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  • hypertension  (164)
  • Springer  (164)
  • Blackwell Publishing Ltd
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  • Springer  (164)
  • Blackwell Publishing Ltd
  • 1
    ISSN: 1432-1041
    Keywords: hypertension ; indapamide ; pindolol ; plasma renin activity ; plasma aldosterone concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with essential hypertension completed a double blind factorial trial comparing the effects of indapamide (2.5 mg daily) and pindolol (10 mg daily) on blood pressure, heart rate, plasma renin activity and plasma aldosterone concentration. There were four randomised test phases of eight weeks each during which patients received indapamide alone, pindolol alone, indapamide plus pindolol and no active treatment (placebo). Blood pressure and heart rate were measured every two weeks. Supine mean arterial pressure fell from 117 mm Hg in the placebo phase to 111 mm Hg in the indapamide phase, 106 mm Hg in the pindolol phase and 103 mm Hg in the combined indapamide plus pindolol phase. Factorial analysis confirmed that the hypotensive effects of the two drugs were additive, without evidence of potentiation or antagonism. Indapamide caused significant reductions in plasma potassium and chloride, and increases in plasma bicarbonate and urate concentrations; it also caused increases in plasma renin activity and aldosterone concentration. These changes are similar to those observed with thiazide diuretics.
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  • 2
    ISSN: 1432-1041
    Keywords: guanfacine ; methyldopa ; hypertension ; rebound hypertension ; withdrawal symptoms ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine patients with essential hypertension completed a clinical trial designed to study the effects and side effects of administration and withdrawal of guanfacine (2 mg tds) and methyldopa (250 mg tds) on blood pressure, heart rate, and plasma noradrenaline. The study was of randomised doubleblind crossover design with two active therapy phases of eight weeks each, preceded by an initial 4 week placebo phase, separated by an intermediate 2 week placebo phase, and followed by a final 2 week placebo phase. Patients took bendrofluazide 5 mgs daily throughout the entire trial, during both active and placebo periods. Each patient was admitted to hospital at the end of the 8 week active treatment phases, so that the effects of drug withdrawal on blood pressure, heart rate, plasma noradrenaline and side reactions, could be closely observed and monitored. The main conclusions from analysis of the results were that: 1. The hypotensive efficacy of guanfacine and methyldopa was very similar in the doses used, each of the two drugs lowering the supine mean arterial pressure by about 15 mm Hg and the supine diastolic pressure by about 10 mm Hg. 2. The frequency of side effects was greater with guanfacine than with methyldopa. 3. There was no signficant early rebound phenomenon after withdrawal of either methyldopa or guanfacine. 4. There was tendency for the blood pressure to rise slowly and marginally above initial placebo values, 2 weeks after cessation of guanfacine treatment though this was not significant. It was however, accompanied by a significant increase in plasma noradrenaline at 2 weeks. This was not seen 2 weeks after cessation of methyldopa. There was no single incidence of worrying rebound hypertension or withdrawal symptoms either early or late in any patient following cessation of methyldopa or guanfacine.
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  • 3
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; controlled-release metoprolol ; systolic and diastolic blood pressure ; heart rate ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups 195 hypertensive patients were randomly allocated to treatment with either conventional tablets of metoprolol, 100 mg once daily, or a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily. The dose was doubled if the patient's diastolic blood pressure remained ≥95 mmHg after six weeks on 100 mg, whereas well-controlled patients continued on 100 mg once daily for a further six-week period. In the metoprolol tablet group the 200 mg dose was administered in the form of Durules. There was a significant reduction from the placebo baseline in systolic and diastolic blood pressure and heart rate at 24 h after both six weeks and 12 weeks of active treatment; no significant difference in the mean reduction from baseline between the two groups was demonstrated. However, significantly more patients responded to treatment with metoprolol CR when compared with those patients taking metoprolol tablets. After six weeks of active treatment 61% of the metoprolol CR group and 56% of the conventional metoprolol tablet group had a diastolic blood pressure 〈95 mmHg. After another six weeks the corresponding figures were 83% and 69% respectively. Between week 6 and 12, 36% of patients in the metoprolol CR group and 42% of patients in the conventional metoprolol tablet group were receiving a 200 mg dose. All formulations of metoprolol were well-tolerated. Fewer subjective symptoms were reported during active treatment than during the placebo phase. There were no differences between the groups with regard to changes in laboratory variables from baseline, changes in all combined symptoms, or changes in any one symptom.
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  • 4
    ISSN: 1432-1041
    Keywords: felodipine ; propranolol ; hydrochlorothiazide ; hypertension ; general practice ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighty one patients with uncomplicated hypertension who required additional antihypertensive medication (diastolic Phase V [dBP]≧95 mm Hg) after 4 weeks treatment with hydrochlorothiazide (HCTZ) 25 mg o.m. were randomized to receive felodipine 5 mg b.i.d. (n=40) or propranolol (n=41) 80 mg b.i.d. in addition to HCTZ 25 mg o.m. If the dBP measured about 12 h post-dose was not ≦90 mm Hg after 4 weeks, the dose of felodipine or propranolol was doubled. The double blind trial period was 8 weeks for all patients. Over the 8 week period, felodipine reduced the seated dBP from 100 to 83 mm Hg and propranolol from 101 to 86 mm Hg. The attained seated dBPs were significantly different in the two groups. About one third of patients in each group received the high dose of second-line therapy. After 8 weeks 91% of patients receiving HCTZ+felodipine and 84% receiving HCTZ+propranolol had a dBP ≦ 90 mm Hg. Both regimens were well-tolerated with an equal incidence but different pattern of adverse events (felodipine: flushing, headache and peripheral oedema; propranolol: dyspepsia, fatigue and vasospasm). In this 8-week study, felodipine and propranolol were safe and effective second-line antihypertensive drugs when added to hydrochlorothiazide. At the doses selected, felodipine was at least as effective as propranolol.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 21-24 
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha-adrenergic blockade ; bioavailability ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mm Hg in the supine and 13/18 mm Hg in the standing position. Adverse effects were generally mild and of brief duration.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 20 (1981), S. 163-168 
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; cardiac output ; extracellular fluid volume ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril 450 mg/day for 4 weeks on blood pressure, heart rate, cardiac output and extracellular fluid volume were compared in severe, often drug-resistant hypertension (n=23), mild to moderate hypertension associated with renal artery stenosis (n=10) and mild to moderate essential hypertension (n=20). Plasma renin in the three groups was 52±19, 58±17 and 20±4 µU/ml (mean ± SEM), respectively. Blood pressure fell by 18±4%, 21±2% and 18±1%. The pressure drop was mainly due to a fall in peripheral vascular resistance. Addition of the diuretic hydrochlorothiazide (25–100 mg/day) caused a further fall in resistance. Despite the vasodilator effect of captopril, reflex cardiostimulation and reactive fluid retention were not observed. In severe hypertension, captopril alone was more effective in lowering blood pressure than combined diuretic-betablocker-vasodilator therapy. Moreover, cardiac output in these patients was higher and resistance was lower after captopril than during combined treatment. Thus, captopril was capable of normalising the abnormal haemodynamic state in patients with essential hypertension, and in hypertension associated with renal artery stenosis. Despite marked differences in pre-treatment plasma renin, the effects of captopril on systemic haemodynamics were similar in all the patients.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1985), S. 395-399 
    ISSN: 1432-1041
    Keywords: Ro 31-1118 ; cardioselectivity ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with mild hypertension were given single oral doses of Ro 31-1118 (10, 20, 40, and 80 mg) and placebo in a randomized, double-blind, within-patient study. Plasma concentrations of Ro 31-1118 and supine, standing, exercise, and post-exercise heart rates and blood pressures were measured before and at regular intervals after drug administration. The pharmacokinetic data were consistent with a one-compartment model with first-order absorption and a variable time lag. Peak plasma concentrations and area under curve were linearly related to dose, whereas time to peak concentration, half-time, clearance and apparent volume of distribution were dose-independent. There was a reduction in exercise and post-exercise heart rate of approximately 10% after 10 mg and 20 mg Ro 31-1118, and of approximately 15% after 40 mg and 80 mg. At all doses standing systolic blood pressure was reduced by approximately 5%. A similar fall was seen in exercise and post-exercise systolic blood pressures. There was no substantial effect of Ro 31-1118 on supine or standing heart rates nor on diastolic blood pressure. No adverse effects were reported. It is concluded that Ro 31-1118 has linear pharmacokinetics over the dose range 10–80 mg, and has a weak antihypertensive effect when administered in single doses to patients with mild hypertension.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1985), S. 401-403 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; once daily dosing ; atenolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We report the first placebo controlled parallel group study of once daily endralazine (5–20 mg) in hypertension uncontrolled by a beta-blocker plus a diuretic. Following a 4-week run-in period 22 patients with a sitting mean arterial pressure (MAP) greater than 110 mm Hg were entered into the study and received either endralazine 5 mg or placebo. Blood pressure was measured 2 h and 24 h after dosing and the drug dose doubled at 2 and 4 weeks if the 24-h MAP remained 〉110 mg Hg. The final blood pressure assessment was made after 6 weeks treatment in the 19 patients who completed the study. Three patients withdrew from the study because of side effects. The hypotensive effect (sitting) was in excess of placebo at 2 h by 15.8 mm Hg systolic (NS), 15.4 mm Hg diastolic (p〈0.01), 15.5 mm Hg MAP (p〈0.02) and at 24 hours by 7.7 mm Hg systolic (NS), 8.9 mm Hg diastolic (p〈0.02) and 11.1 mm Hg MAP (p〈0.02). This study suggests that endralazine should be prescribed twice daily.
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  • 9
    ISSN: 1432-1041
    Keywords: captopril ; propranolol ; sympathetic nervous system ; noradrenaline ; aldosterone ; renin ; angiotensin converting enzyme ; hypertension ; isometric exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1986), S. 561-564 
    ISSN: 1432-1041
    Keywords: hypertension ; beta-adrenoceptor blockers platelet aggregation ; cyclic-AMP ; metoprolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with uncomplicated moderate essential hypertension were recruited to evaluate the effect of the non-selective beta-blocker propranolol and the beta1-selective beta-blocker metoprolol on platelet aggregation and cAMP formation. Five patients began treatment with propranolol 80 mg b. i. d. and 5 with metoprolol 100 mg b. i. d., and after 2 weeks the treatments were exchanged. ADP- and adrenaline-induced platelet aggregation and the basal level of platelet cAMP were measured at the end of each treatment period. Platelet aggregation was tested turbidometrically, using the threshold value for irreversible aggregation, and cAMP measurements were performed using a protein-binding assay. Both ADP and adrenaline thrshold values were significantly lower after propranolol than after metoprolol. The basal cAMP level was lower during propranolol than metoprolol treatment. The results indicate that platelet aggregation and basal cAMP level are influenced by beta-blockers in proportion to their affinity to different beta-adrenoceptors. This may be of value in the beta-blocker treatment of patients at high thrombotic risk.
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