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  • hypertension  (130)
  • Springer  (130)
  • 2005-2009
  • 1980-1984  (130)
  • 1925-1929
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  • Springer  (130)
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  • 1
    Electronic Resource
    Electronic Resource
    A controlled study of the antihypertensive effect of carteolol, a newβ-adrenergic receptor blocking drug, in combination with hydrochlorthiazide and amiloride (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 239-244 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; hydrochlorthiazide ; amiloride ; hypertension ; double-blind clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of carteolol, a new β-blocking agent, added to basal diuretic treatment (hydrochlorthiazide 50 mg and amiloride 5 mg) has been assessed in a controlled trial in 17 patients with mild-to-moderate hypertension. The trial was divided into 4 stages: 1) run-in period with no antihypertensive treatment, 2) diuretic period (the diuretic being continued as basal treatment during the two following periods), 3) carteolol titration period, and 4) double-blind cross-over period comparing carteolol with placebo, which lasted 2 times 4 weeks. Although the diuretic effectively reduced the blood pressure, 17 of the 20 patients originally studied still had an elevated diastolic blood pressure (≧ 95 mmHg) after the diuretic period, thus fulfilling the inclusion criteria for the study. During the titration period carteolol 5 to 20 mg b. i. d. significantly reduced the elevated blood pressure. The blood pressure was reduced to normal in all 17 patients, although in two patients this occurred only during the double-blind period. During the double-blind period, the dose of carteolol was used which had given a satisfactory response during the titration period. The blood pressure in the 14 patients who completed the trial remained low both with carteolol and placebo during the double-blind stage, and was only slightly lower with carteolol than with placebo. This is probably due to a “carry-over” effect. Three patients discontinued the trial due to side effects (1 urticaria, 1 insomnia and 1 nausea) while on carteolol. There was no other difference between carteolol and placebo in the number or severity of side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562799
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  • 2
    Electronic Resource
    Electronic Resource
    Within patient comparison of prazosin and UK-33,274. A new alpha-adrenoceptor-antagonist (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 397-401 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; prazosin ; alpha-adrenoceptors ; alpha-blocking drugs ; UK-33,274
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients with uncomplicated essential hypertension received increasing single daily doses of UK-33,274, a new alpha-1 adrenoceptor antagonist, and prazosin for 4 days, in a open cross-over study. Doses were increased until a satifactory blood pressure response was obtained. Average doses reached were 4.5 mg for UK-33,274 and 2.4 mg for prazosin. The maximum effect of the two drugs on standing blood pressure was similar, but prazosin was more effective in the supine position. Both drugs had a greater effect on standing than on supine blood pressure. UK-33,274 caused a consistent increase in heart rate while prazosin did not. Whereas there was no clear difference between the two compounds in the duration of the reduction in blood pressure the onset of action was more gradual for UK-33,274. The incidence of side-effects was similar for both drugs. The data suggest that UK-33,274 is less effective than prazosin in reducing blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00605988
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  • 3
    Electronic Resource
    Electronic Resource
    Comparative evaluation of the new vasodilator carprazidil and minoxidil in the treatment of moderate to severe hypertension (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 483-489 
    Details
    ISSN: 1432-1041
    Keywords: carprazidil ; minoxidil ; hypertension ; catecholamines ; renin ; aldosterone ; blood volume ; hypertrichosis ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy and side effects of the new vasodilator carprazidil and the established vasodilator minoxidil were compared in 18 hypertensive patients inadequately controlled by 2 to 4 conventional drugs; the latter included diuretics, beta-blockers and/or sympatholytics and, in half the cases, vasodilators, such as hydralazine, diazoxide or the postsynaptic alpha-blocker prazosin. The vasodilators were withdrawn and, using a crossover design all patients received carprazidil (mean final dose 88 mg) and minoxidil (20 mg) for an average period of 5 to 6 months. The effects of the 2 agents appeared to be qualitatively and quantitatively similar. Both tended to cause sodium retention and an increase in heart rate, which required an increased dose of diuretic in one third of the cases or of a beta-blocker in a quarter. With this approach mean body weight and blood volume were not altered in the established phase of carprazidil or minoxidil treatment; heart rate and plasma norepinephrine tended to be only minimally increased, plasma renin was slightly increased, and plasma aldosterone and epinephrine were largely unchanged. Supine and upright blood pressure were reduced from initial values of 189/113 and 167/113 mm Hg, to 149/95 and 138/95 mm Hg (−18 and −17%), respectively, during carprazidil, and to 154/95 and 141/96 mm Hg (−17 and −15%) during minoxidil therapy. Hypertrichosis occurred with both agents in almost all patients, and limits their more prolonged use in females. No adverse side effects on haematological parameters, liver or renal function were observed, nor was antinuclear antibody detected. It is concluded that carprazidil and minoxidil are equivalent vasodilator agents in the treatment of severe hypertension, particularly in males.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637493
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  • 4
    Electronic Resource
    Electronic Resource
    Penbutolol (Hoe 893 d) in primary hypertension (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 95-99 
    Details
    ISSN: 1432-1041
    Keywords: penbutolol ; hypertension ; primary hypertension ; blood pressure response ; plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penbutolol (Hoe 893 d), a long-acting non-selective beta-adrenoceptor blocking agent, was given once daily to 23 patients with primary hypertension, WHO Stages I–II. The dose (50–100 mg) needed to achieve the therapeutic goal, i.e. supine diastolic BP〈95 mm Hg, was titrated individually. On a daily dose of penbutolol 83±19 mg (mean±SD) blood pressure (BP, mean±SD) fell from 180±21/112±8 mmHg on placebo to 154±25/94±14 mmHg. 18 patients who reached the therapeutic goal (responders) continued in a double blind, cross-over study versus placebo, during which the supine BP fell on average 20/10 mmHg on the same dose of penbutolol, and 2/1 mmHg on placebo. Plasma concentrations (mean±SD) of free 0.10±0.07 µg/ml) and total (2.02±1.39 µg/ml) penbutolol did not differ between responders and nonresponders, and were not correlated with the fall in BP. Side effects were mild and mostly well tolerated. One patient developed dermatitis and another an elevation of liver enzymes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542451
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  • 5
    Electronic Resource
    Electronic Resource
    Acute effects of a new vasodilator, Ro 12-4713, on blood pressure, plasma renin activity, aldosterone and catecholamine levels, and renal function in hypertensive and normal subjects (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 169-177 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544594
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of once daily indapamide and pindolol on blood pressure, plasma aldosterone concentration and plasma renin activity in a general practice setting (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 191-196 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; indapamide ; pindolol ; plasma renin activity ; plasma aldosterone concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with essential hypertension completed a double blind factorial trial comparing the effects of indapamide (2.5 mg daily) and pindolol (10 mg daily) on blood pressure, heart rate, plasma renin activity and plasma aldosterone concentration. There were four randomised test phases of eight weeks each during which patients received indapamide alone, pindolol alone, indapamide plus pindolol and no active treatment (placebo). Blood pressure and heart rate were measured every two weeks. Supine mean arterial pressure fell from 117 mm Hg in the placebo phase to 111 mm Hg in the indapamide phase, 106 mm Hg in the pindolol phase and 103 mm Hg in the combined indapamide plus pindolol phase. Factorial analysis confirmed that the hypotensive effects of the two drugs were additive, without evidence of potentiation or antagonism. Indapamide caused significant reductions in plasma potassium and chloride, and increases in plasma bicarbonate and urate concentrations; it also caused increases in plasma renin activity and aldosterone concentration. These changes are similar to those observed with thiazide diuretics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545213
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  • 7
    Electronic Resource
    Electronic Resource
    Interaction between oxprenolol and indomethacin on blood pressure in essential hypertensive patients (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 197-201 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545214
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  • 8
    Electronic Resource
    Electronic Resource
    Studies on the autonomic nervous system in borderline hypertension (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 285-288 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548394
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  • 9
    Electronic Resource
    Electronic Resource
    Clinical evaluation of labetalol alone and combined with chlorthalidone in essential hypertension: A double-blind multicentre controlled study (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 289-293 
    Details
    ISSN: 1432-1041
    Keywords: labetalol ; chlorthalidone ; hypertension ; fixed combination ; antihypertensive therapy ; side effects ; multicentre study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a multicentre, double-blind, crossover, placebo-controlled study, the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg, given alone or in combination, has been assessed in 32 hypertensive patients. The combination had a greater effect in reducing blood pressure than did its separate components. This was particularly evident after exercise. Heart rate increased during chlorthalidone therapy, decreased during labetalol therapy, and a summation effect was observed during treatment with the combination. In most cases additivity was observed, as no interaction between the single components was observed, except for heart rate after exercise, and for diastolic blood pressure in the upright position. No interaction was observed either in the biochemical indices or in the clinical side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548395
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  • 10
    Electronic Resource
    Electronic Resource
    Withdrawal of guanfacine after long-term treatment in essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 19-24 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558376
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  • 11
    Electronic Resource
    Electronic Resource
    Long-term clonidine effects on autonomic function in essential hypertensive man (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 25-32 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; baroreceptor reflex ; mode of action ; sympathetic activity ; urinary catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 ± 0.15 mg/day) alone in 13 essential hypertensive men, assessing several biochemical indices of sympathetic function, as well as physiologic parameters, including baroreflex sensitivity, the cold pressor test, and the hypotensive response to alpha adrenergic blockade. Clonidine diminished mean arterial pressure (from 104±5 to 84±3 mmHg;p〈0.01), without associated changes in several biochemical parameters of sympathetic outflow (urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid; allp〉0.1). Circulatory baroreflex function was not enhanced by clonidine, during either the amylnitrite test or the phenylephrine test, before or after parasympathetic blockade with atropine. The cold pressor test, an index of efferent sympathetic pressor function, was also unaltered. The enhanced mean arterial pressure response to phentolamine during clonidine therapy (from a fall of 14.8±4.3 to 39.4±5.2 mmHg,p〈0.01), suggested an increase in alpha adrenergic vascular tone, perhaps mediated by clonidine's alpha agonist properties in vascular smooth muscle. The antihypertensive mechanism of longterm low dose clonidine cannot reliably be ascribed either to baroreflex enhancement or to suppression of sympathetic outflow.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558378
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  • 12
    Electronic Resource
    Electronic Resource
    Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 399-405 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542090
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  • 13
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of trichlormethiazide in hypertensive patients with normal and compromised renal function (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 453-457 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542099
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  • 14
    Electronic Resource
    Electronic Resource
    Combination therapy in hypertension (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 1-8 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609580
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  • 15
    Electronic Resource
    Electronic Resource
    Effect of indapamide on renal plasma flow, glomerular filtration rate and arginine vasopressin in plasma in essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 543-547 
    Details
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; glomerular filtration ; arginine vasopressin ; free water clearance ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal plasma flow (RPF), glomerular filtration rate (GFR), arginine vasopressin in plasma (AVP), free water clearance ( $${\text{C}}_{{\text{H}}_{\text{2}} {\text{O}}}$$ ) and blood pressure (BP) were determined in 11 patients with essential hypertension at the end of 3 consecutive periods of observation each of 6 of weeks duration; indapamide 2.5 mg daily was given in period 2 and placebo in periods 1 and 3. RPF and GFR were reduced by 9% and BP by 9%/14% supine and 14%/12% standing during indapamide treatment. Changes in renal haemodynamics were not correlated with those in BP. AVP was not significantly altered by indapamide and was not correlated with BP. Indapamide reduced $${\text{C}}_{{\text{H}}_{\text{2}} {\text{O}}}$$ possibly due to the reduction in GFR. It is concluded that indapamide evidently induces redistribution of the cardiac output, with enhanced muscle blood flow and reduced renal perfussion, and that AVP does not seem to be involved in blood pressure regulation in mild to moderate essential hypertension under basal conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543482
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  • 16
    Electronic Resource
    Electronic Resource
    Pafenolol, a new β1-selective blocking agent, in mild hypertension. Result of an inpatient study and a subsequent outpatient follow-up (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 549-553 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543483
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  • 17
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of endralazine (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 661-661 
    Details
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; elimination half-liefe ; compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543509
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  • 18
    Electronic Resource
    Electronic Resource
    Pharmacodynamics and kinetics of etozolin/ozolinone in hypertensive patients with normal and impaired kidney function (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 687-693 
    Details
    ISSN: 1432-1041
    Keywords: etozolin ; ozolinone ; furosemide ; hypertension ; renin ; catecholamines ; chronic renal failure ; steady state kinetics ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on urinary electrolyte excretion, renin release and plasma norepinephrine of single oral doses of 400 mg etozolin (E) and of 40 mg furosemide (F) were studied in hypertensive patients with normal (n=6) and impaired kidney function (n=6). E caused a marked saluresis up to 24 hours, showing its long duration of action. F, however, displayed a brief, brisk peak diuresis, followed by a rebound from the 4th to the 24th hours. The brisk peak diuresis induced by F was associated with pronounced release of renin, almost twice that induced by E. In chronic renal failure the renin release in relation to the magnitude of the diuresis was increased, i.e. the sensitivity of these patients to changes in water homeostasis was increased. E and F stimulated the sympathetic system to roughly the same extent. Patients with essential hypertension had higher plasma levels of norepinephrine than hypertensive patients with chronic renal failure. In addition, hypertensive patients with normal renal function (n=4) and varying degrees of renal impairment (n=11) were also given 400 mg daily for 2 weeks. Effects on blood pressure and electrolyte homeostasis were monitored, as well as the plasma kinetics of metabolite I, ozolinone. At the end of the 2 week treatment E had significantly lowered systolic (−12 mm Hg) and diastolic (−9 mm Hg) blood pressure, and had produced a significant loss of body weight, without altering plasma electrolytes or blood chemistry. There was no accumulation of the effective metabolite ozolinone under conditions of severe impairment of kidney function. It is concluded that E can effectively control high blood pressure in patients with normal and impaired kidney function. Its effective metabolite ozolinone did not accumulate in chronic renal failure.
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    URL: http://dx.doi.org/10.1007/BF00541926
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  • 19
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    Long acting nifedipine in the treatment of severe hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 13-17 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure decrease ; drug combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.
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    URL: http://dx.doi.org/10.1007/BF02395199
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  • 20
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    In vitro and in vivo down-regulation of human plateletα 2-adrenoceptors by clonidine (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 403-409 
    Details
    ISSN: 1432-1041
    Keywords: alpha-2-adrenoceptors ; hypertension ; clonidine ; human platelets ; 3H-yohimbine binding ; receptor regulation ; clonidine withdrawal ; desensitization ; GTP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of clonidine on the number ofα 2-adrenoceptors in human platelet membranes, determined by3H-yohimbine binding, was investigatedin vitro andin vivo. Incubation of platelet membranes with clonidine (1–100 µM) for 16 h at 25 °C led to a concentration-dependent decrease in the number of3H-yohimbine binding sites of 10–25%; the affinity of3H-yohimbine to the sites was not changed (KD approximately 3–4 nM). In such “desensitized” membranes, inhibition of3H-yohimbine binding by clonidine resulted in steep, monophasic displacement curves, which in comparison to the curves from control membranes (IC50 for clonidine 90 nM), were shifted to the right (IC50: 321 nM) and were not affected by 10−4M guanosine-5′-triphosphate (GTP). Treatment of 3 hypertensive patients with clonidine (3×150 µg/d for 7 days) reduced blood pressure and heart rate. Simultaneously, both3H-yohimbine binding sites on platelet membranes and plasma catecholamine levels decreased within three days and remained at a reduced level during treatment. After abrupt cessation of clonidine treatment, blood pressure, heart rate and plasma catecholamines rapidly increased, reaching values after two days similar to or higher than those before treatment.3H-yohimbine binding sites, however, initially decreased further before returning to control values. In platelet membranes derived from hypertensive patients treated with clonidine for at least three weeks, GTP (10−4M) had no influence on inhibition of3H-yohimbine binding by (—)-adrenaline and clonidine. It is concluded that clonidine desensitizesα 2-adrenoceptors in human platelet membranesin vitro andin vivo. An important step in the desensitization process is the uncoupling of receptor occupancy by agonists and adenylate cyclase activity, as indicated by loss of the regulatory activity of GTP on desensitized membranes. The clonidine withdrawal syndrome may be caused by enhanced release of endogenous catecholamines not adequately regulated by presynapticα 2-adrenoceptors, which have become subsensitive after chronic clonidine treatment.
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    URL: http://dx.doi.org/10.1007/BF00605989
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  • 21
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    Sequential changes in plasma renin activity and plasma catecholamines in mildly hypertensive patients during acute, furosemide-induced body-fluid loss (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 299-302 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF01037937
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  • 22
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    Chronic propranolol administration during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 481-490 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00542115
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  • 23
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    Propranolol vs metoprolol vs labetalol: A comparative study in essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 1-6 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; beta-blockers ; propranolol ; metoprolol ; labetalol ; exercise ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind, within patient investigation of twenty-four patients (nineteen males and five females) with a mean age of 46.3 years (SD 10.9 years) with mild to moderate essential hypertension a comparison between equipotent beta-blocking doses of propranolol, metoprolol and labetalol was carried out. Blood pressure and pulse rate were measured in lying, sitting and standing positions and before, during and after isometric and dynamic exercise. Peak expiratory flow was recorded before and during dynamic exercise. All the active treatments were better than placebo in reducing blood pressure and heart rate. Comparing the effects of treatment, labetalol lowered sitting diastolic pressure significantly more than propranolol and standing diastolic pressure than both propranolol and metoprolol. Metoprolol and propranolol were more effective in reducing heart rate. Propranolol significantly reduced peak flow rate compared to labetalol. During the exercise, both isometric and dynamic, the heart rate and the blood pressure, both systolic and diastolic, of the treated patients were lower than those on placebo. There was little difference between the drugs in the influence on blood pressure, but metoprolol and propranolol were significantly more effective than labetalol in lowering the heart rate.
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    URL: http://dx.doi.org/10.1007/BF00546699
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  • 24
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    Long-term effects of captopril on renal function in hypertensive patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 315-323 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00548761
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  • 25
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    Nifedipine in the treatment of hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 713-715 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; calcium antagonist ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nifedipine, a calcium antagonist with a predominant vasodilator action, was evaluated for the treatment of hypertension. A 20 mg-tablet, with a slower absorption and a more sustained blood-level than provided by the 10 mg-capsule was administered to 20 patients. The duration of the trial was 20 weeks. All patients achieved a significant reduction in both systolic (p〈0.05) and diastolic (p〈0.001) blood-pressure (B.P.), but 10 patients were withdrawn before completion of the trial period. Two patients, although achieving a fall in B.P. which was significant, did not reach to target level (〈160/90) on maximal dosage, one patient suffered a stroke due to a cerebral infarct, and seven patients were withdrawn because of side-effects due mainly to vasodilatation. The remaining 10 patients obtained a satisfactory response. In nine patients, who had achieved a satisfactory result, there was no change in plasma renin activity (P.R.A.) during chronic nifedipine administration.
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    URL: http://dx.doi.org/10.1007/BF00542507
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  • 26
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    Antihypertensive effect of fractionated sublingual administration of nifedipine in moderate essential hypertension (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 161-164 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure ; heart rate ; plasma renin activity ; aldosterone ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The magnitude and duration of the antihypertensive effect of nifedipine were studied in 7 cases of moderate essential hypertension. In a double-blind crossover study, nifedipine 10 mg or a placebo were administered sublingually 4 times a day for 2 days, and the results were compared. Each dose of nifedipine reduced systolic and diastolic blood pressure by 14% both in the supine and upright positions. The antihypertensive action lasted for about 3 h and it was not cumulative. The reduction in blood pressure was associated with a temporary increase in heart rate. Administration of nifedipine 10 mg did not significantly raise plasma renin activity or plasma aldosterone. The drug was well tolerated and no side effects were detected.
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    URL: http://dx.doi.org/10.1007/BF00561894
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  • 27
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    Pharmacokinetics of atenolol in hypertensive subjects with and without co-administration of chlorthalidone (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 333-337 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; chlorthalidone ; hypertension ; chronic treatment ; co-administration ; plasma half-life ; urine half-life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of atenolol with and without the co-administration of chlorthalidone were studied in five hypertensive subjects. Concomitant administration of chlorthalidone appears to have little if any effect on the pharmacokinetics of atenolol during treatment for 7 days. The atenolol elimination half-lives were 6.7±1.1 and 6.3±0.9 h, respectively, with and without chlorthalidone. Two healthy volunteers also received a single 50 mg oral dose of chlorthalidone. Their blood profiles and pharmacokinetics were similar to those observed in hypertensive subjects, but a statistically significant difference (p〈0.01) was found between the urinary excretion half-lives of chlorthalidone. This difference may be because chronic administration of the drug caused saturation of red cell binding.
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    URL: http://dx.doi.org/10.1007/BF00558445
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  • 28
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    Single daily dose penbutolol in the treatment of hypertension: A double blind crossover comparison with propranolol (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 409-413 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00570156
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  • 29
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    Renin-angiotensin-aldosterone system (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 105-108 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00561486
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  • 30
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    Comparison of the effects of propranolol and labetalol on renal haemodynamics at rest and during exercise in essential hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 135-139 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00561580
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  • 31
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    Influence of propranolol and pindolol on the haemodynamic effects of papaverine, isoprenaline and noradrenaline in hypertensive patients (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 141-146 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00561581
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  • 32
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    Chronic treatment with the new potent vasodilator Ro 12-4713 in moderate to severe hypertension: Effects on blood pressure, endocrine function, sodium and plasma volume (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 79-84 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00607141
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  • 33
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    Antihypertensive and hormonal effects of single oral doses of Captopril and Nifedipine in essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 157-161 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; nifedipine ; plasma renin activity ; aldosterone ; vasopressin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a single-dose crossover study Captopril (SQ 14225), 1 mg/kg body weight, and Nifedipine (Bay a 1040) 20 mg were administered orally to 12 hospitalized patients with essential hypertension (Stage 1 or 2, W. H. O.). Both drugs significantly reduced blood pressure, but each dose acted differently: the mean maximum arterial pressure reduction was faster and greater with Nifedipine than with Captopril: −23±2% at 37±15 min and −17±1% at 86±25 min, respectively. Captopril inhibited angiotensin II and aldosterone production, but did not accelerate heart rate or stimulate vasopressin release. Nifedipine stimulated vasopressin release and increased heart rate, but the renin angiotensin aldosterone system was not significantly affected. The blood pressure reduction was related to the initial level of activation of the renin angiotensin system only for Captopril. The blood pressure reduction induced by one drug was not related to that produced by the other in the same patient.
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    Ticrynafen and hydrochlorothiazide a comparison in hypertensive patients with renal impairment (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 203-206 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00545215
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    Changes in renal function induced by endralazine, a new antihypertensive drug (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 307-314 
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    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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    The use of long-acting propranolol (‘Inderal’ LA) in the management of elderly hypertensive patients (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 379-381 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; elderly patients ; long-acting propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen elderly patients whose hypertension was controlled by conventional propranolol 80 mg twice a day had their medication changed to one capsule of ‘Inderal’ LA1 (160 mg) daily. The blood pressure, heart rate and propranolol concentrations were measured at various time points when the patients were receiving the conventional preparation and these assessments were repeated when the long-acting preparation was administered. Although the heart rate was lower with conventional propranolol than with ‘Inderal’ LA there was no significant difference in the blood pressure levels. The mean peak blood level of propranolol was, however, significantly lower with ‘Inderal’ LA compared with conventional propranolol and occurred later. At 12 h the plasma propranolol levels were higher after ‘Inderal’ LA than following the intake of conventional propranolol (p〈0.01); there was no difference in the plasma levels at 24 h. The area under the concentration time curve was significantly higher on conventional propranolol. Compared with published data, the plasma levels were higher than those in younger patients. ‘Inderal’ LA was well tolerated and side effects were minimal.
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  • 37
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    Titration of nadolol in the treatment of hypertension (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 487-489 
    Details
    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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  • 38
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    Effects of a new long-acting beta-blocker bopindolol (LT 31-200) on blood pressure, plasma catecholamines, renin and cholesterol in patients with arterial hypertension (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 491-493 
    Details
    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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  • 39
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    Antihypertensive, saluretic and hypokalaemic effects of cyclothiazide in comparison with hydrochlorthiazide with amiloride supplement (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 495-499 
    Details
    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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  • 40
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    Pharmacokinetics and hypotensive effect in healthy volunteers of pinacidil, a new potent vasodilator (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 603-608 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; pinacidil pyridine-N-oxide ; urinary excretion ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Preliminary investigation in 3 healthy volunteers suggested that intravenous pinacidil in a dose of 0.2 mg/kg had a potent but well-tolerated hypotensive action in the supine position. Facial flushing, uncomfortable chest sensation and distressing postural hypotension occurred at serum concentrations above 300 ng/ml. Pinacidil, 0.2 mg/kg, was given intravenously over 4 min to 15 healthy volunteers in the supine position. Maximum fall in mean arterial pressure (MAP) was 15.7±6.0 mmHg. Maximum rise in heart rate was 23.8±6.6 beats/min. Pinacidil serum distribution half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\alpha }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\alpha }$}}}$$ ) was 13.4±8.5 min and elimination half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\beta }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\beta }$}}}$$ ) was 2.13±0.49 h. The apparent volume of distribution (Vdβ) was 90.3±13.21 and total body clearance was 31.1±9.61/h. Pinacidil was approximately 40% bound to plasma protein over the concentration range 40–400 ng/ml. Urinary excretion of unchanged pinacidil accounted for 5.7 ± 1.3% of the administered dose over 24 hours and urinary excretion of the major metabolite, pinacidil pyridine-N-oxide, was 31.6±9.2% of the administered dose. It was concluded that intravenous pinacidil is a potent vasodilator hypotensive compound, with a duration of action between 1.5 and 2 h.
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  • 41
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    Antihypertensive mechanism of the diuretic muzolimine in mild renal failure (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 215-220 
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    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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  • 42
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    Nifedipine in the treatment of difficult hypertensives (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 1-5 
    Details
    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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  • 43
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    Absence of an effect of mianserin on the actions of clonidine or methyldopa in hypertensive patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 15-19 
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    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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    URL: http://dx.doi.org/10.1007/BF00613921
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  • 44
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    Haemodynamic effects of a new vasodilator drug, felodipine, in healthy subjects (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 49-53 
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    ISSN: 1432-1041
    Keywords: felodipine ; hypertension ; cardiac failure ; haemodynamic effects ; non-invasive monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of a new vasodilating drug, felodipine, were studied in eight, healthy, male subjects, aged 22–31 years. The drug was given as an oral solution in the dose of 0.15 mg/kg. Thirty-five minutes later further dose of 0.15 mg/kg was administered. Felodipine induced a pronounced decrease in diastolic blood pressure (maximal effect 15±4 mm Hg) and in the systemic vascular resistance. Cardiac output increased (maximum by 4.2±0.3 l/min), due to an increase both in the stroke volume and the heart rate. The maximal increase in the stroke volume (measured from echo cardiograms) and the heart rate were 33±5 ml and 23±3 beats/min, respectively. Felodipine caused a significant decrease in the pre-ejection period (23±3 ms) and an increase in the left ventricular ejection time (29±3 ms). The quotient PEP/LVET fell from 0.36±0.01 to 0.28±0.01. Significant activity of felodipine could be recorded at a plasma level of about 15 nmol/l. When the maximal haemodynamic effects were recorded the plasma level was about 40 nmol/l. After a cumulative dose of 0.30 mg/kg, there was a twofold variation in the maximal plasma level (from 31 to 61 nmol/l). The results of the present investigation are in agreement with previous haemodynamic studies in animals. It would appear that felodipine is a potent arteriolar vasodilator and it might well be of considerable value in the management of patients with hypertension or congestive cardiac failure.
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  • 45
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    Comparison of the antihypertensive effect of a double dose of metoprolol versus the addition of hydrochlorothiazide to metoprolol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 581-583 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; metoprolol ; hydrochlorothiazide ; drug combination ; adverse reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 27 hypertensive patients whose blood pressure could not be adequately controlled with 200 mg metoprolol Durules alone, the effect of a double dose of metoprolol Durules® (400 mg once daily) was compared with a fixed combination of 200 mg metoprolol and 25 mg hydrochlorothiazide (Selokomb®). The study followed a double-blind cross-over schedule in 2 parallel groups. The reduction in diastolic blood pressure (p〈0.01) was comparable in the two groups. A significant fall (p〈0.01) in systolic blood pressure occurred with the metoprolol/hydrochlorothiazide combination. The subsequent change from the double dose of metoprolol Durules to the combination therapy also resulted in a fall in systolic blood pressure (p〈0.05). Mean serum potassium and blood glucose levels did not change after each alteration in therapy. Most of the side-effects mentioned were mild and transient in character.
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  • 46
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    Pharmacokinetic aspects of guanfacine withdrawal syndrome in a hypertensive patient with chronic renal failure (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 463-466 
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    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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  • 47
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    Pharmacokinetics of oral hydralazine in chronic heart failure (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 467-473 
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    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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  • 48
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    Effect of beta-blocking drugs on beta-cell function and insulin sensitivity in hypertensive non-diabetic patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 13-17 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocking drugs ; insulin sensitivity ; pancreatic beta-cell function ; hypertension ; propranolol ; atenolol ; insulin secretion ; plasma GIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p=0.037 and p=0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p=0.0036 and p=0.0003, respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
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  • 49
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    Should the acetylator phenotype be determined when prescribing hydralazine for hypertension? (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 39-42 
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    ISSN: 1432-1041
    Keywords: acetylator phenotype ; hydralazine response ; hypertension ; blood pressure control ; lupus syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and β-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p〈0.01). Despite higher doses of hydralazine the blood pressure was controlled in only 27% of rapid acetylators compared to 65% of slow acetylators (p〈0.02). The relation of acetylator phenotype to blood pressure response was statistically independent of initial blood pressure, age, sex, body weight and serum creatinine (p〈0.005). Current recommendations on hydralazine dosage are unsatisfactory for the 40% of hypertensive patients who are rapid acetylators. We suggest measurement of the acetylator phenotype in patients who respond incompletely to 200 mg hydralazine daily. About 70% of these patients will be rapid acetylators in whom the dose of hydralazine can be increased safely.
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  • 50
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    Piretanide, a potassium stable diuretic, in the treatment of essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 407-414 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; hypertension ; triamterene ; double blind comparison ; potassium ; magnesium ; side-effects ; serum electrolytes ; serum parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomized, double blind, parallel group study in out patients with mild to moderate essential hypertension the effects of piretanide on serum electrolytes and on blood pressure were compared with those of triamterene alone and the combination piretanide + triamterene. 136 patients entered the study; 18 patients did not fulfill the inclusion criteria (RRdiast was below 95 mmHg or above 120 mmHg) at the end of the placebo period, 6 dropped out due to side effects, and 1 due to lack of efficacy. Data from 1 patient were not evaluated because the patient did not come regularly for checkups. The results for 110 patients were analyzed. Piretanide 6 mg b.d. and piretanide 6 mg + triamterene 50 mg b.d. produced a significant reduction both in supine and erect blood pressure, which was evident at 2 weeks and which increased over the ensuing 12 week trial period. A mean maximal fall of 16.5% was noted in the piretanide group and 15% in the piretanide + triamterene group. Triamterene alone (50 mg b.d.) also reduced diastolic and systolic blood pressures but the reduction was significantly less (diastolic blood pressure) than in both the piretanide groups, and it showed a more rapid return to pretreatment level during a placebo washout phase at the end of the study. A reduction in standing diastolic blood pressure below 95 mmHg was attained in 84% of patients in the piretanide group, 82% in the piretanide + triamterene group and in only 58% of the triamterene group. There were no significant changes within groups nor differences between the three groups in serum potassium or magnesium. 7 patients were withdrawn from the study because of side-effects due to too marked a clinical action (polyuria, orthostatic disorders and hypotension), one from the piretanide group, and the others in the piretanide + triamterene group. One patient in the triamterene group left the study prematurely due to the lack of effect.
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    Double-blind comparison of once-daily bopindolol, pindolol and atenolol in essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 529-534 
    Details
    ISSN: 1432-1041
    Keywords: beta-adrenoceptor blocking agents ; hypertension ; adverse reactions ; atenolol ; bopindolol ; pindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of once-daily bopindolol, a nonselectiveβ-adrenoceptor blocking agent with partial agonist activity, and of pindolol and atenolol in the treatment of essential hypertension has been compared. 369 patients were investigated in a double-blind parallel-group study. The treatment period was 10 weeks. Blood pressure normalisation (diastolic BP equal to or less than 90 mmHg) was to be achieved by a stepwise increase in the dose of the test drugs, and, if required, by addition of a diuretic. Normalisation of blood pressure was achieved in 71 to 76% of the subjects, with no significant differences between bopindolol, pindolol, and atenolol. Special attention was given to evaluation of side effects by using two methods for registration of all adverse events during the study. A low incidence of drug-induced side effects was observed, with no significant difference between bopindolol, pindolol, and atenolol. There was no evidence of unsuspected adverse reactions due to bopindolol.
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    Long acting nifedipine in the treatment of severe hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 13-17 
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    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure decrease ; drug combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.
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    Double-blind trial comparing guanfacine and methyldopa in patients with essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 309-315 
    Details
    ISSN: 1432-1041
    Keywords: guanfacine ; methyldopa ; hypertension ; rebound hypertension ; withdrawal symptoms ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine patients with essential hypertension completed a clinical trial designed to study the effects and side effects of administration and withdrawal of guanfacine (2 mg tds) and methyldopa (250 mg tds) on blood pressure, heart rate, and plasma noradrenaline. The study was of randomised doubleblind crossover design with two active therapy phases of eight weeks each, preceded by an initial 4 week placebo phase, separated by an intermediate 2 week placebo phase, and followed by a final 2 week placebo phase. Patients took bendrofluazide 5 mgs daily throughout the entire trial, during both active and placebo periods. Each patient was admitted to hospital at the end of the 8 week active treatment phases, so that the effects of drug withdrawal on blood pressure, heart rate, plasma noradrenaline and side reactions, could be closely observed and monitored. The main conclusions from analysis of the results were that: 1. The hypotensive efficacy of guanfacine and methyldopa was very similar in the doses used, each of the two drugs lowering the supine mean arterial pressure by about 15 mm Hg and the supine diastolic pressure by about 10 mm Hg. 2. The frequency of side effects was greater with guanfacine than with methyldopa. 3. There was no signficant early rebound phenomenon after withdrawal of either methyldopa or guanfacine. 4. There was tendency for the blood pressure to rise slowly and marginally above initial placebo values, 2 weeks after cessation of guanfacine treatment though this was not significant. It was however, accompanied by a significant increase in plasma noradrenaline at 2 weeks. This was not seen 2 weeks after cessation of methyldopa. There was no single incidence of worrying rebound hypertension or withdrawal symptoms either early or late in any patient following cessation of methyldopa or guanfacine.
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    URL: http://dx.doi.org/10.1007/BF00544579
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    Fixed combination of sotalol and hydrochlorothiazide in the treatment of uncomplicated hypertension (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 395-401 
    Details
    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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    Time course of blood pressure, pulse rate, plasma renin and metoprolol during treatment of hypertensive patients (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 321-328 
    Details
    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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    Reserpine, hydrochlorothiazide and pituitary-gonadal hormones in hypertensive patients (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 329-332 
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    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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    Double-blind controlled trial of molsidomine in hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 231-235 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00563004
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    Maximal exercise power after a single dose of metoprolol and of slow-release metoprolol (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 225-229 
    Details
    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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    Prazosin depression of baroreflex function in hypertensive man (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 7-14 
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    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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    Long-term therapy of arterial hypertension with nifedipine given alone or in combination with a beta-adrenoceptor blocking agent (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 101-103 
    Details
    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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    Time-course of the anti-hypertensive action of atenolol: Comparison of response to first dose and to maintained oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 365-374 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
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    Increased oral clearance of metoprolol in pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 217-220 
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    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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    Prolactin secretion during reserpine and syrosingopine treatment (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 347-349 
    Details
    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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    Endralazine, a new peripheral vasodilator. Evaluation of safety and efficacy over a 3 year period (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 301-305 
    Details
    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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    Sotalol and metoprolol comparison of their anti-hypertensive effect (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 87-92 
    Details
    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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    Relationship between pharmacokinetic and pharmacodynamic behaviour of bufuralol and its metabolite Ro 3-7410 in hypertensive patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 479-484 
    Details
    ISSN: 1432-1041
    Keywords: bufuralol ; hypotensive therapy ; pharmacokinetics ; hypertension ; 1-hydroxybufuralol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationship between the plasma concentrations of bufuralol and its major hydroxymetabolite (Ro 3-7410) and β-blocking activity was studied in 10 patients with uncomplicated essential hypertension. Blood samples and haemodynamic data were obtained during rest and after a single-level exercise test on a bicycle cycloergometer, prior to and up to 32 h after administration of a single oral dose of bufuralol 30 mg. Bufuralol was rapidly absorbed, following a first-order process with a lag time. The calculated maximal plasma concentration ranged from 44.6 to 200.3 ng/ml. The half-life of bufuralol was 2.75±1.15 h (mean±SD). Up to 50% of the parent drug was transformed into Ro 3-7410, which showed less interpatient variability in concentration and a fairly constant half-life, which was three times longer than that of the parent drug. In general, the heart rate (HR) was slightly decreased, although 2/10 patients showed an initial increase. The resting HR returned to its pre-treatment level within 6 h, the exercise HR took up to 32 h to return to the pre-treatment level. The drug reduced both resting and exercise blood pressure (BP). The former was reduced from 153.0±14.2/93.5±8.5 to 134.5±14.0/77.0±6.8 mmHg (systolic/diastolic BP; mean±SD) with 6 h after treatment. Similarly, the exercise BP was reduced from 199.0±15.2/98.5±8.8 to 171.0±9.9/88.5±8.5 mmHg at the 6th h post-dosing. The BP values had not returned to their pre-treatment levels even 32 h after treatment. Thus, bufuralol and its metabolite Ro 3-7410 induced a long-lasting antihypertensive effect and inhibited the cardio-acceleratory effect of exercise, and there was a good correlation between the pharmacokinetic and pharmacodynamic behaviour of the drug.
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    Comparison of methods to detect side-effect on clinical application of chloranolol, a beta-adrenergic receptor inhibitor (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 555-562 
    Details
    ISSN: 1432-1041
    Keywords: Tobanum® ; beta-blocker ; chloranolol ; hypertension ; angina pectoris ; arrhythmia ; detection methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The incidence of side-effects on administration of chloranolol (Tobanum®), a beta-adrenergic receptor blocking drug, to 2066 patients with hypertension, angina pectoris or arrhythmias was measured by three different methods. In 600 patients in an efficacy trial (Group 1) both spontaneously reported complaints and objective signs were tabulated. A side effect — directed method, utilising a questionnaire containing a list of possible side-effects was also used, with the questionnaire being completed by the physician. 35 questions referred to anticipated and other side-effects. The trial was performed in two groups: in 537 patients a placebo was also given (Group 2), and in another set of 929 patients (Group 3) the questionnaire inquiry was performed uncontrolled, without placebo. All three groups were comparable in their distribution of sexes, ages and diagnoses, the mean daily dose of chloranolol its use alone or in combination, and in a similar duration of treatment. 55% of all patients received chloranolol therapy for a period of more than 3 months. The ratio of in- and outpatients was 1:5. The side-effect incidence was independent of the age and sex of the patients and of the dose of chloranolol. The incidence was also unaffected whether chloranolol was used alone or in combination. The number of side-effects differed markedly between the three groups, their ratio was 1:10:24 in Groups 1, 2 and 3. Two-thirds of the side-effects subsided spontaneously within 1 month of their onset. The duration of the side-effects varied according to their character: cardiorespiratory side-effects were of the shortest duration and those affecting the central nervous system were the most enduring. The appreciable differences in incidence could be attributed to the methods of collection of the data. It has been stated that placebo controlled trials using a detailed questionnaire are the most suitable for estimating the incidence of side-effects; recording side-effects spontaneously reported by patients are insufficiently sensitive, and uncontrolled trials using a questionnaire have been shown to be too sensitive. The revealed incidence of side effects leading to interruption of treatment is less affected by the method chosen. In 100 patients (4.8%) therapy had to be suspended because of the side-effects of chloranolol (Group 1: 1%, Group 2: 6.20%, Group 3: 6.6%). Comparison of the incidence of cessation of therapy due to side-effects did not show an appreciable difference between the various beta-adrenergic receptor blocking agents, including chloranolol.
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    Effect of spironolactone on systemic blood pressure, limb blood flow and response to sympathetic stimulation in hypertensive patients (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 263-267 
    Details
    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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    Response of blood pressure and plasma norepinephrine to propranolol, metoprolol and clonidine during isometric and dynamic excercise in hypertensive patients (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 275-279 
    Details
    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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    The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide in essential hypertensives (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 287-291 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00637615
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    Is the feeling of cold extremities experienced by hypertensive patients due to their disease or their treatment? (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 47-49 
    Details
    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; ISA ; CS ; cold extremities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with essential hypertension were interviewed prior to entering therapeutic studies in general practice. Patients' age, sex and details of antihypertensive therapy (if any) were noted, as were their spontaneously reported symptoms. Complaints of cold extremities were highest in those taking a beta-blocker (4.1%). Those untreated or taking other therapies complained less often. Those patients taking a beta-blocker with ISA complained less often (3.1%) of cold extremities than those taking a beta-blocker without ISA (5.2%).
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    URL: http://dx.doi.org/10.1007/BF00553153
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  • 72
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    Acute effects of prizidilol on blood pressure, heart rate, catecholamines, renin and aldosterone in essential hypertension (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 289-296 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00613608
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    Prizidilol (SK & F 92657), a new vasodilator with beta-blocking properties in the treatment of essential hypertension (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 411-415 
    Details
    ISSN: 1432-1041
    Keywords: prizidilol ; hypertension ; side effects ; chronic treatment ; antihypertensive effect ; anaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of a new vasodilator with betablocking properties (SK & F 92657) was investigated in 10 patients with mild to moderate essential hypertension. After a mean treatment period of 26,5 weeks (6,5–49 weeks) blood pressure was significantly reduced, from 168±22/106±6 mmHg to 144±19/94±12 mmHg (p〈0.05 and 0.025). The mean dose was 410 mg (100–700 mg). Heart rate decreased slightly from 77±12 to 70±8 beats/min. Plasma renin activity and plasma aldosterone showed only minor changes. Nausea, heavy dreams, facial and hand flushing and mild depression were reported as side effects. In most patients the symptoms disappeared without reduction in the dose. In one patient anaemia developed after 7 weeks and treatment with prizidilol was stopped. A slight but statistically significant decrease in haemoglobin concentration of 1.1±0.6 g/dl was observed in 5 of the 10 patients (p〈0.02). Thus, a mean dose of prizidilol of 410±242 mg/day had a mean blood pressure lowering effect of 24/12 mmHg. In 7 of the 10 patients (70%) diastolic blood pressure could be reduced to 95 mmHg or less. However, the observed haematological side-effects should be carefully monitored in further studies and may limit the clinical use of prizidilol.
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    URL: http://dx.doi.org/10.1007/BF00605990
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  • 74
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    Comparison of two doses of betaxolol and placebo in hypertension: A randomized, double-blind cross-over trial (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 491-494 
    Details
    ISSN: 1432-1041
    Keywords: betaxolol ; hypertension ; double-blind trial ; cross-over trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Betaxolol is a cardioselective beta-blocker, which has a bioavailability of 90% and a T1/2 of 20 h. A four group, cross-over double-blind trial was conducted to select between betaxolol 20 mg and 40 mg for long term trials. 60 patients were allocated randomly to one of the sequences placebo-20 mg, 20 mg-placebo, placebo-40 mg and 40 mg-placebo, each treatment lasting for 2 weeks. Groups were homogenous for baseline diastolic blood pressure (DBP), age and male/female ratio, and were slightly unbalanced for weight. A two-way ANOVA (3 treatments, 2 sequences) showed no treatment-sequence interaction nor sequence effect. The mean reduction in DBP was 14.2±1.8 mm Hg following 20 mg and 18.0±1.8 following 40 mg betaxolol, and 4.0±1.2 mm Hg during placebo (p〈0.001). Age, weight, baseline DBP and duration of hypertension did not influence the treatment effect. The 95% confidence intervals of the reduction in DBP were 10.4–17.9 for 20 mg and 14.3–21.6 mm Hg for betaxolol 40 mg. Aiming at a mean reduction to 90 mm Hg, betaxolol 20 mg would appear to be adequate in similar patient populations.
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    URL: http://dx.doi.org/10.1007/BF00637494
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  • 75
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    Pinacidil, a new vasodilator, in the treatment of patients with moderate to severe hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 287-289 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; vasodilator ; patients ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new vasodilator drug, pinacidil, N″-cyano-N-4-pyridyl-N′-1, 2,2-trimethylpropylguanidine, was studied in an open trial in 15 patients with moderate to severe hypertension. Four patients received pinacidil monotherapy, and in 11 patients it was used with a diuretic or a beta-blocker. In all but one patient normotension was achieved with a mean daily pinacidil dose of 46.7 mg b.i.d. (range 20–100 mg). Side effects were few and were action-related. There was no evidence of early toxicity. Pinacidil is a promising new antihypertensive vasodilator, which deserves further clinical evaluation.
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    URL: http://dx.doi.org/10.1007/BF00542161
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  • 76
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    Acute antihypertensive effect and pharmacokinetics of a tablet preparation of nifedipine (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 145-150 
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    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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    URL: http://dx.doi.org/10.1007/BF00613808
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    Cadralazine (ISF 2469): Dose-related antihypertensive activity after single oral administration to patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 157-161 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00613810
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  • 78
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    Pinacidil, a new vasodilator: Pharmacokinetics and pharmacodynamics of a new retarded release tablet in essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 557-561 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
    Source: Springer Online Journal Archives 1860-2000
    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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    URL: http://dx.doi.org/10.1007/BF00542128
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    Cardiovascular response to exercise and regional haemodynamics during treatment with prizidilol hydrochloride (SK&F 92 657) in moderately severe essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 577-580 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00542341
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    The effect of captopril and propranolol on the responses to posture and isometric exercise in patients with essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 721-728 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00542509
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    Long term treatment with tienilic acid or thiazides: Comparison of antihypertensive and metabolic effects (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 835-837 
    Details
    ISSN: 1432-1041
    Keywords: tienilic acid ; hydrochlorothiazide ; amiloride ; blood pressure control ; biochemical effects ; serum uric acid ; serum potassium ; prolonged treatment ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A comparison has been made of arterial pressure and major metabolic parameters during long term treatment with tienilic acid and a hydrochlorothiazide-amiloride combination, using a randomized single-blind study without cross-over. A significant fall in systolic and diastolic blood pressure and no change in most biochemical parameters was observed with both drugs. Serum uric acid concentration was decreased during tienilic acid and was slightly increased whilst subjects took the hydrochlorothiazide-amiloride combination; serum potassium was slightly decreased on tienilic acid. No sign of hepatotoxicity was detected.
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    URL: http://dx.doi.org/10.1007/BF00542531
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    Felodipine — A new vasodilator, in addition to β-receptor blockade in hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 571-575 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00542340
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    Reduced peripheral vascular symptoms in elderly patients treated with α-methyldopa — A comparison with propranolol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 325-329 
    Details
    ISSN: 1432-1041
    Keywords: alpha-methyldopa ; propranolol ; hypertension ; side effects ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A multicentre study of 6–10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.
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    Effect of oxprenolol and metoprolol on serum lipid concentration (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 331-334 
    Details
    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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    Evidence for a peripheral component in the sympatholytic actions of clonidine and guanfacine in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 23-27 
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    ISSN: 1432-1041
    Keywords: hypertension ; alpha2-adrenoceptors ; blood pressure ; clonidine ; guanfacine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of the changes in plasma growth hormone and noradrenaline concentrations in response to 15 min infusions of clonidine 0.2 mgs and guanfacine 2 mgs, were studied in six normal volunteers, in a double-blind, randomised, crossover study. Plasma noradrenaline fell within 15 min of the commencement of drug administration, by 36±14% after clonidine (p〈0.05) and by 32±11% (p〈0.05) after guanfacine. Plasma growth hormone was not significantly elevated until the 30th minute to 12.0±4.7 lU/ml (p〈0.05) after clonidine and 14.7±11.5 lU/ml (p〈0.05) after guanfacine, having been undetectable prior to both drugs. The reduction in plasma noradrenaline by these α2-adrenergic agonists, prior to activation of central adrenoceptors as detected by changes in plasma growth hormone, is evidence for a peripheral component in their sympatholytic effect.
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    URL: http://dx.doi.org/10.1007/BF00553149
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    Systemic and cardiac haemodynamic interactions between guanfacine and hydrallazine in hypertensive patients (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 393-396 
    Details
    ISSN: 1432-1041
    Keywords: guanfacine ; hydrallazine ; hypertension ; sympathetic nervous activity ; plasma renin activity ; cardiac and systemic haemodynamics ; blood pressure ; limb blood flow ; limb vascular resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of guanfacine and hydrallazine on cardiovascular haemodynamics and on sympathetic nervous activity has been studied in 16 patients with essential hypertension. Two groups of patients were investigated: in Group A guanfacine brought the blood pressure back to normal (diastolic blood pressure ⩽90 mmHg), and in Group B diastolic blood pressure was 〉 90 mmHg and required the addition of hydrallazine. Guanfacine significantly decreased heart rate, plasma renin activity and urinary excretion of noradrenaline, without altering cardiac contractility. In Group B, guanfacine 2 to 6 mg/day produced a significant decrease in blood pressure from 178.7/112.4 to 164.4/102.9 mmHg and in heart rate from 77.1 to 62.7 beats/min after 4 weeks of treatment. Guanfacine did not significantly alter preejection period, cardiac output or total peripheral resistance. Hydrallazine 50 to 300 mg/day caused a further reduction in blood pressure from 164.4/102.9 to 150.7/90.2 mmHg and an increase in heart rate from 62.7 to 72.1 beats/min. Limb blood flow was increased from 4.55 to 5.93 ml/100 g/min and limb vascular resistance was decreased from 39.55 to 23.6 mmHg 100 g·min/ml. Hydrallazine also caused a slight increase in plasma renin activity and urinary excretion of noradrenaline. It is concluded that guanfacine is a useful agent to block a hydrallazine-induced increase in sympathetic nervous activity.
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    URL: http://dx.doi.org/10.1007/BF00549584
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    Once-daily dosing of timolol in hypertension: A controlled study (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 239-241 
    Details
    ISSN: 1432-1041
    Keywords: timolol ; hypertension ; dose ranging ; double-blind trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine previously untreated patients with mild-moderate hypertension were included in a dose-ranging double-blind trial to determine the effectiveness of daily versus thrice daily timolol administration. In 8 patients control of blood pressure was equally effective though with significantly lower heart rate achieved in the once daily group. One patient was not satisfactorily controlled on the daily regimen demonstrating that many but not all hypertensives can be controlled with daily administration of timolol.
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    URL: http://dx.doi.org/10.1007/BF00625796
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    Simplified antihypertensive therapy with pindolol retard (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 445-449 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542036
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  • 89
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    Comparison of labetalol, propranolol and hydralazine in hypertensive out-patients (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 457-460 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00542038
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  • 90
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    Haemodynamic changes in heart failure induced by a new vasodilator tolesmoxide (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 473-477 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00542041
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  • 91
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    Role of various vasodepressor systems in the acute hypotensive effect of captopril in man (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 1-8 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00554659
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  • 92
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    Relationship between the antihypertensive effect and steady-state plasma concentration of nifedipine given alone or in combination with a beta-adrenoceptor blocking agent (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 287-293 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00561384
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  • 93
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    Pharmacokinetics of sotalol after chronic administration to patients with renal insufficiency (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00561389
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  • 94
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    Haemodynamic profile of captopril treatment in various forms of hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 163-168 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00544593
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  • 95
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    Antihypertensive and renal effects of orally administered verapamil (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 375-382 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00636788
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    Relationship of propranolol pharmacokinetics to antihypertensive effect and beta-adrenergic blockade in the treatment of hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
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    URL: http://dx.doi.org/10.1007/BF00636790
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  • 97
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    Monoamine metabolites in cerebrospinal fluid during treatment of hypertension with prazosin (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 399-401 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00636792
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  • 98
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    A naturalistic study of hypertension in a rural U.K. community (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 191-197 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; beta-blocker ; diuretic ; screening ; naturalistic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A naturalistic study was set up to screen, identify and treat hypertensive patients aged 20–60 years in a rural general practice. 3,222 patients (92%) of a stable population of 3,489 were screened by 2 nurse research assistants and of these 455 patients (14%) were found to be hypertensive or borderline hypertensive. After careful assessment, 192 of these patients were found suitable for treatment and subsequently 138 entered the study. Two well recognised treatment regimes were used and no significant difference between patient response resulted. 84 patients (60.9%) completed the 2 year duration of the study discussed here. The cost of the study is not feasible in an average general practice, but day to day running of such a project, run along clearly defined treatment regimes was managed easily by 2 research assistants: this reduced, therefore, the work load on individual general practitoners.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613816
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  • 99
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    Use of labetalol in hypertensive patients during discontinuation of clonidine therapy (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 237-240 
    Details
    ISSN: 1432-1041
    Keywords: labetalol ; clonidine ; hypertension ; adverse effects ; plasma catecholamines ; plasma cAMP ; withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven hypertensive patients in whom clonidine therapy had to be discontinued, were treated prophylactically with labetalol, in order to avoid a possible hypertensive crisis. Most of the known side effects, which are consistent with the withdrawal phenomenon were observed, e.g. tremor, insomnia and apprehension, but headaches and flushing did not occur. Blood pressure levels remained unchanged, despite up to a 20-fold increase in plasma catecholamines. The lack of change in serial measurements of plasma cyclic AMP level appears to indicate that adequate adrenergic blockade was induced by labetalol. Since labetalol is a potent anti-hypertensive drug, and is also effective in avoiding a possible hypertensive crisis due to withdrawal of clonidine, we propose to use it as the drug of choice whenever discontinuation of clonidine therapy is indicated.
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    URL: http://dx.doi.org/10.1007/BF00618771
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  • 100
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    Correlation between propranolol in plasma and urine, renin-aldosterone system and blood pressure in essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 251-258 
    Details
    ISSN: 1432-1041
    Keywords: aldosterone ; hypertension ; propranolol ; blood pressure ; plasma level ; renin ; urine level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg×4 (Group 1), 80 mg×4 (Group 2) and 160 mg×4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h urinary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradually increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treatment. The maximum reduction in diastolic BP occurred after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduction was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA and PAC fell in all groups, and remained reduced during C and D in Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin-aldosterone system was initially suppressed in all groups, but for unknown reasons it increased towards the control level after seven to eleven weeks of therapy with 320 and 640 mg/day, and that the reduction in systolic BP increased with higher doses of propranolol and with increasing urinary propranolol excretion.
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    URL: http://dx.doi.org/10.1007/BF00618774
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