the patients were significantly better than when on prazosin.
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  • 80
    ISSN: 1432-1041
    Keywords: hypertension ; labetalol ; prazosin ; hydrochlorothiazide ; side-effects ; therapeutic efficacy ; atenolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After screening two local populations in the northern part of The Netherlands for hypertension, patients with a diastolic pressure (DP) between 95 and 120 mmHg were treated daily either with 50 mg hydrochlorothiazide or 100 mg atenolol. Non-responders were given the combination and if necessary the dose of atenolol was increased to 200 mg. Non-responders to the latter combination were randomized and treated either with 50 mg hydrochlorothiazide and labetalol or with 50 mg hydrochlorothiazide, 200 mg atenolol and prazosin. If after 1 month a DP≤90 mmHg had been reached the patient was reassessed after a further 3 months. If a DP〉90 mmHg was found the dose of labetalol or prazosin was increased and the patient was re-examined after 1 month. This protocol was followed until the maximum dose was reached or adverse reactions prevented a further increase in dosage. During 6 months of treatment there was a further drop in systolic and diastolic blood pressures under both regimens of, respectively, 8.6 and 2.4 mmHg for labetalol, and 7.7 and 5.0 mmHg for the prazosin group. At the end of the period the average daily doses of labetalol and prazosin were 1256 mg and 4.3 mg, respectively. There was no significant difference in the average number of complaints between the labetalol and the prazosin group.
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  • 81
    ISSN: 1432-1041
    Keywords: hypertension ; indenolol ; submaximal workload ; haemodynamic effects ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of indenolol on heart rate and blood pressure at rest and after submaximal workload has been studied in 19 patients with established essential hypertension. A stepwise increase from moderate to submaximal exercise was chosen to mimic challenges normally occurring in daily life. After 4 weeks of once a day indenolol therapy a significant, gradual reduction in the following cardiovascular parameters was observed: heart rate at rest fell by 20%, 30% after exercise and 31% after recovery; systolic blood pressure showed a fall of 15% at rest, 19% after workload and 14% after recovery; the reduction in diastolic blood pressure was 15% at rest, 11% after exercise and 12% after recovery. The rate-pressure product was decreased by 32% at rest, 43% after exercise and 42% after recovery. It is concluded that the most important pharmacological effect of indenolol is the significant decrease in myocardial oxygen demand. In patients with essential hypertension indenolol not only produces a definite antihypertensive effect, but it also increases workload tolerance and decreases subjective symptoms during physical activity. Compliance was good and no severe side effects were observed.
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  • 82
    ISSN: 1432-1041
    Keywords: prazosin ; alphamethyldopa ; lipoprotein ; hypertension ; blood lipids ; serum parameters ; hydrochlorothiazide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of prazosin and alphamethyldopa on blood lipids and lipoproteins were assessed in 20 patients with mild or moderate arterial hypertension. Parameters measured included serum cholesterol (CHO), triglycerides (TG), high density lipoprotein-cholesterol (HDL-CHO), insulin (I), glucose (G), and non-esterified fatty acids (NEFA). Prazosin — 4 mg/day for 6 weeks in hydrochlorothiazide-treated patients lowered blood pressure by 18.6/17.2 (systolic/diastolic pressure) mmHg. There was a significant decrease in CHO (−5.8%), in I (−16.5%), and in NEFA (−3.0%), and a significant increase in HDL-CHO (+15.5%). Alphamethyldopa 250–750 mg/day for 6 weeks in hydrochlorothiazide-treated patients lowered blood pressure by 18.8/14.6 (systolic/diastolic pressure) mmHg, accompanied by a non-significant decrease in CHO and TG, and significant increases in HDL-CHO (+10.3%), G (+8.5%) and NEFA (+6.4%). Thus, prazosin appears to have a more beneficial effect on blood lipids and lipoproteins than alphamethyldopa.
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  • 83
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    European journal of clinical pharmacology 28 (1985), S. 659-664 
    ISSN: 1432-1041
    Keywords: BTS 49465 ; hypertension ; pharmacokinetics ; blood pressure effect ; heart rate effect ; side-effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and haemodynamic effects of a 200 mg oral dose of BTS 49465 (7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) were investigated in a double-blind placebo controlled study. BTS 49465 was rapidly absorbed and cleared from the systemic circulation with a half-life of 1.6 h by oxidation to the sulphone metabolite. The metabolite was cleared with a half-life of 37.6 h. Saliva concentrations of both BTS 49465 and its metabolite correlated well with the plasma concentrations. Compared to placebo, BTS 49465 produced statistically significant reductions in blood pressure and increases in heart rate both supine and after a 60° head up tilt. The time course of the haemodynamic changes suggested that the sulphone metabolite contributed to the overall hypotensive response. Plasma Renin Activity was only marginally elevated and there was no evidence of acute fluid retention. BTS 49465 was well tolerated in terms of haematological and biochemical parameters and subjective side-effects.
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  • 84
    ISSN: 1432-1041
    Keywords: captopril ; hydrochlorothiazide ; hypertension ; vascular reactivity ; norepinephrine ; angiotensin II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on arterial pressure of incremental doses of norepinephrine (2 to 10 µg/min) and angiotensin II (50 to 800 ng/min) administered over 10 min periods was studied in sodium-replete hypertensive patients after crossover oral treatments with placebo, captopril 50 mg in a single dose, captopril 50 mg three times daily for one week and hydrochlorothiazide 50 mg daily for a week. Neither captopril nor hydrochlorothiazide affected the dose response to infusions of angiotensin II. In comparison to placebo responses, however, both single and multiple-dose captopril therapy, and hydrochlorothiazide attenuated the pressor responses to infusions of norepinephrine. Captopril significantly depressed angiotensin converting enzyme activity from predose levels and angiotensin II infusions significantly elevated plasma aldosterone concentrations. These results confirm findings reported for single dose captopril in normotensive volunteers and indicate that attenuation of the vascular responsiveness to sympathetic stimulation may contribute to the antihypertensive effects of captopril and hydrochlorothiazide therapy.
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  • 85
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    European journal of clinical pharmacology 28 (1985), S. 85-88 
    ISSN: 1432-1041
    Keywords: debrisoquine oxidation ; metoprolol metabolism ; oxidation phenotype ; β-blockade ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After a single 200 mg oral dose of metoprolol tartrate the mean metoprolol AUC was found to be six-fold higher in poor metabolizers (PMs) of debrisoquine than in extensive metabolizers (EMs). This was associated with impaired metabolic clearance via α-hydroxylation and O-dealkylation. A population study (n=143) has shown a bimodal distribution in the ratio of metoprolol: α-hydroxymetoprolol recovered in urine which was correlated highly with the debrisoquine metabolic ratio. Nine per cent of the population were PMs. Plasma metoprolol concentrations three hours after a 100 mg oral dose of metoprolol were greater than 200 ng/ml in PMs but were lower than this in most EMs. This dose of metoprolol given once daily provided a clinically significant reduction (16%) in exercise heart rate in PMs after 24 hours. EMs require conventional doses (100 mg b.d.) to achieve the same degree of β-blockade. Preliminary data from family studies support the view that the defect in metoprolol oxidation is inherited. In 12 hypertensive patients who were EMs we compared the β-blocking activity and antihypertensive effect of chronic treatment with metoprolol 200 mg once daily (conventional and long-acting formulations), with those of atenolol 100 mg once daily and placebo. The effects of all active preparations were similar at 3.5 hours but atenolol was superior to all metoprolol formulations at 24 hours after dosing. It is concluded that for the majority of patients metoprolol should be prescribed twice daily when using currently available dosage forms. Relationships between oxidation phenotype and side-effects should be examined.
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  • 86
    ISSN: 1432-1041
    Keywords: atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
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  • 87
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    European journal of clinical pharmacology 17 (1980), S. 239-241 
    ISSN: 1432-1041
    Keywords: timolol ; hypertension ; dose ranging ; double-blind trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine previously untreated patients with mild-moderate hypertension were included in a dose-ranging double-blind trial to determine the effectiveness of daily versus thrice daily timolol administration. In 8 patients control of blood pressure was equally effective though with significantly lower heart rate achieved in the once daily group. One patient was not satisfactorily controlled on the daily regimen demonstrating that many but not all hypertensives can be controlled with daily administration of timolol.
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  • 88
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    European journal of clinical pharmacology 18 (1980), S. 391-394 
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
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  • 89
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    European journal of clinical pharmacology 19 (1981), S. 25-32 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; baroreceptor reflex ; mode of action ; sympathetic activity ; urinary catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 ± 0.15 mg/day) alone in 13 essential hypertensive men, assessing several biochemical indices of sympathetic function, as well as physiologic parameters, including baroreflex sensitivity, the cold pressor test, and the hypotensive response to alpha adrenergic blockade. Clonidine diminished mean arterial pressure (from 104±5 to 84±3 mmHg;p〈0.01), without associated changes in several biochemical parameters of sympathetic outflow (urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid; allp〉0.1). Circulatory baroreflex function was not enhanced by clonidine, during either the amylnitrite test or the phenylephrine test, before or after parasympathetic blockade with atropine. The cold pressor test, an index of efferent sympathetic pressor function, was also unaltered. The enhanced mean arterial pressure response to phentolamine during clonidine therapy (from a fall of 14.8±4.3 to 39.4±5.2 mmHg,p〈0.01), suggested an increase in alpha adrenergic vascular tone, perhaps mediated by clonidine's alpha agonist properties in vascular smooth muscle. The antihypertensive mechanism of longterm low dose clonidine cannot reliably be ascribed either to baroreflex enhancement or to suppression of sympathetic outflow.
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  • 90
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    European journal of clinical pharmacology 19 (1981), S. 113-118 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilators ; hypertension ; side-effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and a diuretic. After a 50 mg oral dose mean (± SD) peak plasma concentration of T was 1.13±0.29 µg/ml−1 and occurred 0.79±0.40 h after the dose; mean peak plasma concentration of its sulphone metabolite (M) was 0.37±0.09 µg/ml−1 at 1.92±1.32 h after the dose. Following peak plasma concentrations there was a monoexponential decline in T and M concentrations with half-lives of 2.78±0.77 h and 10.78±7.85 h respectively. There was a linear increase in plasma concentration of T and M during incremental dosing with 50–200 mg t. i. d. During in-patient administration of 600–900 mg T daily (n=6) there was no significant change in blood pressure, pulse rate or body weight. Out-patient administration of 900 mg T daily (n=4) was associated with a significant fall in mean systolic but not diastolic bp (lying −15/+1 mm Hg. standing −25/−8 mm Hg). A further fall was observed in 2 subjects receiving 1200 mg and 1500 mg daily. Supine pulse rate increased (mean ± SD) significantly from 55±5/min to 66±8/min following 900–1500 mg T in 4 out-patients. Severe nausea and other gastro-intestinal side-effects in all subjects receiving 600–900 mg daily eventually necessitated drug withdrawal. In its present from T is not recommended for the treatment of hypertension.
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  • 91
    ISSN: 1432-1041
    Keywords: carteolol ; hydrochlorthiazide ; amiloride ; hypertension ; double-blind clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of carteolol, a new β-blocking agent, added to basal diuretic treatment (hydrochlorthiazide 50 mg and amiloride 5 mg) has been assessed in a controlled trial in 17 patients with mild-to-moderate hypertension. The trial was divided into 4 stages: 1) run-in period with no antihypertensive treatment, 2) diuretic period (the diuretic being continued as basal treatment during the two following periods), 3) carteolol titration period, and 4) double-blind cross-over period comparing carteolol with placebo, which lasted 2 times 4 weeks. Although the diuretic effectively reduced the blood pressure, 17 of the 20 patients originally studied still had an elevated diastolic blood pressure (≧ 95 mmHg) after the diuretic period, thus fulfilling the inclusion criteria for the study. During the titration period carteolol 5 to 20 mg b. i. d. significantly reduced the elevated blood pressure. The blood pressure was reduced to normal in all 17 patients, although in two patients this occurred only during the double-blind period. During the double-blind period, the dose of carteolol was used which had given a satisfactory response during the titration period. The blood pressure in the 14 patients who completed the trial remained low both with carteolol and placebo during the double-blind stage, and was only slightly lower with carteolol than with placebo. This is probably due to a “carry-over” effect. Three patients discontinued the trial due to side effects (1 urticaria, 1 insomnia and 1 nausea) while on carteolol. There was no other difference between carteolol and placebo in the number or severity of side effects.
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  • 92
    ISSN: 1432-1041
    Keywords: beta-blocker ; hypertension ; clonidine ; plasma catecholamines ; metoprolol ; propranolol ; blood pressure responses ; isometric work ; dynamic work
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of metropolol (beta1-selective), propranolol (nonselective) and clonidine (central alpha-stimulant) on plasma norepinephrine, blood pressure and heart rate were assessed at rest, during isometric work and dynamic exercise in 15 patients with moderate hypertension. Metroprolol resulted in a lower diastolic blood pressure during isometric and dynamic exercise than propranolol, which was paralleled by a lower plasma norepinephrine level during dynamic work; both beta-adrenergic blocking compounds resulted in a lower heart rate in all test situations than that obtained with clonidine; clonidine produced similar control of diastolic blood pressure to that obtained with the beta-adrenergic blocking agents, but did not clearly attenuate the systolic blood pressure response to dynamic exercise. Plasma norepinephrine concentrations tended to be lowest following clonidine, especially during dynamic work. The findings support the hypothesis that the central action of clonidine inhibits peripheral release of norepinephrine, but is insufficient to attenuate cardiac stimulation by physical exercise. The fact that propranolol caused higher plasma norepinephrine concentrations than metoprolol during exercise may explain the difference in the blood pressure responses during exercise.
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  • 93
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    European journal of clinical pharmacology 21 (1982), S. 445-449 
    ISSN: 1432-1041
    Keywords: pindolol ; hypertension ; retard formulation ; plasma levels ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 36 out of 52 patients with essential hypertension, whose blood pressure was not normalized with pindolol 15 mg per day, were treated with 30 mg per day for four to six weeks. Pindolol was administered in random order, either as 15 mg twice daily or as one 30 mg retard tablet once daily. Blood pressure was lowered from mean pretreatment levels of 174/111 mmHg to 149/98 mmHg by 15 mg b.d., and to 145/97 mmHg by 30 mg retard. In five patients diurnal variations in blood pressure and plasma pindolol levels were determined. At all times during the day blood pressure was at least as well controlled by 30 mg retard as by 15 mg b.d. Plasma concentration maxima were similar with both forms, but a higher concentration was maintained for a longer time after the retard tablet. Pindolol 30 mg was well tolerated and the incidence of side effects was lower than during treatment with 15 mg b.d. Thus, patients requiring high doses of pindolol for control of hypertension can safely and conveniently be treated with a single tablet of 30 mg pindolol retard.
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  • 94
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    European journal of clinical pharmacology 21 (1982), S. 473-477 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilators ; heart failure ; haemodynamics ; hypertension ; sulphoxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effect of Tolmesoxide, a new sulphoxide chemically dissimilar from other vasodilators, was investigated in eight patients with chronic heart failure subsequent to ischaemic heart disease and/or hypertension. Tolmesoxide significantly increased the cardiac output and reduced the indices of systemic vascular resistance, the mean pulmonary arterial pressure and left ventricular filling pressure in most patients studied. These changes were observed both as acute and chronic effects. No significant effect on the mean arterial pressure, heart rate or myocardial oxygen supply/demand was observed. Tolmesoxide appeared to be therapeutically potent by both intravenous and oral routes.
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  • 95
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; antihypertensive treatment ; catecholamines ; renin ; aldosterone ; blood volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy and endocrine profile of the new antihypertensive agent, Ro 12-4713, were evaluated in 23 patients (17 men and 6 women) with moderate to severe arterial hypertension. Following addition of Ro 12-4713 to pre-existing therapy with diuretics and beta-blockers or sympatholytics, blood pressure in most of the patients was normalized within one month by a daily dose of 60 to 120 mg. Heart rate was only slightly increased. Orthostatic hypotension was not observed. Weight gain or oedema formation occurred in 14 patients within the first four weeks, but could be controlled satisfactorily by intensified diuretic therapy. Increased hair growth occurred in most of the patients. After a mean duration of treatment of 2.8 months, plasma volume and plasma and urine sodium were unaltered, and plasma potassium was slightly decreased. Plasma renin activity was doubled, whereas plasma aldosterone concentrations were unaltered. Plasma norepinephrine levels were high before and increased only slightly during chronic Ro 12-4713 treatment, whereas urinary norepinephrine excretion was unchanged. Plasma and urinary epinephrine were unaltered by Ro 12-4713. Ro 12-4713 appears to be a potent vasodilator for the combination treatment of hypertension in men.
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  • 96
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    European journal of clinical pharmacology 22 (1982), S. 285-288 
    ISSN: 1432-1041
    Keywords: hypertension ; plasma adrenaline ; plasma noradrenaline ; isoprenaline response ; noradrenaline response ; salivation ; parasympathetic nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Parameters of the autonomic nervous system were studied in normotensive subjects (NT; standing blood pressure (BP)≤125/85 mmHg) and in subjects with borderline hypertension (BHT; 140/90≤standing BP〈60/100 mmHg). No differences in plasma noradrenaline and adrenaline levels were found between NT and BHT subjects, neither at rest nor during exercise at 75% of maximum work capacity. The dose of noradrenaline required to increase systolic BP by 10 mmHg was significantly higher in NT than in BHT subjects (5.13±0.42 vs 3.50±0.57 µg · min−1). No difference between NT and BHT subjects was found in the dose of isoprenaline required to increase heart rate by 20 beats · min−1 (1.21±0.12 vs 1.09±0.11 µg · min−1). Resting salivary flow was significantly lower in BHT than in NT subjects (0.39±0.06 vs 0.98±0.06 g · min−1), suggesting decreased parasympathetic activity in the former group. The enhanced pressor effect of noradrenaline, together with the decreased parasympathetic activity, could explain the elevated blood pressure and heart rate in subjects with borderline hypertension.
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  • 97
    ISSN: 1432-1041
    Keywords: bopindolol ; hypertension ; beta-blocker ; blood pressure ; plasma renin ; plasma catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bopindolol (LT 31-200), a new, long-acting, non-selective beta-blocker, was given as monotherapy to 13 patients, 12 with essential hypertension and 1 with renovascular hypertension. After a placebo period of 4–6 weeks, bopindolol was given once daily, starting with 1 mg and subsequently increasing at two-weekly intervals to 2 and 4 mg once daily until a diastolic blood pressure⩽90 mmHg was achieved. The effective dose was continued for 12 weeks. In 10 patients plasma levels of renin, noradrenaline, adrenaline and cholesterol were measured during placebo and after 3 months of therapy. Blood pressure and heart rate were lowered significantly during bopindolol treatment. The mean effective dose was 2.2 mg per day. In 10/13 patients a diastolic blood pressure⩽90 mmHg was achieved. Side effects were minimal. Changes in plasma noradrenaline and adrenaline were small and not significant, but renin and cholesterol were significantly reduced. Thus, LT 31-200 is an effective and well tolerated beta-blocker when given in a once daily dosage.
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  • 98
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    European journal of clinical pharmacology 20 (1981), S. 335-338 
    ISSN: 1432-1041
    Keywords: atenolol ; atherosclerosis ; hypertension ; serum lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum lipoproteins were determined in 15 patients before and during antihypertensive treatment with atenolol 0.1–0.2 g/day for a mean of 8 months. The mean blood pressure fell from 171/103 to 154/93 mm Hg (p〈0.05). Significant lipoprotein changes were an increase in very low density triglycerides (VLDL-TG) from 1.21±0.95 (SD) to 1.62±1.24 mmol/l (p〈0.01) and in low density (LDL) TG from 0.46±0.12 to 0.51±0.12 mmol/l (p〈0.05). Together, these TG increases resulted in development of hypertriglyceridaemia in 7/15 patients during atenolol treatment. No effect on whole serum cholesterol or on the high density lipoprotein cholesterol concentrations were found. Thus, some patients on long term treatment with atenolol seem to receive the benefit of normotension at the cost of hypertriglyceridaemia. This may have practical implications, since hypertriglyceridaemia constitutes an important risk factor for atherosclerosis.
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  • 99
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    European journal of clinical pharmacology 20 (1981), S. 347-349 
    ISSN: 1432-1041
    Keywords: reserpine ; syrosingopine ; prolactin secretion ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 20 mild hypertensive women, reserpine induced a significant increase in mean plasma PRL, both under basal conditions (from 6.6±0.9 to 17.9±2.9 ng/ml), and on repeated determinations during the day. In contrast to reserpine, the administration of syrosingopine, a synthetic compound derived from reserpine, to the same subjects was not followed by a significant change in prolactin level. Beyond their pharmacological interest, these results are of clinical importance when considering that rauwolfia alkaloids are used for long term treatment, and that an increase in PRL levels is important in pathology, both in relation to the function of the hypophyseogonadal axis and in view of its possible facilitation of the growth and development of mammary cancer.
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  • 100
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    European journal of clinical pharmacology 24 (1983), S. 15-19 
    ISSN: 1432-1041
    Keywords: hypertension ; mianserin ; clonidine ; methyldopa ; depression ; α2 receptors ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concurrent administration of tricyclic antidepressants has been shown in man to result in a clinically significant impairment of the antihypertensive effect of clonidine. This interaction is thought to be related to competition for central α2 receptors where clonidine acts as an agonist and the tricyclics act as antagonists. Although it seems to cause less cardiovascular effects than tricyclic antidepressants, the tetracyclic antidepressant, mianserin also has been reported to be an α receptor antagonist and may, therefore, also interfere with the antihypertensive activity of centrally-acting drugs. This study investigates the effects of acute and chronic mianserin administration in patients with essential hypertension established on long term treatment with either clonidine or methyldopa. The first dose of mianserin was not associated with an increase in blood pressure and during a further two weeks of mianserin therapy there were no significant alterations in blood pressure, supine or erect. Similarly, mianserin did not alter heart rate either after acute or after chronic administration. Mianserin itself had a sedative effect but there was no interference with the sedation attributable to clonidine or methyldopa. Mianserin caused no reduction in salivary flow and did not influence the reduced saliva production caused by clonidine. Both clonidine and methyldopa are associated with a reduction in sympathetic outflow but there was no evidence in this study of any further change in plasma noradrenaline or 24 h urinary catecholamine excretion. This study demonstrates that if mianserin is given acutely or chronically, it does not interfere with the effects of the centrally acting antihypertensive drugs, clonidine and methyldopa. Mianserin may therefore be a suitable antidepressant for patients receiving these antihypertensive agents if drug treatment for depression is indicated.
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