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  • hypertension  (276)
  • Springer  (276)
  • Cell Press
  • 1985-1989  (146)
  • 1980-1984  (130)
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  • Springer  (276)
  • Cell Press
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  • 1
    Electronic Resource
    Electronic Resource
    Cardiovascular regulation and lipoprotein profile during administration of co-dergocrine in essential hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 119-125 
    Details
    ISSN: 1432-1041
    Keywords: co-dergocrine ; hypertension ; presynaptic dopamine2-receptors ; norepinephrine ; haemodynamic effects ; side-effects ; renin-angiotensin-aldosterone system ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-dergocrine has recently been demonstrated acutely to lower plasma norepinephrine (NE) and blood pressure (BP) in patients with essential hypertension, and similar results have been obtained during chronic administration of co-dergocrine to healthy men. The present study investigated the effect of 3 weeks of treatment with co-dergocrine 4 mg/day on BP, plasma catecholamines, certain other BP-regulating factors and serum lipoproteins in patients with essential hypertension. Compared to placebo conditions, co-dergocrine decreased supine BP and heart rate by −7% and the upright plasma NE level by −24%. Supine plasma NE also fell (−24%). Total cholesterol and the LDL + VLDL-cholesterol lipoprotein fraction were lowered by −6%. No significant change was observed in plasma renin activity, angiotensin II, aldosterone and epinephrine levels, whole blood and plasma volume, exchangeable sodium, and the cardiovascular responsiveness to NE, angiotensin II and isoproterenol. The findings suggest that in patients with essential hypertension, chronic treatment with co-dergocrine may slightly decrease sympathetic outflow and, at least in the short-term, lower the potentially atherogenic serum LDL + VLDL − cholesterol fraction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609182
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  • 2
    Electronic Resource
    Electronic Resource
    Antihypertensive and hypouricaemic effects of nitrendipine in chronic renal failure (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 223-227 
    Details
    ISSN: 1432-1041
    Keywords: nitrendipine ; renal failure ; hypertension ; uric acid excretion ; metabolic effects ; cardiovascular risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the potential therapeutic value of calcium antagonists in hypertension associated with impaired renal function, blood pressure (BP), certain regulatory factors, and metabolic correlates of cardiovascular risk have been assessed in 15 patients with mild to marked chronic renal failure before and after 6 weeks of therapy with nitrendipine. Compared to placebo, nitrendipine (mean final dose 55 mg/day) decreased supine BP from 173/102 to 146/81 mm Hg and upright BP from 170/105 to 145/86 mm Hg. Heart rate, body weight (+0.8 kg) and exchangeable sodium (+176 mmol, not significant) were minimally increased, and plasma and whole blood volume, plasma angiotensin II and creatinine concentrations, and urinary electrolyte and creatinine excretion were not significantly changed. Nitrendipine increased uric acid excretion and lowered plasma uric acid by 24%; glucose, insulin, serum total lipids, and lipoprotein fractions were unchanged.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558151
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  • 3
    Electronic Resource
    Electronic Resource
    Enalapril and hydrochlorothiazide in hypertensive Africans (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 229-234 
    Details
    ISSN: 1432-1041
    Keywords: enalapril ; hydrochlorothiazide ; hypertension ; side-effects ; Africans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy both of angiotensin converting enzyme (ACE) inhibitors and thiazide diuretics has been claimed to be influenced by plasma renin activity, which declines with age and is low in blacks. In a double-blind, placebo-controlled, double-dummy, randomized, parallel-group preliminary study, the antihypertensive efficacy and tolerability of the ACE inhibitor enalapril (20 mg day−1) and hydrochlorothiazide (50 mg day−1) were evaluated and compared for 4 weeks in 20 African patients with essential hypertension. The two groups had similar baseline clinical features and serum Na+ and K+ levels. Hydrochlorothiazide caused a significant and sustained fall in erect blood pressure with a reflex tachycardia. Enalapril exerted only a modest antihypertensive action, but significantly reduced erect heart rate. Direct comparison of hydrochlorothiazide — and enalapril — induced hypotension suggested a greater fall in subjects on the thiazide. The 95% confidence limits for the thiazide-enalapril difference in antihypertensive action at the end of the study was 39.5 to −7.5 mm Hg systolic and 22.0 to −6.6 mm Hg diastolic. The maximal blood pressure fall after hydrochlorothiazide was positively correlated with age (r=0.50;p〈0.05), whilst that of enalapril was inversely related age to (r=−0.57,p〈0.05). The results are compatible with the notion that ACE inhibitor monotherapy may be less effective than thiazide diuretic treatment in African and black patients with essential hypertension. The findings also support the concept that age and racial factors may influence the response to antihypertensive treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558152
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  • 4
    Electronic Resource
    Electronic Resource
    Antihypertensive effect of slow-release nicardipine. A placebo-controlled cross-over study (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 439-442 
    Details
    ISSN: 1432-1041
    Keywords: calcium antagonists ; nicardipine ; hypertension ; placebo effect ; slow-release preparation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The magnitude and duration of the anti-hypertensive effect of slow-release nicardipine (SR-Nicardipine) have been compared with placebo in 36 uncomplicated essential hypertensives (diastolic BP 95 to 115 mm Hg after 1-month placebo washout). According to a double-blind, randomized, cross-over design they received SR-Nicardipine 40 mg b.d. and placebo for 1 month. At the end of each treatment period, blood pressure and heart rate were measured 12 h after the evening dose and 1, 2, 3 and 4 h after the morning dose. SR-Nicardipine significantly reduced systolic (SBP) and diastolic (DBP) blood pressure at each time after dosing. The absolute decrements peaked 4 h after dosing (−18.3 and −11.7 mm Hg, respectively) and more than 90% of the peak effect persisted 12 h after dosing, both for SBP and DBP. The heart rate was slightly increased by SR-Nicardipine. Adverse effects monitored with a check-list occurred in 31% of patients during SR-Nicardipine treatment and in 28% on placebo. Thus, SR-Nicardipine 40 mg b.d. has a maintained and significant antihypertensive effect lasting up to 12 h in essential hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558066
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  • 5
    Electronic Resource
    Electronic Resource
    Dependent oedema and attenuation of postural vasoconstriction associated with nifedipine therapy for hypertension in diabetic patients (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 333-335 
    Details
    ISSN: 1432-1041
    Keywords: diabetes mellitus ; nifedipine ; hypertension ; oedema ; vasodilator ; blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We studied the incidence of oedema 2 weeks following initation of nifedipine therapy for hypertension in a group of 10 diabetic subjects, and also measured skin blood flow (SBF) with a laser Doppler flowmeter, before and after lowering the foot. SBF with the foot horizontal increased after nifedipine from 0.31V (arbitrary units of flow) to 0.51V (NS). The postural fall in blood flow in dependency was significantly attenuated by nifedipine from 64.4 to 24.0%. Five patients developed ankle oedema. Results were similar in a small group of non-diabetic subjects starting nifedipine. The attenuation of reflex postural vasoconstriction is therefore likely to contribute to development of the oedema associated with starting nifedipine therapy, which should be monitored carefully in diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558495
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  • 6
    Electronic Resource
    Electronic Resource
    Renal and hormonal effects of alpha1-adrenoceptor blockade by bunazosin in essential hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 575-578 
    Details
    ISSN: 1432-1041
    Keywords: bunazosin ; hypertension ; alpha1-adrenoceptor blocker ; blood pressure ; renal blood flow ; renal function ; renin ; aldosterone ; atrial natriuretic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal and hormonal effects of the α1-adrenoceptor blocker bunazosin were examined in 6 patients with essential hypertension. Oral bunazosin for 4 to 12 weeks significantly decreased mean blood pressure by 10%, increased effective renal blood flow and creatinine clearance by 34% and 37%, respectively, the plasma norepinephrine concentration was elevated by 60%, and the plasma atrial natriuretic peptide level was lowered by 22%. The plasma renin activity and aldosterone concentration were unchanged. Thus, a moderate reduction in blood pressure was produced by bunazosin treatment while maintaining renal perfusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637738
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  • 7
    Electronic Resource
    Electronic Resource
    Comparative haemodynamic effects of ketanserin and ritanserin in the proximal and distal upper limb circulations of hypertensive patients (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 215-220 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; ritanserin ; hypertension ; haemodynamics ; alpha1-adrenoceptor blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of ketanserin (40 mg p.o.) on blood pressure and brachial haemodynamics (brachial artery diameter, brachial blood velocity and blood flow) have been compared in a double-blind study with those of ritanserin (10 mg p.o.) and placebo. Haemodynamic parameters were measured before and 1 h after treatment. Patients with mild to moderate essential hypertension participated in this study, 6 each on ketanserin, ritanserin and placebo. Placebo significantly reduced heart rate and did not modify the other parameters. Compared to placebo, ketanserin significantly reduced systolic and diastolic blood pressure, increased brachial blood velocity and flow, and decreased forearm vascular resistance. Compared to placebo, ritanserin slightly decreased blood pressure and slightly increased blood flow, but neither effect was significant. When blood circulation to the hand was excluded, neither ketanserin nor ritanserin modified the proximal arterial resistance or blood flow. It is concluded that the actions of ketanserin and ritanserin essentially occurred in the distal part of the upper limb, and alpha1-receptor blockade is probably involved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00679772
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  • 8
    Electronic Resource
    Electronic Resource
    Once daily nisoldipine in hypertension: cuff and ambulatory intra-arterial blood pressure (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 551-554 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; ambulatory monitoring ; cuff blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cuff blood pressure data has suggested that the calcium channel antagonist nisoldipine has full twenty four hour efficacy. To test this, 24 h ambulatory intra-arterial blood pressure monitoring was performed on 18 untreated hypertensive subjects (12 men, 6 women) (cuff blood pressure 〉150/95 mm Hg) before and after chronic treatment with 10–20 mg oral nisoldipine taken daily at 08.00 h. Twelve patients completed the study, six being withdrawn, four because of side-effects. After baseline intra-arterial monitoring patients were started on 10 mg nisoldipine daily. Response was assessed by cuff pressures taken 24 h after dosing at fortnightly intervals, and if not controlled (〈150/95 or at least 10 mm Hg reduction in diastolic BP) the dose was increased to 20 mg. All patients received at least six weeks' therapy before the second intra-arterial blood pressure monitoring. There was a slight but insignificant reduction in mean daytime heart rate of 3 beats·min−1. Mean significant reduction in daytime systolic and diastolic BP was 19 mm Hg and 13 mm Hg respectively but there was no significant mean night-time reduction. By comparison 8 out of 12 patients were apparently controlled more than 24 h post dose according to cuff pressures. This study suggests that this formulation of nisoldipine does not control blood pressure over a full 24-h period, and emphasises the importance of 24 h ambulatory monitoring in assessing the efficacy of once-daily antihypertensive agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562542
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  • 9
    Electronic Resource
    Electronic Resource
    Effect of nicardipine on insulin secretion, glucose and lipid metabolism in hypertensive, non-insulin dependent diabetics (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 1-4 
    Details
    ISSN: 1432-1041
    Keywords: nicardipine ; insulin ; glucose ; diabetes ; hypertension ; metabolic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Certain acute and chronic metabolic effects of nicardipine have been studied in 20 patients with non-insulin dependent diabetes (NIDD). An intravenous glucose tolerance test (i.v. GTT, glucose 0.33 g/kg as a bolus) and the corresponding insulin response were assessed at the end of a 4 week placebo period, after the first dose and on administration for 12 weeks of nicardipine 20 mg t.i.d. The glucose and insulin responses to the i.v. GTT, evaluated as incremental AUCs, did not change significantly (glucose 30.5 mg/dl·90 min on placebo, 33.1 mg/dl·90 min acutely and 31.4 mg/dl·90 min on chronic administration of nicardipine; insulin 2.08 µU/ml·90 min on placebo, 1.87 µU/ml·90 min acutely and 1.93 µU/ml·90 min after chronic nicardipine). Glucose removal rate (KG) following the i.v. GTT was 0.73%/min on placebo 0.75%/min on acute administration and 0.8%. min−1 with chronic nicardipine. Active treatment produced a significant reduction of blood pressure (from 187/96 mm Hg on placebo to 166/89 mm Hg acutely and 152/83 mm Hg after 12 weeks of nicardipine treatment). It is concluded that the calcium antagonist nicardipine was an effective antihypertensive drug, and that it did not cause deterioration of metabolic control in hypertensive patients with NIDD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561014
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  • 10
    Electronic Resource
    Electronic Resource
    Is captopril effective in controlling blood pressure when administered once daily? An assessment using 24-h ambulatory blood pressure monitoring (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 11-15 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; once-daily administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve patients with essential hypertension receiving captopril monotherapy or captopril in conjunction with a diuretic had their 24-h blood pressure profiles monitored using an automatic, non-invasive ambulatory method. The study examined the efficacy of once a day versus twice a day administration of the ACE inhibitor in controlling blood pressure. Six untreated subjects with borderline hypertension were also studied using the same monitoring equipment and with the same frequency, to act as controls because of the possibility of repeated use of the device causing a ‘familiarisation’ effect. The results obtained indicated that if anything, the once daily dosing produced marginally better blood pressure values. The amplitude of the diurnal blood pressure variation was reduced on a ‘second-wearing’ of the monitoring equipment suggesting some degree of familiarisation with the apparatus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561016
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  • 11
    Electronic Resource
    Electronic Resource
    Effect of carteolol on renal function in healthy subjects and patients with hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 83-86 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; hypertension ; chronic renal failure ; renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of short- and long-term administration of carteolol on renal function has been examined in healthy subjects and in hypertensive patients with or without renal failure. In healthy subjects neither a single dose of 10 mg carteolol nor continuous administration of 20 mg/day for 7 days had any effect on creatinine clearance and renal blood flow. In all subjects the clearance rate of carteolol was about 400 ml/min and its fractional excretion of carteolol exceeded 300%, suggesting that the drug is secreted actively from renal tubules. Twenty-three hypertensive patients with or without renal dysfunction were given carteolol 10 to 20 mg/day for more than 50 weeks in addition to their standard antihypertensive regimens, which were left changed. Laboratory results were compared with the mean values of 50 weeks before and after the addition of carteolol, and none, including plasma creatinine, blood urea nitrogen and electrolytes, were significantly changed. Neither the estimated glomerular filtration rate nor the effect of the drug on blood pressure changed significantly during this prolonged treatment. It is concluded that carteolol had no effect on renal function in healthy subjects and in hypertensive patients with or without renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561030
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  • 12
    Electronic Resource
    Electronic Resource
    Responses of glomerular filtration, renal blood flow and salt-water handling to acute cardioselective and non-selective β-adrenoceptor blockade in essential hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 343-345 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; pindolol ; renal haemodynamics ; salt-water handling ; hypertension ; beta-adrenoceptor blockade ; ISA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects on renal hemodynamics and salt-water handling of equipotent doses of the cardioselective β-blocker metoprolol (M, 100 mg) and of the non-selective (intrinsic sympathetic activity) β-antagonist pindolol (P, 10 mg) were compared in 30 WHO Grade 1–2 hypertensive men. M lowered pulse rate more than P. Systolic pressure was equally reduced by both agents, and diastolic and mean pressures were decreased only after P. Glomerular filtration rate was not significantly altered by either antagonist, and renal blood flow decreased by approximately 11% both after M and P. Renal vascular resistance was unchanged after P, and was increased by 10% after M. It is concluded that, like the effects on central haemodynamics, ISA is more important in the renal response to β-adrenoceptor blockade than is β-receptor selectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558292
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  • 13
    Electronic Resource
    Electronic Resource
    Long-term effect of pindolol on lipids and lipoproteins in men with newly diagnosed hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 347-350 
    Details
    ISSN: 1432-1041
    Keywords: pindolol ; hypertension ; hyperlipidaemia ; chronic treatment ; cholesterol ; HDL ; LDL ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This is the first long-term study of pindolol in a population-based sample of men with newly diagnosed hypertension. Eighty-two patients, with a diastolic pressure of 100 mm Hg or more, were identified after screening 6000 men. Many patients were overweight. 82 population controls, matched by sex, age and body mass index, were also recruited. Fourty-eight per cent of the patients and 25% of the controls had a family history of hypertension. Serum triglyceride and urate values were higher in patients than controls at the baseline investigation. Seventy-four patients were followed for 1 year. The dose of pindolol averaged 7.7 mg once daily after 1 year. The diastolic blood pressure was reduced by 13.4 mm Hg. The target pressure of 95 mm Hg or less was achieved in 89% of the patients. The HDL-cholesterol concentration was normal and did not change, whereas the LDL-cholesterol concentration decreased by 0.15 mmol · l−1 during treatment. The total triglyceride values increased transiently up to 6 months, but no significant increase was seen after one year. It is concluded that pindolol had no adverse effect on serum cholesterol and its HDL- and LDL-fractions during 1 year of treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558293
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  • 14
    Electronic Resource
    Electronic Resource
    Acute calcium entry blockade inhibits the blood pressure but not the hormonal responses to angiotensin II (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 567-573 
    Details
    ISSN: 1432-1041
    Keywords: isradipine ; hypertension ; blood pressure ; calcium entry blockade ; renin angiotensin system ; aldosterone plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of acute calcium entry blockade by isradipine (IS) and placebo (P) on the haemodynamic and humoral responses to angiotensin II (A II) have been compared in two groups of 9 patients with essential hypertension. During 4 sequential periods each of 20 min, an i.v. infusion of A II 0, 2, 4 and 8 ng · kg−1 · min−1 was given before (control) and 30 min after the oral administration either of IS or P. After IS, both the blood pressure and the angiotensin II-induced pressor effect were significantly reduced. Isradipine increased the heart rate and this cardio-acceleration was potentiated by A II. In contrast, when A II was infused in the absence of IS, heart rate tended to decrease. IS stimulated plasma renin activity and reduced plasma aldosterone. However, it did not affect either the inhibition of plasma renin activity or the rise in plasma aldosterone in response to A II. In conclusion, acute calcium entry blockade in patients with essential hypertension reduces the pressor response to A II, but not the A II-induced inhibition of renin and increase in plasma aldosterone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637737
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  • 15
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ramipril in hypertensive patients with renal insufficiency (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 249-256 
    Details
    ISSN: 1432-1041
    Keywords: ramipril ; renal insufficiency ; hypertension ; pharmacokinetics ; ramiprilat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1–2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5–15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15–40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40–80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex. The study indicates that in patients with severe renal insufficiency (creatinine clearance below 30 ml/min) smaller doses of ramipril are required than in patients with normal or borderline renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00679779
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  • 16
    Electronic Resource
    Electronic Resource
    Haemodynamic effects and pharmacokinetics of felodipine at rest and during exercise in hypertensive patients treated with metoprolol or atenolol (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 459-465 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; atenolol ; hypertension ; exercise ; pharmacokinetics ; adverse effects ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure ≥95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558124
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  • 17
    Electronic Resource
    Electronic Resource
    The effect of nisoldipine on renal function in the long-term treatment of hypertension in patients with and without renal impairment (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 437-441 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; renal function/-impairment ; calcium antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of nisoldipine on renal function after 6 weeks treatment was investigated in hypertensive patients with and without renal impairment. Nisoldipine was well tolerated and an effective antihypertensive agent when administered over a period of 6 weeks. There were no significant changes in glomerular filtration, cardiac output, plasma renin activity or serum biochemistry during nisoldipine administration. Effective renal plasma flow was unaffected by treatment in the patients with normal renal function, but in the patients with renal insufficiency, the value decreased by a mean of 12%. Nisoldipine had no major untoward effects on renal function after 6 weeks administration, but minor changes in renal haemodynamics in the patients with renal insufficiency would suggest that careful monitoring of renal function is indicated in such patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558120
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  • 18
    Electronic Resource
    Electronic Resource
    Ambulatory blood pressure monitoring during sustained treatment with conventional and extended-release felodipine in mild-to-moderate hypertension (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 555-557 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; hypertension ; ambulatory blood pressure monitoring ; slow-release formulation ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess the duration of the antihypertensive effect of the dihydropiridine calcium antagonist felodipine in conventional (C-F) and slow-release (ER-F) formulations, 12 patients with essential hypertension underwent ambulatory blood pressure monitoring (ABPM) at the end of a 2-week treatment period with C-F 5 mg b.d., ER-F 10 mg once daily (o.d.) and placebo. C-F, ER-F and placebo were given in a double-blind 3×3 latin square design 4 times replicated. There was no systematic change in the ABP profile over the three study periods regardless of the treatment. In comparison to placebo, the mean 24-h systolic and diastolic blood pressures showed a significant and similar reduction after both formulations of F. Compared to placebo, C-F and ER-F induced a significant reduction in systolic blood pressure for 15 and 21 h, respectively, and of diastolic blood pressure for 16 and 21 h, respectively. Three patients complained of headache (mild in 2, moderately severe in 1), and two patients of nocturia, with either formulation of F.
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    Membrane transport and disease (1989)
    Springer
    Molecular and cellular biochemistry 91 (1989), S. 3-11 
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    ISSN: 1573-4919
    Keywords: calcium ATPase ; glucose transport ; herpes virus ; hypertension ; leaks ; pore-formation ; sodium channels ; stress ; toxins ; transport ; viruses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Four situations in which membrane transport is altered by disease are discussed: (a) non-specific leaks induced by poreforming agents; (b) glucose transport and cellular stress; (c) Ca+-ATPase and hypertension; (d) Na− channels and HSV infection.
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    URL: http://dx.doi.org/10.1007/BF00228073
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  • 20
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    Hemodynamics in emotional responses and in emotional stress (1989)
    Springer
    Neuroscience and behavioral physiology 19 (1989), S. 399-407 
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    ISSN: 1573-899X
    Keywords: hemodynamics ; stress ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In the article, we present experimental data indicating that negative emotional states evoked by electrical stimulation of the ventromedial hypothalamus or by behavioral conflicts are accompanied by a predominance of vascular responses of a presser character possessing the property of summation. In contrast, positive emotional states during a self-stimulation reaction or when animals attain behavioral results satisfying their major biological demands are accompanied by a predominance of pressor-depressor vascular reactions. In individual animals under conditions of experimental emotional stress in conflicting situations of a prolonged character, pronounced disturbances of cardiac-vascular functions occur. Predominantly pressor vascular reactions arise in response to forced stimulation of the ventromedial hypothalamus in such cases. It is shown that changes in vascular tonus plays a leading role in disturbances of AP regulation during stress of immobilization. The most frequent cause of death in animals under such conditions is a progressive fall of AP due to an abrupt decrease in the total peripheral resistance. The resistance of the cardiac-vascular functions to emotional stress is determined to a significant degree by genetic mechanisms.
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    URL: http://dx.doi.org/10.1007/BF01197872
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  • 21
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    Course of wound healing in spontaneously hypertensive rats under the influence of morphine, substance P, and its SP1–4 fragment (1989)
    Springer
    Bulletin of experimental biology and medicine 107 (1989), S. 867-871 
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    ISSN: 1573-8221
    Keywords: wound healing ; morphine ; hypertension ; substance P
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00840765
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  • 22
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    Platelet Na+/H+ exchange in spontaneously hypertensive rats (1989)
    Springer
    Bulletin of experimental biology and medicine 107 (1989), S. 200-202 
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    ISSN: 1573-8221
    Keywords: hypertension ; platelets ; sodium-proton exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00833802
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  • 23
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    Permeability of erythrocyte membranes for monovalent cations (Na+, K+) and their transformation in essential symptomatic (renal) hypertension (1989)
    Springer
    Bulletin of experimental biology and medicine 107 (1989), S. 632-635 
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    ISSN: 1573-8221
    Keywords: hypertension ; erythrocyte membrane permeability ; electron microscopy ; erythrocyte transformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00841769
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  • 24
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    Effect of methyldopa on prolactin serum concentration (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 513-515 
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    ISSN: 1432-1041
    Keywords: methyldopa ; prolactin ; hypertension ; sustained release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a group of ten hypertensive patients, the effects of methyldopa administration in two different formulations on serum prolactin (PRL) were studied. A single oral dose of normal release methyldopa significantly increased serum prolactin levels, peak concentrations occurring 3 to 6 h after drug administration. On the contrary, administration of sustained release methyldopa at the same dose was only followed by slight and not significant fluctuations in prolactin plasma levels. Both formulations produced a significant decrease of systolic and diastolic blood pressures, without significant differences between sustained and normal release methyldopa effects.
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    URL: http://dx.doi.org/10.1007/BF01046712
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  • 25
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    Evaluation of two oxprenolol oral osmotic (OROS) delivery systems in patients with essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 605-611 
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    ISSN: 1432-1041
    Keywords: oxprenolol ; hypertension ; osmotic delivery system ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two oxprenolol oral osmotic (OROS) delivery systems on heart rate and blood pressure before and during recovery from exercise at a predetermined load were examined in twelve patients with hypertension previously responding to beta-blocker monotherapy. Haemodynamic responses were attenuated during the 24 h after single and repeated (15 days') once daily administrations of 10/170 and 16/260 oxprenolol OROS. At 24 h after repeated doses, compared to placebo there were significant reductions in resting blood pressure and in heart rate immediately following exercise. Attenuation of heart rate after exercise was dose related but differences between the systems with respect to resting heart rate and blood pressure were inconsistent. Antihypertensive responses after repeated doses were greater than those after single doses. However, reductions in resting and exercise heart rates were consistently less on chronic therapy. This may reflect enhanced expression of the partial agonist activity of oxprenolol due to altered receptor sensitivity after prolonged beta-blockade. The plasma oxprenolol profiles after both systems indicated slow absorption and substantial concentrations were apparent 24 h after drug administration. These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise.
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    URL: http://dx.doi.org/10.1007/BF00615225
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  • 26
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    Sustained release verapamil in renal hypertension (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. 549-555 
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    ISSN: 1432-1041
    Keywords: verapamil ; sustained release formulation ; hypertension ; renal disease ; kidney function ; angiotensin II ; aldosterone ; arginine vasopressin ; atrial natriuretic peptide ; lipids and lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory and casual blood pressure readings plasma, angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, creatinine clearance, plasma lipids and lipoproteins, and body weight were determined after consecutive 3-week periods on placebo and sustained release verapamil 240 mg/day. Verapamil reduced the mean 24-h ambulatory blood pressure from 152/104 to 142/97 mm Hg. Blood pressure was significantly reduced during the daytime and the evening, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were found in the hormones, creatinine clearance, plasma lipids and lipoproteins, heart rate or body weight. The atrial natriuretic peptide level was significantly correlated with the calculated creatinine clearance (r=−0.797). Thus, sustained release verapamil 240 mg as a single daily dose had a moderate hypotensive effect in patients with chronic renal disease without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increasing body weight, and without altering renal function and plasma lipids and lipoproteins. The negative correlation between atrial natriuretic peptide and glomerular filtration rate supports the hypothesis that the extracellular volume increases during progression of renal disease.
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  • 27
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    A double-blind comparison of felodipine and hydrochlorothiazide added to metoprolol to control hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 21-24 
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    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; hydrochlorothiazide ; hypertension ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained ≥95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective ‘calcium antagonist’ felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metroprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if ‘control’ of BP (dBP 〈90 mmHg) was not achieved on the initial doses. Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose. Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.
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  • 28
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    Pharmacokinetics of lisinopril in hypertensive patients with normal and impaired renal function (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 61-65 
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    ISSN: 1432-1041
    Keywords: lisinopril ; renal failure ; half-life ; drug dose ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of lisinopril was studied after administration of single and multiple doses of 5 mg to hypertensive patients with normal and impaired renal function. In patients with severe renal failure the peak concentrations were higher, the decline in serum concentration was slower and the time to peak concentration was extended. Accumulation of lisinopril was highly correlated with the creatinine clearance. The effective half-life was doubled and tripled in patients with mild and severe renal impairment, respectively, as compared to patients with a normal renal function. Lisinopril lowered blood pressure in all three groups over 24 h. It is suggested that smaller doses of lisinopril should be administered to patients with severe renal failure.
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  • 29
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    A double-blind and cross-over comparison of once daily doxazosin and placebo with steady-state pharmacokinetics in elderly hypertensive patients (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 119-123 
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    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; elderly patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The α1-adrenoceptor antagonist doxazosin has been compared with placebo in 40 elderly hypertensive patients (mean age 71.4 years). At the end of 10 weeks once daily treatment with doxazosin the mean 24-h post-dose changes in standing and supine blood pressure compared with placebo were −6.9/−5.6 mmHg (systolic/diastolic) and −6.2/−5.5 mmHg respectively. The reductions in standing and supine diastolic blood pressures were statistically significant compared with placebo. At the end of treatment steady-state pharmacokinetics were evaluated in 18 patients. The plasma elimination half-life during the dose interval in these patients was 16.1 h (range 10.1–27.1 h) and the median time to peak plasma concentration was 3 h (range 1–4 h). One patient was withdrawn because of adverse effects (headache, weakness, and sweating) during doxazosin treatment. Once daily doxazosin reduced diastolic blood pressure and was well tolerated in these elderly hypertensive patients.
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    Effect of sustained-release verapamil therapy on the blood pressure at rest and on the pressor response to isometric exertion in hypertensive patients (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 549-553 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; hypertension ; sustained-release formulation ; handgrip test ; pressor activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a new formulation of verapamil sustained release (SR) 240 mg tablets on resting blood pressure (BP) and on the pressor response to isometric exertion have been examined in a single-blind, placebo-controlled, cross-over study in 12 hypertensive patients (mean age 45 years). SR verapamil and placebo were administered every 12 h for 6 consecutive weeks. At the end of each period of treatment BP and heart rate (HR) were measured at rest and during isometric exercise, performed as a handgrip (HG) test for 3 min at 30% of the maximum voluntary contraction. There was a significant reduction in resting systolic and diastolic BP, with no change in HR. BP and HR at peak exercise were lower after verapamil than after placebo, but the maximal absolute increase did not change during verapamil therapy. The results are compatible with a role of SR verapamil b.d. in reducing resting BP in hypertension, and in lowering very high pressure at the peak of a HG test, without modifying the physiological reactivity of cardiovascular system.
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    URL: http://dx.doi.org/10.1007/BF00615216
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    Renal function and blood pressure in patients treated with cyclosporin a for uveitis (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 601-604 
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    ISSN: 1432-1041
    Keywords: cyclosporin A ; uveitis ; renal function ; creatinine clearance ; hypertension ; corticosteroids ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal function has been evaluated in 21 patients treated with cyclosporin A (CyA) for 9 months for idiopathic uveitis. Serum creatinine, which was 82 µmol·l−1 before treatment, was significantly elevated after 1 month (111 µmol·l−1). After 9 months of treatment, and despite a decrease in CyA dosage, the mean plasma creatinine remained elevated at 132 µmol·l−1. Hypertension developed in 6 patients, five of them being concomitantly treated with corticosteroids. In 8 patients serum creatinine 3 months after CyA had been stopped had decreased from 148 to 93 µmol·l−1. Two of those patients remained hypertensive 3 months after CyA treatment had ceased. In patients with idiopathic uveitis CyA induces a reversible increase in serum creatinine. However the reversibility of such a biochemical marker does not preclude a histopathological lesion. Chronic renal damage may be responsible for the persistance of hypertension after cessation of CyA treatment
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  • 32
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    Efficacy and tolerability of a new controlled-release formulation of metoprolol: A comparison with conventional metoprolol tablets in mild to moderate hypertension (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S39 
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    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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  • 33
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    A comparison of felodipine and propranolol as additions to hydrochlorothiazide in the treatment of hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 115-118 
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    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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    Haemodynamic effects of short-term treatment with bopindolol in essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 411-413 
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    ISSN: 1432-1041
    Keywords: bopindolol ; hypertension ; beta-adrenoceptor blocker ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients (mean age 53 years) with essential hypertension have been studied at rest and during exercise following oral treatment for 6 weeks with a new beta-adrenoceptor blocking agent, bopindolol. The treatment caused a significant decrease in systolic and diastolic arterial blood pressure and heart rate, both at rest and during exercise. Stroke volume fell, too, and therefore so did cardiac output, whereas the systemic vascular resistance was increased. Left ventricular filling pressure was elevated both at rest and during exercise following bopindolol therapy. However, a different haemodynamic pattern was noted in patients with elevated total peripheral resistance prior to therapy (Group 1) compared to patients with normal or subnormal peripheral resistance (Group 2). A decrease in systemic vascular resistance seemed to be the cause of the fall in blood pressure in Group 1, as the expected increase in vascular resistance did not occur, whereas a reduction in cardiac output was of greater importance in Group 2. During exercise the lowering of arterial blood pressure in both groups was mediated by a reduction in cardiac output.
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    The efficacy and tolerability of atenolol, nifedipine, and their combination in the management of hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 543-548 
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    ISSN: 1432-1041
    Keywords: atenolol ; nifedipine ; hypertension ; adverse effects ; fixed combination ; drug efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this randomized, double-blind, crossover study we investigated the haemodynamic effects of a beta-blocker (atenolol 50 mg) and a calcium antagonist (nifedipine SR 20 mg) given either separately or in combination in three groups of hypertensive patients. Each treatment was administered twice daily. The fixed combination given twice daily for four weeks produced reductions in blood pressure which lasted for at least 12 h after administration of the last dose. The control of blood pressure by the combination was superior to that achieved by its individual components. Adverse effects normally associated with nifedipine were less frequent when it was given with atenolol. Compliance with treatment was good, but best when the drugs were given together rather than separately. A fixed combination of atenolol and nifedipine may prove useful in treating hypertensive patients inadequately controlled on beta-blocker therapy alone.
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    Doxazosin in patients with hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 21-24 
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    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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    The effect of hydralazine on steady-state plasma concentrations of metoprolol in pregnant hypertensive women (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 131-135 
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    ISSN: 1432-1041
    Keywords: metoprolol ; hydralazine ; hypertension ; pregnancy ; pharmacokinetics ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the plasma concentrations levels of metoprolol after its twice daily administration in a dose of 50 mg for 4 days in ten, hypertensive pregnant women to the during monotherapy and in combination with 25 mg of hydralazine given twice daily. Hydralazine increased the median AUC and Cmax of metoprolol by 38% and 88% respectively, and decreased the tmax from 1.5 h to 1.0 h. Hydralazine had no effect on the plasma concentrations of alpha-OH-metoprolol. These results suggest that the effect of hydralazine on metoprolol plasma concentrations is primarily due to a reduction in first-pass elimination.
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    A possible drug interaction between rifampicin and enalapril (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 431-432 
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    ISSN: 1432-1041
    Keywords: rifampicin ; enalapril ; hypertension ; drug interaction ; case report
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary When a 35-year-old man with essential hypertension was treated with antibiotics for brucellosis his blood pressure rose significantly. While all other treatment was kept constant rifampicin was discontinued. On rechallenge rifampicin did not alter serum concentrations of enalapril or the area under the curve (AUC) between 0 and 7 h, but it did reduce the AUC of the active metabolite enalaprilat by 31%. These observations suggest that there may be an interaction between rifampicin and enalapril, causing reduced hypotensive efficacy of enalapril. The mechanism of such an interaction merits further study, but it could be due to enhanced renal clearance of enalaprilat.
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    Cadralazine pharmacokinetics — A pilot study (1988)
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    European journal of clinical pharmacology 35 (1988), S. 571-572 
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    ISSN: 1432-1041
    Keywords: cadralazine ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00558256
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  • 40
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    Ketanserin combined with a beta-blocker or diuretic in essential hypertension. A multicentre study (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 573-577 
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    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; combination therapy ; diuretic ; beta-adrenergic blocker ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of ketanserin 40 mg b.d. in combination with a beta-adrenergic blocking agent or a diuretic was assessed in an open study in 35 patients with essential hypertension, who had not responded to treatment with beta-blockers, diuretics or their combination. The ketanserin/beta-blocker combination decreased mean sitting systolic/diastolic blood pressure (SBP/DBP) from 169/107 mm Hg to 156/91 mm Hg at the end of the 12-week active treatment period. The decrease in systolic blood pressure was significant only at Week 8, while the decrease in diastolic blood pressure was highly significant at all times. A significant reduction in heart rate by 10 beats·min−1 was observed with the ketanserin + β-blocker combination. The ketanserin/diuretic combination led to a significant reduction in mean SBP/DBP from 164/106 mm Hg to 146/92 mm Hg after 12 weeks, with no significant change in heart rate. Body weight slightly increased in both groups. There were significantly fewer adverse reactions with the ketanserin/diuretic combination than with the ketanserin/beta-blocker combination. The results indicate a potentially useful therapeutic role for ketanserin in combination with beta-blockers or diuretics.
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    URL: http://dx.doi.org/10.1007/BF00637591
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    Comparison of the antihypertensive effects of celiprolol and acebutolol (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 125-128 
    Details
    ISSN: 1432-1041
    Keywords: celiprolol ; acebutolol ; hypertension ; beta-blockers ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of the new cardioselective beta-blocker celiprolol and acebutolol have been compared. Thirty patients with arterial hypertension WHO Grade I–II were treated in a double-blind fashion with celiprolol or acebutolol. Before starting the treatment and on Days 15 and 29, before the morning dose, blood samples were taken for measurement of the plasma level of celiprolol. At the same times physical examinations, and clinical and urine chemistry analyses were performed. At the 99% probability level both drugs had significantly lowered the systolic and diastolic blood pressures to normal values at the end of the second and fourth weeks. There was no significant difference between their antihypertensive efficacy. The decrease in diastolic blood pressure at the end of the second week was significantly correlated with the reciprocal of the plasma celiprolol concentration at steady-state at the end of the dosage interval.
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    URL: http://dx.doi.org/10.1007/BF00614547
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    Verapamil and bendrofluazide in the treatment of hypertension: A controlled study of effectiveness alone and in combination (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 249-253 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; bendrofluazide ; hypertension ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of verapamil and bendrofluazide used singly and in combination were examined in patients with primary hypertension in a patient blind, partly observer blind placebo controlled study of parallel group design; there were ten subjects in each arm of the trial. Verapamil 160 mg twice daily caused supine mean arterial pressure to fall by 21 mm Hg; this reduction was significantly greater (p〈0.05) than that induced by bendrofluazide 5 mg daily which caused a fall of only 10 mm Hg. The addition of verapamil 160 mg twice daily to bendrofluazide 5 mg daily caused a further fall in pressure of 18 mm Hg (p〈0.005), but the reduction in pressure when bendrofluazide was added to verapamil was only 1 mm Hg and not significant. Bendrofluazide therapy caused a fall in plasma potassium concentration and an increase in plasma urate concentration; urinary calcium excretion was reduced. Verapamil caused no detectable biochemical alterations in plasma or urine.
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    URL: http://dx.doi.org/10.1007/BF00540951
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    Dose-titration study of alfuzosin, a new alpha1-adrenoceptor blocker, in essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 25-30 
    Details
    ISSN: 1432-1041
    Keywords: alfuzosin ; alpha1-adrenoceptor blockers ; hypertension ; adverse reactions ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week runin placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was 〉90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypothensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml. Nine of the 11 patients reached the end-point (supine diastolic BP≤90 mm Hg) at the end of 28 days: 1 at the dose of 5 mg b.d., 6 at 10 mg b.d. and 2 at 20 mg q.i.d. At the high dose they both complained of palpitations. Two other patients complained of mild and transient palpitations at lower doses.
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    URL: http://dx.doi.org/10.1007/BF00555503
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    Effect of clonidine on beta-endorphin, ACTH and cortisol secretion in essential hypertension and obesity (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 115-121 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; obesity ; betaendorphin ; ACTH ; cortisol ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of alpha2-adrenoceptor stimulation by clonidine on the secretion of beta-endorphin, ACTH, and cortisol in essential hypertension and obesity was studied in 45 subjects: 15 non-obese hypertensives, 10 obese hypertensives, 11 obese normotensives, and 9 healthy subjects. The circadian rhythm of plasma beta-endorphin, ACTH, and cortisol was determined after placebo and after three days on clonidine 0.45 mg daily. Clonidine lowered the blood pressure and blood ACTH and cortisol levels in all the subjects. A significant decrease in beta-endorphin after clonidine occurred in the healthy subjects. In obese normotensives basal beta-endorphin concentrations were significantly higher than in healthy subjects and did not change after clonidine. In about 50% of non-obese and obese hypertensives a significant increase in beta-endorphin secretion after clonidine was noted (responders). In the subgroup of non-obese hypertensive responders no circadian rhythm of beta-endorphin was observed. The results suggest that adrenergic regulation of beta-endorphin secretion is altered in obesity and in certain patients with essential hypertension.
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    URL: http://dx.doi.org/10.1007/BF00609239
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    Effect of controlled-release metoprolol on blood pressure and exercise heart rate in hypertension: A comparison with conventional tablets (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S33 
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    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; tolerability ; exercise ; once-daily dosing ; controlled-release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily, was compared with conventional metoprolol tablets, 100 mg once daily, in 27 patients with primary hypertension. Exercise tests on a bicycle ergometer were undertaken 24 h after intake of the last dose of the drug following a four-week placebo run-in period and after four weeks of active treatment. Heart rate, measured in the supine position and during exercise at the highest comparable workload, was reduced significantly more by metoprolol CR (p〈0.05), thus indicating a higher degree of β1-blockade at the end of the dose interval with metoprolol CR. There was a greater reduction in supine systolic pressure (p〈0.05) but not in supine diastolic pressure after metoprolol CR than after conventional tablets at 24 h. There was no significant difference between the two groups with respect to reduction in systolic blood pressure during exercise. The 24-h plasma concentrations of metoprolol CR and conventional tablets correlated with the effects on heart rate, but not with blood pressure. The tolerability of metoprolol CR was comparable with that of metoprolol administered as conventional tablets. In conclusion, there was significantly greater β1-blockade 24 h after the intake of drug after metoprolol CR compared with conventional tablets.
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    24-hour control of blood pressure by once daily doxazosin: a multicentre double-blind comparison with placebo (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 613-618 
    Details
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; adverse effects ; multicentre study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy of the new, once daily, alpha1-adrenoceptor inhibitor, doxazosin, was compared with placebo in 40 patients with mild to moderate hypertension. Following a dose titration the mean final daily doxazosin dose in 20 patients was 13.1 mg. Through-the-day blood pressure control was assessed by frequent measurements during 24 h hospitalisation in the 9 th week of double-blind treatment compared with similar measurements made during a 2 week single-blind placebo run-in. Mean reductions in standing and supine systolic and diastolic blood pressure during doxazosin treatment were statistically significantly greater than during placebo treatment at most hourly time points during the 24 h post-dose period. Twenty-four post-dose the mean falls in standing and supine diastolic blood pressure during doxazosin treatment were statistically significant when compared with placebo. Adverse effects during doxazosin treatment were generally minor and were tolerated or disappeared with continued therapy. No patients were withdrawn from the study due to adverse effects. We conclude that once daily doxazosin provides smooth and effective blood pressure control throughout a 24 h post-dose period.
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    URL: http://dx.doi.org/10.1007/BF00615226
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    Effects of dilevalol, an R, R-isomer of labetalol, on blood pressure and renal function in patients with mild-to-moderate essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 9-15 
    Details
    ISSN: 1432-1041
    Keywords: dilevalol ; hypertension ; labetolol R-R-isomer ; renal function ; plasma renin activity ; plasma aldosterone ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of oral dilevalol (an R, R-isomer of labetalol), a new β-adrenoceptor blocker with β2-receptor stimulating and α-recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks. Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study. Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA. The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects.
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    URL: http://dx.doi.org/10.1007/BF00555500
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    The effects of the 5 HT2 antagonist ritanserin on blood pressure and serotonin-induced platelet aggregation in patients with untreated essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 123-129 
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    ISSN: 1432-1041
    Keywords: ritanserin ; hypertension ; serotonin ; (5 HT) ; blood pressure ; platelet aggregation ; QT interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have given the selective 5 HT2 antagonist ritanserin in a dose of 10 mg twice daily for 4 weeks in a double-blind, randomized, placebocontrolled, parallel group study of 18 patients with untreated essential hypertension. The fall in single platelet count due to 5 HT-induced platelet aggregation was significantly reduced by ritanserin compared with placebo (p〈0.05). There were no significant changes in supine or erect blood pressure or heart rate after ritanserin compared to placebo. Forearm blood flow, measured by mercury-in-strain gauge venous occlusion plethysmography, was not significantly altered by ritanserin. Ritanserin caused prolongation of the QTc interval by 41 (SEM 11) ms (p〈0.05 compared to placebo) but had no detectable effect on QRS duration, features suggestive of Class III antiarrhythmic activity. These findings do not support an independent role of the 5 HT2 receptor in maintaining raised arterial pressure in essential hypertension.
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    URL: http://dx.doi.org/10.1007/BF00609240
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    Inhibition of the aldosterone response to sodium depletion in man by stimulation of dopamine DA2 receptors (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 323-326 
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    ISSN: 1432-1041
    Keywords: aldosterone ; DA2-receptor ; co-dergocrine ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study we have investigated the effect of co-dergocrine, a selective DA2-agonist, on plasma aldosterone concentrations (PAC) in twelve patients with essential hypertension both in basal conditions and during sodium depletion. Sodium depletion resulted in an increase of PAC from 38 (13) pg/ml to 297 (21) pg/ml. The PAC response to sodium depletion was reduced to 155 (29) pg/ml by co-dergocrine. No significant PAC changes were found in patients maintained on a normal sodium intake. In addition the drug did not significantly modify plasma renin activity (PRA) in either experimental group. These results suggest that the dopaminergic inhibition of aldosterone secretion in man is mediated by DA2-receptors in the adrenal cortex.
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    URL: http://dx.doi.org/10.1007/BF00558273
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    Increased Na+/H+ exchange in erythrocytes of hypertensive patients (1988)
    Springer
    Bulletin of experimental biology and medicine 106 (1988), S. 1246-1249 
    Details
    ISSN: 1573-8221
    Keywords: erythrocytes ; Na+/H+ exchange ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00834485
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    Development of high blood pressure in spontaneously hypertensive rats is delayed by treatment with cyclosporin at an early age (1987)
    Springer
    Cellular and molecular life sciences 43 (1987), S. 403-405 
    Details
    ISSN: 1420-9071
    Keywords: SHR ; cyclosporin ; immune mechanisms ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In spontaneously hypertensive rats the effect of the T-cell inhibitor cyclosporin was studied at different ages. If treatment was started at the age of 2 weeks the development of hypertension was delayed, but the ultimate level of blood pressure was not affected. These results indicate the involvement of immune mechanisms in the early development of hypertension in spontaneously hypertensive rats.
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    URL: http://dx.doi.org/10.1007/BF01940428
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    A comparative study of the pharmacokinetics and pharmacodynamics of atenolol, hydrochlorothiazide and amiloride in normal young and elderly subjects and elderly hypertensive patients (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 53-60 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; amiloride ; hydrochlorothiazide ; young ; elderly ; pharmacokinetics ; pharmacodynamics ; volunteers ; patients ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six normal young and six normal elderly volunteers and six elderly hypertensive patients took part in an acute and chronic dose study of a combination capsule containing atenolol (50 mg), hydrochlorothiazide (25 mg) and amiloride (2.5 mg) designed for the treatment of hypertension. No difference in any of the drug pharmacokinetic parameters could be detected between the hypertensives and the normal elderly subjects. The bio-availability and the 24-h blood concentrations of all three drugs, half-life of atenolol and amiloride and the peak concentration of hydrochlorothiazide was significantly greater in the elderly. The 24-h blood concentrations of atenolol and hydrochlorothiazide did not alter with chronic dosing, but amiloride concentrations were significantly higher at this time in all groups. A significant fall in the blood pressure was observed in the hypertensive group. Heart rate fell more in the normal and hypertensive elderly subjects than in the young. The combination has shown to be an effective and well tolerated antihypertensive in the elderly patient with a 24-h duration of action.
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    The influence of ibuprofen, diclofenac and sulindac on the blood pressure lowering effect of hydrochlorothiazide (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 553-557 
    Details
    ISSN: 1432-1041
    Keywords: ibuprofen ; diclofenac ; sulindac ; anti-inflammatory drugs ; hypertension ; NSAIDs ; hydrochlorothiazide ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open triple crossover study in 8 patients with essential hypertension, the possibility has been investigated of whether the blood pressure lowering effect of hydrochlorothiazide 50 mg once daily was attenuated by co-administration for 4 weeks of ibuprofen 400 mg t.i.d., diclofenac 25 mg t.i.d. or sulindac 200 mg b.i.d. Only a slight, statistically non-significant change was found, with the exception of a significant increase in systolic blood pressure after 4 weeks treatment with ibuprofen. There was considerable variation in the blood pressure response during treatment with all three NSAIDs, with slight rises in blood pressure in 13 out of 24 periods. Body weight increased significantly on treatment both with ibuprofen and diclofenac, whereas the increase on sulindac was less and was transient. No significant change was found in various biochemical parameters, including plasma electrolytes, plasma renin activity (PRA), aldosterone, albumin and creatinine, in haematocrit or in the 24-h urinary excretion of sodium and potassium. The sole exception was a decrease in PRA during ibuprofen treatment. From these observations it is concluded that ibuprofen and diclofenac differ from sulindac in their interaction with the diuretic action of hydrochlorothiazide. It appears that all three NSAIDs can safely be combined with hydrochlorothiazide in hypertensive patients, but blood pressure should be monitored carefully when an NSAID are added.
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    Prazosin partly blocks clonidine-induced hypotension in patients with essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 331-334 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; clonidine ; interaction ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prazosin has been reported to reduce the hypotensive and/or bradycardic effect of clonidine in various animal models. Investigations in humans have given conflicting conclusions about the effectiveness of the combination of clonidine and prazosin. In patients with essential hypertension prazosin significantly reduced the hypotensive effect of intravenous clonidine, but it failed to affect the clonidine-induced bradycardia. This finding means that the combination of prazosin and clonidine is inappropriate in antihypertensive therapy.
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    The haemodynamic and humoral effects of treatment for one month with the angiotensin converting enzyme inhibitor perindopril in salt replete hypertensive patients (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 519-524 
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    ISSN: 1432-1041
    Keywords: perindopril ; hypertension ; angiotensin converting enzyme inhibition ; renin-angiotensin system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the effects of treatment for one month with perindopril, 4 or 8 mg once daily, in seven hypertensive patients. Blood pressure was lowered from 164/93 mm Hg to 145/84 mm Hg by 4 mg of perindopril and after one month remained at 142/82 mm Hg. Neither postural hypotension nor tachycardia occurred. Inhibition of plasma angiotensin converting enzyme (ACE) lasting for over 24 h was achieved and there was a significant increase in plasma renin activity (PRA). Maximum plasma concentrations of the active metabolite of perindopril, S-9780, were detected four h after oral administration. After treatment for one month there was evidence of reduced sensitivity of plasma ACE to the action of the inhibitor. The plasma concentration of S-9780 required to produce 50% inhibition of plasma ACE rose from 2.4 ng · ml−1 following the first dose to 5.5 ng · ml−1 after one month.
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    Effects of bisoprolol on blood pressure, serum lipids and HDL-cholesterol in essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 77-80 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; bisoprolol ; beta1-adrenoceptor blocker ; serum lipoproteins ; HDL-cholesterol ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifty patients with essential hypertension WHO Grades I–II have been treated for 3 months with bisoprolol, a new selective betablocker, in doses up to 40 mg once daily. Forty-three patients reached the preset target diastolic blood pressure of ≤ 90 mmHg on a mean daily dose of 16.8 mg bisoprolol. There was no effect on serum lipids and HDL-cholesterol during the study. The side-effects were mild and were those usually associated with beta-blocking therapy.
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    Pharmacodynamics and pharmacokinetics of urapidil in hypertensive patients: A crossover study comparing infusion with an infusion-capsule combination (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 61-65 
    Details
    ISSN: 1432-1041
    Keywords: urapidil ; hypertension ; alpha-adrenoceptor blocker ; antihypertensive agent ; pharmacodynamics ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and haemodynamic effects of infused urapidil and an infusion-capsule combination were followed to study the correlation between the serum urapidil level and the blood pressure. Prior to urapidil administration, basal blood pressure and heart rate were measured for 16 h in 12 male hypertensive patients. Six patients received infusions lasting for 4 h of urapidil 10, 2.5 and 5 mg/h. Six patients were infused with urapidil 10 mg/h for 4 h and 2 h after the end of the infusion each took a 60-mg capsule. After a 5 day washout period the procedures were crossed over. A maximum serum urapidil level of 625±232 ng/ml was achieved at the end of the 10 mg/h infusion, when the fall in blood pressure was 37/21 mmHg. During the 2.5 and 5 mg/h infusions the serum urapidil level was 330 and 420 ng/ml, respectively, and the corresponding decreases in blood pressure were 28/16 mmHg and 31/8 mmHg. Although the urapidil concentration 1 hour after beginning the infusion was only 184±89 ng/ml a near maximal blood pressure decrease had already occurred 33±9/20±8 mmHg, whereas, 1 h after the end of the infusion the reduction in blood pressure was only 10±12/3±8 mm, with a urapidil concentration of 358±120 ng/ml. During the plateau phases of both the infusion and infusion-capsule treatments the falls in blood pressure followed the serum urapidil levels. Only in the initial rising and final falling phases of the treatments were the pharmacodynamics and pharmacokinetics of urapidil not correlated.
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    Acute natriuretic effect of nifedipine in hypertensive patients and normotensive controls – a proximal tubular effect? (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 121-126 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; renal function ; proximal tubule effect ; uric acid ; calcium blockade ; sodium excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute effects of buccal nifedipine 20 mg on blood pressure, renal haemodynamics and electrolyte excretion were compared in 16 untreated patients (HT) with uncomplicated arterial hypertension (WHO I-II), 11 normotensives (NT) and 6 normotensives given a placebo. Nifedipine caused a significant fall in the systolic and diastolic blood pressures (BP) of 25.7±12/26.5±10 mmHg in the hypertensives, and a minor but significant fall in diastolic BP in the normotensives. Renal vascular resistance fell significantly and renal plasma flow was increased non-significantly in the hypertensives. No changes in these parameters were seen in NT. Glomerular filtration rate remained constant in all groups, also in HT despite the marked haemodynamic changes. Natriuresis was significantly increased to the same degree in the HT and NT groups, in spite of their different haemodynamic responses. Uric acid excretion showed a parallel acute increase in both groups. The significant and close relationship between the acute changes in the excretion of sodium and uric acid provides evidence for a proximal tubular natriuretic effect of nifedipine.
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    Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 335-338 
    Details
    ISSN: 1432-1041
    Keywords: chlorthalidone ; magnesium depletion ; hypertension ; adverse effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K+ or Mg++. In the BB-group there was a statistically significant trend towards retention of Mg++ in a loading test, but the effect was clinically marginal. BB + CTD reduced serum K+ and Mg++ and caused significant Mg++ depletion, as shown by the Mg++ loading test. All the effects were highly significant and were clinically important. The metabolic perturbations due to CTD are potentially dangerous and make this drug unattractive as ‘first choice’ treatment for hypertension.
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    The effects of substituting frusemide for a thiazide diuretic in the drug regimens of patients with essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 31-34 
    Details
    ISSN: 1432-1041
    Keywords: thiazide diuretics ; hypertension ; electrolytes ; frusemide ; loop diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighteen patients with mild to moderate hypertension on a drug regimen which included a thiazide diuretic had the latter substituted by frusemide for twelve weeks after an initial two-week placebo wash-out period. Blood pressure and heart rate and a number of plasma and urinary biochemical indices were measured. Significant findings included a reduction in standing blood pressure and an elevation of plasma sodium, potassium, chloride, osmolarity, creatinine and alkaline phosphatase levels at the end of the twelve week frusemide phase relative to the values on the thiazide. However the means for all the biochemical indices remained within the normal laboratory reference limits. In the 24-hour urinary studies, no significant findings emerged, apart from an elevated calcium. The foregoing suggest that frusemide is an effective component of an anti-hypertensive drug regimen and that in a dose of 40 mg/day it produces no detectable perturbations of plasma electrolytes. The significance of the enhanced levels of urinary calcium excretion in conjunction with the augmented plasma alkaline phosphatase is unclear.
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    Comparison of nicardipine and propranolol in the treatment of mild and moderate hypertension (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 119-126 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; nicardipine ; propranolol ; serum lipids ; electrocardiogram ; side-effects ; ECG changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind controlled trial 22 patients with mild or moderate essential hypertension were treated with nicardipine 30 mg t.d.s. and 19 patients with propranolol 80 mg t.d.s. as monotherapy for 24 weeks. Blood pressure in both groups at the end of trial was equally and significantly reduced; systolic pressure 22.2 mmHg and diastolic pressure 15.5 mmHg in the supine position, and 24.4 mmHg and 18.4 mmHg, respectively, in the standing position in those on nicardipine, and by 23.7 and 16.2 mmHg and 28.0 and 19.2 mmHg, respectively, in the propranolol group. There was an initial increase in heart rate in the nicardipine group, but the rise was only moderate (3 beats/min supine p=0.3219, and 7 beats/min standing, p=0.0203) at the end of the 24 weeks. In the propranolol group heart rate was reduced markedly. Adverse effects occurred in 77% of patients on nicardipine and in 63% of those on propranolol, and there were no unexpected findings. The effects were mild in both groups and did not lead any patient to stop medication. One patient on propranolol was withdrawn from the trial because of poor blood pressure control and suspected angina pectoris after 5 weeks on active medication. There were no significant changes in blood chemistry, including lipoprotein classes. Overall, in comparison with propranolol, nicardipine was effective, well-tolerated and safe to use in the monotherapy of mild or moderate essential hypertension.
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    URL: http://dx.doi.org/10.1007/BF00544554
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  • 62
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    Metabolic effects of long-term therapy with muzolimine and chlorthalidone in hypertension (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 515-517 
    Details
    ISSN: 1432-1041
    Keywords: muzolimine ; chlorthalidone ; hypertension ; serum electrolytes ; potassium ; ion transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous short-term studies of muzolimine (a diuretic with frusemide-like activity) had shown that it did not induce a significant change in the serum potassium concentration. In the present study sodium and potassium handling and other metabolic variables have been compared during 16 weeks of therapy with muzolimine and chlorthalidone, a thiazide-like diuretic. During muzolimine treatment, plasma and red cell potassium concentrations remained unchanged, while a significant fall in potassium occured with chlorthalidone. Neither drug affected the activity of sodium-potassium cotransport or sodium-lithium countertransport in red cells in vitro. Muzolimine and chlorthalidone had similar effects on arterial pressure and on the other metabolic variables tested.
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    URL: http://dx.doi.org/10.1007/BF00544246
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  • 63
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    Acute systemic and renal haemodynamic effects and long-term antihypertensive action of cadralazine in patients pretreated with β-blockers and diuretics (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 513-518 
    Details
    ISSN: 1432-1041
    Keywords: cadralazine ; hypertension ; haemodynamic effects ; renal blood flow ; glomerular filtration ; renal function ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of the hydralazine-related compound cadralazine (2-{3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl}ethyl carbazate, ISF 2469), were investigated in 16 patients with primary hypertension concurrently treated with β-blockers and diuretics. The protocol included a double-blind placebo controlled haemodynamic evaluation after the first tablet and two 4-week double-blind placebo controlled cross-over periods followed by an open evaluation during 2 months. Cadralazine induced a moderate, prolonged fall in blood pressure that was associated with vasodilatation and slight increases in cardiac output (dye-dilution) and heart rate. Renal plasma flow (PAH) and glomerular filtration rate (51Cr-EDTA) were not significantly influenced, but the filtration fraction was reduced. Plasma concentrations of noradrenaline and adrenaline rose, whereas plasma renin activity was unchanged. The haemodynamic parameters were not correlated with the plasma concentrations of cadralazine. During chronic cadralazine treatment the supine blood pressure was significantly lower than during the double-blind placebo phase (160/93 vs 174/102 mmHg). The compound was generally well tolerated but the body weight increased slightly (1.1 kg), probably because of fluid retention. Several patients who had previously experienced side effects with hydralazine, including one with hydralazine-syndrome, tolerated cadralazine well. This suggests that cadralazine does not cross-react with hydralazine.
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    URL: http://dx.doi.org/10.1007/BF00606622
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    Pharmacokinetics of ketanserin in patients with essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 259-265 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; ketanserin-ol ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketanserin and its main metabolite ketanserin-ol, and the antihypertensive effects of intravenous, single oral and chronic oral (40 mg once daily) administration of ketanserin, have been investigated in a single blind study of 10 patients with uncomplicated mild hypertension. Ketanserin had a terminal half-life of 29.2 h, a plasma clearance of 518 ml/min and a volume of distribution of 18.0 l/kg. Chronic oral intake of 40 mg ketanserin (tablet formulation) gave a peak concentration of unchanged ketanserin of 88 ng/ml after 1.1 h. Its absolute bioavailability was 48%. During chronic therapy the maximal concentration of ketanserin-ol was 208 ng/ml and its half-life of elimination was 35.0 h. As this metabolite can be oxidized back to ketanserin, it contributes to the prolonged half-life of unchanged ketanserin seen during chronic therapy. The blood pressure was reduced by approximately 15% by oral ketanserin. The maximal reduction in blood pressure coincided with the peak concentration of unchanged ketanserin. During chronic therapy with 40 mg once daily blood pressure was reduced over 24 h. The heart rate was slightly reduced and the cardiovascular responses and the plasma noradrenaline concentrations during isometric exercise were only slightly influenced by ketanserin therapy. Thus, unchanged ketanserin has a relatively long half-life during chronic oral therapy and its pharmacokinetics in middle-aged hypertensive patients is similar to that in normal young volunteers.
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    URL: http://dx.doi.org/10.1007/BF00607573
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    Comparison of concomitant nicardipine hydrochloride and propranolol with propranolol alone in patients with essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 21-25 
    Details
    ISSN: 1432-1041
    Keywords: nicardipine ; propranolol ; hypertension ; concomitant administration ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A twelve-week parallel study was conducted to compare the efficacy and safety of nicardipine plus propranolol with that of propranolol alone in 67 patients with mild to moderate essential hypertension. Efficacy data was analysed for 50 patients. The regimens used were 90 mg · day−1 of nicardipine and 120 mg · day−1 of propranolol. Both treatments significantly reduced supine and standing systolic and diastolic blood pressure from baseline values at all visits. At all visits, concomitant administration of nicardipine and propranolol produced a greater reduction in systolic and diastolic pressures than did propranolol alone, although the difference between treatments did not always reach statistical significance. Few adverse events were reported, and none was clinically important. We conclude that nicardipine taken concomitantly with propranolol is more effective than propranolol alone in treating patients with hypertension and that the combined regimen is well tolerated.
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    URL: http://dx.doi.org/10.1007/BF00610374
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  • 66
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    The pharmacokinetics of ketanserin after a single dose and at steady-state in hypertensive subjects (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 423-426 
    Details
    ISSN: 1432-1041
    Keywords: Ketanserin ; pharmacokinetics ; hypertension ; ketanserinol ; predicted plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of ketanserin in 6 hypertensive patients after a single oral 40 mg dose and at steady-state after 4 weeks treatment with 20 mg and then 40 mg 12-hourly. Pharmacokinetic variables after a single dose were similar to those reported in healthy volunteers, with median values for Cmax 112 ng·ml−1, tmax 1 h, and t1/2 19 h. The corresponding values for the metabolite ketanserinol were Cmax 155 ng·ml−1, tmax 2 h, and t1/2 25 h. The median AUC was 3.3 times greater for ketanserinol than for the parent drug. These results were used to predict the mean steady-state plasma concentrations of ketanserin and ketanserinol. Predicted values were on average similar to those observed after four weeks treatment with 40 mg 12-hourly, although there were marked differences between the observed and predicted values in some patients. There was no evidence of time- or dose-dependent kinetics for ketanserin, but the study had insufficient power to exclude the occurrence of these phenomena entirely.
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    URL: http://dx.doi.org/10.1007/BF00637642
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  • 67
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    Assessment of ‘once daily’ verapamil for the treatment of hypertension using ambulatory, intra-arterial blood pressure recording (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 549-553 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; hypertension ; bicycle exercise ; isometric hand-grip
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new, slow release formulation of verapamil, “verapamil o.d.” was administered to 12 patients with essential hypertension. Drug administration was started at a dose of 240 mg and increased to 480 mg after 2 weeks of treatment if the cuff blood pressure response was unsatisfactory. The drug reduced the daytime intra-arterial blood pressure significantly from 180.7/106.8 mm Hg to 157.3/89.4 mm Hg. The daytime heart rate fell from 88.1 to 71.8 beats/min. The nighttime blood pressure decreased from 155.7/87.2 mm Hg to 140.5/75.3 mm Hg. The nocturnal heart rate decreased from 62.8 to 57 beats/min. Hourly plots of mean systolic and diastolic pressure showed a significant reduction of systolic pressure for 21 of 24 h and of diastolic pressure for all 24 h following a single morning dose. The drug modified the absolute blood pressure and heart-rate response during both forms of exercise, but did not alter the magnitude or rate of blood pressure change. The tilt-test produced no evidence of postural hypotension. Only one patient experienced any side effects whilst taking the drug. These results indicate good 24-h blood pressure control and reduced exercise blood pressure levels during treatment with this new formulation of verapamil. The reduced frequency of drug administration should improve patient complicance with treatment of hypertension.
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    URL: http://dx.doi.org/10.1007/BF02455986
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    The efficacy of a transdermal formulation of clonidine in mild to moderate hypertension and its effects on the arterial and venous vasculature of the forearm (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 111-114 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; transdermal administration ; baroreflex ; arterial compliance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the efficacy of clonidine hydrochloride administered transdermally once a week for 9 to 15 weeks in 12 patients with mild to moderate hypertension. Clonidine reduced both supine and standing blood pressures on average, but only 8 subjects were responders, i.e. had a decrease in supine diastolic blood pressure to below 90 mm Hg or more than 10% from baseline. Supine heart rate was unchanged, but in the responders the orthostatic increase in heart rate was reduced by clonidine from baseline (p〈0.05). Moreover, in all the patients the change in the orthostatic increase in heart rate was correlated with the change in supine diastolic pressure (p〈0.05). Brachial artery blood flow, forearm arterial compliance, vascular resistance, and venous tone were not affected by clonidine. Thus, transdermal clonidine reduced blood pressure, probably by a baroreflex-mediated effect, but did not affect the vasculature of the forearm.
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  • 69
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    Flosequinan as a third agent for the treatment of hypertension: A placebo controlled, double-blind study (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 203-204 
    Details
    ISSN: 1432-1041
    Keywords: flosequinan ; hypertension ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and short term antihypertensive effect of flosequinan was determined in 16 hypertensive patients whose blood pressure was inadequately controlled despite treatment with a β-adrenoceptor blocking agent and a diuretic. Erect and supine systolic and diastolic blood pressure was significantly reduced by flosequinan over the treatment period as compared to placebo. Heart rate was unchanged by flosequinan. Adverse effects were limited to mild headache in 3 patients and taste disturbance in 1 patient, possibly due to salivary excretion of the drug. Flosequinan is a potentially useful vasodilator for the treatment of hypertension.
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  • 70
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    Plasma renin activity does not predict the antihypertensive efficacy of chlorthalidone (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 221-226 
    Details
    ISSN: 1432-1041
    Keywords: renin-angiotensin system ; chlorthalidone ; hypertension ; multicentre study ; plasma renin activity ; dose prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It has been established that angiotensin II stimulation may limit the antihypertensive potential of diuretic therapy in some patients. It is less clear, however, whether renin-angiotensin II stimulation is the cause of the flat blood pressure dose-response relationship to diuretics. To investigate this, 75 out-patients with essential hypertension were treated with chlorthalidone 12.5, 25 or 50 mg o.d. for 3 weeks, in a double-blind, placebo controlled cross-over study. Chlorthalidone significantly reduced blood pressure in all the groups, a plateau being reached at 25 mg o.d. Similarly, plasma renin activity was increased by each dose level of chlorthalidone, but it showed a different trend, being increased to a comparable extent at 12.5 mg and 25 mg o.d., and still higher at 50 mg o.d. Thus, greater stimulation of renin was coincident with the levelling of the blood pressure response to chlorthalidone. However no significant correlation was found between interindividual plasma renin activity and change in blood pressure, either in the entire series, or in each treatment subset. The data suggest overall that renin stimulation may influence the characteristic dose-hypotensive response relationship to diuretic agents in antihypertensive therapy, but it is unlikely that measurement of individual plasma renin activity will provide an useful guide to the optimal dose of a diuretic agents.
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    Adrenergic system and carbohydrate metabolism. Effects of beta-receptor blockade on insulin secretion and peripheral insulin sensitivity in normoglycaemic patients (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 273-277 
    Details
    ISSN: 1432-1041
    Keywords: beta-adrenoreceptor blockers ; normoglycaemia ; glucose tolerance ; insulin secretion and -sensitivity ; hypertension ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique. Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment. The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin.
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    Lisinopril in hypertensive patients with and without renal failure (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 11-16 
    Details
    ISSN: 1432-1041
    Keywords: lisinopril ; hypertension ; converting enzyme inhibition ; serum drug concentratoin ; blood pressure ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Lisinopril (MK521), a lysine analogue of enalaprilic acid, the bioactive metabolite of enalapril, has a longer half-life than enalaprilic acid, and is excreted unchanged in the urine. Its kinetic profile and antihypertensive and hormonal effects have been investigated in an open study in 3 groups each of 6 hypertensive patients, with normal, moderate and severe impairment of renal function. Serum drug level, blood pressure, converting enzyme activity (CEA), plasma renin activity (PRA), aldosterone concentration (PAC), and serum potassium and creatinine were measured during 1 week following a single oral dose and subsequently following 8 daily doses of 5 mg lisinopril. Accumulation of lisinopril was found in the severe renal failure group. CEA was suppressed to less than 10% of its initial value from 4 to 24 h after the initial dose in all three groups, and the suppression was more marked and lasted longer in patients with severe renal failure. An inverse correlation was found in all patients between log serum lisinopril concentration and log CEA. Lisinopril lowered blood pressure in all three groups over 24 h. PRA rose and PAC fell similarly in the groups. Serum potassium increased in the renal failure groups and creatinine remained unchanged in all groups. Thus, when lisinopril 5 mg is given daily to patients with severe renal failure it may accumulate. The high serum lisinopril concentration does not cause an excessive antihypertensive effect. In patients with severe renal failure, adjustment of the dose or the dosing frequency to the degree of renal failure is recommended to avoid administration of doses in excess of those required to achieve adequate inhibition of converting enzyme.
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    Acute haemodynamic and humoral responses to felodipine and metoprolol in mild hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 71-75 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; hypertension ; aldosterone ; angiotensin ; cardiac output ; catecholamines ; pulmonary vascular resistance ; renin ; systemic vascular resistance ; haemodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oral administration of felodipine to 10 patients with mild essential hypertension acutely reduced systemic vascular resistance (SVR) by 40% after 30 min. The change in SVR was significantly related to age (r=−0.74). The reduction in the intraarterially measured brachial artery pressure was limited to 15/13 mmHg, due to a rise in cardiac output (CO). The tachycardia was sustained for 90 min, as was an elevation of plasma noradrenaline. There was a transient increase in stroke volume, associated with a reduction in pulmonary capillary wedge pressure, which was at least partly due to a reduced intravascular volume. In contrast to SVR, pulmonary vascular resistance was not affected by felodipine. Addition of intravascular metoprolol after 90 min decreased HR and CO and augmented SVR. The felodipine-induced rise in plasma renin activity (PRA) of 100% was completely reversed by metoprolol. Plasma angiotensin II (PA II) rose by 15% during felodipine, whereas plasma aldosterone concentration (PAC) was not affected. Thus, actuely administered felodipine was a potent dilator of systemic but not of pulmonary arterioles, it stimulated the sympathetic nervous system, and reduced left ventricular filling pressure. The rise in plasma renin did not result in a higher plasma aldosterone level, due partly to reduced generation of angiotensin II.
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    The effects of prazosin and propranolol in combination with thiazide diuretics on blood pressure and serum lipids: a multicentre study (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 339-344 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; propranolol ; hypertension ; antihypertensive effects ; lipid metabolism ; multicentre study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have carried out randomized 12-week multicentre study to compare the effects of prazosin and propranolol on blood pressure and serum lipids in 70 patients with essential hypertension after a 4 week minimum period of treatment with thiazide diuretics. After 12 weeks treatment with prazosin (n=40, 1.5–12.0 mg per day) or propranolol (n=30, 30–120 mg per day) with diuretics there was a significant blood pressure reduction from 165.1/97.9 mmHg to 151.2/90.6 mmHg and from 167/96.5 mmHg to 153/91.9 mmHg, respectively. In the 12th week a significant decrease was noted in triglyceride and in low-density lipoprotein cholesterol (LDL + VLDL-C), but no significant effects were seen in high-density lipoprotein cholesterol (HDL-C) in patients receiving prazosin. On the other hand, a significant decrease in lecithin cholesterol acyltransferase (LCAT) was seen in patients receiving propranolol. Twenty-six of 40 patients receiving prazosin were given an additional 12 weeks of treatment. Twenty-two of 30 patients initially treated with propranolol were switched from propranolol to prazosin after 13 weeks and given prazosin up to the 24th week. At 24 weeks, the blood pressure was 149/93.0 mmHg in the prazosin group and 155/89.2 mmHg in the group which switched from propranolol to prazosin. Triglyceride remained reduced in the prazosin group at the 24th week. In the group which switched from propranolol to prazosin, triglyceride decreased significantly over the next 12 weeks.
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    Reversal by the selective D-2 dopamine receptor blocker sulpiride of the hypotensive effect of co-dergocrine in elderly hypertensives (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 519-521 
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    ISSN: 1432-1041
    Keywords: co-dergocrine ; sulpiride ; hypertension ; DA-2 receptors ; dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the study was to define the role of peripheral dopaminergic mechanisms in the regulation of blood pressure. The data suggest that the hypotensive effect of the dopaminergic agonist co-dergocrine in elderly hypertensive patients is mediated by interaction with peripheral DA-2 receptors, since it was reversed by the selective antagonist sulpiride in a dose that does not significantly cross the blood brain barrier. The findings suggest the possible therapeutic use of dopamine DA-2 agonists in elderly hypertensive patients.
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    Human renovascular effects of dopexamine hydrochloride: A novel agonist of peripheral dopamine and beta2-adreno-receptors (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 1-4 
    Details
    ISSN: 1432-1041
    Keywords: dopexamine ; hypertension ; renal blood flow ; cardiac output
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of dopexamine on the renal circulation have been examined to show whether any augmentation of renal blood flow (RBF) was secondary to the effect of the drug on cardiac output (CO) or whether it had any additional direct renal vasodilator activity. Eight male patients with mild to moderate hypertension, who were undergoing renal vein catheterization for renin estimation, were studied. Dose related increments in RBF (baseline (B)=504 ml·min−1; after treatment (D)=605 ml·min−1), CO (B=5.9 l·min−1; D=6.7 l·min−1), heart rate (B=77 beats/min; D=100 beats/min) and systolic blood pressure (B=143 mmHg; D=166 mmHg) were observed on administration of dopexamine 3 µg·kg−1·min−1, with insignificant changes in diastolic blood pressure (B=84.4 mmHg; D=90 mmHg) and total peripheral resistance (B=17.85; D=17.25 Units). There was a slight but significant reduction in renal vascular resistance (B=20.59, D=18.75). The ratio of RBF to CO (%) confirmed that the increase in RBF due to dopexamine hydrochloride was greater that attributable to the increase in CO or perfusion pressure alone (RBF/CO B=8.5%, D=9%), consistent with selective renal vasodilation. The fall in renin activity and lack of systemic vasodilatation suggest that this was a DA1-receptor mediated effect.
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    Regulation of atrial natriuretic peptide receptors in the rat brain (1987)
    Springer
    Cellular and molecular neurobiology 7 (1987), S. 151-173 
    Details
    ISSN: 1573-6830
    Keywords: neuropeptides ; atrial natriuretic factor ; atriopeptins ; quantitative autoradiography ; receptors ; circumventricular organs ; dehydration ; hypertension ; cardiovascular control ; fluid metabolism ; choroid plexus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 1. We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (ANP; 99–126) in the rat brain. 2. Quantitative autoradiographic techniques and a125I-labeled ligand,125I-ANP (99–126), were employed. Afterin vitro autoradiography, quantification was achieved by computerized microdensitometry followed by comparison with125I-standards. 3. ANP receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood-pressure control. 4. Spontaneously (genetic) hypertensive rats showed much lower numbers of ANP receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the choroid plexus. These changes are in contrast to those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of ANP. 5. Under conditions of acute dehydration after water deprivation, as well as under conditions of chronic dehydration such as those present in homozygous Brattleboro rats, there was an up-regulation of ANP receptors in the subfornical organ. 6. Our results indicate that in the brain, circumventricular organs contain ANP receptors which could respond to variations in the concentration of circulating ANP. In addition, brain areas inside the blood-brain barrier contain ANP receptors probably related to the endogenous, central ANP system. 7. The localization of ANP receptors and the alterations in their regulation present in genetically hypertensive rats and after dehydration indicate that brain ANP receptors are probably related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function. ANP and angiotensin II could act as mutual antagonists in the brain as they do in the periphery. 8. ANP receptors in the choroid plexus may be related to the formation of cerebrospinal fluid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00711552
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    Kinins in cerebrospinal fluid: Reduced concentration in spontaneously hypertensive rats (1986)
    Springer
    Cellular and molecular life sciences 42 (1986), S. 1238-1239 
    Details
    ISSN: 1420-9071
    Keywords: Kinins ; bradykinin ; kallidin ; cerebrospinal fluid ; HPLC ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Rat cerebrospinal fluid contains peptides which displace radiolabeled bradykinin from its specific antibodies. Two peptides which showed the same retention time as kallidin and bradykinin in a reverse phase high pressure liquid chromatography system were detected in cerebrospinal fluid of rats. The concentration of radioimmunologically detected kinins in the cerebrospinal fluid of spontaneously hypertensive rats of the Okamoto strain was lower than that of the Wistar Kyoto control rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01946402
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    Effects of combined therapy with amiloride and hydrochlorothiazide on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in hypertensive patients (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 151-156 
    Details
    ISSN: 1432-1041
    Keywords: amiloride ; hydrochlorothiazide ; hypertension ; total body potassium ; plasma potassium ; renin-angiotensin-aldosterone system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After a run-in period of 8 weeks on a regimen of hydrochlorothiazide (HCT, median dosage 75 mg/day), patients with essential hypertension were randomly allocated to continued hydrochlorothiazide therapy (Group I) or additional treatment with amiloride (Group II, median dosage 15 mg/day, or 5 mg per 25 mg hydrochlorothiazide) for the following 12 weeks. Thereafter all the patients were changed to treatment with a fixed combination tablet containing 5 mg amiloride and 50 mg hydrochlorothiazide (Moduretic), keeping the thiazide dosage unchanged for an additional 12 weeks. In Group I patients there was no change in plasma potassium, total body potassium content or the renin-angiotensin-aldosterone system during the 12 weeks on HCT. When the treatment was changed to Moduretic, significant increases were found of 10% in plasma potassium and 3% in total body potassium content. No important stimulation of the renin-angiotensin-aldosterone system was found. In Group II patients addition of an average of 15 mg amiloride to the hydrochlorothiazide treatment led to significant increases in plasma potassium and total body potassium content of approximately 15% and 4%, respectively. There was also a significant increase in the plasma concentrations of renin, angiotensin II and aldosterone. Reducing the average dose of amiloride to 7.5 mg/day by use of Moduretic did not lead to decrease in plasma potassium or total body potassium content. Plasma concentrations of renin, angiotensin II, and aldosterone were decreased, but the individual changes varied markedly and no significant overall change was found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614293
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  • 80
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    Intra-individual comparison of captopril and enalapril in patients undergoing regular haemodialysis (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 257-262 
    Details
    ISSN: 1432-1041
    Keywords: haemodialysis ; captopril ; enalapril ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and long-term efficacy, tolerance and safety of two orally active angiotensin converting enzyme (ACE) inhibitors, captopril (C) and enalapril (E) were compared in patients on regular haemodialysis (RHD). C and E were successively administered for 6 months to 8 RHD patients with hypertension unresponsive to fluid withdrawal and conventional antihypertensive therapy. The fall in blood pressure after a starting dose of 25 mg C or 5 mg E was of the same magnitude. It was not correlated with the initial PRA levels, which were normal in all patients. The mean daily dose of ACE inhibitor was 45±28 mg during the C period and 19.4±17.6 mg at the end of the E period. Three patients required additional treatment, comprising beta-blockers and/or calcium antagonists. The individual daily dose of ACE inhibitor, the need for additional treatment and the antihypertensive response achieved were highly correlated during both study periods. During C administration 4 out of 8 patients presented a taste disturbance, which disappeared 2 weeks after substituting E for C. Serum electrolytes, liver enzymes, haemoglobin concentration and white cell and platelet counts remained unchanged throughout both study periods. It is concluded that RHD patients with hypertension are responsive to ACE inhibitors, C and E being equally effective.
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    URL: http://dx.doi.org/10.1007/BF00541524
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  • 81
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    Evaluation of once daily endralazine in hypertension (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 553-557 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; endralazine ; once daily therapy ; hydralazine ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Endralazine, a novel vasodilator related to hydralazine, exhibits a longer half-life and is only minimally influenced by acetylator status. The antihypertensive action of once daily endralazine has been studied in 17 patients previously controlled with an antihypertensive regimen which included hydralazine and a beta-blocker. Hydralazine was discontinued but other medications were unchanged. Pre-study dosage of hydralazine ranged from 25 mg b.i.d. to 50 mg g.i.d., mean daily dose 126.5 mg. End-ralazine was started at a dose of 10 mg o.d. and increased by 10 mg to a maximum of 40 mg o.d. until seated DBP was controlled below 95 mmHg. All 17 patients completed the study. Seated BP significantly decreased from 147.5/99.7 to 133.8/83.9 and standing BP from 145.8/99.2 to 133.6/87.3 mmHg. Ten patients (59%) were successfully controlled with endralazine once daily but 7 patients required twice daily dosage schedules because of lack of BP control at 24 h after dosing or excessive hypotension shortly after dosing. Other adverse effects were headache, palpitations and fatigue. There was a statistically insignificant average weight gain of 1 kg but pedal edema was not observed. Endralazine is an effective antihypertensive agent with adverse symptoms similar to those experienced with hydralazine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542414
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  • 82
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    Pharmacodynamics and pharmacokinetics of three different doses of urapidil infused in hypertensive patients (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 549-552 
    Details
    ISSN: 1432-1041
    Keywords: urapidil ; pharmacodynamics ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The study was designed to follow the haemodynamic effects and pharmacokinetics under steady-state conditions of three different doses of urapidil infused continuously. Nine male hypertensive patients received three randomly assigned intravenous infusions of 32.5, 65 and 130 mg urapidil, over 14 h during 6 consecutive days, in a change-over fashion. Blood pressure and heart rate were measured over a period of 28 h after the infusion began and were compared with a reference profile obtained prior to the treatment periods. Urapidil and its main metabolite, parahydroxylated urapidil, were also determined for 28 h after the infusion began using HPLC. The 32.5 mg dose of urapidil caused a maximum decrease in systolic blood pressure of 33±8 mmHg, the 65 mg dose a maximum decrease of 39±12 mmHg and the 130 mg dose a maximum decrease of 50±12 mmHg. The 32.5 and 65 mg doses resulted in similar serum urapidil concentrations, with maximum levels in the 100 to 200 ng/ml range, and the 130 mg dose caused a maximum level approximately four times that achieved with the 32.5 mg dose. The serum concentration of parahydroxy urapidil was proportional to the corresponding dose of urapidil. Four patients reported mild headache, fatigue, weakness, pressure in the head, perspiration and orthostatic dysregulation. The side-effects were probably drug related but required no specific therapy. In summary, the 32.5 mg dose of urapidil resulted in a pronounced decrease in blood pressure. The average pressure reduction over the 14-h infusion period showed further dose-dependent increases after the 65 and 130 mg doses. In severe hypertension, the 130 mg dose can be employed, since it does result in a further, significantly larger decrease in blood pressure.
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    URL: http://dx.doi.org/10.1007/BF00542413
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  • 83
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    Renal effects of pinacidil in hypertensive patients on chronic beta-blocker therapy (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 641-647 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; vasodilators ; renal function and — haemodynamics ; beta-blockers ; guanidines ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and chronic effects of pinacidil on blood pressure (BP) and renal function were investigated in 10 patients with moderate arterial hypertension insufficiently controlled by chronic beta-blockade. Acute i. v. administration of pinacidil caused a significant fall in BP of 29.9/18.3 mm Hg and, despite beta-blockade, a concomitant rise in heart rate (HR) of 21%. Renal vascular resistance (RVR) showed a marked reduction as a consequence of the fall in BP, and a transient rise in renal plasma flow (RPF). Diuresis and renal clearance of sodium and uric acid showed a parallel fall. The excretion rates of albumin and β2-microglobulin were also significantly reduced. Pharmacokinetic studies indicated that glomerular filtration was responsible for elimination of the parent drug, and that proximal tubular secretion was the pathway of excretion of the main metabolite, pinacidil pyridine-N-oxide. During therapy for 4 months there was no further significant reduction in BP, despite increases in the daily dose of pinacidil. The effects on HR were less conspicious after 4 months; renal haemodynamic parameters and body weight were not significantly changed. The initial level of RVR and the initial acute reduction in this parameter appeared to be major determinants of the long-term BP response. The drug was well tolerated apart from one patient who developed slight fluid retention. However, concomitant administration of a diuretic will probably be necessary during routine use of this therapeutic combination.
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    URL: http://dx.doi.org/10.1007/BF00608209
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    Peripheral vascular effects of bufuralol in hypertensive and normal subjects: A comparison with propranolol and pindolol (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 649-652 
    Details
    ISSN: 1432-1041
    Keywords: bufuralol ; propranolol ; pindolol ; peripheral blood flow ; systemic blood pressure ; beta-adrenoceptor antagonist ; hypertension ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, single oral dose, crossover study, the effects of bufuralol (60 mg) on heart rate, blood pressure, and peripheral vascular responses were compared with those of propranolol (160 mg), pindolol (10 mg), and placebo in a group of 12 healthy volunteers. All three beta-adrenoceptor antagonists reduced exercise tachycardia, but at the doses chosen the effects of bufuralol were less than those of propranolol. Forearm blood flow was reduced by propranolol and pindolol, but not by bufuralol. The antihypertensive and peripheral vascular effects of bufuralol (30–60 mg bd) were also compared with those of propranolol (40–80 mg bd) in a double-blind crossover study in 10 patients with mild hypertension. Propranolol and bufuralol produced comparable reductions in systemic blood pressure over a two-week period, but the decreases in forearm and finger blood flow were greater with propranolol. These studies suggest that bufuralol is a beta-adrenoceptor antagonist with antihypertensive properties, and that it produces less peripheral vasoconstriction than propranolol or pindolol.
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    URL: http://dx.doi.org/10.1007/BF00608210
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    Relative potency of a beta-blocking and a calcium entry blocking agent as antihypertensive drugs in black patients (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 523-527 
    Details
    ISSN: 1432-1041
    Keywords: nitrendipine ; acebutolol ; hypertension ; blacks
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The short-term efficacy of nitrendipine (N) as a first stage antihypertensive drug in black patients has been assessed and compared with acebutolol (A) in a double-blind study. Forty patients were randomized and after a 4 week run-in period on placebo, the active treatment was administered for 6 weeks starting with 20 mg N or 200 mg A once daily. The dose was increased up to 60 mg N or 600 mg A as needed. Nitrendipine appeared to be more efficient than acebutolol in reducing blood pressure and the N-induced fall in blood pressure was achieved after 2 weeks. After 2 and 6 weeks on N, the recumbent blood pressure was decreased by 13% and 12% for the systolic and by 14% and 11% for the diastolic pressure. The concurrent decreases in the A group averaged 4% and 5% for the systolic and 5% and 10% for the diastolic pressure after 2 and 6 weeks. Pulse rate and plasma renin activity in the N group were slightly increased and body weight was decreased at the end of the active treatment period.
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    URL: http://dx.doi.org/10.1007/BF00635887
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    Pharmacokinetics and effects on blood pressure of a single oral dose of milrinone in healthy subjects and in patients with renal impairment (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 549-553 
    Details
    ISSN: 1432-1041
    Keywords: milrinone ; renal impairment ; hypertension ; pharmacokinetics ; healthy subjects ; antihypertensive effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30–63 ml/min) and 7 patients with severe renal impairment (CRI II, creatinine clearance 9–29 ml/min). All except one of the patients with renal impairment had hypertension. The mean urinary recovery of milrinone was 82% in healthy subjects, the renal clearance was 288 ml/min and the plasma half-life (t1/2) was 0.94 h. In CRI the mean plasma t1/2 was prolonged (CRI I 1.78 h, CRI II 3.24 h). There was a significant linear relationship between creatinine clearance and the elimination rate constant, and between creatinine clearance and the renal clearance of milrinone. During the study day there was a tendency to a decrease in supine BP from 1 to 6–8 h after dosing, with the maximal decrease at 2–3 h (healthy subjects 118/71→107/56, CRI 159/95→136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2–6 h after dosing. Changes in BP and HR are difficult to evaluate since the study was not placebo-controlled. The plasma elimination rate of milrinone was decreased in CRI and dose adjustment may be necessary. Placebo-controlled studies of milrinone in hypertensive patients would be required to validate its possible antihypertensive effect.
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    URL: http://dx.doi.org/10.1007/BF00635891
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  • 87
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    Effect of metoprolol and propranolol on platelet aggregation and cAMP level in hypertensive patients (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 561-564 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00635893
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  • 88
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    Intraindividual comparison of moxonidine and prazosin in hypertensive patients (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 645-650 
    Details
    ISSN: 1432-1041
    Keywords: moxonidine ; prazosin ; hypertension ; intraindividual comparison ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty hypertensive outpatients were treated with moxonidine for 4 weeks in an intraindividual comparison study. After a wash-out period of at least 2 weeks the same patients were given prazosin for 4 weeks. The initial daily doses were 0.2 mg moxonidine and 1 mg prazosin. The antihypertensive dose was titrated individually until the diastolic blood pressure (BP) fell below 95 mm Hg. Within 3 days of dose titration, a mean dose of 0.37 mg moxonidine produced a significant decrease in BP from a mean of 184/100 to 155/90 mm Hg, while in prazosin treated patients 5 to 8 days were necessary to reduce the BP from 180/100 to 149/89 mm Hg; the mean prazosin dose was 2.8 mg. In addition to the lower dose of moxonidine compared to prazosin, it was found that in 67% of patients moxonidine was given once daily whilst prazosin was administered three-time daily in 73%. Within the first week of moxonidine treatment 14/30 patients experienced dryness of the mouth, but it was so mild that the patients did not want to discontinue the trial. In contrast, 3/30 patients discontinued therapy with prazosin because of side effects. The most frequent adverse effects of prazosin were orthostatic dysregulation in 6 patients, pain in the chest in 5, giddiness and tachycardia in 4 and nervousness in 3 patients; no patient had these complaints whilst on moxonidine. In intraindividual comparisons with moxonidine, efficacy, tolerance and the well-being of the patients were significantly better than when on prazosin.
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  • 89
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    Torasemide, a new potent diuretic (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 29-34 
    Details
    ISSN: 1432-1041
    Keywords: torasemide ; hypertension ; diuretic potency ; furosemide ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic effects of torasemide, a new potent loop diuretic, were compared with those of furosemide in a double blind controlled study in 18 hypertensive patients with oedema of various origins. Given orally for 5 days, torasemide was clinically very effective and well tolerated. On a weight basis, the diuretic, natriuretic and chloruretic effects of torasemide were about 8-times greater than those of furosemide. However, the kaliuretic effect of torasemide was only 3-times greater than that of furosemide, suggesting that torasemide is more potassium sparing than furosemide. Torasemide displayed a rapid onset of action, similar to that of furosemide but had a longer diuretic effect without any rebound phenomenon. Torasemide and furosemide did not effect creatinine clearance or uric acid excretion. Both furosemide and torasemide lowered systolic blood pressure but the effect of torasemide was more marked than that of furosemide. In this group of aged and hypertensive patients with oedema, the pharmacokinetics of torasemide was comparable to that reported in young healthy volunteers, and were similar on the first and fifth days of treatment. The long duration of action and the potassium sparing effect of torasemide compared to furosemide are promising features of this new loop diuretic in the treatment of oedema and hypertension.
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  • 90
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    A pharmacokinetic study of prazosin in patients with varying degrees of chronic renal failure (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 333-337 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; renal failure ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic parameters of prazosin (t1/2, tmax, Cmax and AUC have been studied in 18 hypertensive patients with varying degrees of chronic renal failure (serum creatinine ranging from 1.6 to 11.4 mg/dl). An oral dose of 2 mg of prazosin was added to the preexisting antihypertensive medication. The degree of renal impairment did not influence the peak drug concentration, the time to peak or the serum half-life. On the other hand, the hypotensive action after 2 mg prazosin, was more pronounced in patients with severe chronic renal failure. This effect could not be explained by a difference in the pharmacokinetics of prazosin in severe as compared to moderate chronic renal failure or to normal renal function.
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    URL: http://dx.doi.org/10.1007/BF00981133
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  • 91
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    Sustained release verapamil in hypertension. Results from a noninvasive ambulatory blood pressure monitoring and a clinical study (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 255-259 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; hypertension ; sustained-release formulation ; noninvasive ambulatory pressure monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of a new sustained-release matrix formulation of verapamil 200 mg was investigated in a dose-response study in patients with mild to moderate essential hypertension. Noninvasive ambulatory blood pressure measurements were recorded over 24 h in 6 patients with diastolic blood pressure ≥100 mmHg. The patients received sustained-release verapamil 200 mg once daily and twice daily in a randomized order. Each medication period lasted 2 weeks. Verapamil 200 mg twice daily had a better antihypertensive effect than the same dose once daily. After a 6-week placebo period 27 patients with a diastolic blood pressure ≥100 mmHg were included in a double-blind clinical trial. The patients received sustained release verapamil 200 mg once daily and twice daily in a randomized crossover manner. Each medication period lasted 6 weeks, with an intervening 6-week placebo period. A diastolic blood pressure of ≤95 mmHg was achieved in 6 patients with the once-daily regimen and in 14 with the twice-daily regimen. The mean fall in diastolic blood pressure was 4 and 9 mmHg, respectively (p〈0.05). We conclude that sustained-release verapamil 200 mg once daily gives a satisfactory blood pressure response only in a minority of patients, while 200 mg twice daily has a significantly better antihypertensive effect. Both doses were well tolerated.
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    URL: http://dx.doi.org/10.1007/BF00981120
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    Blood pressure and catecholamines following exercise during selective beta-blockade in hypertension (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 283-287 
    Details
    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; catecholamines ; exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study examines and compares the hemodynamic and sympathoadrenal response to bicycle exercise in hypertensive subjects during two weeks' treatment with a cardio-selective (metoprolol) and nonselective (propranolol) beta-blocker. The increase in plasma norepinephrine and epinephrine concentration following exercise was augmented to a similar degree with each beta-blocker. Pre-exercise blood pressure and heart rate were similar for the two drugs. However immediately after exercise and particularly after resting for 20 min post exercise, diastolic blood pressure was lower during metoprolol treatment. Systolic blood pressure was also lower 20 min post exercise during metoprolol treatment. These observations indicate that cardio-selective beta-blockers offer advantages in blood pressure control during exercise through intact vascular β2-adrenoceptors opposing sympathetically mediated vasoconstriction.
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    URL: http://dx.doi.org/10.1007/BF00541529
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    Effect of a single dose of sublingual captopril in hypertensive patients (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 379-380 
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    ISSN: 1432-1041
    Keywords: captopril ; hypertension ; sublingual administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541550
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  • 94
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    Studies on the antihypertensive effect of single doses of the angiotensin converting enzyme inhibitor ramipril (HOE 498) in man (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 541-547 
    Details
    ISSN: 1432-1041
    Keywords: ramipril (HOE 498) ; hypertension ; angiotensin converting inhibition ; dose-response relationship ; time course
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of the blood pressure lowering effect and the dose-response relationship of the new angiotensin converting enzyme inhibitor ramipril (HOE 498) were studied in 8 patients with essential hypertension. As compared with placebo, a single oral dose of 2.5 mg ramipril lowered systolic and diastolic blood pressure. The antihypertensive action of single oral doses of 5, 7.5 and 10 mg ramipril was more pronounced. No change in heart rate occurred. Angiotensin converting enzyme activity was suppressed after all doses of ramipril studied. Plasma renin activity increased after 2.5 mg and 5 mg ramipril. Plasma aldosterone was not affected by 2.5 mg, but it fell after 5 mg ramipril. Thus, ramipril produced prolonged inhibition (more than 12 hours) of angiotensin converting enzyme activity and lowered blood pressure in patients with essential hypertension.
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    URL: http://dx.doi.org/10.1007/BF00542412
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    Therapeutic traditions in Northern Ireland, Norway and Sweden: II. Hypertension (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 521-525 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; hypertensive therapy ; drug utilization ; therapeutic traditions ; international differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A questionnaire survey based on hypertension case histories was performed among a representative sample of 400 GP's and hospital doctors in Northern Ireland, Norway and Sweden, countries having markedly different utilization of antihypertensive drugs. We found a greater propensity to start antihypertensive drug treatment in Northern Ireland than in Norway and Sweden. This was true both in mild diastolic and isolated systolic hypertension. Yet the utilization of antihypertensive drugs in Sweden is about 60% higher than in Northern Ireland and 30% higher than in Norway. Swedish physicians preferred beta-blockers as their first choice to a greater extent than physicians in Northern Ireland and Norway who selected thiazides more often. In general, the choice of drugs agreed with the sales and prescribing patterns in the three countries. Besides providing more insight in therapeutic traditions the study indicates that the lower prescribing of antihypertensive drugs in Northern Ireland, and to some extent in Norway, compared to Sweden, might be due to differences in true or apparent morbidity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542409
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  • 96
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    Electronic Resource
    Dose response and length of action of nifedipine capsules and tablets in patients with essential hypertension: A randomised crossover study (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 723-725 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; capsules ; tablets ; comparative dose response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve patients with essential hypertension on no other drug treatment were entered into a randomised crossover study of 5, 10 and 20 mg capsules of nifedipine given 3 times a day and 20 mg tablets given twice a day. Each dose was given for 2 weeks in a random order. All forms of nifedipine were effective in lowering blood pressure. However, 5 mg capsules were less effective than the 10 and 20 mg capsules or 20 mg tablets. There was little to choose between the latter. All doses of nifedipine were more effective 1 and 3 h after the dose compared to subsequent times afterwards. Indeed, as time elapsed after the last dose up to 12 h, there was a gradual increase in blood pressure. However, even at 12 h the 10, 20 mg capsules and 20 mg tablets were still causing an approximate 10% reduction in blood pressure. Nifedipine tablets are as effective as capsules though they might be longer acting, particurarly around 6 h after the last dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608223
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  • 97
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of trimazosin and its effects on blood pressure, renal function and proteinuria during short-term therapy of patients with impaired renal function and hypertension (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 63-68 
    Details
    ISSN: 1432-1041
    Keywords: trimazosin ; proteinuria ; chronic renal insufficiency ; hypertension ; glomerular filtration rate ; renal vascular resistance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics and short-term (10 weeks) effects of trimazosin, an alpha1-adrenoreceptor antagonist, on renal function and blood pressure in patients with moderate chronic renal insufficiency and hypertension, have been studied for the first time. Eight patients in whom the blood pressure was not normalized with a diuretic alone underwent pharmacokinetic studies and assessment of the renal function during a 10-week period of trimazosin therapy. Trimazosin significantly lowered blood pressure (recumbent and upright) without significantly altering renal function. Renal vascular resistance was decreased by 14%. Fractional sodium excretion, proteinuria and laboratory serum tests remained unchanged. Neither body weight nor pulse rate were affected. Moderate renal insufficiency did not modify the pharmacokinetics of the drug. Thus, trimazosin, as second-step antihypertensive agent, appeared to be safe and effective in patients with moderate renal insufficiency and hypertension, without exerting favourable or adverse renal effects during short-term therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00870988
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  • 98
    Electronic Resource
    Electronic Resource
    Antihypertensive effects of bisoprolol during once daily administration in patients with essential hypertension (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 517-521 
    Details
    ISSN: 1432-1041
    Keywords: bisoprolol ; hypertension ; beta-adrenoceptor blocker ; once-a-day administration ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Biosprolol is a new beta1-selective beta-blocking agent with a plasma half-time of 10–12 h and without partial agonist properties. Forty-eight patients with essential hypertension were randomly treated with 5, 10, or 20 mg bisoprolol given once daily for 8 weeks. All measurements were made 24 hours after the last dose. Bisoprolol had antihypertensive and beta-blocking properties both at rest and during exercise. The 20 mg dosage regimen was more effective than that of 5 mg and 10 mg. The drug was well tolerated and all the 48 patients completed the trial.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635886
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  • 99
    Electronic Resource
    Electronic Resource
    Antihypertensive efficacy of pinacidil — Automatic ambulatory blood pressure monitoring (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 133-141 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hydralazine ; ambulatory blood pressure monitoring ; vasodilation ; hypertension ; diastolic blood pressure decrease ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Forty-three patients with mild essential hypertension were randomized into two double-blind studies: pinacidil vs. placebo or pinacidil vs. hydralazine. Pinacidil (62±18 mg/day) decreased office systolic and diastolic blood pressures from 145 to 137 mm Hg and from 98 to 89 mm Hg, respectively, after 6 weeks of therapy. Similarly, hydralazine (128±28 mg/day) reduced supine systolic blood pressure from 140 to 134 mm Hg and supine diastolic blood pressure from 93 mm Hg to 84 mm Hg. Significant tachycardia was not noted with either drug. Ambulatory blood pressure was monitored for 24 h during the placebo-washout and efficacy phases with both pinacidil and hydralazine. Mean 24-h blood pressure was 128 systolic and 81 diastolic with pinacidil and 121 systolic and 76 diastolic with hydralazine. Reduction in awake hypertensive diastolic blood pressure was significant for both pinacidil and hydralazine. Normal sleep diastolic blood pressure was not reduced by pinacidil but was reduced by hydralazine. Side-effects with both drugs included edema, headache, and palpitations. These data demonstrate that pinacidil is as effective an antihypertensive agent as hydralazine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606649
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  • 100
    Electronic Resource
    Electronic Resource
    Response to tilting in hypertensive patients receiving ketanserin (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 505-506 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; orthostatic hypotension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613533
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