Effects of spironolactone on serum and muscle electrolytes in patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension

Summary The effect of adding spironolactone (Aldactone) on muscle electrolytes was studied in 48 patients with arterial hypertension and/or congestive heart failure who had received conventional diuretic treatment, including a potassium supplement, for more than 1 year. After 6 months on spironolactone 100 mg/day as well as the original conventional diuretic therapy, there was a significant increase in both skeletal muscle potassium and magnesium. At the same time these parameters decreased in the control group. In the spironolactone group there was also a significant increase in the mean serum potassium and creatinine levels. There was a significant fall in blood pressure in the spironolactone-treated group.     

An open, multicentre study of acebutolol in hypertension.

Four hundred and twenty-seven hypertensive patients in the United Kingdom have so far been admitted to two on-going open multicentre trials, and have been treated with acebutolol for periods ranging from 1 to 6 months. Oral dosages were within the range of 100 mg to 1200 mg/day in divided doses and were increased or decreased to suit individual requirements. The data on 366 patients completing more than 1 month's treatment were analysed. A high significant reduction in mean diastolic pressure was observed. This reduction was progressive up to 6-month's treatment and was the more marked as pre-treatment values were higher. There was a highly significant correlation between pre-treatment mean diastolic pressure and mean fall of diastolic pressure at 6-months' treatment. There was also a highly sigificant association between initial values and response, and between duration of treatment and response. The higher the pre-treatment value, the less likely was non-response. Response also increased as treatment duration increased. Although asthmatic patients were not excluded, only 2 of the 427 patients included in the present study had to discontinue treatment because of the occurrence of airways obstruction; only 1 of these patients had experienced asthma previously.     

An open,multicentre study of acebutolol in hypertension

Summary

Four hundred and twenty-seven hypertensive patients in the United Kingdom have so far been admitted to two on-going open multicentre trials, and have been treated with acebutolol for periods ranging from 1 to 6 months. Oral dosages were within the range of 100 mg to 1200?mg/day in divided doses and were increased or decreased to suit individual requirements. The data on 366 patients completing more than 1 month's treatment were analysed.

A highly significant reduction in mean diastolic pressure was observed. This reduction was progressive up to 6-month 's treatment and was the more marked as pre-treatment values were higher. There was a highly significant correlation between pre-treatment mean diastolic pressure and mean fall of diastolic pressure at 6-months' treatment. There was also a highly significant association between initial values and response, and between duration of treatment and response. The higher the pre-treatment value, the less likely was non-response. Response also increased as treatment duration increased. Although asthmatic patients were not excluded, only 2 of the 427 patients included in the present study had to discontinue treatment because of the occurrence of airways obstruction: only 1 of these patients had experienced asthma previously.     

Raised aldosterone to renin ratio predicts antihypertensive efficacy of spironolactone: a prospective cohort follow-up study

AIMS: Aldosterone/renin ratio is an index for inappropriate aldosterone activity, and it is increasingly being used to screen for primary aldosteronism within the hypertensive population. It may also be a good index to help predict the response to spironolactone. To assess the blood pressure response to oral spironolactone in hypertensive patients with primary aldosteronism identified with raised aldosterone to renin ratio. METHODS: We conducted a prospective cohort study of hypertensive patients with raised aldosterone/renin ratio, who failed to suppress plasma aldosterone with salt loading and fludrocortisone suppression test. These patients were treated with spironolactone and were followed-up for a period of up to 3 years. RESULTS: We studied 28 (12 male) subjects with a mean age of 55 (s.d. 10) years who were followed up for a mean period of 12.9 (7) months. At baseline, the patients were taking a mean of 2.1 (1.2) antihypertensive drugs, but despite this 16/28 (57%) had diastolic BP >90 mmHg, 39% with systolic BP >160 mmHg. After commencing spironolactone, three patients complained of breast tenderness but continued treatment and one patient was intolerant of spironolactone and had to stop treatment. Of the remaining 27 patients, the mean number of antihypertensive drugs used dropped to spironolactone plus 0.7 (s.d. 0.9). All but one patient (96%) achieved a diastolic BP相似文献   

Effect of spironolactone on systemic blood pressure,limb blood flow and response to sympathetic stimulation in hypertensive patients

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.     

后腹腔镜治疗肾上腺疾病

目的:探讨腹腔镜在肾上腺手术中的应用。方法:2004—05～2005—05对4例肾上腺疾病患者施行腹腔镜肾上腺切除术,全部经后腹腔途径。其中皮质醇症1例,无功能腺瘤3例.结果:4例均获得成功,手术时间:95～130min,平均106min。所有患者术中及术后均未输血,无明显并发症。结论:腹膜后腹腔镜肾上腺切除术具有损伤小、术后恢复快和住院时间短等优点,可望成为治疗肾上腺占位性病变的首选方法。     

Controlled,eight-hour haemodynamic study of a sustained-release formulation of isosorbide dinitrate in moderate left ventricular failure

Summary The aim of the study was to assess the duration of the haemodynamic effects of a new sustained-release oral formulation of isosorbide dinitrate (ISDN). Twenty patients (17 men and 3 women; mean age 60 years) with acute myocardial infarction (10 anterior, 10 inferior) complicated by moderate left ventricular failure took part in a randomized controlled trial. Ten patients were randomly assigned to the placebo group and 10 to the ISDN group, who received 40 mg sustained release isosorbide dinitrate. Haemodynamic variables were measured before treatment, after 0.5 and 1 h and then every 2 hours up to the 8th hour after treatment. There was no significant change in any haemodynamic parameter in the placebo group, during the study period. In the ISDN group there was a significant fall in pulmonary artery diastolic pressure at 4 and 8 h, from 19.0±1.0 mmHg to 16.5±1.2 mmHg and 15.5±0.8 mmHg, respectively. The mean pulmonary capillary wedge pressure fell progressively from 17.9±1.0 to 12.5±1.2 mmHg at 2 h (p<0.001 in comparison with the placebo group. The fall remained significant up to 8 h. There was no statistically significant change in heart rate, cardiac index, systemic blood pressure or systemic and pulmonary vascular resistances. On the whole the cardiac index remained unchanged. There were numerous individual variations of cardiac index in relation to the initial mean pulmonary capillary wedge pressure and the magnitude of its fall following administration of ISDN. The change in cardiac index was inversely correlated with the control cardiac index (r=–0.69, p<0.02).     

高血压患者中原发性醛固酮增多症的检出率及特点

【摘要】目的探讨高血压患者中原发性醛固酮增多症（PA）的检出率及临床特点。方法197例高血压患者检测PA及其他相关指标,排除其他继发性高血压。将研究对象分PA组及原发性高血压组（EH组）。对2组患者行卧、立位试验,卡托普利试验或静脉高钠试验,血钾及肾上腺薄层CT,部分患者行午夜地塞米松抑制试验、促肾上腺皮质激素（ACTH）及性激素测定,主要指标为血醛固酮、肾素活性及醛固酮与肾素活性比值（ARR）。结果（1）197例高血压患者中确诊PA38例（19.29%）,13例经病理诊断证实,醛固酮腺瘤6例,单侧肾上腺增生7例,未发现无功能腺瘤。（2）2组患者的高血压病程及体质指数（BMI）的差异无统计学意义,PA组及EH组男性均多于女性。（3）与EH组比较,PA组的起病年龄相对年轻,收缩压与舒张压水平更高,但差异均无统计学意义;PA组卧位、立位血醛固酮水平及ARR均显著升高,血肾素活性均显著下降（均P＜0.01）,血钾水平差异无统计学意义。结论同期住院的高血压患者中PA的检出率较高,其中醛固酮腺瘤和单侧肾上腺增生的比例相近,低钾血症不常见。     

后腹腔镜手术治疗肾上腺良性疾病（附45例报告）

目的探讨后腹腔镜手术治疗肾上腺疾病的手术技巧及临床效果。方法对45例肾上腺良性病变患者行后腹腔镜肾上腺切除术。肾上腺肿瘤41例（库兴综合征14例,嗜铬细胞瘤6例,原发性醛固酮增多症11例,无功能腺瘤10例）,肾上腺囊肿4例。结果45例手术均获成功,无中转开放者;手术时间35—65分钟,平均45分钟;术中估计出血量20—90ml,平均55ml;术后住院时间3-6天,平均4．5天。术中及术后无明显并发症。39例术后获随访6—38个月,影像学检查无复发。结论后腹腔镜肾上腺切除术是一种安全、有效、微创、恢复快的术式,是肾上腺良性疾病的理想治疗方法。     

Single and divided daily dose piretanide in the treatment of uncomplicated essential hypertension: A double-blind comparison with a combination of hydrochlorothiazide and amiloride

Summary In a randomised double blind study in patients with mild to moderate hypertension, piretanide 6 mg once and twice daily significantly reduced both supine and erect blood pressure. This was seen after only 2 weeks and a further progressive reduction was evident over the ensuing 12-week trial period. The higher dose produced a mean maximal fall of 29% in supine diastolic pressure, compared with 23% after the lower dose; the difference is not significant. Hydrochlorothiazide 50 mg/amiloride 5 mg twice daily (HCT/A) also reduced supine blood pressure significantly after 2 weeks, but the reduction in erect diastolic blood pressure did not achieve statistical significance until 8 weeks. The maximal effect (a 13% fall in supine diastolic blood pressure) was significantly less than that of either piretanide regimen. Blood pressures in this group also returned more rapidly to pretreatment levels during the placebo washout phase at the end of the study.HCT/A produced a significant sustained rise in serum potassium and a reduction in serum sodium and chloride. Piretanide had minimal effects on serum electrolytes.     

Aldosterone receptor antagonists and cardiovascular disease: do we need a change of the guard?

Aldosterone is a mineralocorticoid primarily produced in the zona glomerulosa of the adrenal gland. For many years, aldosterone (Aldo) was thought to have its sole site of action in the kidney, where it regulated sodium excretion and potassium reabsorption. It is now known that Aldo is produced in cardiovascular tissues, and has been implicated in the development of ventricular hypertrophy and cardiac fibrosis. The precise mechanisms whereby Aldo acts in cardiac tissues are diverse. It was assumed that Aldo production could be limited by angiotensin-converting enzyme (ACE) inhibition, but serial measurements during therapy reveal only a transient decrease in Aldo levels. Moreover, the effects of Aldo on cardiac tissues occur even when angiotensin II (Ang II) has been suppressed or eliminated. Multiple investigators have examined effects of Aldo receptor blockade in human subjects and various animal models using the two Aldo receptor antagonists (ARAs), spironolactone and eplerenone. Major clinical trials involving spironolactone (RALES) and eplerenone (EPHESUS) ARAs have shown significant benefits in the treatment of congestive heart failure (CHF). In RALES, patients with New York Heart Association (NYHA) Class III or IV systolic heart failure treated with spironolactone had a 30% relative risk decrease in mortality. Although spironolactone is an effective competitive inhibitor of the mineralocorticoid receptor (MR), progestational and antiandrogenic side effects limit its use in some patients. Eplerenone, a more selective ARA, lacks these undesirable side effects. Although eplerenone is 20-fold less potent at the MR, it demonstrates efficacy similar to spironolactone, possibly due to decreased protein binding. Eplerenone has fewer side effects than spironolactone, which has been attributed to the low cross-reactivity with androgen and progesterone receptors. In EPHESUS, patients with left ventricular systolic dysfunction [Ejection Fraction (EF) <40%] and CHF following an acute myocardial infarction (AMI), were treated with eplerenone, resulting in a 17% reduction in cardiovascular mortality. However, these studies were limited in that diastolic function was not evaluated, although approximately 1/2 of CHF is due to diastolic dysfunction alone. To date, neither ARA has been studied for the treatment of diastolic dysfunction in a major clinical trial. However, numerous animal studies employing ARAs have shown a decrease in cardiac hypertrophy and fibrosis, indicating the potential benefits of these agents in the treatment of diastolic heart failure. In this review, we discuss possible underlying mechanisms responsible for Aldo effects on cardiovascular function and compare the beneficial effects of spironolactone and eplerenone in the treatment of heart disease.     

Piretanide,a potassium stable diuretic,in the treatment of essential hypertension

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 (RR_diast 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.     

Placebo-controlled trial of a combination of bemetizide and triamterene (‘Hypertane’) in mild or moderate hypertension

Summary

A double-blind, randomized, placebo-controlled clinical trial was carried out to assess the efficacy and tolerance of the diuretic combination 25?mg bemetizide plus 50?mg triamterene (‘Hypertane’) in 39 patients with essential hypertension. Treatment was given for 8 weeks with either the diuretic preparation or placebo, the initial dose of 2 tablets daily being reduced to 1 tablet daily if and when a sustained reduction in blood pressure occurred; this proved possible in 40% of the diuretic-treated group as compared with 17% of the placebo group. Standing blood pressure showed a highly significant reduction (mean 25/13 mmHg) by the end of 4-weeks' treatment with bemetizide/triamterene whereas there was very little change in placebo-treated patients. By the end of 8-weeks' treatment, standing systolic pressure levels were reduced in 75%, and diastolic levels in 70%, of the active-treated patients. Lying blood pressure showed similar trends with a highly significant reduction (mean 22/14 mmHg) during bemetizide/triamterene treatment. Blood pressure reduction was significantly greater with the diuretic than with placebo therapy. Responders showed changes during 8-weeks' treatment from 166.4/108.7 to 130.7/90.3 mmHg for standing pressures and from 173.7/104.4 to 141.7/85.8 mmHg for lying pressures. Serum potassium levels decreased significantly during diuretic treatment (mean fall 0.47 mmol/l) in 78% of the patients, although only 4 decreased to below the normal range (lowest 3.1 mmol/l) and no patient exhibited any symptoms of hypokalemia. No appreciable increases in potassium levels were seen. Urea levels increased significantly during bemetizide/triamterene treatment (mean increase 2.45 mmol/l). Serum creatinine showed comparable but less marked changes. Uric acid levels increased significantly during diuretic treatment (mean increase 132 μmol/l), the increase occurring in 94% of the patients. By the end of 8-weeks' treatment, levels were above the normal range in 61%. No clinical manifestations of hyperuricaemia were seen. Only infrequent and minor symptoms were reported during bemetizide/triamterene treatment, no more than in the placebo group. The results indicate that bemetizide/triamterene is an effective treatment for mild to moderate hypertension. It appeared to be well tolerated, the only biochemical abnormalities being those expected of a preparation containing a thiazide diuretic. The potassium-sparing effect of the drug has been demonstrated by the absence of any marked decrease in serum potassium levels.     

Comparison of natriuretic, uricosuric, and antihypertensive properties of tienilic acid, bendrofluazide, and spironolactone.

The antihypertensive properties of the new diuretic tienilic acid were investigated. Thirteen previously untreated hypertensive patients took part in a double-blind crossover study in which 30 days' treatment with tienilic acid 250 mg, bendrofluazide 5 mg, and spironolactone 100 mg were compared. Bendrofluazide caused the greatest natriuresis on the first treatment day and the most rapid fall in blood pressure. The ultimate antihypertensive effect of all three drugs was similar. Tienilic acid caused a noticeable reduction in serum urate concentrations and a rise in urate clearance, in contrast to the other two agents, which caused slight urate retention. Tienilic acid and bendrofluazide caused falls and spironolactone a rise in plasma potassium concentrations. No untoward effects were seen from any of the drugs. It is concluded that tienilic acid is a moderately potent diuretic that lowers plasma urate concentrations. It may be the drug of first choice for hypertensive patients who already have gout or are likely to develop it when taking thiazide diuretics.     

Trial of slow release diltiazem for essential hypertension in general practice

In New Zealand diltiazem has been approved since 1984 for the treatment of angina pectoris and was available only as short acting tablets. This study was a trial of a slow release formulation in the treatment of hypertension. A single blind placebo controlled study was undertaken on 24 patients in general practice using a once daily dose with a maximum of 360 mg. The mean fall in resting supine diastolic blood pressure was 17.3 mmHg, 95% CI 14.4 to 20.2; t = 12.2, df = 23, p = 0.0001. Twelve patients (50%) achieved a fall in diastolic pressure to 90 mmHg or less with the minimum dose (120 mg) while 19 patients (79%) achieved this level with up to 360 mg daily and 22 patients (92%) had a fall of diastolic pressure of 10 mmHg or more. One patient was withdrawn because of a rash. Other adverse reactions were mild and usually tolerable.     

A clinical trial of a spironolactone/thiazide combination in the treatment of hypertension in Zambian Africans

Summary

A clinical trial was carried out to compare the eflects of placebo and of a spironolactone-althiazide combination in the treatment of 24 Zambian Africans with hypertension. After an initial 2 weeks on placebo, patients received 100?mg spironolactone plus 60?mg althiazide daily for 12 weeks. They were then treated with placebo again for 3 to 5 weeks, followed by a second active treatment period of 6 to 8 weeks in dosages ranging from 50?mg spironolactone plus 30?mg althiazide to 150?mg spironolactone plus 90?mg althiazide according to the previous response. A statistically significant (p <0.001) reduction was noted in both systolic and diastolic blood pressures whilst on active treatment. Mean reductions were 30/16 mmHgfor supine and 35/21 mmHg for standing blood pressures. Treatment with the combination product did not influence serum potassium or creatinine levels. Mean blood urea, however, increased from 23.6 to 35.1?mg/100 ml and the mean serum uric acid from 6.7 to 8.9?mg/100 ml. No serious side-effects were seen.     

Abnormal circulatory control in falciparum malaria: the effects of antimalarial drugs

Summary We have studied blood pressure and heart rate responses to standing in 29 previously ambulant adult Thai patients with acute uncomplicated falciparum malaria before and after treatment with quinine or mefloquine.There was significant, symptomatic, and usually profound orthostatic hypotension in 12 patients (41%) before antimalarial treatment. The median maximum fall in systolic pressure was 24 mm Hg, significantly greater than the maximum fall in diastolic pressure 16 mm Hg.Blood pressure fell in two phases: an initial transient and usually asymptomatic fall immediately on standing, and a progressive, usually symptomatic fall, worsening over several minutes without a rise in pulse rate. Orthostatic hypotension was associated with core temperature (r=0.37, P=0.05).Antimalarial treatment accentuated the delayed orthostatic hypotension during malaria, despite (in the case of quinine) a significant reduction in fever. Both antimalarial drugs attenuated the cardioacceleratory response to symptomatic postural hypotension; the mean reduction in heart rate at the time of lowest blood pressure was 22 beats·min^–1.The electrocardiograph ratio of RR intervals at the 30th and 15th beats was reduced significantly in acute malaria, but was not affected further by the drugs. When restudied in convalescence all the patients had normal postural cardiovascular responses.Acute falciparum malaria is associated with impaired circulatory control and the tendency to postural hypotension is worsened significantly by antimalarial treatment with the quinoline antimalarials quinine and mefloquine.     

Lacidipine in the treatment of hypertension in black African people: antihypertensive, biochemical and haematological effects

This is an open trial investigating the efficacy and metabolic effects of 3 months' treatment with lacidipine in 25 Nigerian Africans with mild to moderate hypertension. There was a significant fall in sitting diastolic blood pressure, with treatment (p = 0.01). There were no significant weight changes. The heart rate initially rose significantly with the drug but this normalised with time. All biochemical and haematological indices remained essentially unchanged during therapy. Lacidipine therefore proved an efficacious and metabolically neutral antihypertensive in mild to moderate hypertension in Africa.     

卡托普利、美托洛尔、安体舒通联用治疗慢性心力衰竭的疗效

目的:采用卡托普利、美托洛尔、安体舒通联合疗法对慢性心力衰竭进行治疗,观察其疗效。方法:选取2018年1月~12月收治的慢性心力衰竭患者60例,对照组采用传统疗法进行治疗,观察组采用联合疗法(卡托普利、美托洛尔、安体舒通)治疗,比较两组临床疗效。结果:治疗4周后,所有患者心功能均有所提升,左室舒张末径减小、LVEF增加;治疗12周后观察组心功能、左室舒张末径、LVEF明显优于对照组(P<0.05);治疗后与治疗前相比,组间血钾情况无明显异常(P>0.05)。结论:卡托普利、美托洛尔、安体舒通联合疗法可明显改善慢性心力衰竭患者心功能、左室舒张末径、左室射血分数,值得推广应用。     

A study of the antihypertensive action of xipamide using ambulatory intra-arterial monitoring.

1 The antihypertensive activity of the diuretic xipamide has been studied in 18 patients with mild/moderate essential hypertension using the technique of continuous ambulatory intra-arterial blood pressure recording. Full data from 48 h blood pressure recordings before and after treatment were available from 13 patients. 2 After a mean period of 3 months' treatment with xipamide 20 mg once daily, both systolic and diastolic blood pressure were markedly reduced throughout the whole 24 h day, the reductions of systolic being statistically significant throughout the whole period, and of diastolic for 19 out of the 24 hourly periods measured. There was no postural hypotension seen during treatment and there was a conspicuous lack of side effects. 3 Xipamide would appear to be as effective as many beta-adrenoceptor blockers but without their side effects and produces a better control of blood pressure throughout the whole day and night.