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  • Artikel  (402)
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  • hypertension
  • Springer  (402)
  • Cambridge University Press
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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 48 (1992), S. 345-351 
    ISSN: 1420-9071
    Schlagwort(e): Renin-angiotensin ; development ; hypertension ; SHR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1572-8773
    Schlagwort(e): hypertension ; inductively coupled plasma-mass spectrometry ; inorganic content ; rat tissues
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The inorganic contents of bone, brain, erythrocyte, heart, kidney cortex, kidney medulla, liver, lung, muscle and plasma from spontaneously hypertensive rats were compared with those of the same tissues from healthy Sprague-Dawley rats. A general inductively coupled plasma-mass spectrometry method developed for multi-element determinations of most of the elements present in biological tissues was used. Variations were found not only for major elements, as expected, but also for many trace elements in several tissues.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 40 (1991), S. 435-436 
    ISSN: 1432-1041
    Schlagwort(e): Atenolol ; hypertension ; ß-adrenoceptor blockade ; blood pressure ; heart rate ; ambulatory ; circadian rhythm
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 39 (1990), S. 435-439 
    ISSN: 1432-1041
    Schlagwort(e): co-dergocrine mesylate ; hypertension ; aldosterone ; catecholamines ; nifedipine ; renin side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Co-dergocrine mesylate (Cod), which inhibits norepinephrine secretion by stimulating presynaptic dopamine receptors, and has no known metabolic side effect, has an additive antihypertensive effect to that of Nifedipine (Nif). Plasma norepinephrine, epinephrine, renin activity and aldosterone have been measured after acute administration of Nif and Cod alone and in combination to 18 patients with a diastolic blood pressure 〉 105 mm Hg in a cross-over, randomized, double-blind study. Every patient received 4 mg Cod then 20 mg Nif, placebo then 20 mg Nif and 4 mg Cod then placebo. The second treatment was always given 1 h after the first medication. Blood pressure was measured before and every 15 min during the study period. Blood for measurement of catecholamines, aldosterone and renin activity was collected before medication, 1 h after the first dose and 90 min after the second treatment. Blood pressure was significantly lower (P 〈 0.05) where Cod preceded Nif. Cod caused a significant decrease in plasma norepinephrine from 293 to 202 pg · ml−1 and in epinephrine from 67 to 55 pg · ml−1. The Nif-induced increase in norepinephrine from a pre-treatment value of 293 pg · ml−1 with preceding Cod to 331 pg · ml−1 was much less than the increase with placebo as premedication, from 284 to 440 pg · ml−1. Nif caused an increase in renin activity but no increase in aldosterone. Nif-related side effects, such as flushing and headache, occurred in 6 patients of whom 5 had no received Cod as premedication. Due to the stabilizing action of Cod on catecholamines and on the side effects of Nif, Cod may be preferable to other antihypertensives in augmenting the antihypertensive action of Nif.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 43 (1992), S. 11-15 
    ISSN: 1432-1041
    Schlagwort(e): Stress ; Atenolol ; Bopindolol ; catecholamines ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a study in mild hypertensives, the impact of mental and physical stress on plasma epinephrine (E), norepinephrine (NE), and on their ratio (NE/E) was evaluated. The effect of twoβ-adrenoceptor blocking drugs, atenolol and bopindolol, on plasma catecholamine levels was also examined. Each stressful stimulus significantly increased the NE and E levels compared to rest. The increase was progressive from mental stress, through the handgrip test to the treadmill test. A slight decrease in the NE/E ratio was observed following mental stress and the handgrip test, while this ratio increased during the treadmill test. No significant impact of beta blocking treatment on catecholamine levels was observed under any test condition.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-1041
    Schlagwort(e): Insulin secretion ; Nifedipine ; non insulin-dependent-diabetes mellitus- ; hyperglycaemia ; plasma insulin ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of 7-days of nifedipine treatment on insulin secretion has been analyzed in hypertensive patients with non-insulin-dependent mellitus (NIDDM). Pancreatic β-cell function was assessed as insulin release following stimulation with arginine after potentiation by hyperglycaemia. Two groups of 5 patients with NIDDM (fasting blood glucose 139.2 mg·dl−1), on the same controlled diet, were compared; one was treated with nifedipine 30 mg per d and the other was the control. The mean blood pressure in the nifedipine group decreased (110 vs 102 mm Hg). Fasting blood glucose and basal plasma insulin were not affected by nifedipine. The acute insulin response (AIR) to 5 g arginine after potentiation by hyperglycaemia (clamped at 240 and 350 mg/dl for 30 min) was significantly (P〈0.05) decreased, as well as the potentiation slope (line relating AIR and plasma glucose level) in those patients, and were unchanged in the control group. Thus, nifedipine may impair insulin secretion at high glucose levels in patients with NiDDM.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 42 (1992), S. 43-46 
    ISSN: 1432-1041
    Schlagwort(e): Isradipine ; hypertension ; platelet function ; prostaglandin system ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of treatment for eight weeks with isradipine 1.25 mg twice daily for 4 weeks and thereafter 2.5 mg twice daily for 4 weeks on ex vivo platelet function was investigated in 10 male hypertensive patients, aged 51 (6.1) y. Systolic and diastolic blood pressure, platelet aggregation in response to ADP, serum thromboxane B2 and β-thromboglobulin levels were significantly decreased at rest before exercise ergometry, during exercise and at rest after exercise. The platelet count, platelet sensitivity and the plasma levels of 6-oxo-prostaglandin F1α were not affected by isradipine. It is concluded that a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit in the routine treatment of hypertension.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 150-155 
    ISSN: 1432-1041
    Schlagwort(e): Dopamine ; renal blood flow ; hypertension ; renal failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of an intravenous infusion of dopamine (0.5 to 1.25 µg/kg/min) for periods of between 36 and 105h has been studied in eight patients with hypertension and varying degrees of renal impairment. There was a significant rise in the glomerular filtration rate (GFR) from 31.2±20.2 to 42.8±26.8 ml/min (p〈.05) after four hours of the infusion but after 48 h of infusion the mean GFR was no different from the control value. The paraaminohippuric acid (PAH) clearance also rose from 129.8±115.4 ml/min to 173.1±164.3 ml/min (p〈0.05) after four hours of infusion, but like the GFR it was no different from control after 48 h of the infusion. The daily urine volumes increased significantly during the dopamine infusion from 2176.0±49.2 ml/day to 3809.0±118.8 ml/day (p〈0.002) but had returned to control values after 48 h of continuing dopamine infusion. Following the end of the infusion there was a significant reduction in the urine volume to 1213.0±195.0 ml/day (p〈0.001). There was a rise in sodium excretion during the dopamine infusion from 94.8±50.7 meq/day to 264.7±172.8 meq/day (p〈0.01) with a fall after the end of the infusion to 33.2±27.5 meq/day (p〈0.05). There was no change in the blood urea during the dopamine infusion but after stopping the infusion the blood urea rose from 83.5±39.4 mg% to 95.1±39.0 mg% (p〈0.02). We conclude that intravenous infusion of dopamine to patients with hypertension and renal impairment may produce initial clinical improvement but is of little therapeutic benefit when given for prolonged periods.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 217-219 
    ISSN: 1432-1041
    Schlagwort(e): Beta-blockade ; substituted indoles ; hypertension ; heart rate ; clinical trial ; pindolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Forty patients with essential hypertension were treated with a new beta-blocking agent, 4-2 (2-hydroxy-3-isopropyl-amino-propoxy)-indole, pindolol (Viskén®). Pindolol caused a significantly greater reduction of blood pressure in most of the patients than a placebo and the effects persisted for some time after its withdrawal. There were few side effects. Its mode of action and a safe dosage regime are discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 7 (1974), S. 401-405 
    ISSN: 1432-1041
    Schlagwort(e): Chlorthalidone ; spironolactone ; hypertension ; potassium deficiency ; diuretic ; Kühns' test
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Kühns' oral test for potassium deficiency (KDT) has been used to evaluate potassium balance after treatment with diuretics. The test was first standardised in 23 patients, both with and without known potassium deficiency. Subsequently, 18 patients with essential hypertension were investigated before and after the use of 3 different diuretics, each for a period of 6 weeks; all patients received all three forms of treatment but in different sequence. Before treatment the patients excreted an average of 121 mEq potassium a day in urine after oral administration of potassium 127 mEq (citrate). After treatment with chlorthalidone (Hygroton®), 50 mg a day, the excretion of potassium decreased significantly to 83 mEq, suggesting an intracellular deficit of it. Treatment with chlorthalidone 50 mg and potassium chloride 2 g daily (Hygroton — K®), led to potassium excretion of 100 mEq after loading, which was distinctly, but not significantly, larger than in the period of treatment with chlorthalidone alone. After chlorthalidone 50 mg daily and spironolactone (Aldactone “Searle”®), 25 mg q. i. d., the excretion of potassium was 121 mEq, which was the same as before treatment. The mean serum potassium before treatment was 4.4 mEq/l, after chlorthalidone 3.8 mEq/l, after chlorthalidone plus potassium chloride 3.9 mEq/l, after chlorthalidone combined with spironolactone 3.9 mEq/l. The results were in agreement with previously published investigations of “exchangeable potassium” after similar treatments. As the test for potassium deficiency gave better information about the amount of intracellular potassium in the body than analysis of serum potassium, it is suitable for the evaluation of potassium deficiency associated with diuretic therapy.
    Materialart: Digitale Medien
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  • 11
    ISSN: 1432-1041
    Schlagwort(e): α-methyldopa ; plasma concentration ; hypertension ; sulphate conjugation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentrations of free α-methyldopa and methyldopa sulphate conjugate were measured in 7 hypertensive patients with normal renal function following α-methyldopa (1 g) orally. Five of these patients subsequently received α-methyldopa ethyl ester (250 mg) (methyldopate) intravenously and two further patients received 250 mg of α-methyldopa intravenously. After oral administration a large amount of total plasma α-methyldopa was present as sulphate conjugate. There were wide interindividual differences in the ratio of free: conjugated α-methyldopa in plasma (ratio at 4 hours ranged from 3.73 – 0.83) suggesting that individual differences in the extent of sulphate conjugation may occur. There was no close correlation between the degree of conjugation and the fall in arterial pressure. At all time intervals examined, plasma concentrations were higher following intravenous α-methyldopa than α-methyldopate. The plasma concentration of α-methyldopa (free and esterified) 60 minutes after i.v. α-methyldopate was 1.7±0.3 µg/ml wile at the same time after the same dose of methyldopa by the same route the mean concentration was 5.9 µg/ml. Although small amounts of sulphate conjugate were detected after i.v. α-methyldopate, insignificant quantities of conjugate were found after i.v. α-methyldopa. The average fall in mean arterial pressure was 27 mm Hg following i.v. α-methyldopa but only 2.7 mm Hg following α-methyldopate. These results suggest that sulphate conjugation of α-methyldopa occurs in the gastrointestinal tract during absorption. Hydrolysis of α-methyldopa ethyl ester does not appear to be instantaneous and pharmacokinetic differences between the ester and free α-methyldopa have been demonstrated.
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 8 (1975), S. 387-392 
    ISSN: 1432-1041
    Schlagwort(e): Left ventricular pressure ; left ventricular contractility ; hypertension ; diazoxide ; beta-adrenergic blockade ; isometric exercise
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of diazoxide on left ventricular performance during rest and isometric exercise (handgrip) was examined in 16 unselected hypertensive patients, 6 of whom had been pretreated with the beta-adrenergic blocking agent pindolol. Diazoxide regularly and promptly produced a fall in left ventricular systolic and end diastolic pressures, and an increase in heart rate and left ventricular dp/dtmax. Haemodynamic changes were maximal 2 minutes after injection of the drug and decreased little over the next 8 minutes. After beta-adrenergic blockade, diazoxide caused a more pronounced reduction in left ventricular systolic pressure and a less marked fall in end-diastolic pressure, whilst the diazoxide-induced rise in heart rate was partially and the increase of dp/dtmax was completely inhibited. The increase in systolic pressure during isometric exercise was not influenced by diazoxide, but the positive inotropic reaction was augmented. The findings appear to show that cardiac stimulation by diazoxide is due to a reflex mechanism transmitted by baroreceptors, and that improvement of cardiac performance is mainly due to a reduction of left ventricular after-load.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    ISSN: 1432-1041
    Schlagwort(e): Beta-blockade ; penbutolol ; hypertension ; plasma and urinary catecholamines ; plasma renin ; aldosterone excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of penbutolol (Hoe 893 d), a new non-selective beta-receptor blocking agent, were studied in 5 patients with moderate hypertension. Initially, it was shown that 2–4 mg given orally once or twice daily tended to lower blood pressure and pulse rate, both at rest and following submaximal work. In prolonged trials (3–8 months) 40–60 mg/day were required to produce an acceptable antihypertensive effect. Penbutolol had no effect on the normal increase in plasma noradrenaline and adrenaline on standing, nor did it alter basal urinary catecholamine excretion. Submaximal work caused no significant change in plasma catecholamines before treatment, but there was a marked rise both in plasma noradrenaline and adrenaline during treatment with penbutolol. In short term studies there was a fall in plasma renin by 4 hours after oral administration of penbutolol 2–4 mg, which persisted for 24 hours. Prolonged treatment with penbutolol 20–30 mg twice daily inhibited renin production under basal conditions and following submaximal work, as well as lowered basal urinary aldosterone excretion. In one patient slight asthmatic symptoms appeared after treatment for 3 months with penbutolol. In other respects penbutolol was well tolerated.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 9 (1976), S. 361-365 
    ISSN: 1432-1041
    Schlagwort(e): Propranolol ; atenolol ; hypertension ; cardio-selective ; beta-adrenergic blockade ; antihypertensive therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Propranolol was given to 30 patients with essential hypertension following randomised, double-blind administration of either placebo or a new cardioselective beta-adrenergic receptor antagonist, atenolol (Tenormin®, ICI 66 082). Both atenolol and propranolol caused statistically significant reduction of recumbent and erect blood pressure and heart rate. There were no important differences between these variables on comparison of atenolol and propranolol.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 9 (1976), S. 355-360 
    ISSN: 1432-1041
    Schlagwort(e): Propranolol ; minoxidil ; hypertension ; cardiac output ; plasma renin activity ; non-invasive techniques
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A study, using non-invasive techniques, was carried out in ten patients with essential hypertension to examine the mechanism of the hypotensive effect of propranolol when used in combination with a potent vasodilator antihypertensive — minoxidil. The hypotensive effect of minoxidil, a mean (± SEM) decrease of 42.4±4.3 mm Hg, was accompanied by a marked increase in heart rate, cardiac index and plasma renin activity and a significant decrease in total peripheral resistance, limb vascular resistance and pre-ejection period. Addition of propranolol further reduced mean arterial pressure by an average of 12.9±2.0 mm Hg. Propranolol returned cardiac index to control values and total peripheral resistance index rose but not to control levels. Plasma renin activity was significantly reduced by propranolol. By multiple regression analysis no correlation was found between propranolol-induced decrease in mean arterial pressure and changes in cardiac index, total peripheral resistance index or plasma renin activity. Quantitatively, the reduction in cardiac index observed probably accounted for the hypotensive effect of propranolol. The role of plasma renin activity reduction in the hypotensive effect of propranolol in this situation remains to be clarified. The findings in the present study were consonant with the known actions of vasodilator antihypertensive agents and propranolol and indicate the applicability of non-invasive methodology to the investigation of cardiovascular drugs in man.
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 42 (1992), S. 65-70 
    ISSN: 1432-1041
    Schlagwort(e): Lipids ; Pinacidil ; Hydrochlorothiazide ; hypertension ; triglyceride ; cholesterol ; apolipoproteins
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary This study determined the effect of pinacidil on the concentration of plasma lipids and apolipoproteins in male patients previously equilibrated with 25 mg hydrochlorothiazide twice daily. Pinacidil therapy given to 52 hypertensives at 25 to 100 mg daily for 8 weeks resulted in a reduction of systolic and diastolic blood pressure concurrently to reductions in plasma cholesterol and triglycerides with no change in low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C). There was an associated decrease in apolipoproteins (Apo)B, C-III and E and elevation in ApoA-I. A parallel placebo group of 44 patients experienced reduction in diastolic blood pressure and an elevation in ApoA-I. These changes indicate that pinacidil will be a useful antihypertensive agent having properties on lipoprotein metabolism which would favor decreased risks of atherosclerosis.
    Materialart: Digitale Medien
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  • 17
    ISSN: 1432-1041
    Schlagwort(e): arrhythmia ; hypertension ; LVH ; holter monitoring ; BP monitoring
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To evaluate the relationship among supraventricular and ventricular arrhythmias with blood pressure and heart rate (HR) values, we studied 2 groups of 20 hypertensive men with (group I) and without (group II) left ventricular hypertrophy. Ambulatory electrocardiographic tracings were recorded continuously, together with ambulatory arterial pressure. Systolic (SBP) and diastolic (DBP) blood pressure values measured over 24 h showed no difference between the two groups, but we found greater variability in SBP in group I. The incidence of ventricular and supraventricular arrhythmias was significantly higher in patients of group I; moreover, we found a strong correlation between the incidence of ventricular extrasystoles (VPCs) and SBP, DBP, and HR values in group I, whereas in group 11 the incidence of supraventricular extrasystoles (APCs) was higher during peaks of SBP and HR values. The relationship between APCs and SBP observed in group II may be attributable to the pressure stimulus on a normal atrium, and the significant correlation between VPCs and SBP, DBP, and HR values may be due to episodes of subendocardial ischemia or to the influence of adrenergic stimulation on previously compromised myocardial tissue.
    Materialart: Digitale Medien
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 307-311 
    ISSN: 1432-1041
    Schlagwort(e): Calcium antagonists ; Amlodipine ; hypertension ; renal function
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In this study the efficacy and safety of short-term amlodipine administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduced blood pressure induced by treatment was associated with maintenance of renal function. After a run-in period with placebo, 30 hypertensive patients without cardiac or renal diseases were randomly allocated to a double-blind 4 weeks controlled study with amlodipine 10 mg once a day (15 patients) or placebo (15 patients). Renal haemodynamic measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, with methods described by Schlegel and Gates, respectively. In addition, effective renal blood flow [ERBF=ERPF/(1-Ht)], filtration fraction (FF=GFR/ERPF) ERPF) and renal vascular resistance (RVR=MBP×80/ERBF) were calculated. Plasma renin activity (PRA), serum aldosterone (ALD) and urinary excretion of sodium (NaU) were evaluated. At the end of amlodipine administration a significant decrease (P〈0.001) in SBP, DBP and MBP from baseline values was observed. A significant decrease (P〈0.01) in RVR and significant increases (P〈0.05) in ERPF, ERBF and in NaU were also found, without relevant changes in GFR, FF, PRA and ALD. No significant variation in clinical and renal measurements was observed in the placebo group. No relevant side effects were observed in either group. In conclusion, amlodipine was effective in lowering blood pressure in mild to moderate hypertension and exerted favourable effects on renal haemodynamics and function.
    Materialart: Digitale Medien
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 46 (1994), S. 119-122 
    ISSN: 1432-1041
    Schlagwort(e): Isradipine ; Fourier ; rhythm ; hypertension ; diurnal blood pressure rhythm
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract In this study, using the two-step truncated Fourier series with four harmonics, we analysed the diurnal blood pressure profile in 13 mild-moderate essential hypertensive patients during isradipine long-term therapy. Circadian parameters such as the amplitudes and phases of the four harmonics and the overall amplitude and phase were obtained from the model. The total duration of the study was 26 weeks. Ambulatory blood pressure was measured at 15-min, intervals using a Takeda TM 2420 device after 2 weeks of placebo and after 6 and 26 weeks of isradipine (5 mg daily) respectively. After 6 and 26 weeks therapy the blood pressure values showed a significant decrease, although the daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by isradipine treatment. Both the night/day differences and the overall amplitude/acrophases were statistically significant at 0,6 and 26 weeks. According the nocturnal blood pressure fall, we found that long-term therapy with isradipine increased the number of patients with nocturnal blood pressure fall and reducing the early morning blood pressure rise. In conclusion, the two-step method Fourier analysis represents a novel and useful statistical approach to evaluate the presence of a significant diurnal blood pressure rhythm and to provide the circadian parameters of the 24-h blood pressure profile during pharmacological therapy.
    Materialart: Digitale Medien
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 8 (1975), S. 21-31 
    ISSN: 1432-1041
    Schlagwort(e): Multicentre controlled trial ; hypertension ; oxprenolol ; hydrochlorothiazide dihydralazine ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a multicentre, double-blind, between-patient study the hypotensive effect of oxprenolol was investigated in 329 patients with mild to moderate hypertension. A factorial experimental design with three factors was chosen: oxprenolol — none or daily doses of 20, 40, 60 and 80 mg; dihydralazine and hydrochlorothiazide, respectively, none or 30 mg daily. Each treatment was given for 4 weeks after an adequate period of withdrawal from any other possible hypotensive therapy and one week of placebo wash-out. Irrespective of the association with dihydralazine and/or hydrochlorothiazide, oxprenolol had a hypotensive effect linearly related to dose for standing systolic (P〈0.05) and diastolic (P〈0.01) pressure, and for lying diastolic (P〈0.05) pressure. The addition of dihydralazine enhanced the time-course of the hypotensive effect of oxprenolol, particularly the 80 mg dose level. In general, the combination of oxprenolol with dihydralazine and hydrochlorothiazide caused larger reductions in blood pressure, particularly with oxprenolol 80 mg. In the latter group, the eventual falls in blood pressure were 30.5 and 14.4 mmHg for lying systolic and diastolic, respectively; and 32.1 and 20.0 mmHg for the standing systolic and diastolic pressures. The drug was well tolerated; major side effects (heart failure and bronchospasm) occurred in three patients.
    Materialart: Digitale Medien
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 38 (1990), S. 209-211 
    ISSN: 1432-1041
    Schlagwort(e): Isradipine ; hypertension ; pharmacokinetics ; pharmacodynamics ; clinical trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In conjunction with a multicentre clinical trial of the calcium antagonist isradipine in hypertension, pharmacokinetic and pharmacodynamic studies were conducted in 9 subjects. An initial dose of 5 mg (capsule formulation) of isradipine was given orally. The mean Cmax, tmax and AUC(0–8) were 6.0 ng · ml−1, 1.5 h and 15.1 h · ng · ml−1 respectively. Seven subjects repeated the study at steady state after 10 week's dose titration with isradipine. Cmax, tmax and AUC(0–8) were 3.7 ng · ml−1, 1.2 h and 12.2 h · ng · ml−1 respectively indicating that the drug does not accumulate over time. Control of blood pressure paralleled plasma isradipine concentrations which suggested that the drug should be given at least twice daily. Pharmacokinetic studies performed in conjunction with clinical trials can provide valuable information about the patterns of drug response.
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 4 (1972), S. 217-221 
    ISSN: 1432-1041
    Schlagwort(e): Bethanidine ; guanethidine ; hypertension ; adrenergic blockade ; blood pressure ; dose response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A dosing schedule for the administration of oral bethanidine is described, which achieved optimal cumulative effect in each of 8 patients in 3 days or less. Individual patient dosage titration is necessary, because the required cumulative dose cannot be predicted on the basis of blood pressure, or creatinine clearance. The time course of the blood pressure response after the peak acute hypotensive effect was found to be variable and dependent upon the magnitude of effect and time of day. No blood pressure effect was noted in the recumbent position.
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 40 (1991), S. 131-134 
    ISSN: 1432-1041
    Schlagwort(e): trimazosin ; hypertension ; alpha1-adrenoceptor blocker ; essential ; exercise ; extracellular fluid volume ; haemodynamics ; plasma volume ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The long-term haemodynamic effect of sustained-release trimazosin (mean daily dose 418 mg) at rest and during exercise has been examined in 14 male patients (age 30–61 y) with previously untreated mild or moderate essential hypertension. Cardiac output (dye dilution), heart rate and intra-arterial blood pressure were measured supine and sitting at rest, and during bicycle exercise. After 11 months of trimazosin treatment the mean casual blood pressure was reduced from 165/106 mm Hg to 147/92 mm Hg. The intra-arterial systolic and diastolic pressure was reduced by 3–7% at rest and during 50, 100 and 150 W exercise. Total peripheral resistance was reduced by 8–14% and cardiac output was slightly higher (2–8%) in all situations. Stroke volume and heart rate remained unchanged, as did body fluid volumes (isotope dilution) and body weight. Side effects were minor and transient. Thus, the haemodynamic responses to trimazosin are similar to but weaker than those of other alpha1-adrenoceptor blockers. The efficacy of the sustained-release formulation of trimazosin was low and daily doses above 600 mg are likely to be needed by many patients.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 40 (1991), S. 321-326 
    ISSN: 1432-1041
    Schlagwort(e): Fibrinolysis ; hypertension ; atenolol ; doxazosin ; tissue plasminogen activator ; plasminogen activator inhibitor ; cholesterol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Disturbances in the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the fibrinolytic system have been evaluated. Eighty four subjects with previously untreated mild to moderate hypertension and elevated serum cholesterol were randomized to receive atenolol or doxazosin in a double-blind study over 6 months. Tissue plasminogen activator(tPA) and plasminogen activator inhibitor (PAI-1) were measured in citrated plasma samples before and after venous occlusion before and at the end of the study period. tPA activity after venous occlusion and tPA capacity were significantly increased after doxazosin as compared to pretreatment values. The fibrinolytic variables did not change in the atenolol group. Thus, doxazosin but not atenolol, improved the activity of the fibrinolytic system in patients with hypertension and an elevated serum cholesterol level. This effect of doxazosin warrants consideration when selecting a first-line antihypertensive drug.
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  • 25
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 11 (1977), S. 79-83 
    ISSN: 1432-1041
    Schlagwort(e): Reserpine ; cancer ; mammary gland ; women ; benign breast disease ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Exposure to reserpine was compared in 181 women interviewed prior to biopsy and found to have breast cancer and 307 women found to have a benign disorder of the breast. The age-adjusted relative risk of breast cancer in those who had taken reserpine was 0.6 (95% confidence limits: 0.4 and 1.1). When the 181 breast cancer patients were compared with a second control group of 101 women with a benign condition requiring surgery, the relative risk was 0.9 (95% confidence limits: 0.4 and 1.7). Neither long-term exposure nor its timing, gave any evidence of an association with breast cancer. The findings in this study do not support the hypothesis that rauwolfia derivatives initiate or promote breast cancer.
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 11 (1977), S. 125-128 
    ISSN: 1432-1041
    Schlagwort(e): Clonidine ; alprenolol ; amine metabolites ; cerebrospinal fluid ; hypertension ; noradrenaline
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Lumbar cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline (4-hydroxy-3-methoxyphenyl glycol, HMPG), serotonin (5-hydroxyindoleacetic acid) and dopamine (homovanillic acid) were measured before and during the administration of clonidine or alprenolol to hypertensive patients. The noradrenaline receptor stimulant clonidine significantly decreased the CSF level of HMPG, but there was no consistent change in the concentration of serotonin or dopamine metabolites. Patients on alprenolol showed no change in the levels of these metabolites in CSF.
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 11 (1977), S. 155-157 
    ISSN: 1432-1041
    Schlagwort(e): Propranolol ; plasma concentration ; hypertension ; individual drug dosage ; plasma renin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sixteen patients with essential hypertension were treated with propranolol 160 to 640 mg daily for three months. Significant decreases both in recumbent and standing blood pressure were observed after three days treatment and subsequently. Reduction of blood pressure was more pronounced when the dose of propranolol was increased. However, neither the mean dose nor the plasma concentration of propranolol could be correlated with the mean decrease in blood pressure. There was great interindividual variation in the plasma concentrations of propranolol produced by the same daily dose. The initial stimulation of plasma renin activity and the therapeutic response to propranolol could not be correlated.
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 12 (1977), S. 97-103 
    ISSN: 1432-1041
    Schlagwort(e): beta adrenergic blockers ; diuretics ; hypertension ; renin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty-four patients with mild to moderate hypertension were treated for up to 60 weeks with hydrochlorothiazide and either placebo, timolol, or timolol and amiloride. The effect of adding timolol and amiloride to hydrochlorothiazide was evaluated in a double blind trial. In 22 of the 24 patients a supine diastolic blood pressure below or equal to 95 mm Hg was produced by hydrochlorothiazide and timolol. Replacing a potassium supplement with amiloride increased the antihypertensive effect.
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 12 (1977), S. 171-174 
    ISSN: 1432-1041
    Schlagwort(e): Tolamolol ; hypertension ; pharmacokinetics ; mean steady-state concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Tolamolol was administered in a “double-blind” study to fifteen hypertensive patients by dose-titration against arterial blood pressure. Mean steady-state plasma tolamolol concentrations (Css) were determined for each patient from the area under the plasma concentration — time curve during a dosage interval whilst patients were receiving optimal tolamolol doses. No significant correlation was observed between daily tolamolol dose and Css; the relationship between fall in lying mean arterial pressure and Css also failed to reach conventional levels of statistical significance, but Css was observed to be correlated with the fall in standing pressure. The results suggest that plasma concentrations in excess of 200 ng/ml may be required to achieve an effective hypotensive response with the drug.
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 14 (1978), S. 77-81 
    ISSN: 1432-1041
    Schlagwort(e): Oxprenolol ; slow release oxprenolol ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sixteen patients with uncomplicated hypertension were studied in a double-blind within-patient trial comparing slow release oxprenolol (SRO) with conventional oxprenolol (CO). The antihypertensive effect of SRO once daily was greater than that of CO once daily, although this did not reach statistical significance. CO once daily was less effective than CObd and this difference was statistically significant for lying diastolic blood pressure. After exercise testing 26 hours post-dose, blood pressure and pulse rate were marginally lower on SRO than on CO, but this difference was not significant. Blood pressure readings 24 h post-dose were lower following morning dosing than following evening dosing, although pulse rates showed the opposite trend.
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 14 (1978), S. 93-94 
    ISSN: 1432-1041
    Schlagwort(e): Atenolol ; transplacental passage ; pregnancy ; hypertension ; maternal-fetal ratio
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Maternal and umbilical serum concentrations of atenolol, a hydrophilic, cardioselective beta-adrenoceptor antagonist, were studied at delivery in seven cases of pregnancy hypertension. The drug had been administered to each patient for at least one week. Atenolol was detected in both maternal and umbilical serum in six cases, showing that there is transplacental passage of the drug. In the seventh case, who had stopped taking atenolol more than one day before delivery, neither maternal nor umbilical serum contained a measurable quantity of the drug. Atenolol concentration varied 3- to 6-fold between individuals, but there was no systematic difference between maternal and umbilical levels. It seems reasonable to assume that during steady state conditions the blood level of atenolol in mother and fetus is approximately equal, and that fetal accumulation of the drug does not occur.
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 19-24 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; guanfacine ; central antihypertensives ; withdrawal ; catecholamines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 14 (1978), S. 309-317 
    ISSN: 1432-1041
    Schlagwort(e): General practitioners ; hypertension ; diagnosis/therapy/control ; prescription pattern ; hypotensive drugs ; drugsale statistics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Based upon regional drug sales statistics, two Norwegian counties with a consumption of hypotensives below and two above average were selected for a prescription study among general practitioners (GPs). The first part of the study involved collection of all the GPs' prescriptions for antihypertensive treatment during the month of October 1975. Immediately afterwards the GPs filled in a questionnaire in which they described their diagnostic and therapeutic criteria and procedures for arterial hypertension. Both parts of the study were analysed and compared. Of the GPs approached 154 (54%) participated. A total of 4095 prescriptions for 3253 patients were collected, 65% of whom were females and 35% were males. GPs alone treated 72% of the patients, and of the others 11% had been referred to specialists, 8% had been admitted to hospital, and 5% had had both procedures. The decision of whether or not to start drug treatment was based upon absolute systolic and diastolic BP levels as related to age, but various other patient factors, such as complicating diseases, family history of cardiovascular disease and cooperation/motivation for treatment, were also considered. The average control interval was 4.4 months (range 1 to more than 6 months) and it increased with the age of the patients. About half of the GPs started drug treatment in young patients with beta-blockers, whereas diuretics were preferred for older subjects. Of the total number of prescriptions, diuretics accounted for 50%, synthetic hypotensives (α-methyldopa, hydralazine, guanethidine etc.) for 33%, and beta-blockers for 17%. The therapeutic efficacy, in terms of BP reduction upon drug treatment, was evaluated in relation to age, both in those patients treated solely by GPs and in those referred to a specialist. Patient compliance and adverse drug reactions were also registered, although with considerable variation between the individual participating GPs. During postproject discussions, the GP-participants stated that this type of project was a valuable model for post-graduate training through testing of individual criteria for diagnostic and therapeutic procedures.
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 225-229 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; hypertension ; slow-release preparations ; maximal exercise power ; fatigue
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 399-401 
    ISSN: 1432-1041
    Schlagwort(e): prazosin ; hypertension ; central monoaminergic neurons ; monoamine metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 105-108 
    ISSN: 1432-1041
    Schlagwort(e): renin ; angiotensin ; aldosterone ; hypertension ; hypoaldosteronism ; pseudohypoaldosteronism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 135-139 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; labetalol ; propranolol ; renal haemodynamics ; glomerular filtration rate ; blood pressure ; exercise ; renal blood flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 39
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 231-235 
    ISSN: 1432-1041
    Schlagwort(e): molsidomine ; hypertension ; hypotension ; angina pectoris
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 40
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; beta-adrenoceptor blockade ; hypotensive action ; adverse effects ; combination therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 375-382 
    ISSN: 1432-1041
    Schlagwort(e): calcium antagonist ; verapamil ; hypertension ; vasodilators ; plasma renin activity ; mode of action ; sodium balance ; fluid balance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 309-315 
    ISSN: 1432-1041
    Schlagwort(e): guanfacine ; methyldopa ; hypertension ; rebound hypertension ; withdrawal symptoms ; plasma noradrenaline
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 287-291 
    ISSN: 1432-1041
    Schlagwort(e): tolmesoxide ; hypertension ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 363-367 
    ISSN: 1432-1041
    Schlagwort(e): labetalol ; clonidine ; hypertension ; dose titration ; bendrofluazide ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 7-14 
    ISSN: 1432-1041
    Schlagwort(e): prazosin ; baroreflexes ; hypertension ; reflex tachycardia ; alpha adrenergic blockade ; dopamine-beta-hydroxylase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 197-201 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; oxprenolol ; indomethacin ; drug interaction ; hypotensive effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 163-168 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; captopril ; cardiac output ; extracellular fluid volume ; renin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 48
    ISSN: 1432-1041
    Schlagwort(e): vasodilator ; hypertension ; haemodynamic effects ; renal plasma flow ; renal tubular function ; plasma renin activity ; aldosterone ; Ro 12-4713
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 495-499 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; cyclothiazide ; hydrochlorthiazide ; thiazide diuretics ; potassium-sparing diuretics ; saluretic effect ; hypokalaemia ; hyperuricaemia ; amiloride
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 157-161 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; cadralazine ; single dose ; dose response curve ; hypotensive action ; prolonged effect ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 217-220 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 307-314 
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; hypertension ; blood pressure ; heart rate ; renal clearance ; plasma renin activity ; plasma aldosterone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 579-583 
    ISSN: 1432-1041
    Schlagwort(e): indapamide ; hypertension ; baroreflex ; vascular reactivity ; heart rate ; blood pressure change
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 143-144 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; plasma concentration ; blood pressure response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
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  • 55
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; hypertension ; plasma renin activity ; plasma adrenaline ; plasma noradrenaline ; body fluid loss ; diuretic response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 307-312 
    ISSN: 1432-1041
    Schlagwort(e): ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 571-575 
    ISSN: 1432-1041
    Schlagwort(e): beta-blocker ; felodipine ; calcium antagonist ; hypertension ; vasodilator ; side effects ; plasma levels ; metoprolol ; propranolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 58
    ISSN: 1432-1041
    Schlagwort(e): prizidilol ; hypertension ; exercise test ; beta-blockade ; vasodilatation ; haemodynamic effects ; vascular tone ; muscle blood flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 59
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 309-313 
    ISSN: 1432-1041
    Schlagwort(e): clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 331-334 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; oxprenolol ; hypertension ; beta-blockers ; HDL-cholesterol ; intrinsic sympathomimetic activity ; cardioselectivity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 549-553 
    ISSN: 1432-1041
    Schlagwort(e): pafenolol ; hypertension ; antihypertensive therapy ; beta1-blocking agent ; exercise tests ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 62
    ISSN: 1432-1041
    Schlagwort(e): etozolin ; ozolinone ; furosemide ; hypertension ; renin ; catecholamines ; chronic renal failure ; steady state kinetics ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 397-405 
    ISSN: 1432-1041
    Schlagwort(e): indapamide ; hypertension ; cardiovascular reflexes ; diuretic effect ; blood pressure variability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 10 (1976), S. 177-182 
    ISSN: 1432-1041
    Schlagwort(e): Hydrochlorothiazide ; hypertension ; serum potassium ; total body potassium ; serum uric acid ; fasting blood sugar
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The antihypertensive activity and side effects of three doses of hydrochlorothiazide combined with a potassium supplement (Esidrex®-K novum, Ciba) were determined in 40 hypertensive subjects in a double-blind, cross-over study. The lowest daily dose (12.5 mg) gave almost the same blood pressure reduction as the doses in common use (25 mg and 50 mg) and as the adrenergic beta-blocking agents previously employed. Metabolic side effects in the form of decreased serum potassium and increased fasting blood sugar and serum uric acid were observed in patients on the lower dose and, with the exception of serum uric acid, were only slightly more pronounced with the higher doses. The frequency of subjective side effects, on the other hand, increased with increasing dose. No changes were noted in total body potassium at any dose level. It is suggested that hydrochlorothiazide in low dose, alone or in combination with other antihypertensive agents, is a useful therapeutic regimen in mild hypertension.
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  • 65
    ISSN: 1432-1041
    Schlagwort(e): Tolamolol ; methyldopa ; comparative trial ; hypertension ; beta-blockade
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The efficacy and toxicity of tolamolol and methyldopa in hypertensive patients has been compared by a dose-titrated, double-blind, cross-over study. Thirteen patients completed the trial. Within the dose ranges investigated (tolamolol — 300 mg/day — 900 mg/day; methyldopa — 750 mg/day — 2250 mg/day) both drugs produced significant falls in laying and standing, systolic and diastolic blood pressures. Although the hypotensive effects of methyldopa were more marked than tolamolol, these only achieved conventional (P〈0.05) levels of significance for lying blood pressure. There were no objective changes in haematological or biochemical indices during treatment with either drug, but patients complained of tiredness, weak limbs and mouth dryness significantly more during methyldopa treatment, than during either placebo or tolamolol therapy.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 14 (1978), S. 163-166 
    ISSN: 1432-1041
    Schlagwort(e): Propranolol ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Propranolol was administered in a single dose of 80 mg, 120 mg, 160 mg, 240 mg, or 320 mg, to 23 patients with essential mild to moderate hypertension in a randomised, double-blind cross-over study. All treatments produced a significant fall in lying and standing blood pressures compared with placebo, but there was no statistically significant difference in the effects of the different doses. The percentage of patients showing a satisfactory fall in blood pressure was not different in the five treatment groups. The major anti-hypertensive effect of each dose was present by two weeks. The frequency of side-effects were similar on all the doses.
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  • 67
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 239-241 
    ISSN: 1432-1041
    Schlagwort(e): timolol ; hypertension ; dose ranging ; double-blind trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 69
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; thiazides diuretics ; hypertension ; haemodynamic effects ; renal function ; body fluid volume
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In fifteen patients with essential hypertension WHO I–II (eight men and seven; mean age 45 years) blood pressure (BP), plasma volume (PV;125I-Albumin space), extracellular volume (ECV;82Brdistribution space) and glomerular filtration rate (GFR;51Cr-EDTA clearance) were measured before and during long-term antihypertensive therapy with metoprolol, alone, and in combination with thiazide diuretics. Metoprolol given alone to all patients for an average of 5 months (mean dose 230 mg) resulted in a reduction in systolic and diastolic pressure by 11% and 8%, respectively. In eight patients the BP reduction was considered inadequate (non-responders). In the group as a whole, ECV increased significantly by 5%. The increase in ECV in the non-responders was five times larger than in the responders (1.025 ml against 205 ml), which may in part account for the inadequate BP control. Addition of a thiazide diuretic for an average of 3.5 months resulted in reduction of ECV to its pretreatment level and a pronounced additional fall in BP, comparable to that in the responders. No systematic change in PV or GFR could be demonstrated. No difference was found between the two groups regarding sex, pretreatment BP, body fluid volumes or renal function. On average the non-responders were 20 years older than the responders. The clinical importance of the apparent age-related expansion of ECV and the mechanism behind fluid retention during antihypertensive treatment with beta-blocking drugs are discussed. As failure of BP control during treatment with beta-blockers may be due to fluid retention, concurrent use of diuretics is indicated.
    Materialart: Digitale Medien
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  • 70
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 25-32 
    ISSN: 1432-1041
    Schlagwort(e): clonidine ; hypertension ; baroreceptor reflex ; mode of action ; sympathetic activity ; urinary catecholamines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 113-118 
    ISSN: 1432-1041
    Schlagwort(e): tolmesoxide ; vasodilators ; hypertension ; side-effects ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 73
    ISSN: 1432-1041
    Schlagwort(e): carteolol ; hydrochlorthiazide ; amiloride ; hypertension ; double-blind clinical trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 74
    ISSN: 1432-1041
    Schlagwort(e): beta-blocker ; hypertension ; clonidine ; plasma catecholamines ; metoprolol ; propranolol ; blood pressure responses ; isometric work ; dynamic work
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 445-449 
    ISSN: 1432-1041
    Schlagwort(e): pindolol ; hypertension ; retard formulation ; plasma levels ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 76
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 473-477 
    ISSN: 1432-1041
    Schlagwort(e): tolmesoxide ; vasodilators ; heart failure ; haemodynamics ; hypertension ; sulphoxide
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 77
    ISSN: 1432-1041
    Schlagwort(e): vasodilator ; hypertension ; antihypertensive treatment ; catecholamines ; renin ; aldosterone ; blood volume
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 285-288 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; plasma adrenaline ; plasma noradrenaline ; isoprenaline response ; noradrenaline response ; salivation ; parasympathetic nervous system
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 79
    ISSN: 1432-1041
    Schlagwort(e): bopindolol ; hypertension ; beta-blocker ; blood pressure ; plasma renin ; plasma catecholamines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 80
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 335-338 
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; atherosclerosis ; hypertension ; serum lipoproteins
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 347-349 
    ISSN: 1432-1041
    Schlagwort(e): reserpine ; syrosingopine ; prolactin secretion ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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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  • 82
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 15-19 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; mianserin ; clonidine ; methyldopa ; depression ; α2 receptors ; interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 1-5 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; calcium antagonists ; beta-blockers ; vasodilators ; diuretics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nifedipine has been assessed as a possible alternative to other third line drugs in the management of patients with difficult to control hypertension. A group of 20 patients whose blood pressure was unsatisfactory on a 3 drug regimen had their third drug stopped and after a 2 week period nifedipine was added to their beta-blocker plus diuretic therapy. Eleven became normotensive on 30 mg nifedipine daily and a further 6 on 60 mg daily; giving on overall success rate of 85%. This result was achieved with a reduction in side effects and an absence of any haemodynamic or metabolic complications.
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  • 84
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 301-305 
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; hypertension ; pindolol ; peripheral vasodilator ; acetylator phenotypes ; antinuclear antibodies ; SLE-syndrome ; side-effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nineteen out-patients with moderate to severe essential hypertension were treated daily for 3 years, with an average dose of 13 mg endralazine, a new peripheral vasodilator, in free combination with pindolol 3×5 mg. The blood pressure showed a statistically significant reduction from 172/110 mmHg to 154/92 mmHg after treatment for 3 weeks. Tachyphylaxis was not observed during the 3 year period. Oedema was the most frequent side-effect, but it disappeared spontaneously. No difference in efficacy and tolerance between slow and fast acetylators was found. Only 2 patients developed a weak positive antinuclear antibody titre, which disappeared spontaneously from one during continued treatment. No clinical evidence of a systemic lupus erythematosus-like syndrome was noted. It is concluded that the differences between endralazine and hydralazine in dosage and metabolism may explain the lower immunogenic activity of endralazine.
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  • 85
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; beta-adrenoceptor blockade ; long-term treatment ; adverse effects ; propranolol ; timolol ; metoprolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The antihypertensive effect of nifedipine during long-term therapy was investigated in 5 patients receiving nifedipine as the sole drug and in 10 patients who had nifedipine in combination with a beta-adrenoceptor blocking drug. Nifedipine monotherapy was problematic because of side-effects and development of resistance to therapy after a few months. In patients who received the combined therapy significant and stable blood pressure reductions were maintained during the whole observation period (12–33 months). However, the occurrence of peripheral oedema in 4 of the patients necessitated the addition of a thiazide diuretic. It is concluded that nifedipine is not a first choice drug for the long-term treatment of arterial hypertension. When given in addition to a beta-blocker it is well tolerated and powerful but fluid retention may occur and if not counteracted by a diuretic it will limit the antihypertensive potential of the drug.
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 481-490 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
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  • 87
    ISSN: 1432-1041
    Schlagwort(e): pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I–II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p〈0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p〈0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the changes in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p〈0.05); four patients complained of oedema. Therapy was discontinued in one patient after a fainting episode following an increase in the dose. Thus, pinacidil was able to lower blood pressure during monotherapy for 4 weeks provided that an adequate serum concentration was achieved. The present retarded tablet formulation is not suitable for b. d. dosing. The tendency towards fluid-retention suggests that pinacidil should be used in combination with a diuretic.
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  • 88
    ISSN: 1432-1041
    Schlagwort(e): captopril ; propranolol ; sympathetic nervous system ; noradrenaline ; aldosterone ; renin ; angiotensin converting enzyme ; hypertension ; isometric exercise
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations. The expected acute increase in heart rate on standing and during isometric exercise was blunted by propranolol, but the changes in blood pressure and plasma noradrenaline were unaffected. We conclude that in essential hypertension noradrenaline is involved in the pressor response to isometric exercise. Angiotensin converting enzyme inhibition by captopril did not interfere with the responses of the sympathetic nervous system to postural changes and isometric exercise. During propranolol treatment there was no evidence that reduced sympathetic activity was involved in the hypotensive response.
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  • 89
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 197-201 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; hypertension ; low dose ; plasma concentration ; acute and long-term treatment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The acute and long-term hypotensive effects of low doses of nifedipine, and the correlation between the fall in the blood pressure (BP) and the plasma nifedipine concentration, were investigated in patients with essential hypertension. The oral administration of nifedipine 5 mg rapidly decreased BP from 163±22/101±10 to 127±12/82±9 mmHg (mean±SD; p〈0.001), and increased heart rate from 72±8 to 76±6 beats/min (p〈0.05), plasma renin activity rose from 1.2±0.6 to 1.4±0.8 ng/ml/h (p〈0.05), and plasma nifedipine concentration was 75.6±22.0 ng/ml 30 min after administration (n=7). The nifedipine concentration was significantly correlated both with the fall in BP (r=0.410, p〈0.02, n=31) and the rise in the heart rate (r=0.412, p〈0.02, n=31). Treatment with nifedipine 5 mg t.d.s. alone or in combination either with propranolol 10 mg t.d.s., or thiazide 1 tablet daily, or propranolol and thiazide, controlled BP in 36 patients during the 22 week study period. During the long-term nifedipine therapy, the plasma nifedipine level was significantly correlated with the fall in systolic (r=0.577, p〈0.01, n=20) and diastolic (r=0.595, p〈0.01, n=20) BP. It was concluded that the plasma nifedipine concentration could be correlated with the fall in BP, and that low doses of nifedipine, either as monotherapy or in combination, were effective in the acute and long-term treatment of patients with essential hypertension.
    Materialart: Digitale Medien
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  • 90
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 215-220 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; muzolimine ; mild renal functional impairment ; diuretic treatment ; body sodium ; catecholamines ; cardiovascular pressor responsiveness
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eighteen patients with mild impairment of renal function (glomerular filtration rate 65±5 ml/min: m±SEM) and hypertension (168/105±6/3 mmHg) were shown on average to have abnormally increased cardiovascular pressor responsiveness to infused norepinephrine (NE; p〈0.05), whereas plasma and urinary NE, exchangeable body sodium and blood-volume did not differ significantly from normal. A slightly increased pressor responsiveness to angiotensin II was associated with a tendency to low plasma renin activity (PRA). Compared to placebo conditions, treatment with the loop-diuretic muzolimine in a mean dose of 35±2 mg/day for six weeks decreased blood-pressure and exchangeable sodium (p〈0.05), and NE pressor responsiveness was restored to normal values, whilst plasma and urinary NE were not significantly changed. This was consistent with improvement of the initially abnormal relationship between NE levels and NE responsiveness factors. In contrast, the pressor dose of angiotensin II and PRA were increased to an approximatively similar extent during muzolimine treatment. These observations suggest that removal of body sodium and a decrease in NE reactivity without an equivalent increase in sympathetic nervous activity may be important complementary factors in the antihypertensive mechanisms of diuretic treatment in patients with mild renal functional impairment.
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  • 91
    ISSN: 1432-1041
    Schlagwort(e): prizidilol ; vasodilator ; hypertension ; beta blocker ; plasma renin ; aldosterone ; catecholamines ; acetylator type
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (〈107 mmHg) from 3 to 7 h and was still below predose levels 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to 〈95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidilol.
    Materialart: Digitale Medien
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 315-323 
    ISSN: 1432-1041
    Schlagwort(e): captopril ; hypertension ; glomerular filtration ; para-aminohippuric acid ; renal function ; severe drug reaction ; nephrotic syndrome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of captopril up to 450 mg/day on blood pressure and renal function were investigated during sustained treatment of 10 patients whose severe hypertension had not responded to previous therapy. All the patients were kept on diuretics and most of them on β-blockers, too. A control determination of glomerular filtration rate (GFR) and para-aminohippuric acid clearance (CPAH) was performed during the prior treatment. The effect of the addition (or substitution) of captopril were assessed after an average of 25 days (short-term) and 26 weeks (long-term). Short-term treatment produced a 15.5% decrease in mean blood pressure and interindividually variable effects on renal function. On average GFR was somewhat lower and CPAH slightly higher than the control values (not significant). This pattern is quite similar to the effects of most other antihypertensive drugs. On long-term therapy GFR rose by a mean of 9% (NS) and CPAH by 17% (p〈0.02). However, in a patient who developed a captopril-induced nephrotic syndrome, GFR dropped to 56% and CPAH to 50% of the control values. In another patient a transient rise in serum creatinine accompanied a severe drug reaction.
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  • 93
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 145-150 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; hypertension ; pharmacokinetics ; tablet formulation ; dose-response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (−18%) and lasted longer (12 h) after 60 mg than after 20 mg (−11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration — time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r=0.61,p〈0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 38 (1990), S. S139 
    ISSN: 1432-1041
    Schlagwort(e): carvedilol ; serum lipid metabolism ; hypertension ; normotension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of carvedilol (an α · β-blocker) on lipid metabolism were assessed in addition to its hypotensive effect. The subjects were 18 men and 18 women, 20 with hypertension and 16 normotensives with other conditions requiring carvedilol treatment. They were aged from 31 to 79 years and were given a daily dose of 5–20 mg carvedilol (average, 9.7 mg/day) for 12 weeks. Significant falls were seen in blood pressure and heart rate after 12 weeks in the hypertensive subjects (mean ± SE) (systolic: from 164 ± 2 to 141 ± 2 mm Hg,P 〈 0.001; diastolic: from 98 ± 1 to 85 ± 2 mm Hg,P 〈 0.001; heart rate: from 71 to 65 beats/min,P 〈 0.001). Smaller changes in blood pressure and heart rate were seen in the normotensive subjects, with the fall in systolic pressure being significant (from 143±3 to 135 ± 2 mm Hg,P 〈 0.01). There were no significant changes in the overall serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and phospholipid levels. In the subgroup with a pretreatment serum triglyceride level of 〉 150 mg/dl, a significant fall of 52.1 mg/dl was seen (P 〈 0.05). Lipoprotein analysis showed a significant fall in α-lipoprotein levels (P 〈 0.05). The atherogenic index did not change significantly, and it was concluded that carvedilol was an effective antihypertensive agent that produced no adverse effects and possibly had beneficial effects on lipid metabolism.
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  • 95
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; combination treatment ; hydrochlorothiazide ; carvedilol ; atenolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Carvedilol [25 mg once daily] (o. d.) was compared to atenolol (50 mg o. d.) as an adjunct to pre-existing hydrochlorothiazide (HCTZ) monotherapy in patients with mild to moderate hypertension [diastolic blood pressure (DBP),100–115 mm Hg]. After a placebo run-in phase of 2 weeks, 131 patients received 25 mg HCTZ o. d. for 4 weeks. In all, 122 patients were transferred to the double-blind phase, in which 25 mg carvedilol or 50 mg atenolol was randomly added to HCTZ. After an additional 6 weeks of treatment, 112 patients were evaluable for efficacy (C/HCTZ group,n = 54; A/HCTZ group,n = 58). Blood pressure was measured and the heart rate was counted before medication, at 2-week intervals throughout the trial, and 2 h after medication on the 1st and the last day of the combination treatment period. Serum lipids were measured in addition to routine laboratory variables. A therapeutic response was defined as a reduction in supine and standing diastolic blood pressure to values of 〈 90 mmHg. In a relatively low number of patients (6 of 131), a response as defined above was achieved with HCTZ alone. This may be accounted for by the fact that patients were required to have a diastolic blood pressure of at least 100 mgHg and by the relatively short period of monotherapy. The two groups of patients receiving different combination treatments were well matched for demographic data and blood pressure values before the adjunct was added. In both groups there was a marked additional blood pressure decrease on the initiation of combined treatment. At the end of the study the medians of all blood pressure values were well within normal ranges, which was not the case with HCTZ alone. On the last day of the trial, the responders comprised 67% of the C/HCTZ group and 71% of the A/HCTZ group. No relevant changes in lipid values were observed with combination treatment vs diuretic monotherapy. No serious adverse event attributable to one of the study drugs was reported. The results of the present trial suggest that the antihypertensive efficacy of both combinations is superior to that of HCTZ alone and that there is no difference in efficacy between the two combinations. Adding carvedilol or atenolol to pre-existing HCTZ appears to be safe. The tolerability of the antihypertensive treatment does not seem to decline, despite considerable additional decreases in blood pressure.
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  • 96
    ISSN: 1432-1041
    Schlagwort(e): Verapamil ; renal replacement therapy ; hypertension ; pharmakokinetics ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty-eight hypertensive patients on renal replacement therapy (HD, HF, PD) were treated with verapamil (Isoptin RR-slow release) in an open label study. Blood pressure was satisfactorily reduced in 21 patients (84%). Due to adverse reactions the treatment had to be discontinued in 4 patients. Verapamil clearances were calculated according to different dialysis methods. No changes in dose or mode of application of verapamil were necessary using any mode of renal replacement therapy.
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  • 97
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; verapamil haemodynamics ; atrial natriuretic peptide ; elderly ; clinical trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The antihypertensive effect of the calcium-antagonist verapamil was investigated in two groups of patients, adult hypertensives (AH, 〈 65 years of age) and elderly hypertensives (EH, 〉 65 years of age), who were treated with 240 mg p. o. sustained-release (SR) verapamil for 4 months. Arterial blood pressure was significantly reduced in both groups: the responders' rate was 65% in the AH group and 82% in the EG group. The heart rate was slightly but not significantly reduced. An improvement in cardiac haemodynamics was observed [cardiac index (CI), from 3.00 ± 0.51 to 3.25 ± 0.83 ml min−1 m−2 in AH and from 2.35 ± 1.08 to 3.04 ± 0.86 ml min−1 m−2 in EG]. We also evaluated the plasma concentrations of atrial natriuretic peptide (ANP) before and after treatment; ANP levels increased significantly only in the EH group. No serious side effects occurred. In conclusion, verapamil SR provided effective and well-tolerated antihypertensive treatment in both adult and elderly patients.
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  • 98
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 39 (1990), S. 539-543 
    ISSN: 1432-1041
    Schlagwort(e): Felodipine ; hypertension ; vasodilator ; haemodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sixteen patients with previously untreated mild/moderate hypertension (WHO Stage I) were studied: 7 women and 9 men, mean age 56.2 y. Haemodynamics, central and pulmonary blood volumes were measured by radionuclide techniques and repeated after 8 weeks felodipine therapy. To achieve a target diastolic blood pressure of 〈 95 mm Hg 12 patients required 5 mg bid, 2 10 mg bid and 1 2.5 mg bid; 1 withdrew after 2 weeks. Mean (SD) arterial blood pressure (mm Hg) was 189/106 before, and 182/103 after 2 weeks placebo treatment and fell to 148/84 after 8 weeks felodipine therapy. Relative systemic vascular resistance fell by 19% from 2146 to 1734 dyn.s.cm−5. There were no significant changes in heart rate, cardiac index, total blood volume, pulmonary blood volume or left ventricular ejection fraction. Plasma renin activity did not rise significantly. Short lived vasodilator side effects occurred in 7/16 patients during initial treatment and mild ankle oedema persisted in 4/16 patients. In contrast to the haemodynamic changes seen acutely with felodipine, the only sustained changes after 8 weeks therapy are reductions in systemic vascular resistance and blood pressure.
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  • 99
    ISSN: 1432-1041
    Schlagwort(e): Captopril ; Diabetes ; nephropathy ; hypertension ; glucose tolerance ; plasma lipids ; blood pressure ; long-term treatment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of the angiotensin converting enzyme inhibitor captopril on blood pressure, proteinuria, creatinine clearance and metabolic control in diabetic nephropathy have been evaluated. Captopril 144 mg per day was given to 8 longstanding, insulin-dependent, diabetic females with nephropathy. The blood pressure was significantly reduced (systolic 45.4, diastolic pressure 30.6 and mean arterial pressure 33.8 mm Hg after 24 weeks of treatment). Plasma renin activity rose significantly from a basal value of 1.60 to 6.71 ng·ml−1·h−1, and so did serum potassium (from 4.57 to 4.83 mEq·l−1). Serum aldosterone fell from 161 to 70.9 pgm·ml−1 and from 27.3 to 15.3 μg·24 h−1 in plasma and urine, respectively, after 6 months on captopril therapy. Urinary protein excretion was decreased by about 48% and creatinine clearance remained unchanged throughout the study. Plasma triglycerides and cholesterol also remained unchanged, and glycosylated haemoglobin was significantly reduced from 13.8 to 10.2% after captopril. The results suggest that captopril is a useful drug to treat hypertension in patients suffering from diabetic nephropathy, as the decline in kidney function can be reduced without impairing glucose tolerance or the lipid profile.
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  • 100
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 5 (1973), S. 151-153 
    ISSN: 1432-1041
    Schlagwort(e): Beta-blockade ; substituted indole ; hypertension ; glucose tolerance ; serum insulin ; clinical trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Glucose tolerance tests were done in hypertensive patients before and after treatment for several months with the beta-blocking compound pindolol, Visken. The mean blood sugar and serum insulin levels did not alter significantly during the treatment.
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