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  • hypertension  (174)
  • Springer  (174)
  • Annual Reviews
  • Cambridge University Press
  • 1980-1984  (130)
  • 1975-1979  (44)
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  • Springer  (174)
  • Annual Reviews
  • Cambridge University Press
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  • 1
    ISSN: 1432-1041
    Keywords: α-methyldopa ; plasma concentration ; hypertension ; sulphate conjugation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of free α-methyldopa and methyldopa sulphate conjugate were measured in 7 hypertensive patients with normal renal function following α-methyldopa (1 g) orally. Five of these patients subsequently received α-methyldopa ethyl ester (250 mg) (methyldopate) intravenously and two further patients received 250 mg of α-methyldopa intravenously. After oral administration a large amount of total plasma α-methyldopa was present as sulphate conjugate. There were wide interindividual differences in the ratio of free: conjugated α-methyldopa in plasma (ratio at 4 hours ranged from 3.73 – 0.83) suggesting that individual differences in the extent of sulphate conjugation may occur. There was no close correlation between the degree of conjugation and the fall in arterial pressure. At all time intervals examined, plasma concentrations were higher following intravenous α-methyldopa than α-methyldopate. The plasma concentration of α-methyldopa (free and esterified) 60 minutes after i.v. α-methyldopate was 1.7±0.3 µg/ml wile at the same time after the same dose of methyldopa by the same route the mean concentration was 5.9 µg/ml. Although small amounts of sulphate conjugate were detected after i.v. α-methyldopate, insignificant quantities of conjugate were found after i.v. α-methyldopa. The average fall in mean arterial pressure was 27 mm Hg following i.v. α-methyldopa but only 2.7 mm Hg following α-methyldopate. These results suggest that sulphate conjugation of α-methyldopa occurs in the gastrointestinal tract during absorption. Hydrolysis of α-methyldopa ethyl ester does not appear to be instantaneous and pharmacokinetic differences between the ester and free α-methyldopa have been demonstrated.
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  • 2
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    Springer
    European journal of clinical pharmacology 8 (1975), S. 387-392 
    ISSN: 1432-1041
    Keywords: Left ventricular pressure ; left ventricular contractility ; hypertension ; diazoxide ; beta-adrenergic blockade ; isometric exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of diazoxide on left ventricular performance during rest and isometric exercise (handgrip) was examined in 16 unselected hypertensive patients, 6 of whom had been pretreated with the beta-adrenergic blocking agent pindolol. Diazoxide regularly and promptly produced a fall in left ventricular systolic and end diastolic pressures, and an increase in heart rate and left ventricular dp/dtmax. Haemodynamic changes were maximal 2 minutes after injection of the drug and decreased little over the next 8 minutes. After beta-adrenergic blockade, diazoxide caused a more pronounced reduction in left ventricular systolic pressure and a less marked fall in end-diastolic pressure, whilst the diazoxide-induced rise in heart rate was partially and the increase of dp/dtmax was completely inhibited. The increase in systolic pressure during isometric exercise was not influenced by diazoxide, but the positive inotropic reaction was augmented. The findings appear to show that cardiac stimulation by diazoxide is due to a reflex mechanism transmitted by baroreceptors, and that improvement of cardiac performance is mainly due to a reduction of left ventricular after-load.
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  • 3
    ISSN: 1432-1041
    Keywords: Beta-blockade ; penbutolol ; hypertension ; plasma and urinary catecholamines ; plasma renin ; aldosterone excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of penbutolol (Hoe 893 d), a new non-selective beta-receptor blocking agent, were studied in 5 patients with moderate hypertension. Initially, it was shown that 2–4 mg given orally once or twice daily tended to lower blood pressure and pulse rate, both at rest and following submaximal work. In prolonged trials (3–8 months) 40–60 mg/day were required to produce an acceptable antihypertensive effect. Penbutolol had no effect on the normal increase in plasma noradrenaline and adrenaline on standing, nor did it alter basal urinary catecholamine excretion. Submaximal work caused no significant change in plasma catecholamines before treatment, but there was a marked rise both in plasma noradrenaline and adrenaline during treatment with penbutolol. In short term studies there was a fall in plasma renin by 4 hours after oral administration of penbutolol 2–4 mg, which persisted for 24 hours. Prolonged treatment with penbutolol 20–30 mg twice daily inhibited renin production under basal conditions and following submaximal work, as well as lowered basal urinary aldosterone excretion. In one patient slight asthmatic symptoms appeared after treatment for 3 months with penbutolol. In other respects penbutolol was well tolerated.
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  • 4
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    European journal of clinical pharmacology 9 (1976), S. 361-365 
    ISSN: 1432-1041
    Keywords: Propranolol ; atenolol ; hypertension ; cardio-selective ; beta-adrenergic blockade ; antihypertensive therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol was given to 30 patients with essential hypertension following randomised, double-blind administration of either placebo or a new cardioselective beta-adrenergic receptor antagonist, atenolol (Tenormin®, ICI 66 082). Both atenolol and propranolol caused statistically significant reduction of recumbent and erect blood pressure and heart rate. There were no important differences between these variables on comparison of atenolol and propranolol.
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  • 5
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    European journal of clinical pharmacology 9 (1976), S. 355-360 
    ISSN: 1432-1041
    Keywords: Propranolol ; minoxidil ; hypertension ; cardiac output ; plasma renin activity ; non-invasive techniques
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study, using non-invasive techniques, was carried out in ten patients with essential hypertension to examine the mechanism of the hypotensive effect of propranolol when used in combination with a potent vasodilator antihypertensive — minoxidil. The hypotensive effect of minoxidil, a mean (± SEM) decrease of 42.4±4.3 mm Hg, was accompanied by a marked increase in heart rate, cardiac index and plasma renin activity and a significant decrease in total peripheral resistance, limb vascular resistance and pre-ejection period. Addition of propranolol further reduced mean arterial pressure by an average of 12.9±2.0 mm Hg. Propranolol returned cardiac index to control values and total peripheral resistance index rose but not to control levels. Plasma renin activity was significantly reduced by propranolol. By multiple regression analysis no correlation was found between propranolol-induced decrease in mean arterial pressure and changes in cardiac index, total peripheral resistance index or plasma renin activity. Quantitatively, the reduction in cardiac index observed probably accounted for the hypotensive effect of propranolol. The role of plasma renin activity reduction in the hypotensive effect of propranolol in this situation remains to be clarified. The findings in the present study were consonant with the known actions of vasodilator antihypertensive agents and propranolol and indicate the applicability of non-invasive methodology to the investigation of cardiovascular drugs in man.
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  • 6
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    European journal of clinical pharmacology 8 (1975), S. 21-31 
    ISSN: 1432-1041
    Keywords: Multicentre controlled trial ; hypertension ; oxprenolol ; hydrochlorothiazide dihydralazine ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a multicentre, double-blind, between-patient study the hypotensive effect of oxprenolol was investigated in 329 patients with mild to moderate hypertension. A factorial experimental design with three factors was chosen: oxprenolol — none or daily doses of 20, 40, 60 and 80 mg; dihydralazine and hydrochlorothiazide, respectively, none or 30 mg daily. Each treatment was given for 4 weeks after an adequate period of withdrawal from any other possible hypotensive therapy and one week of placebo wash-out. Irrespective of the association with dihydralazine and/or hydrochlorothiazide, oxprenolol had a hypotensive effect linearly related to dose for standing systolic (P〈0.05) and diastolic (P〈0.01) pressure, and for lying diastolic (P〈0.05) pressure. The addition of dihydralazine enhanced the time-course of the hypotensive effect of oxprenolol, particularly the 80 mg dose level. In general, the combination of oxprenolol with dihydralazine and hydrochlorothiazide caused larger reductions in blood pressure, particularly with oxprenolol 80 mg. In the latter group, the eventual falls in blood pressure were 30.5 and 14.4 mmHg for lying systolic and diastolic, respectively; and 32.1 and 20.0 mmHg for the standing systolic and diastolic pressures. The drug was well tolerated; major side effects (heart failure and bronchospasm) occurred in three patients.
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  • 7
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    European journal of clinical pharmacology 11 (1977), S. 79-83 
    ISSN: 1432-1041
    Keywords: Reserpine ; cancer ; mammary gland ; women ; benign breast disease ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Exposure to reserpine was compared in 181 women interviewed prior to biopsy and found to have breast cancer and 307 women found to have a benign disorder of the breast. The age-adjusted relative risk of breast cancer in those who had taken reserpine was 0.6 (95% confidence limits: 0.4 and 1.1). When the 181 breast cancer patients were compared with a second control group of 101 women with a benign condition requiring surgery, the relative risk was 0.9 (95% confidence limits: 0.4 and 1.7). Neither long-term exposure nor its timing, gave any evidence of an association with breast cancer. The findings in this study do not support the hypothesis that rauwolfia derivatives initiate or promote breast cancer.
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  • 8
    ISSN: 1432-1041
    Keywords: Clonidine ; alprenolol ; amine metabolites ; cerebrospinal fluid ; hypertension ; noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Lumbar cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline (4-hydroxy-3-methoxyphenyl glycol, HMPG), serotonin (5-hydroxyindoleacetic acid) and dopamine (homovanillic acid) were measured before and during the administration of clonidine or alprenolol to hypertensive patients. The noradrenaline receptor stimulant clonidine significantly decreased the CSF level of HMPG, but there was no consistent change in the concentration of serotonin or dopamine metabolites. Patients on alprenolol showed no change in the levels of these metabolites in CSF.
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  • 9
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    European journal of clinical pharmacology 11 (1977), S. 155-157 
    ISSN: 1432-1041
    Keywords: Propranolol ; plasma concentration ; hypertension ; individual drug dosage ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with essential hypertension were treated with propranolol 160 to 640 mg daily for three months. Significant decreases both in recumbent and standing blood pressure were observed after three days treatment and subsequently. Reduction of blood pressure was more pronounced when the dose of propranolol was increased. However, neither the mean dose nor the plasma concentration of propranolol could be correlated with the mean decrease in blood pressure. There was great interindividual variation in the plasma concentrations of propranolol produced by the same daily dose. The initial stimulation of plasma renin activity and the therapeutic response to propranolol could not be correlated.
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  • 10
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    European journal of clinical pharmacology 12 (1977), S. 97-103 
    ISSN: 1432-1041
    Keywords: beta adrenergic blockers ; diuretics ; hypertension ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-four patients with mild to moderate hypertension were treated for up to 60 weeks with hydrochlorothiazide and either placebo, timolol, or timolol and amiloride. The effect of adding timolol and amiloride to hydrochlorothiazide was evaluated in a double blind trial. In 22 of the 24 patients a supine diastolic blood pressure below or equal to 95 mm Hg was produced by hydrochlorothiazide and timolol. Replacing a potassium supplement with amiloride increased the antihypertensive effect.
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  • 11
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    European journal of clinical pharmacology 12 (1977), S. 171-174 
    ISSN: 1432-1041
    Keywords: Tolamolol ; hypertension ; pharmacokinetics ; mean steady-state concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolamolol was administered in a “double-blind” study to fifteen hypertensive patients by dose-titration against arterial blood pressure. Mean steady-state plasma tolamolol concentrations (Css) were determined for each patient from the area under the plasma concentration — time curve during a dosage interval whilst patients were receiving optimal tolamolol doses. No significant correlation was observed between daily tolamolol dose and Css; the relationship between fall in lying mean arterial pressure and Css also failed to reach conventional levels of statistical significance, but Css was observed to be correlated with the fall in standing pressure. The results suggest that plasma concentrations in excess of 200 ng/ml may be required to achieve an effective hypotensive response with the drug.
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  • 12
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    European journal of clinical pharmacology 14 (1978), S. 77-81 
    ISSN: 1432-1041
    Keywords: Oxprenolol ; slow release oxprenolol ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with uncomplicated hypertension were studied in a double-blind within-patient trial comparing slow release oxprenolol (SRO) with conventional oxprenolol (CO). The antihypertensive effect of SRO once daily was greater than that of CO once daily, although this did not reach statistical significance. CO once daily was less effective than CObd and this difference was statistically significant for lying diastolic blood pressure. After exercise testing 26 hours post-dose, blood pressure and pulse rate were marginally lower on SRO than on CO, but this difference was not significant. Blood pressure readings 24 h post-dose were lower following morning dosing than following evening dosing, although pulse rates showed the opposite trend.
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  • 13
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    European journal of clinical pharmacology 14 (1978), S. 93-94 
    ISSN: 1432-1041
    Keywords: Atenolol ; transplacental passage ; pregnancy ; hypertension ; maternal-fetal ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Maternal and umbilical serum concentrations of atenolol, a hydrophilic, cardioselective beta-adrenoceptor antagonist, were studied at delivery in seven cases of pregnancy hypertension. The drug had been administered to each patient for at least one week. Atenolol was detected in both maternal and umbilical serum in six cases, showing that there is transplacental passage of the drug. In the seventh case, who had stopped taking atenolol more than one day before delivery, neither maternal nor umbilical serum contained a measurable quantity of the drug. Atenolol concentration varied 3- to 6-fold between individuals, but there was no systematic difference between maternal and umbilical levels. It seems reasonable to assume that during steady state conditions the blood level of atenolol in mother and fetus is approximately equal, and that fetal accumulation of the drug does not occur.
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  • 14
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    European journal of clinical pharmacology 18 (1980), S. 321-326 
    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
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  • 15
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    European journal of clinical pharmacology 19 (1981), S. 19-24 
    ISSN: 1432-1041
    Keywords: hypertension ; guanfacine ; central antihypertensives ; withdrawal ; catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1. Guanfacine (2–6 mg/day) a centrally acting antihypertensive drug, was effective in controlling blood pressure in 5 essential hypertensives and lowered plasma noradrenaline and urinary catecholamine excretion. 2. Withdrawal of guanfacine by blind substitution of identical placebo tablets under observation in hospital led to a gradual recovery of blood pressure over 2–4 days. 3. Salivary flow, which was reduced on guanfacine, returned to pretreatment levels by 2 days after withdrawal and significantly exceeded control for the next two days. 4. Urinary catecholamine excretion returned to pretreatment levels by 3 days but did not exceed control levels during the period of study. 5. Plasma noradrenaline returned gradually to pretreatment levels, and by day 4 significantly exceeded them. 6. No patient experienced symptoms suggesting catecholamine excess although four out of five reported a headache from the second day onwards. 7. Guanfacine, a centrally acting drug which pharmacologically resembles clonidine, has a slow offset of hypotensive effect over 2–3 days. Symptoms or biochemical evidence of catecholamine excess were not encountered within 48 h of withdrawal, possibly reflecting the longer duration of action and plasma half-life of guanfacine.
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  • 16
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    European journal of clinical pharmacology 14 (1978), S. 309-317 
    ISSN: 1432-1041
    Keywords: General practitioners ; hypertension ; diagnosis/therapy/control ; prescription pattern ; hypotensive drugs ; drugsale statistics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Based upon regional drug sales statistics, two Norwegian counties with a consumption of hypotensives below and two above average were selected for a prescription study among general practitioners (GPs). The first part of the study involved collection of all the GPs' prescriptions for antihypertensive treatment during the month of October 1975. Immediately afterwards the GPs filled in a questionnaire in which they described their diagnostic and therapeutic criteria and procedures for arterial hypertension. Both parts of the study were analysed and compared. Of the GPs approached 154 (54%) participated. A total of 4095 prescriptions for 3253 patients were collected, 65% of whom were females and 35% were males. GPs alone treated 72% of the patients, and of the others 11% had been referred to specialists, 8% had been admitted to hospital, and 5% had had both procedures. The decision of whether or not to start drug treatment was based upon absolute systolic and diastolic BP levels as related to age, but various other patient factors, such as complicating diseases, family history of cardiovascular disease and cooperation/motivation for treatment, were also considered. The average control interval was 4.4 months (range 1 to more than 6 months) and it increased with the age of the patients. About half of the GPs started drug treatment in young patients with beta-blockers, whereas diuretics were preferred for older subjects. Of the total number of prescriptions, diuretics accounted for 50%, synthetic hypotensives (α-methyldopa, hydralazine, guanethidine etc.) for 33%, and beta-blockers for 17%. The therapeutic efficacy, in terms of BP reduction upon drug treatment, was evaluated in relation to age, both in those patients treated solely by GPs and in those referred to a specialist. Patient compliance and adverse drug reactions were also registered, although with considerable variation between the individual participating GPs. During postproject discussions, the GP-participants stated that this type of project was a valuable model for post-graduate training through testing of individual criteria for diagnostic and therapeutic procedures.
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  • 17
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    European journal of clinical pharmacology 18 (1980), S. 225-229 
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; slow-release preparations ; maximal exercise power ; fatigue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The treatment of hypertension with a single daily-dose of a beta-blocker gives rise to high peak-plasma concentrations 1.5 h after ingestion. After slow release-preparations of beta-blockers, the peak concentrations are half those produced by the conventional preparation at the same oral dose. A frequently occurring side-effect of beta-blocker therapy is fatigue. In this study the effect of a single dose of metoprolol 300 mg, 200 mg, 200 mg slow-release and a placebo on maximal exercise power was tested in 6 healthy subjects, 1.5 h and 24 h after ingestion. Maximal exercise power was significantly reduced 1.5 h after ingestion of metoprolol 300 mg and 200 mg. No change was found 1.5 h after 200 mg of a slow-release preparation. The possible reasons for reduced maximal exercise power are discussed. It is concluded that use of a beta-blocker for the treatment of hypertension in a single daily-dose regimen may be a reason to prefer a slow-release preparation.
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  • 18
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    European journal of clinical pharmacology 18 (1980), S. 399-401 
    ISSN: 1432-1041
    Keywords: prazosin ; hypertension ; central monoaminergic neurons ; monoamine metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six hypertensive patients were treated with prazosin up to a final dose of 3–4.5 mg/day. There was a significant reduction of blood pressure. The cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline, dopamine and serotonin were unchanged. This indicates that the antihypertensive effect is not mediated via central monoaminergic neurons as suggested by animal studies.
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  • 19
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    European journal of clinical pharmacology 18 (1980), S. 105-108 
    ISSN: 1432-1041
    Keywords: renin ; angiotensin ; aldosterone ; hypertension ; hypoaldosteronism ; pseudohypoaldosteronism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is increased activity of the renin, angiotensin, aldosterone (RAA) system in infancy and childhood. An inverse relationship between plasma renin, aldosterone and age has been demonstrated. In childhood hypertension due to renovascular disease or pyelonephritic scarring peripheral plasma renin is increased. Renal vein renin measurements in children with renal hypertension have proved valuable in predicting surgical curability of the underlying lesion. The upper limit of normal for the renal venous renin ratio in normotensive children without renal disease is 1.5. Pharmacological blockade of the RAA system has a place in diagnosis and treatment of hypertensive children. The plasma renin aldosterone profile is diagnostically useful in the investigation of salt-wasting disease and can easily distinguish between aldosterone biosynthetic defects and pseudohypoaldosteronism.
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  • 20
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    European journal of clinical pharmacology 18 (1980), S. 135-139 
    ISSN: 1432-1041
    Keywords: hypertension ; labetalol ; propranolol ; renal haemodynamics ; glomerular filtration rate ; blood pressure ; exercise ; renal blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of exercise on renal haemodynamics was examined in young patients with mild essential hypertension. Four groups of subjects were studied: 13 normotensive, healthy control subjects, and 15 untreated, 11 propranolol-treated, and 6 labetalol-treated patients. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during four consecutive periods, a pre-exercise control period, two exercise periods with loads of 450 kpm/min and 600 kpm/min, respectively, and a post-exercise control period. In the untreated patients RPF and GFR were lower during exercise than in the normotensive control subjects, whereas no significant differences were found at rest. In the propranolol-treated patients the reduction in RPF and GFR during exercise was more pronounced than in the untreated hypertensives. In the labetalol-treated patients however, RPF and GFR were reduced only to the same degree as in the untreated hypertensives. The reduced renal blood flow in propranolol-treated patients may be attributed to a compensatory increase in sympathetic activity caused by an impaired cardiac response to exercise. The lack of reduction in renal blood flow during labetalol therapy could partly be related to alpha-adrenergic blockade in the renal vascular bed induced by labetalol, and partly to the smaller reduction in cardiac output during labetalol than during propranolol therapy.
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  • 21
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    European journal of clinical pharmacology 18 (1980), S. 231-235 
    ISSN: 1432-1041
    Keywords: molsidomine ; hypertension ; hypotension ; angina pectoris
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Molsidomine (M), a new long-lasting antianginal compound, was studied in 38 hypertensive patients to assess its antihypertensive properties. Six patients were selected for an acute, single dose comparative trial with placebo over 8 h after treatment. The remaining 32 patients were used in a 1 month trial to study the effect on BP of more prolonged treatment. Systolic, diastolic and mean BP were significantly reduced after a single dose of M 4 mg, and the effect lasted for about 8 h. M also inhibited the hypertensive response to isometric exercise in handgrip tests performed 1 and 8 h after M ingestion. A dose-related decrease in systolic and diastolic BP in the one month trial was also observed. In addition to its antianginal properties, M appears to possess an interesting effect on BP in mildly to moderately hypertensive patients. A fall in BP is also a valuable effect in coronary patients with augmented metabolic demands of the heart.
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  • 22
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; beta-adrenoceptor blockade ; hypotensive action ; adverse effects ; combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of nifedipine (10–20 mg t.i.d.) given alone, or in combination with a beta-adrenoceptor blocking drug, was related to the observed plasma concentration during one dosage interval at steady-state (Pl-Nifss). The study was carried out as a within-patient comparison of treatment with nifedipine or placebo for 4 weeks. A highly significant reduction in blood pressure was obtained during monotherapy, as well as during combined treatment. The blood pressure reduction when nifedipine was added to beta-adrenoceptor blockade was of the same magnitude as that observed on nifedipine monotherapy. A considerable variation in Pl-Nifss was noted (range: 2–70 ng/ml). No significant correlation was found between the percentage reduction in blood pressure and Pl-Nifss in either of the two groups. There was a close relationship between Pl-Nifss and the concentration found 4 h after the morning dose. Side-effects were common during nifedipine monotherapy and were the reason for discontinuation of treatment in 4 of 18 patients. In contrast, none of the 9 patients on combined treatment dropped-out. In neither of the treatment groups was there any evidence for sodium retention and volume expansion during the first 4 weeks expressed as weight gain or signs of cardiac insufficiency. However, in 13 patients who continued on long-term treatment for 3–14 months, a definite need for concomitant diuretic therapy was found. The results indicate that nifedipine is effective in lowering blood pressure in patients with mild to moderate essential hypertension, either when given alone or in addition to beta-adrenoceptor blockade. It appears best tolerated as combination therapy. Long-term treatment requires addition of a diuretic. Pl-Nifss did not seem to be a major determinant of the magnitude of the hypotensive response.
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  • 23
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    European journal of clinical pharmacology 18 (1980), S. 375-382 
    ISSN: 1432-1041
    Keywords: calcium antagonist ; verapamil ; hypertension ; vasodilators ; plasma renin activity ; mode of action ; sodium balance ; fluid balance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 12 in-patients with moderate uncomplicated hypertension, maintained on constant sodium intake for 15 days, single-blind oral administration of verapamil 80–160 mg t. i. d. for 10 days had a significant antihypertensive effect: in the supine position systolic blood pressure decreased from 177±5 to 150±3 mmHg, and diastolic pressure from 111±3 to 96±2 mmHg; standing values were similarly lowered from 171±7 to 143±4 mmHg, systolic, and from 118±4 to 97±2 mmHg, diastolic. The heart rate did not show any significant change (from 79±3 to 77±2 beats/min, supine, and from 92±3 to 87±3 beats/min, upright). The antihypertensive effect was uniform throughout the day, being similar 2, 3, 6 and 8 h after administration of a dose. Dynamic exercise (75–100 watts on a cycle-ergometer) caused identical increases in arterial pressure and heart rate on the last day of placebo and again on the last day with verapamil, but the peak levels of systolic pressure reached during exercise were lower after verapamil than with placebo, because of the lower blood pressure before exercise. Reduction of arterial pressure by verapamil was not accompanied by increased plasma renin activity, or by renal retention of sodium and water: there was a small increase in sodium excretion, at least during the first days of verapamil administration (from 107±15 to 113±15 mEq Na+/day), and a slight significant reduction in body weight (from 74.2±3.7 to 73.5±3.7 kg). It is concluded that oral administration of verapamil significantly lowers blood pressure without simultaneously inducing cardiac stimulation, renin secretion or salt and water retention.
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  • 24
    ISSN: 1432-1041
    Keywords: guanfacine ; methyldopa ; hypertension ; rebound hypertension ; withdrawal symptoms ; plasma noradrenaline
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine patients with essential hypertension completed a clinical trial designed to study the effects and side effects of administration and withdrawal of guanfacine (2 mg tds) and methyldopa (250 mg tds) on blood pressure, heart rate, and plasma noradrenaline. The study was of randomised doubleblind crossover design with two active therapy phases of eight weeks each, preceded by an initial 4 week placebo phase, separated by an intermediate 2 week placebo phase, and followed by a final 2 week placebo phase. Patients took bendrofluazide 5 mgs daily throughout the entire trial, during both active and placebo periods. Each patient was admitted to hospital at the end of the 8 week active treatment phases, so that the effects of drug withdrawal on blood pressure, heart rate, plasma noradrenaline and side reactions, could be closely observed and monitored. The main conclusions from analysis of the results were that: 1. The hypotensive efficacy of guanfacine and methyldopa was very similar in the doses used, each of the two drugs lowering the supine mean arterial pressure by about 15 mm Hg and the supine diastolic pressure by about 10 mm Hg. 2. The frequency of side effects was greater with guanfacine than with methyldopa. 3. There was no signficant early rebound phenomenon after withdrawal of either methyldopa or guanfacine. 4. There was tendency for the blood pressure to rise slowly and marginally above initial placebo values, 2 weeks after cessation of guanfacine treatment though this was not significant. It was however, accompanied by a significant increase in plasma noradrenaline at 2 weeks. This was not seen 2 weeks after cessation of methyldopa. There was no single incidence of worrying rebound hypertension or withdrawal symptoms either early or late in any patient following cessation of methyldopa or guanfacine.
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  • 25
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    European journal of clinical pharmacology 21 (1982), S. 287-291 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
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  • 26
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    European journal of clinical pharmacology 21 (1982), S. 363-367 
    ISSN: 1432-1041
    Keywords: labetalol ; clonidine ; hypertension ; dose titration ; bendrofluazide ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B (5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits until normotension was achieved, or intolerable side-effects occurred. The treatment with B and L or C was then continued in a cross-over fashion for two 6-week periods, with 3 week diuretic washouts and subsequent dose-titration periods between the treatment periods. At the end of B, the supine blood pressure (BP) was 156/101, and at the end of B + L and B + C it was 136/91 (p〈0.001) and 137/91 (p〈0.001), respectively, pooling the data from both periods. At the end of B, the standing BP was 155/115, and at the end of B + L and B + C 134/100 (p〈0.001) and 139/106 (p〈0.001), respectively. The mean daily doses required were L 476mg and C 0.335 mg. On a weight basis, labetalol had about 1/1400 of the potency of clonidine. 12 patients complained of tiredness and dry mouth on clonidine and 2 patients of unsteadiness on labetalol. Labetalol caused a psoriasiform rash on the hands in one patient and limb weakness in one patient.
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  • 27
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    European journal of clinical pharmacology 22 (1982), S. 7-14 
    ISSN: 1432-1041
    Keywords: prazosin ; baroreflexes ; hypertension ; reflex tachycardia ; alpha adrenergic blockade ; dopamine-beta-hydroxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prazosin is a post synaptic alpha adrenergic blocker effective in hypertension, whose hypotensive effect is unaccompanied by reflex tachycardia or hyperreninemia, nor by other evidence of increased sympathetic activity. We studied the baroreceptor reflex arc as a potential mediator of these effects. Twenty-two essential hypertensive men were treated with prazosin alone versus placebo, and experienced a blood pressure fall (from 114.8±3.6 down to 101.1±2.5 mm Hg,p〈0.005) unaccompanied by any change in heart rate, plasma renin activity, or several other indices of sympathetic nervous system activity (plasma dopamine-β-hydroxylase activity; urinary excretion of free catecholamines and vanillyl mandelic acid; allp〉0.1). Concomitant with the blood pressure fall, there was a significant depression of baroreflex arc sensitivity, from 11.4±2.0 ms/mmHg down to 6.6±1.9 ms/mmHg (p〈0.05), without an associated change in cardiac vagal inhibition (291.2±46.2 versus 300.3±19.2 ms,p〉0.1). Baroreflex arc sensitivity depression may in part explain the lack of reflex sympathetic outflow noted during prazosin treatment of hypertension.
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  • 28
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    European journal of clinical pharmacology 22 (1982), S. 197-201 
    ISSN: 1432-1041
    Keywords: hypertension ; oxprenolol ; indomethacin ; drug interaction ; hypotensive effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double-blind, cross-over study in 16 patients with essential hypertension was carried out, to evaluate any possible interference by indomethacin, a known prostaglandin-synthetase inhibitor, with the antihypertensive effect of oxprenolol, a non-selective beta-adrenoceptor blocking agent. Both indomethacin and oxprenolol, as well as the two drugs combined, inhibited plasma renin activity; no change was found in urinary sodium excretion or body weight. Oxprenolol alone caused a highly significant decrease in the systolic (−10.4 mmHg,p〈0.001), diastolic (−7.4 mmHg,p〈0.001) and mean (−7.7 mmHg,p〈0.01) blood pressures, whereas indomethacin did not influence blood pressure. When the two drugs were given in combination, blood pressure decreased (systolic: −5.9 mmHg; diastolic: −4.0 mmHg; mean: −4.6 mmHg), but the changes induced in blood pressure were reduced by about 50% when compared with those in the oxprenolol alone period. The data show that indomethacin seems to interfere with the antihypertensive effect of oxprenolol, by an action which may be due to the inhibition of prostaglandin synthesis.
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  • 29
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    European journal of clinical pharmacology 20 (1981), S. 163-168 
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; cardiac output ; extracellular fluid volume ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril 450 mg/day for 4 weeks on blood pressure, heart rate, cardiac output and extracellular fluid volume were compared in severe, often drug-resistant hypertension (n=23), mild to moderate hypertension associated with renal artery stenosis (n=10) and mild to moderate essential hypertension (n=20). Plasma renin in the three groups was 52±19, 58±17 and 20±4 µU/ml (mean ± SEM), respectively. Blood pressure fell by 18±4%, 21±2% and 18±1%. The pressure drop was mainly due to a fall in peripheral vascular resistance. Addition of the diuretic hydrochlorothiazide (25–100 mg/day) caused a further fall in resistance. Despite the vasodilator effect of captopril, reflex cardiostimulation and reactive fluid retention were not observed. In severe hypertension, captopril alone was more effective in lowering blood pressure than combined diuretic-betablocker-vasodilator therapy. Moreover, cardiac output in these patients was higher and resistance was lower after captopril than during combined treatment. Thus, captopril was capable of normalising the abnormal haemodynamic state in patients with essential hypertension, and in hypertension associated with renal artery stenosis. Despite marked differences in pre-treatment plasma renin, the effects of captopril on systemic haemodynamics were similar in all the patients.
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  • 30
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; haemodynamic effects ; renal plasma flow ; renal tubular function ; plasma renin activity ; aldosterone ; Ro 12-4713
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Selected cardiovascular and endocrine effects of the new oral vasodilator Ro 12-4713 have been evaluated in an acute single dose study. In five patients with essential hypertension, Ro 12-4713 caused a dose-dependent decrease in supine and upright blood pressure and an increase in heart rate. Initial effects occurred one to 2 h after drug ingestion and maximal effects were noted after five hours and persisted for at least 8 h. Blood pressure was normalized, and the antihypertensive and chronotropic effects persisted for 24 h after a dose of about 300 mg/1.73 m2. Plasma and urinary norepinephrine and plasma renin levels tended to be raised, whereas plasma and urinary epinephrine and plasma aldosterone did not change. Changes in supine heart rate were inversely correlated with changes in mean blood pressure (r=−0.60; P〈0.02), and positively with those in plasma norepinephrine (r=0.55; P〈0.05) and renin (r=0.62, P〈0.01); changes in supine plasma renin level were also inversely correlated with those in mean blood pressure (r=−0.65; P〈0.01), and positively with those in plasma norepinephrine (r=0.58; P〈0.05). 24 h-urinary sodium excretion was significantly (P〈0.001) decreased; it was positively correlated with mean blood pressure (r=0.51; P〈0.05) and inversely with supine plasma renin activity (r=−0.63; P〈0.01). In six normal subjects and six patients with essential hypertension, effective renal plasma flow and the renal clearance of sodium, potassium, calcium and uric acid were not significantly altered five hours after a dose of Ro 12-4713 of about 250 mg/1.73 m2; glomerular filtration rate tended to be slightly decreased, and filtration fraction was significantly (P〈0.05) reduced in the hypertensive patients. At the same time blood pressure was decreased and plasma norepinephrine (P〈0.01) and renin (ns) were slightly increased in both groups. Ro 12-4713 in a single oral dose of about 300 mg appeared to be a potent, long acting, hypotensive vasodilator.
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  • 31
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    European journal of clinical pharmacology 22 (1982), S. 495-499 
    ISSN: 1432-1041
    Keywords: hypertension ; cyclothiazide ; hydrochlorthiazide ; thiazide diuretics ; potassium-sparing diuretics ; saluretic effect ; hypokalaemia ; hyperuricaemia ; amiloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive, saluretic and hypokalaemic effects of a small dose of cyclothiazide (2.5 mg daily) were compared with those of a conventional dose of an hydrochlorthiazide-amiloride hydrochloride combination (50+5 mg daily). Both preparations were given to 13 patients with mild (WHO I) hypertension in a cross-over manner for six weeks, with an intervening wash-out phase of three weeks. The antihypertensive efficacy of cyclothiazide was well comparable to that of the hydrochlorthiazide-amiloride combination, although cyclothiazide tended to inhibit renal sodium reabsorption less than the combination. Cyclothiazide tended to cause hypokalaemia, apparently due to increased potassium loss, but with the present dosage none of the 13 patients developed marked hypokalaemia (serum potassium less than 3.3 mmol/l). Both drugs led to a comparable increase in serum urate concentration. Neither of the preparations affected creatinine or free-water clearance. The results suggest that even in relatively small doses thiazides effectively decrease blood pressure, and combining thiazides with potassium-sparing diuretics is advantageous only in patients with marked hypokalaemia and its associated risks.
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  • 32
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    European journal of clinical pharmacology 24 (1983), S. 157-161 
    ISSN: 1432-1041
    Keywords: hypertension ; cadralazine ; single dose ; dose response curve ; hypotensive action ; prolonged effect ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cadralazine (ISF 2469) was administered to 24 hypertensive patients in single oral doses of 7.5, 10, 15, 20 and 30 mg, according to a single-blind, placebo-controlled, within-patient change-over design. The study was done in 2 stages: in the first a range including the upper and lower doses was studied (7.5, 15, 30 mg and placebo), and in the second the range of doses was restricted (10, 15, 20 mg and placebo). The drug produced a significant decrease in blood pressure in the supine and standing positions. The decrease became clinically important starting from the 15 mg dose. Its action was still significant 12 h after administration. A significant increase in heart rate was also observed. All the effects were correlated with the dose. Side effects occurred mainly after the 30 mg dose. Thus, cadralazine, in a single oral dose in man, showed good antihypertensive activity starting from the 15 mg dose, and its effect was dose-related, slow in onset and long-lasting.
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  • 33
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    European journal of clinical pharmacology 24 (1983), S. 217-220 
    ISSN: 1432-1041
    Keywords: metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
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  • 34
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    European journal of clinical pharmacology 24 (1983), S. 307-314 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; blood pressure ; heart rate ; renal clearance ; plasma renin activity ; plasma aldosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of endralazine, a new antihypertensive hydrazinopyridazine derivative, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), effective renal plasma flow (CPAH), urine volume (V), the clearance of Na, K, urea (Ur) and uric acid (UA), plasma renin activity (PRA) and plasma aldosterone (PA) were studied in hypertensive patients after a single oral dose of 10–15 mg, and after 8–17 days of treatment with daily doses of 15–90 mg. In the acute experiments, heart rate increased by 27%, mBP decreased on average by 17% and GFR by 33% and CPAH fell by only 5%. Urine volume and electrolyte clearance were also depressed. There was a significant increase in PRA and PA. The fall in GFR correlated directly with mBP, CPAH and the product (mBP×CPAH). The logarithms of the Na clearance and V were correlated with GFR and mBP. The logarithms of the fractional excretion of Na and water also correlated with mBP, suggesting that tubular reabsorption of sodium and water may be affected by change in mBP. The fractional potassium excretion correlated directly with CPAH and ln PA. In contrast, on sustained daily treatment, mBP was less depressed (9%), but GFR increased strikingly by 27% and CPAH by 46%. The body weight increased by 4.5% as a consequence of salt and water retention. GFR was correlated with CPAH, the product (mBP×CPAH) and the increase in body weight. Thus, the improvement in GFR and effective renal plasma flow observed under these conditions may be due, in part, to volume expansion. However, a direct renal vasodilating effect of the drug appears to be the more important determinant.
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  • 35
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    European journal of clinical pharmacology 24 (1983), S. 579-583 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; baroreflex ; vascular reactivity ; heart rate ; blood pressure change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic treatment with indapamide on blood pressure (BP), baroreceptor sensitivity (BRS) and vascular reactivity (VR) were investigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135±6 to 112±2 mmHg (p〈0.001); the heart rate (HR) had not changed, VR had decreased from 6.1±1.2 to 4.8±1.8 (pg·min·kg)−1 (p〈0.05), and BRS had increased from 8.3±3.7 to 12.2±5.3 ms/mmHg (p〈0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r=0.59; p〈0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations.
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  • 36
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    European journal of clinical pharmacology 25 (1983), S. 143-144 
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; plasma concentration ; blood pressure response
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  • 37
    ISSN: 1432-1041
    Keywords: furosemide ; hypertension ; plasma renin activity ; plasma adrenaline ; plasma noradrenaline ; body fluid loss ; diuretic response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and ∼65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.
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  • 38
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    European journal of clinical pharmacology 25 (1983), S. 307-312 
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
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  • 39
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    European journal of clinical pharmacology 25 (1983), S. 571-575 
    ISSN: 1432-1041
    Keywords: beta-blocker ; felodipine ; calcium antagonist ; hypertension ; vasodilator ; side effects ; plasma levels ; metoprolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, cross-over trial, 10 men with primary hypertension, not adequately controlled with a β-blocker alone, were also given felodipine or placebo for periods of one week. Placebo was administered single-blind for 2 weeks and 1 week, respectively, before randomization and between treatments. The dose of felodipine ranged from 6.25 mg to 25 mg. The addition of felodipine resulted in a pronounced (20%), statistically significant reduction in blood pressure (BP) and a small but significant increase in heart rate (HR). The effects were seen within 1–2 h and were maximal after 3–4 h. During steady state treatment the duration of BP reduction was at least 12 h. No orthostatic reaction was seen. There was a significant correlation between the plasma concentration of felodipine and change in BP. The most frequently reported side-effects were headache and ankle oedema, the latter probably being due to pronounced pre-capillary vasodilatation. There was no weight increase and thus no indication of general water retention. No clinically significant change in laboratory variables and no influence on the P-Q time were seen. Thus, felodipine in combination with a β-blocker seems to be a useful addition to the treatment of hypertensive patients whose BP is not adequately controlled with a β-blocker alone.
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  • 40
    ISSN: 1432-1041
    Keywords: prizidilol ; hypertension ; exercise test ; beta-blockade ; vasodilatation ; haemodynamic effects ; vascular tone ; muscle blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fourteen men with moderately severe essential hypertension were treated with prizidilol hydrochloride 400–700 mg once daily (mean±S.D. 612±56 mg/day). The study was open and ambulatory, with an initial placebo period followed by dose titration of prizidilol. Prior to treatment and during optimal control of blood pressure cardiovascular adaptation was examined in a submaximal exercise test. Plethysomographic assessment of vascular flow, resistance and tone in the calf musculature during supine rest and during maximal vasodilatation was also performed. A highly significant reduction in systolic (from 164±4.5 to 141±2.7 mmHg; p〈0.001) and diastolic blood pressure (from 105±1.6 to 87±1.3 mmHg; p〈0.001) at supine rest was noted during therapy with prizidilol. There was no significant change in heart rate. Systolic pressure in the standing position was reduced (from 159±4.2 to 139±2.9 mmHg; p〈0.001) and so was the diastolic pressure (from 111±2.5 to 95±1.9 mmHg; p〈0.001). The heart rate in the standing position was significantly increased compared to supine rest in the placebo period and during optimal treatment with prizidilol. The β-adrenoceptor blocking properties of prizidilol were apparent as a reduction in the exercise-induced heart rate response at even the lowest work load. During prizidilol therapy an increase in resting calf muscle blood flow was found from 3.1±1.5 ml/min·100 ml to 4.3±2.1 ml/min·100 ml (p〈0.025). Vascular resistance and vascular tone were significantly reduced. No change regarding blood flow or resistance during maximal vasodilatation was noted. It is considered that prizidilol has a clear antihypertensive effect combining β-receptor blocking and vasodilator properties.
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  • 41
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    European journal of clinical pharmacology 26 (1984), S. 309-313 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 µg/kg to patients with essential hypertension (n=6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time — plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the antihypertensive effect was established. At a plasma clonidine concentration of 0.65±0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
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  • 42
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    European journal of clinical pharmacology 26 (1984), S. 331-334 
    ISSN: 1432-1041
    Keywords: metoprolol ; oxprenolol ; hypertension ; beta-blockers ; HDL-cholesterol ; intrinsic sympathomimetic activity ; cardioselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present study was to evaluate whether a reduction in HDL-cholesterol is peculiar to non cardioselective beta blockers or whether it is also produced by cardioselective beta1-blockers. 16 patients with primary arterial hypertension on a balanced isocaloric diet were given oxprenolol 120 to 240 mg/day or metoprolol 100 to 200 mg/day in a random cross-over study. No significant change was observed after either treatment in fasting blood glucose, serum total cholesterol and triglycerides. HDL-cholesterol concentration was significantly decreased on metoprolol, from 41 to 36 mg/dl (p〈0.05), while oxprenolol did not affect it at all. The difference might depend on intrinsic sympathomimetic activity which is possessed by oxprenolol and which metoprolol lacks.
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  • 43
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    European journal of clinical pharmacology 26 (1984), S. 549-553 
    ISSN: 1432-1041
    Keywords: pafenolol ; hypertension ; antihypertensive therapy ; beta1-blocking agent ; exercise tests ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pafenolol, a new selective adrenergic beta1-blocking agent, has been tested for the first time in 6 hypertensive patients. After single oral doses of pafenolol 25 to 100 mg, there was a marked reduction in heart rate and systolic blood pressure during exercise tests. These effects were dose dependent. A significant positive correlation was found between the reduction in heart rate during exercise and the plasma level of pafenolol 5 hours after drug intake (correlation coefficient r=0.94). Side effects were mild and seemed to be dose dependent. It is concluded that this new beta1-blocking agent was effective in reducing blood pressure and was well tolerated.
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  • 44
    ISSN: 1432-1041
    Keywords: etozolin ; ozolinone ; furosemide ; hypertension ; renin ; catecholamines ; chronic renal failure ; steady state kinetics ; plasma levels
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on urinary electrolyte excretion, renin release and plasma norepinephrine of single oral doses of 400 mg etozolin (E) and of 40 mg furosemide (F) were studied in hypertensive patients with normal (n=6) and impaired kidney function (n=6). E caused a marked saluresis up to 24 hours, showing its long duration of action. F, however, displayed a brief, brisk peak diuresis, followed by a rebound from the 4th to the 24th hours. The brisk peak diuresis induced by F was associated with pronounced release of renin, almost twice that induced by E. In chronic renal failure the renin release in relation to the magnitude of the diuresis was increased, i.e. the sensitivity of these patients to changes in water homeostasis was increased. E and F stimulated the sympathetic system to roughly the same extent. Patients with essential hypertension had higher plasma levels of norepinephrine than hypertensive patients with chronic renal failure. In addition, hypertensive patients with normal renal function (n=4) and varying degrees of renal impairment (n=11) were also given 400 mg daily for 2 weeks. Effects on blood pressure and electrolyte homeostasis were monitored, as well as the plasma kinetics of metabolite I, ozolinone. At the end of the 2 week treatment E had significantly lowered systolic (−12 mm Hg) and diastolic (−9 mm Hg) blood pressure, and had produced a significant loss of body weight, without altering plasma electrolytes or blood chemistry. There was no accumulation of the effective metabolite ozolinone under conditions of severe impairment of kidney function. It is concluded that E can effectively control high blood pressure in patients with normal and impaired kidney function. Its effective metabolite ozolinone did not accumulate in chronic renal failure.
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  • 45
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    European journal of clinical pharmacology 27 (1984), S. 397-405 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; cardiovascular reflexes ; diuretic effect ; blood pressure variability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.
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  • 46
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    European journal of clinical pharmacology 10 (1976), S. 177-182 
    ISSN: 1432-1041
    Keywords: Hydrochlorothiazide ; hypertension ; serum potassium ; total body potassium ; serum uric acid ; fasting blood sugar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive activity and side effects of three doses of hydrochlorothiazide combined with a potassium supplement (Esidrex®-K novum, Ciba) were determined in 40 hypertensive subjects in a double-blind, cross-over study. The lowest daily dose (12.5 mg) gave almost the same blood pressure reduction as the doses in common use (25 mg and 50 mg) and as the adrenergic beta-blocking agents previously employed. Metabolic side effects in the form of decreased serum potassium and increased fasting blood sugar and serum uric acid were observed in patients on the lower dose and, with the exception of serum uric acid, were only slightly more pronounced with the higher doses. The frequency of subjective side effects, on the other hand, increased with increasing dose. No changes were noted in total body potassium at any dose level. It is suggested that hydrochlorothiazide in low dose, alone or in combination with other antihypertensive agents, is a useful therapeutic regimen in mild hypertension.
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  • 47
    ISSN: 1432-1041
    Keywords: Tolamolol ; methyldopa ; comparative trial ; hypertension ; beta-blockade
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy and toxicity of tolamolol and methyldopa in hypertensive patients has been compared by a dose-titrated, double-blind, cross-over study. Thirteen patients completed the trial. Within the dose ranges investigated (tolamolol — 300 mg/day — 900 mg/day; methyldopa — 750 mg/day — 2250 mg/day) both drugs produced significant falls in laying and standing, systolic and diastolic blood pressures. Although the hypotensive effects of methyldopa were more marked than tolamolol, these only achieved conventional (P〈0.05) levels of significance for lying blood pressure. There were no objective changes in haematological or biochemical indices during treatment with either drug, but patients complained of tiredness, weak limbs and mouth dryness significantly more during methyldopa treatment, than during either placebo or tolamolol therapy.
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  • 48
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    European journal of clinical pharmacology 14 (1978), S. 163-166 
    ISSN: 1432-1041
    Keywords: Propranolol ; hypertension
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol was administered in a single dose of 80 mg, 120 mg, 160 mg, 240 mg, or 320 mg, to 23 patients with essential mild to moderate hypertension in a randomised, double-blind cross-over study. All treatments produced a significant fall in lying and standing blood pressures compared with placebo, but there was no statistically significant difference in the effects of the different doses. The percentage of patients showing a satisfactory fall in blood pressure was not different in the five treatment groups. The major anti-hypertensive effect of each dose was present by two weeks. The frequency of side-effects were similar on all the doses.
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  • 49
    ISSN: 1432-1041
    Keywords: atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
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  • 50
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    European journal of clinical pharmacology 17 (1980), S. 239-241 
    ISSN: 1432-1041
    Keywords: timolol ; hypertension ; dose ranging ; double-blind trial
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine previously untreated patients with mild-moderate hypertension were included in a dose-ranging double-blind trial to determine the effectiveness of daily versus thrice daily timolol administration. In 8 patients control of blood pressure was equally effective though with significantly lower heart rate achieved in the once daily group. One patient was not satisfactorily controlled on the daily regimen demonstrating that many but not all hypertensives can be controlled with daily administration of timolol.
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  • 51
    ISSN: 1432-1041
    Keywords: metoprolol ; thiazides diuretics ; hypertension ; haemodynamic effects ; renal function ; body fluid volume
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In fifteen patients with essential hypertension WHO I–II (eight men and seven; mean age 45 years) blood pressure (BP), plasma volume (PV;125I-Albumin space), extracellular volume (ECV;82Brdistribution space) and glomerular filtration rate (GFR;51Cr-EDTA clearance) were measured before and during long-term antihypertensive therapy with metoprolol, alone, and in combination with thiazide diuretics. Metoprolol given alone to all patients for an average of 5 months (mean dose 230 mg) resulted in a reduction in systolic and diastolic pressure by 11% and 8%, respectively. In eight patients the BP reduction was considered inadequate (non-responders). In the group as a whole, ECV increased significantly by 5%. The increase in ECV in the non-responders was five times larger than in the responders (1.025 ml against 205 ml), which may in part account for the inadequate BP control. Addition of a thiazide diuretic for an average of 3.5 months resulted in reduction of ECV to its pretreatment level and a pronounced additional fall in BP, comparable to that in the responders. No systematic change in PV or GFR could be demonstrated. No difference was found between the two groups regarding sex, pretreatment BP, body fluid volumes or renal function. On average the non-responders were 20 years older than the responders. The clinical importance of the apparent age-related expansion of ECV and the mechanism behind fluid retention during antihypertensive treatment with beta-blocking drugs are discussed. As failure of BP control during treatment with beta-blockers may be due to fluid retention, concurrent use of diuretics is indicated.
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  • 52
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    European journal of clinical pharmacology 18 (1980), S. 391-394 
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
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  • 53
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    European journal of clinical pharmacology 19 (1981), S. 25-32 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; baroreceptor reflex ; mode of action ; sympathetic activity ; urinary catecholamines
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 ± 0.15 mg/day) alone in 13 essential hypertensive men, assessing several biochemical indices of sympathetic function, as well as physiologic parameters, including baroreflex sensitivity, the cold pressor test, and the hypotensive response to alpha adrenergic blockade. Clonidine diminished mean arterial pressure (from 104±5 to 84±3 mmHg;p〈0.01), without associated changes in several biochemical parameters of sympathetic outflow (urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid; allp〉0.1). Circulatory baroreflex function was not enhanced by clonidine, during either the amylnitrite test or the phenylephrine test, before or after parasympathetic blockade with atropine. The cold pressor test, an index of efferent sympathetic pressor function, was also unaltered. The enhanced mean arterial pressure response to phentolamine during clonidine therapy (from a fall of 14.8±4.3 to 39.4±5.2 mmHg,p〈0.01), suggested an increase in alpha adrenergic vascular tone, perhaps mediated by clonidine's alpha agonist properties in vascular smooth muscle. The antihypertensive mechanism of longterm low dose clonidine cannot reliably be ascribed either to baroreflex enhancement or to suppression of sympathetic outflow.
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  • 54
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    European journal of clinical pharmacology 19 (1981), S. 113-118 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilators ; hypertension ; side-effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and a diuretic. After a 50 mg oral dose mean (± SD) peak plasma concentration of T was 1.13±0.29 µg/ml−1 and occurred 0.79±0.40 h after the dose; mean peak plasma concentration of its sulphone metabolite (M) was 0.37±0.09 µg/ml−1 at 1.92±1.32 h after the dose. Following peak plasma concentrations there was a monoexponential decline in T and M concentrations with half-lives of 2.78±0.77 h and 10.78±7.85 h respectively. There was a linear increase in plasma concentration of T and M during incremental dosing with 50–200 mg t. i. d. During in-patient administration of 600–900 mg T daily (n=6) there was no significant change in blood pressure, pulse rate or body weight. Out-patient administration of 900 mg T daily (n=4) was associated with a significant fall in mean systolic but not diastolic bp (lying −15/+1 mm Hg. standing −25/−8 mm Hg). A further fall was observed in 2 subjects receiving 1200 mg and 1500 mg daily. Supine pulse rate increased (mean ± SD) significantly from 55±5/min to 66±8/min following 900–1500 mg T in 4 out-patients. Severe nausea and other gastro-intestinal side-effects in all subjects receiving 600–900 mg daily eventually necessitated drug withdrawal. In its present from T is not recommended for the treatment of hypertension.
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  • 55
    ISSN: 1432-1041
    Keywords: carteolol ; hydrochlorthiazide ; amiloride ; hypertension ; double-blind clinical trial
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of carteolol, a new β-blocking agent, added to basal diuretic treatment (hydrochlorthiazide 50 mg and amiloride 5 mg) has been assessed in a controlled trial in 17 patients with mild-to-moderate hypertension. The trial was divided into 4 stages: 1) run-in period with no antihypertensive treatment, 2) diuretic period (the diuretic being continued as basal treatment during the two following periods), 3) carteolol titration period, and 4) double-blind cross-over period comparing carteolol with placebo, which lasted 2 times 4 weeks. Although the diuretic effectively reduced the blood pressure, 17 of the 20 patients originally studied still had an elevated diastolic blood pressure (≧ 95 mmHg) after the diuretic period, thus fulfilling the inclusion criteria for the study. During the titration period carteolol 5 to 20 mg b. i. d. significantly reduced the elevated blood pressure. The blood pressure was reduced to normal in all 17 patients, although in two patients this occurred only during the double-blind period. During the double-blind period, the dose of carteolol was used which had given a satisfactory response during the titration period. The blood pressure in the 14 patients who completed the trial remained low both with carteolol and placebo during the double-blind stage, and was only slightly lower with carteolol than with placebo. This is probably due to a “carry-over” effect. Three patients discontinued the trial due to side effects (1 urticaria, 1 insomnia and 1 nausea) while on carteolol. There was no other difference between carteolol and placebo in the number or severity of side effects.
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  • 56
    ISSN: 1432-1041
    Keywords: beta-blocker ; hypertension ; clonidine ; plasma catecholamines ; metoprolol ; propranolol ; blood pressure responses ; isometric work ; dynamic work
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of metropolol (beta1-selective), propranolol (nonselective) and clonidine (central alpha-stimulant) on plasma norepinephrine, blood pressure and heart rate were assessed at rest, during isometric work and dynamic exercise in 15 patients with moderate hypertension. Metroprolol resulted in a lower diastolic blood pressure during isometric and dynamic exercise than propranolol, which was paralleled by a lower plasma norepinephrine level during dynamic work; both beta-adrenergic blocking compounds resulted in a lower heart rate in all test situations than that obtained with clonidine; clonidine produced similar control of diastolic blood pressure to that obtained with the beta-adrenergic blocking agents, but did not clearly attenuate the systolic blood pressure response to dynamic exercise. Plasma norepinephrine concentrations tended to be lowest following clonidine, especially during dynamic work. The findings support the hypothesis that the central action of clonidine inhibits peripheral release of norepinephrine, but is insufficient to attenuate cardiac stimulation by physical exercise. The fact that propranolol caused higher plasma norepinephrine concentrations than metoprolol during exercise may explain the difference in the blood pressure responses during exercise.
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  • 57
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    European journal of clinical pharmacology 21 (1982), S. 445-449 
    ISSN: 1432-1041
    Keywords: pindolol ; hypertension ; retard formulation ; plasma levels ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 36 out of 52 patients with essential hypertension, whose blood pressure was not normalized with pindolol 15 mg per day, were treated with 30 mg per day for four to six weeks. Pindolol was administered in random order, either as 15 mg twice daily or as one 30 mg retard tablet once daily. Blood pressure was lowered from mean pretreatment levels of 174/111 mmHg to 149/98 mmHg by 15 mg b.d., and to 145/97 mmHg by 30 mg retard. In five patients diurnal variations in blood pressure and plasma pindolol levels were determined. At all times during the day blood pressure was at least as well controlled by 30 mg retard as by 15 mg b.d. Plasma concentration maxima were similar with both forms, but a higher concentration was maintained for a longer time after the retard tablet. Pindolol 30 mg was well tolerated and the incidence of side effects was lower than during treatment with 15 mg b.d. Thus, patients requiring high doses of pindolol for control of hypertension can safely and conveniently be treated with a single tablet of 30 mg pindolol retard.
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  • 58
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    European journal of clinical pharmacology 21 (1982), S. 473-477 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilators ; heart failure ; haemodynamics ; hypertension ; sulphoxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effect of Tolmesoxide, a new sulphoxide chemically dissimilar from other vasodilators, was investigated in eight patients with chronic heart failure subsequent to ischaemic heart disease and/or hypertension. Tolmesoxide significantly increased the cardiac output and reduced the indices of systemic vascular resistance, the mean pulmonary arterial pressure and left ventricular filling pressure in most patients studied. These changes were observed both as acute and chronic effects. No significant effect on the mean arterial pressure, heart rate or myocardial oxygen supply/demand was observed. Tolmesoxide appeared to be therapeutically potent by both intravenous and oral routes.
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  • 59
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; antihypertensive treatment ; catecholamines ; renin ; aldosterone ; blood volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy and endocrine profile of the new antihypertensive agent, Ro 12-4713, were evaluated in 23 patients (17 men and 6 women) with moderate to severe arterial hypertension. Following addition of Ro 12-4713 to pre-existing therapy with diuretics and beta-blockers or sympatholytics, blood pressure in most of the patients was normalized within one month by a daily dose of 60 to 120 mg. Heart rate was only slightly increased. Orthostatic hypotension was not observed. Weight gain or oedema formation occurred in 14 patients within the first four weeks, but could be controlled satisfactorily by intensified diuretic therapy. Increased hair growth occurred in most of the patients. After a mean duration of treatment of 2.8 months, plasma volume and plasma and urine sodium were unaltered, and plasma potassium was slightly decreased. Plasma renin activity was doubled, whereas plasma aldosterone concentrations were unaltered. Plasma norepinephrine levels were high before and increased only slightly during chronic Ro 12-4713 treatment, whereas urinary norepinephrine excretion was unchanged. Plasma and urinary epinephrine were unaltered by Ro 12-4713. Ro 12-4713 appears to be a potent vasodilator for the combination treatment of hypertension in men.
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  • 60
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    European journal of clinical pharmacology 22 (1982), S. 285-288 
    ISSN: 1432-1041
    Keywords: hypertension ; plasma adrenaline ; plasma noradrenaline ; isoprenaline response ; noradrenaline response ; salivation ; parasympathetic nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Parameters of the autonomic nervous system were studied in normotensive subjects (NT; standing blood pressure (BP)≤125/85 mmHg) and in subjects with borderline hypertension (BHT; 140/90≤standing BP〈60/100 mmHg). No differences in plasma noradrenaline and adrenaline levels were found between NT and BHT subjects, neither at rest nor during exercise at 75% of maximum work capacity. The dose of noradrenaline required to increase systolic BP by 10 mmHg was significantly higher in NT than in BHT subjects (5.13±0.42 vs 3.50±0.57 µg · min−1). No difference between NT and BHT subjects was found in the dose of isoprenaline required to increase heart rate by 20 beats · min−1 (1.21±0.12 vs 1.09±0.11 µg · min−1). Resting salivary flow was significantly lower in BHT than in NT subjects (0.39±0.06 vs 0.98±0.06 g · min−1), suggesting decreased parasympathetic activity in the former group. The enhanced pressor effect of noradrenaline, together with the decreased parasympathetic activity, could explain the elevated blood pressure and heart rate in subjects with borderline hypertension.
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  • 61
    ISSN: 1432-1041
    Keywords: bopindolol ; hypertension ; beta-blocker ; blood pressure ; plasma renin ; plasma catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bopindolol (LT 31-200), a new, long-acting, non-selective beta-blocker, was given as monotherapy to 13 patients, 12 with essential hypertension and 1 with renovascular hypertension. After a placebo period of 4–6 weeks, bopindolol was given once daily, starting with 1 mg and subsequently increasing at two-weekly intervals to 2 and 4 mg once daily until a diastolic blood pressure⩽90 mmHg was achieved. The effective dose was continued for 12 weeks. In 10 patients plasma levels of renin, noradrenaline, adrenaline and cholesterol were measured during placebo and after 3 months of therapy. Blood pressure and heart rate were lowered significantly during bopindolol treatment. The mean effective dose was 2.2 mg per day. In 10/13 patients a diastolic blood pressure⩽90 mmHg was achieved. Side effects were minimal. Changes in plasma noradrenaline and adrenaline were small and not significant, but renin and cholesterol were significantly reduced. Thus, LT 31-200 is an effective and well tolerated beta-blocker when given in a once daily dosage.
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  • 62
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    European journal of clinical pharmacology 20 (1981), S. 335-338 
    ISSN: 1432-1041
    Keywords: atenolol ; atherosclerosis ; hypertension ; serum lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum lipoproteins were determined in 15 patients before and during antihypertensive treatment with atenolol 0.1–0.2 g/day for a mean of 8 months. The mean blood pressure fell from 171/103 to 154/93 mm Hg (p〈0.05). Significant lipoprotein changes were an increase in very low density triglycerides (VLDL-TG) from 1.21±0.95 (SD) to 1.62±1.24 mmol/l (p〈0.01) and in low density (LDL) TG from 0.46±0.12 to 0.51±0.12 mmol/l (p〈0.05). Together, these TG increases resulted in development of hypertriglyceridaemia in 7/15 patients during atenolol treatment. No effect on whole serum cholesterol or on the high density lipoprotein cholesterol concentrations were found. Thus, some patients on long term treatment with atenolol seem to receive the benefit of normotension at the cost of hypertriglyceridaemia. This may have practical implications, since hypertriglyceridaemia constitutes an important risk factor for atherosclerosis.
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  • 63
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    European journal of clinical pharmacology 20 (1981), S. 347-349 
    ISSN: 1432-1041
    Keywords: reserpine ; syrosingopine ; prolactin secretion ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 20 mild hypertensive women, reserpine induced a significant increase in mean plasma PRL, both under basal conditions (from 6.6±0.9 to 17.9±2.9 ng/ml), and on repeated determinations during the day. In contrast to reserpine, the administration of syrosingopine, a synthetic compound derived from reserpine, to the same subjects was not followed by a significant change in prolactin level. Beyond their pharmacological interest, these results are of clinical importance when considering that rauwolfia alkaloids are used for long term treatment, and that an increase in PRL levels is important in pathology, both in relation to the function of the hypophyseogonadal axis and in view of its possible facilitation of the growth and development of mammary cancer.
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  • 64
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    European journal of clinical pharmacology 24 (1983), S. 15-19 
    ISSN: 1432-1041
    Keywords: hypertension ; mianserin ; clonidine ; methyldopa ; depression ; α2 receptors ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concurrent administration of tricyclic antidepressants has been shown in man to result in a clinically significant impairment of the antihypertensive effect of clonidine. This interaction is thought to be related to competition for central α2 receptors where clonidine acts as an agonist and the tricyclics act as antagonists. Although it seems to cause less cardiovascular effects than tricyclic antidepressants, the tetracyclic antidepressant, mianserin also has been reported to be an α receptor antagonist and may, therefore, also interfere with the antihypertensive activity of centrally-acting drugs. This study investigates the effects of acute and chronic mianserin administration in patients with essential hypertension established on long term treatment with either clonidine or methyldopa. The first dose of mianserin was not associated with an increase in blood pressure and during a further two weeks of mianserin therapy there were no significant alterations in blood pressure, supine or erect. Similarly, mianserin did not alter heart rate either after acute or after chronic administration. Mianserin itself had a sedative effect but there was no interference with the sedation attributable to clonidine or methyldopa. Mianserin caused no reduction in salivary flow and did not influence the reduced saliva production caused by clonidine. Both clonidine and methyldopa are associated with a reduction in sympathetic outflow but there was no evidence in this study of any further change in plasma noradrenaline or 24 h urinary catecholamine excretion. This study demonstrates that if mianserin is given acutely or chronically, it does not interfere with the effects of the centrally acting antihypertensive drugs, clonidine and methyldopa. Mianserin may therefore be a suitable antidepressant for patients receiving these antihypertensive agents if drug treatment for depression is indicated.
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    European journal of clinical pharmacology 24 (1983), S. 1-5 
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; calcium antagonists ; beta-blockers ; vasodilators ; diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nifedipine has been assessed as a possible alternative to other third line drugs in the management of patients with difficult to control hypertension. A group of 20 patients whose blood pressure was unsatisfactory on a 3 drug regimen had their third drug stopped and after a 2 week period nifedipine was added to their beta-blocker plus diuretic therapy. Eleven became normotensive on 30 mg nifedipine daily and a further 6 on 60 mg daily; giving on overall success rate of 85%. This result was achieved with a reduction in side effects and an absence of any haemodynamic or metabolic complications.
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  • 66
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    European journal of clinical pharmacology 24 (1983), S. 301-305 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; pindolol ; peripheral vasodilator ; acetylator phenotypes ; antinuclear antibodies ; SLE-syndrome ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nineteen out-patients with moderate to severe essential hypertension were treated daily for 3 years, with an average dose of 13 mg endralazine, a new peripheral vasodilator, in free combination with pindolol 3×5 mg. The blood pressure showed a statistically significant reduction from 172/110 mmHg to 154/92 mmHg after treatment for 3 weeks. Tachyphylaxis was not observed during the 3 year period. Oedema was the most frequent side-effect, but it disappeared spontaneously. No difference in efficacy and tolerance between slow and fast acetylators was found. Only 2 patients developed a weak positive antinuclear antibody titre, which disappeared spontaneously from one during continued treatment. No clinical evidence of a systemic lupus erythematosus-like syndrome was noted. It is concluded that the differences between endralazine and hydralazine in dosage and metabolism may explain the lower immunogenic activity of endralazine.
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  • 67
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; beta-adrenoceptor blockade ; long-term treatment ; adverse effects ; propranolol ; timolol ; metoprolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of nifedipine during long-term therapy was investigated in 5 patients receiving nifedipine as the sole drug and in 10 patients who had nifedipine in combination with a beta-adrenoceptor blocking drug. Nifedipine monotherapy was problematic because of side-effects and development of resistance to therapy after a few months. In patients who received the combined therapy significant and stable blood pressure reductions were maintained during the whole observation period (12–33 months). However, the occurrence of peripheral oedema in 4 of the patients necessitated the addition of a thiazide diuretic. It is concluded that nifedipine is not a first choice drug for the long-term treatment of arterial hypertension. When given in addition to a beta-blocker it is well tolerated and powerful but fluid retention may occur and if not counteracted by a diuretic it will limit the antihypertensive potential of the drug.
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  • 68
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    European journal of clinical pharmacology 25 (1983), S. 481-490 
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
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  • 69
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I–II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p〈0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p〈0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the changes in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p〈0.05); four patients complained of oedema. Therapy was discontinued in one patient after a fainting episode following an increase in the dose. Thus, pinacidil was able to lower blood pressure during monotherapy for 4 weeks provided that an adequate serum concentration was achieved. The present retarded tablet formulation is not suitable for b. d. dosing. The tendency towards fluid-retention suggests that pinacidil should be used in combination with a diuretic.
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  • 70
    ISSN: 1432-1041
    Keywords: captopril ; propranolol ; sympathetic nervous system ; noradrenaline ; aldosterone ; renin ; angiotensin converting enzyme ; hypertension ; isometric exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations. The expected acute increase in heart rate on standing and during isometric exercise was blunted by propranolol, but the changes in blood pressure and plasma noradrenaline were unaffected. We conclude that in essential hypertension noradrenaline is involved in the pressor response to isometric exercise. Angiotensin converting enzyme inhibition by captopril did not interfere with the responses of the sympathetic nervous system to postural changes and isometric exercise. During propranolol treatment there was no evidence that reduced sympathetic activity was involved in the hypotensive response.
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  • 71
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    European journal of clinical pharmacology 23 (1982), S. 197-201 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; low dose ; plasma concentration ; acute and long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and long-term hypotensive effects of low doses of nifedipine, and the correlation between the fall in the blood pressure (BP) and the plasma nifedipine concentration, were investigated in patients with essential hypertension. The oral administration of nifedipine 5 mg rapidly decreased BP from 163±22/101±10 to 127±12/82±9 mmHg (mean±SD; p〈0.001), and increased heart rate from 72±8 to 76±6 beats/min (p〈0.05), plasma renin activity rose from 1.2±0.6 to 1.4±0.8 ng/ml/h (p〈0.05), and plasma nifedipine concentration was 75.6±22.0 ng/ml 30 min after administration (n=7). The nifedipine concentration was significantly correlated both with the fall in BP (r=0.410, p〈0.02, n=31) and the rise in the heart rate (r=0.412, p〈0.02, n=31). Treatment with nifedipine 5 mg t.d.s. alone or in combination either with propranolol 10 mg t.d.s., or thiazide 1 tablet daily, or propranolol and thiazide, controlled BP in 36 patients during the 22 week study period. During the long-term nifedipine therapy, the plasma nifedipine level was significantly correlated with the fall in systolic (r=0.577, p〈0.01, n=20) and diastolic (r=0.595, p〈0.01, n=20) BP. It was concluded that the plasma nifedipine concentration could be correlated with the fall in BP, and that low doses of nifedipine, either as monotherapy or in combination, were effective in the acute and long-term treatment of patients with essential hypertension.
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  • 72
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    European journal of clinical pharmacology 23 (1982), S. 215-220 
    ISSN: 1432-1041
    Keywords: hypertension ; muzolimine ; mild renal functional impairment ; diuretic treatment ; body sodium ; catecholamines ; cardiovascular pressor responsiveness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighteen patients with mild impairment of renal function (glomerular filtration rate 65±5 ml/min: m±SEM) and hypertension (168/105±6/3 mmHg) were shown on average to have abnormally increased cardiovascular pressor responsiveness to infused norepinephrine (NE; p〈0.05), whereas plasma and urinary NE, exchangeable body sodium and blood-volume did not differ significantly from normal. A slightly increased pressor responsiveness to angiotensin II was associated with a tendency to low plasma renin activity (PRA). Compared to placebo conditions, treatment with the loop-diuretic muzolimine in a mean dose of 35±2 mg/day for six weeks decreased blood-pressure and exchangeable sodium (p〈0.05), and NE pressor responsiveness was restored to normal values, whilst plasma and urinary NE were not significantly changed. This was consistent with improvement of the initially abnormal relationship between NE levels and NE responsiveness factors. In contrast, the pressor dose of angiotensin II and PRA were increased to an approximatively similar extent during muzolimine treatment. These observations suggest that removal of body sodium and a decrease in NE reactivity without an equivalent increase in sympathetic nervous activity may be important complementary factors in the antihypertensive mechanisms of diuretic treatment in patients with mild renal functional impairment.
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  • 73
    ISSN: 1432-1041
    Keywords: prizidilol ; vasodilator ; hypertension ; beta blocker ; plasma renin ; aldosterone ; catecholamines ; acetylator type
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (〈107 mmHg) from 3 to 7 h and was still below predose levels 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to 〈95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidilol.
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  • 74
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    European journal of clinical pharmacology 26 (1984), S. 315-323 
    ISSN: 1432-1041
    Keywords: captopril ; hypertension ; glomerular filtration ; para-aminohippuric acid ; renal function ; severe drug reaction ; nephrotic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of captopril up to 450 mg/day on blood pressure and renal function were investigated during sustained treatment of 10 patients whose severe hypertension had not responded to previous therapy. All the patients were kept on diuretics and most of them on β-blockers, too. A control determination of glomerular filtration rate (GFR) and para-aminohippuric acid clearance (CPAH) was performed during the prior treatment. The effect of the addition (or substitution) of captopril were assessed after an average of 25 days (short-term) and 26 weeks (long-term). Short-term treatment produced a 15.5% decrease in mean blood pressure and interindividually variable effects on renal function. On average GFR was somewhat lower and CPAH slightly higher than the control values (not significant). This pattern is quite similar to the effects of most other antihypertensive drugs. On long-term therapy GFR rose by a mean of 9% (NS) and CPAH by 17% (p〈0.02). However, in a patient who developed a captopril-induced nephrotic syndrome, GFR dropped to 56% and CPAH to 50% of the control values. In another patient a transient rise in serum creatinine accompanied a severe drug reaction.
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  • 75
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    European journal of clinical pharmacology 24 (1983), S. 145-150 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; pharmacokinetics ; tablet formulation ; dose-response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (−18%) and lasted longer (12 h) after 60 mg than after 20 mg (−11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration — time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r=0.61,p〈0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.
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  • 76
    ISSN: 1432-1041
    Keywords: labetalol ; furosemide ; hypertension ; aldosterone ; blood pressure ; plasma catecholamines ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Arterial blood pressure and plasma catecholamines, renin activity and aldosterone concentration in 12 patients with severe essential hypertension were studied before and after combined α-and β-adrenergic receptor blockade induced by oral labetalol treatment for 2 months. Furosemide in a fixed dose was employed as a basic antihypertensive agent throughout the study. Blood pressure was adequately controlled in only 6 patients. Mean body weight increased by 1.8 kg and there was a rise in body weight which was inversely correlated with the fall in standing mean blood pressure. The mean plasma noradrenaline concentration decreased from 0.30 to 0.20 ng/ml, whereas plasma adrenaline did not change significantly. Plasma renin activity and aldosterone concentration varied greatly, but the mean values did not change significantly. Change in body weight was correlated inversely with changes in plasma noradrenaline and renin. The results suggest that labetalol, through its combined α- and β-adrenergic receptor blocking action, induces a rise in body weight, probably due to sodium and fluid retention, which partly counterbalances the antihypertensive effect of labetalol, and partly modifies both renin and sympathetic nervous activity.
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  • 77
    ISSN: 1432-1041
    Keywords: tientilic acid ; hydrochlorothiazide ; hypertension ; diuretics ; hyperuricemia ; hypouricemic drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To compare the clinical and metabolic effects of a new diuretic uricosuric agent, tienilic acid, with those of hydrochlorothiazide, a multicentre double-blind trial was performed in 56 hypertensive patients. Twenty — eight patients were randomly assigned to take tienilic acid and 28 to take hydrochlorothiazide. The diuretic and anti-hypertensive actions of the two compounds were similar. No significant differences were observed between tienilic acid and hydrochlorothiazide in their effects on urinary and serum electrolytes, hepatic and renal function tests, and fasting lipids. The patients who received tienilic acid showed a significant fall in serum uric acid, mediated by the uricosuric effect. The availability of an agent combining diuretic, anti-hypertensive and hypouricemic effects offers promise in the treatment of arterial hypertension.
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  • 78
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    European journal of clinical pharmacology 13 (1978), S. 195-201 
    ISSN: 1432-1041
    Keywords: Diuretics ; thiazides ; hydrochlorothiazide ; hypertension ; plasma level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine previously untreated hypertensive patients (WHO Stage I and II) were given hydrochlorothiazide (hct) 12.5, 25, 50 and 75 mg for two weeks after an initial four week period of placebo treatment. Blood pressure recordings were made casually and after 30 min rest in lying, sitting and standing positions. Plasma concentrations of the drug were measured by GLC. A significant decrease in BP was seen during treatment with hct 12.5 mg except in the casual standing position. Doubling of the dose twice produced very little further decrease in BP. The mean steady state concentration was 111 ng · ml−1 during treatment with hct 75 mg. A linear relationship was found between the plasma concentration of hct at 0 and 5 h and the various dose levels of hct. No relation was found between plasma concentration and reduction in blood pressure.
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  • 79
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    European journal of clinical pharmacology 17 (1980), S. 329-332 
    ISSN: 1432-1041
    Keywords: reserpine ; hydrochlorothiazide ; pituitary hormones ; gonadal hormones ; hypertension ; serum concentration ; antihypertensive therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sex histories and serum samples were obtained from 27 hypertensive men before and after 3 months of therapy with either 100 mg of hydrochlorothiazide or 0.25 mg of reserpine daily. Sera were analyzed for testosterone, dihydrotestosterone, estradiol, luteinizing hormone and prolactin. Both drugs effectively lowered blood pressure. The incidence of impaired sexual performance was low and insignificantly different in the two treatment groups. There were no significant changes in serum hormone concentrations as a result of drug therapy.
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  • 80
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    European journal of clinical pharmacology 17 (1980), S. 409-413 
    ISSN: 1432-1041
    Keywords: penbutolol ; hypertension ; propranolol ; double-blind crossover comparison ; blood pressure ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penbutolol is a potent long-acting non-cardioselective beta-adrenergic blocker with partial agonist activity. A double-blind cross-over comparison of penbutolol given in a single daily dose and propranolol given twice daily in the treatment of ambulant patients with moderate hypertension is described. Fourteen patients completed the study and were treated with each drug for 12 weeks. Penbutolol in daily doses of 20–120 mg and propranolol in daily doses of 80–400 mg produced similar significant reductions in both supine and erect blood pressure. Penbutolol did not reduce heart rate to the same extent as propranolol, in equivalent doses. Penbutolol appears to produce adequate control of moderate hypertension when administered once a day, and this effect appears to be equivalent to divided doses of propranolol. No serious adverse effects were reported, although one patient receiving penbutolol experienced severe eye pains at a dose of 40 mg which resolved on crossing over to treatment with propranolol.
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  • 81
    ISSN: 1432-1041
    Keywords: papaverine ; propranolol ; pindolol ; hypertension ; isoprenaline ; haemodynamic effects ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of two β-adrenoceptor antagonists, propranolol and pindolol, on the haemodynamic effects of papaverine, isoprenaline and noradrenaline was investigated in 9 male patients with first degree essential hypertension. Propranolol and pindolol were given according to a doubleblind, crossover scheme. Heart rate and blood pressure were measured before and after each treatment. Propranolol 670 µg/kg i. v. reduced the supine and standing systolic blood pressures by 2.3% and 1.6%, respectively. Similarly, the intravenous administration of pindolol 35 µg/kg reduced supine and standing systolic blood pressure by 5.5% and 8.3% respectively (clinically insignificant). Neither drug affected diastolic blood pressure. Following propranolol, there were moderate reductions in supine and standing heart rates, respectively by 24% and 20% (p〈0.001). Similarly, but to a lesser extent, pindolol reduced supine and standing heart rate by 12% and 17% (p〈0.001). The effects of papaverine, which, at 1.5 mg/kg i. v. reduced systolic blood pressure by 5–10% and increased heart rate by 8–15%, were not significantly influenced by the β-blockers. The blood pressure and heart rate responses to isoprenaline, on the other hand, were attenuated or inhibited by both β-blockers. While the β-blockers inhibited the β-adrenoceptor component of noradrenaline, the pressor component of noradrenaline, which is mediated through the α-adrenoceptors, was not influenced by propranolol, but was inhibited after pindolol. It is concluded that pindolol differs qualitatively from propranolol in that it inhibited both the α-and β-adrenoceptor effects of noradrenaline.
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  • 82
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    European journal of clinical pharmacology 19 (1981), S. 395-401 
    ISSN: 1432-1041
    Keywords: sotalol ; hydrochlorothiazide ; hypertension ; combination fixed ratio ; serum potassium ; long term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The combination of sotalol and hydrochlorothiazide in a fixed ratio of 6.4:1 was evaluated in thirty patients with uncomplicated hypertension. In the first part of the study, once daily administration of an optimal dose of the combination was significantly more effective than either hydrochlorothiazide or sotalol alone in lowering both the supine and standing systolic and diastolic blood pressure. Blood pressure was still controlled 24 h after the previous dose. Serum potassium fell by 0.37 mEq/l from the mean pretreatment value after treatment with the combination, but it still remained within the normal range. In the second part of the study the long term effect of the combination on blood pressure, heart rate and biochemical parameters was studied in twenty patients. Supine and standing blood pressure fell by 28.7/15.3 mmHg and 29.5/17.6 mmHg, respectively (p〈0.001). Serum potassium was 3.98±0.07 mEq/l after twelve months of therapy; potassium supplements were not administered. Like serum potassium, the other biochemical parameters remained within the normal range. The combination was well tolerated on long term use, and only one patient withdrew from the study.
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  • 83
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    European journal of clinical pharmacology 17 (1980), S. 321-328 
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
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  • 84
    ISSN: 1432-1041
    Keywords: debrisoquine ; hypertension ; renin ; catecholamines ; platelet monoamine oxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The 24 h urinary excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and vanillylmandelic acid, plasma renin activity and plasma and urinary debrisoquine were measured before and during chronic treatment with oral debrisoquine in 14 in-patients with essential hypertension. There was a significant fall (mean ±SD) in the 24 h urinary excretion of vanillylmandelic acid (15.3±2.8 to 6.7±1.9 µmol) noradrenaline (199.0±105.8 to 125.2±43.3 nmol) and plasma renin activity (0.71±0.47 to 0.40±0.20 pmol Angio I ml−1 h−1) while the urinary normetadrenaline/noradrenaline ratio increased (10.4±6.1 to 17.1±5.1). No significant change was seen in the output of adrenaline or of O-methylated metabolites. Debrisoquine produces extensive noncompetitive inhibition of platelet monoamine oxidase in vivo at low therapeutic plasma concentrations. These changes support the view that treatment with debrisoquine produces intraneuronal inhibition of monoamine oxidase and post-ganglionic blockage. There was a significant correlation between the change in standing diastolic blood pressure and the daily dose (rs=−0.52), pre-dose plasma concentration (rs=−0.85) and mean daily urinary recovery (rs=−0.80), of debrisoquine. The full extent of the biochemical changes were seen at low dose and low plasma concentration and were not directly correlated with the fall in standing or supine blood pressure.
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  • 85
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    European journal of clinical pharmacology 16 (1979), S. 149-153 
    ISSN: 1432-1041
    Keywords: beta-adrenergic blockade ; penbutolol ; haemodynamics ; hypertension ; prolonged treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirteen men with previously untreated essential hypertension (WHO Stage I) were studied as out-patients. Oxygen consumption, heart rate, cardiac index and brachial arterial pressure were recorded at rest supine and whilst sitting position, and during steady state exercise at 50, 100 and 150 W. The subjects were then treated with penbutolol 20–80 mg/day. In 12 responding patients hemodynamic study after 1 year demonstrated that systolic, diastolic and mean arterial pressure were reduced by approximately 20% at rest and 18% during exercise. Heart rate was reduced about 24% at rest and 26% during exercise. The stroke index did not show any significant change during rest, but during exercise the post-treatment values were 8%, 13% and 18% higher than the pre-treatment values at the 50, 100 and 150 W exercise levels, the last two changes being significant. Thus, the reduction in cardiac index during exercise was less than the reduction in heart rate — about 15%, but 24% when sitting at rest. The total peripheral resistance index did not show any significant change at rest or during exercise. Dizziness or muscular fatigue occurred in 6 patients during the first two weeks of treatment. From then on no side-effects were noted. It is concluded that the hemodynamic effects of longterm treatment with penbutolol in mild to moderate hypertension largely resemble those after the majority of other beta-blockers.
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  • 86
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    European journal of clinical pharmacology 21 (1982), S. 263-267 
    ISSN: 1432-1041
    Keywords: hypertension ; spironolactone ; hypotensive action ; peripheral circulation ; plethysmography ; handgrip test ; cold pressure test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Since there is only scanty, indirect information about the mechanism of the hypotensive effect of spironolactone, 9 patients with essential hypertension were studied according to a randomised double-blind, cross-over protocol. Spironolactone 100mg b.i.d. and placebo were each given for one month and the following parameters were studied: blood pressure, heart rate, response to cold pressure and hand-grip tests, as well as blood flow in the calf and finger vessels. Flow in the calf and fingers representing muscle and skin arteries, respectively, was measured semicontinuously with an ECG-triggered venous occlusion plethysmograph. After spironolactone there was a significant decrease in the systolic and diastolic blood pressures in the supine, sitting and standing positions; the sitting systolic and diastolic blood pressure decreased by (mean ± SE) 27±4mm Hg (p〈0.001) and 11±4mm Hg (p〈0.02), respectively. No orthostatic response was observed. Heart rate remained unchanged. Blood flow through muscle and skin vessels increased in 6 out of 9 patients, and in these patients calculated vascular resistance in these areas decreased. Spironolactone did not significantly change the response of systemic blood pressure to the handgrip and cold pressure tests. The present data confirm the hypotensive properties of spironolactone and show that this effect is associated with dilatation of muscle and skin arteries in many but not in all the patients. The data do not support the hypothesis that spironolactone decreases the responsiveness of systemic blood pressure to orthosympathetic stimulation.
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  • 87
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    European journal of clinical pharmacology 20 (1981), S. 1-8 
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; angiotensin ; renin ; aldosterone ; catecholamines ; prostaglandins ; kininase II ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute hypotensive effect of captopril 25 mg was investigated in 26 hypertensive patients (11 with essential and 15 with renal arterial disease). Intra-arterial blood pressure was recorded continuously and arterial blood was sampled for renin, angiotensin I and II, aldosterone, kininase II, catecholamines and prostaglandins. Captopril led to an increase in plasma renin activity, active and total plasma renin concentration and angiotensin I, a decrease in plasma kininase II activity, angiotensin II, aldosterone, prostaglandins E2 and F2* and no change in plasma (nor)adrenaline, dopamine and inactive renin concentration. The hypotensive effect of captopril was related to the changes in plasma angiotensin II level and inversely to the change in prostaglandin E2; the correlation coefficients were low, respectively 0.61 and −0.44. It is likely that the acute hypotensive effect of captopril to some extent is related to changes in plasma angiotensin II and in prostaglandins E2 and F2*. There is no evidence for a role of the adrenergic systems in the hypotensive response.
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  • 88
    ISSN: 1432-1041
    Keywords: hypertension ; indapamide ; pindolol ; plasma renin activity ; plasma aldosterone concentration
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with essential hypertension completed a double blind factorial trial comparing the effects of indapamide (2.5 mg daily) and pindolol (10 mg daily) on blood pressure, heart rate, plasma renin activity and plasma aldosterone concentration. There were four randomised test phases of eight weeks each during which patients received indapamide alone, pindolol alone, indapamide plus pindolol and no active treatment (placebo). Blood pressure and heart rate were measured every two weeks. Supine mean arterial pressure fell from 117 mm Hg in the placebo phase to 111 mm Hg in the indapamide phase, 106 mm Hg in the pindolol phase and 103 mm Hg in the combined indapamide plus pindolol phase. Factorial analysis confirmed that the hypotensive effects of the two drugs were additive, without evidence of potentiation or antagonism. Indapamide caused significant reductions in plasma potassium and chloride, and increases in plasma bicarbonate and urate concentrations; it also caused increases in plasma renin activity and aldosterone concentration. These changes are similar to those observed with thiazide diuretics.
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  • 89
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    European journal of clinical pharmacology 22 (1982), S. 487-489 
    ISSN: 1432-1041
    Keywords: nadolol ; hypertension ; effective dose range ; compliance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, observer-blind, therapeutic titration trial was carried out in 28 patients with mild or moderate essential hypertension to determine the effective dose range of nadolol given once a day. 11 patients became normotensive (supine diastolic blood pressure 90 mm Hg or below) with 80 mg, 4 with 120 mg and 1 with 160 mg. The largest step in the reduction of blood pressure was achieved with the first dose step of 80 mg, and only a small, non-significant further decrease was obtained with higher dose levels. Thus, nadolol, unlike propranolol, has a narrow effective dose range, and this should permit a brief dose adjustment period, which would be important in improving patient compliance.
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  • 90
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    European journal of clinical pharmacology 23 (1982), S. 93-97 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilator ; hypertension ; pharmacokinetics ; haemodynamics ; plasma renin activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic response and pharmacokinetics of single dose oral tolmesoxide were studied at various dose levels in 4 patients with severe hypertension. There was a reproducible fall in mean arterial pressure from baseline of 24.2% and a rise in heart rate of 37.6% following administration of tolmesoxide. The onset of antihypertensive action occurred within 1 h, with a peak effect at 3 h after dosing. The mean duration of action was up to 12.0 h. Tolmesoxide had a mean half-life of 3.0 h. It was rapidly absorbed with a mean peak plasma level occurring at 1.0 h. Plasma levels correlated well with the doses administered. Side-effects included mild nausea, facial flushing and postural symptoms.
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  • 91
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    European journal of clinical pharmacology 20 (1981), S. 399-405 
    ISSN: 1432-1041
    Keywords: alpha-adrenergic blocker ; hypertension ; blood pressure ; pulse rate ; noradrenaline ; plasma renin activity ; plasma aldosterone ; dopamine-beta-hydroxylase ; E-643
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To determine whether E-643, a new α-blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine-β-hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 → 151±28/89±14 mmHg), sitting (158±22/101±11 → 138±28/89±15 mmHg) and standing (153±32/103±21 → 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 → 69±10 beats/min), but was increased in the sitting (68±10 → 73±9 beats/min) and standing (73±10 → 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine-β-hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine-β-hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.
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  • 92
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    European journal of clinical pharmacology 20 (1981), S. 407-411 
    ISSN: 1432-1041
    Keywords: chlorthalidone ; hypertension ; dose response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The dose response curve for 25, 50, 75 and 100 mg doses of chlorthalidone was studied in double blind fashion over an 8 week period in patients who presented with untreated mild hypertension. One hundred and thirty four patients completed this multicentre, family practice study. After 2 week's medication, a decline in blood pressure was noted in all dosage groups and this was maximal by 4 weeks. At 8 weeks all doses of chlorthalidone induced a significant reduction in both systolic and diastolic blood pressures (mean −18 and −10 mmHg respectively). Amongst the 4 dosage groups, no differences in response were noted resulting in a flat dose response curve. During the study, mean blood urea and serum uric acid rose whilst serum potassium fell, the urea and potassium being least affected in the 25 mg dosage group. As the dosage of chlorthalidone increased, so the tendency for abnormal laboratory values increased. Unwanted effects sought during the study were relatively few in number. No clear dose response relationship was evident although the positive responses in the 25 mg dosage group were less than in the higher dosages. These results suggest that 25 mg chlorthalidone is the optimum dosage for initiation of therapy in patients with mild to moderate hypertension. This dosage is associated with less adverse biochemical changes and unwanted effects than the higher dosages studied.
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  • 93
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    European journal of clinical pharmacology 20 (1981), S. 453-457 
    ISSN: 1432-1041
    Keywords: diuretics ; trichlormethiazide ; hypertension ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of trichlormethiazide (TCZ) was studied in twelve patients after a single 4 mg dose. Seven patients had normal renal function with creatinine clearances greater than 90 ml/min. Five patients had compromised renal function with creatinine clearances averaging 48±29 ml/min. The TCZ plasma half life and area under the plasma concentration-time curve (AUC) were significantly greater in patients with impaired function, compared to patients with normal renal function. There were no significant differences between the two patient groups in terms of either rate of drug absorption or total urinary recovery of unchanged drug. Furthermore, there was no correlation between peak drug levels or AUC and renal excretion of water or electrolytes.
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  • 94
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    European journal of clinical pharmacology 21 (1981), S. 1-8 
    ISSN: 1432-1041
    Keywords: hypertension ; combination therapy ; population survey ; drug treatment ; prescription patterns ; population incidence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a cross-sectional study, antihypertensive drug treatment was studied in a representative population sample of people aged 30–64 years, using a combination of postal survey, personal interview, clinical assessment and drug prescriptions. 11% of the men and 16% of the women were currently taking antihypertensives; 54% of patients used one, 38% used two, and 8% used three or more preparations. Men used slightly more drugs than women. Diuretics were used by 62% and betablockers by 49% of the sample population. Fixed combinations of thiazides and potassium-sparing agents formed 70% of all diuretic preparations used. Only 12% of the patients used fixed antihypertensive combinations, of which over half were diuretic-reserpine-vasodilator combinations; women and older patients used them most often. The most common freely combined preparations were diuretics and betablockers, which formed almost half of all two-drug combinations, and were also present in 70% of all triple combinations. Adequate control of blood pressure (DBP 〈100 mmHg) was achieved by slightly under 50% of the patients, the BP of women being more adequately controlled than that of men. Differences in BP control were found between the different drugs and combinations. Antihypertensive combination therapy is important in successful treatment, but we still cannot be sure whether fixed combination preparations or, as in this study, free combinations of marketed preparations are better alternatives for treatment.
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  • 95
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    European journal of clinical pharmacology 21 (1981), S. 87-92 
    ISSN: 1432-1041
    Keywords: hypertension ; metoprolol ; sotalol ; comparison ; plasma levels ; serum uric acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 28 patients, aged 35–62 years, with uncomplicated hypertension, entered a double-blind, crossover study, in which the effects of single daily doses of sotalol and metoprolol were compared. Both drugs exerted a clinically useful anti-hypertensive effect as monotherapy, or in combination with a thiazide diuretic. No significant difference in hypotensive effects was noted between the two beta-blocking agents, when the dose was titrated to an optimal clinical effect. Treatment with sotalol and metoprolol was associated with a clinically insignificant increase in serum uric acid concentration. The side-effects observed were few, and in only two cases was therapy discontinued. We regard both sotalol and metoprolol as useful anti-hypertensive drugs.
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  • 96
    ISSN: 1432-1041
    Keywords: frusemide ; saralasin ; hypertension ; reninangiotensin ; sodium ; diet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of tests of the renin-angiotensin system for predicting antihypertensive responses to frusemide combined with dietary sodium deprivation was evaluated in eighteen patients with severe hypertension. No relationship could be shown between changes in blood pressure induced by the angiotensin analogue, saralasin, and the short-term or long-term therapeutic effects of diuretic- and diet-induced sodium depletion. Mean values for saralasin response and initial plasma renin activity in eight patients whose blood pressure was adequately controlled by therapeutic sodium depletion were closely similar to those obtained in the remaining ten patients, who proved refractory to this treatment.
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  • 97
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    European journal of clinical pharmacology 21 (1982), S. 457-460 
    ISSN: 1432-1041
    Keywords: hypertension ; propranolol ; hydralazine ; labetalol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomised cross-over trial the combination labetalol/hydrochlorothiazide was compared with the combination of propranolol/hydralazine/hydrochlorothiazide in 34 uncomplicated hypertensive patients, who were not satisfactorily controlled with hydrochlorothiazide 50 mg alone. The elevated diastolic pressure (D.P.) in 27 patients responded satisfactorily to the labetalol schedule and in 28 patients to the propranolol/hydralazine schedule. No difference was found in the rate of decrease of D.P., nor in the disappearance of hypertension — related complaints. Although the duration of the washout between treatments was at least one month, treatment was significantly more efficacious during the second period. Labetalol pre-treatment especially seemed to enhance the effect of subsequent propranolol/hydralazine administration. Side effects due to therapy were rare and were not related to any particular treatment. The median daily dose of labetalol in responders was 600 mg and that of propranolol/hydralazine 120/60 mg (in both therapies hydrochlorothiazide 50 mg was given in addition). Patients showed a slight preference for the labetaol medication. It is concluded that labetalol/hydrochlorothiazide and propranolol/hydralazine/hydrochlorothiazide are equally satisfactory in the treatment of uncomplicated hypertension.
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  • 98
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    European journal of clinical pharmacology 25 (1983), S. 467-473 
    ISSN: 1432-1041
    Keywords: hydralazine ; heart failure ; pharmacokinetics ; bioavailability ; metabolism ; hypertension ; dapsone ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of various disease states, other than hypertension, on the pharmacokinetic behaviour of hydralazine is not completely known. In the present study the pharmacokinetics of oral hydralazine has been evaluated in 7 patients with severe, chronic heart failure, using 8 compensated hypertensives as controls. The pharmacokinetics was evaluated by measuring the plasma concentrations of hydralazine (“apparent” and “real” hydralazine) and hydralazine pyruvate hydrazone, and by assessing acetylator phenotype after a small dose of dapsone. The AUC (area under the plasma concentration curve) following a single, oral 50 mg dose was significantly larger in patients with chronic heart failure NYHA Class III–IV than in patients with essential hypertension without cardiac decompensation. A decreased rate of hepatic elimination of hydralazine is suggested as a major contributory factor to this finding.
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  • 99
    ISSN: 1432-1041
    Keywords: guanfacine ; hypertension ; phenobarbital ; withdrawal syndrome ; enzyme induction ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The unusual observation of a withdrawal syndrome due to guanfacine in a hypertensive patient with chronic renal failure led to a study of the kinetics of the drug in this patient. The principal pharmacokinetic parameters of guanfacine were greatly altered, with extended biotransformation and a decrease in the half-life compared to the values observed in other cases of severe renal insufficiency. Associated treatment with phenobarbital had had a considerable effect, as shown by the results of a further kinetic study 2 months after withdrawal of the phenobarbital. The findings then were in good agreement with reference values which strongly suggests a consequence of the enzyme inducing effect of phenobarbital. Advice about the dosage regimen in such cases is given.
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  • 100
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    European journal of clinical pharmacology 22 (1982), S. 203-206 
    ISSN: 1432-1041
    Keywords: hypertension ; ticrynafen ; hydrochlorothiazide ; renal impairment ; uricosuria ; diuretic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of ticrynafen in the treatment of hypertension in patients with moderate renal impairment was compared with that of hydrochlorothiazide in a randomised, double-blind crossover trial in eleven subjects with renal insufficiency. Significant reductions in blood pressure occurred with both treatments, with the maximum responses occurring at different time intervals and to different degrees in individual patients. Thus, although ticrynafen caused a significant reduction in blood pressure in this group of hypertensive patients with renal insufficiency, it was not consistently different from that which could be achieved with hydrochlorothiazide. Ticrynafen also significantly reduced the serum uric acid concentration, compared with a significant rise with hydrochlorothiazide. No major biochemical abnormalities or side-effects were encountered in any subject. Thus, in these patients with renal insufficiency, ticrynafen still demonstrated a uricosuric effect as well as a useful anti-hypertensive action.
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