Antihypertensive effect of manidipine

Manidipine is a lipophilic, third-generation, highly vasoselective, dihydropyridine (DHP) calcium channel antagonist, which, when given on a once-daily basis, effectively reduces blood pressure (BP) in patients with mild-to-moderate essential hypertension. Manidipine has a gradual onset and a long duration of action, effectively maintaining reduced BP levels throughout the 24-hour dosing period, and is effective in the long term with no evidence of intolerance. The BP-lowering capacity of manidipine is similar to that of other established DHPs and of angiotensin-converting enzyme inhibitors. Diabetic patients and very elderly patients with mild-to-moderate hypertension also respond favourably to treatment with manidipine. Manidipine has neutral effects on glucose and lipid metabolism and is generally well tolerated. Manidipine thus represents a first-line option for lowering BP in patients with mild-to-moderate hypertension.     

伊拉地平缓释胶囊对高血压的疗效

伊拉地平（ｉｓｒａｄｉｐｉｎｅ）缓释胶囊５－１０ｍｇｑｄｐｏ连续６ｗｋ治疗原发性高血压３０例，男性１７例、女性１３例，年龄５０±ｓ８ａ，发现对轻、中型高血压有效率达９０％，治疗后收缩压下降１２％，舒张压下降１５％。除轻微头痛、头晕外，无心动过速及其他严重不良反应。伊拉地平缓释胶囊降压效果良好，作用持久平稳，服用方便，不良反应小，有较大应用前景。     

Antihypertensive effect of single doses of enalapril in hypertensive patients treated with bendrofluazide.

This study was designed to investigate the validity of the then current recommendations for initiation of therapy with enalapril in hypertensive patients on treatment with a diuretic. Enalapril in single doses of 10 and 20 mg was given to 13 hypertensive patients on treatment with bendrofluazide 5 mg daily in a randomised, crossover, placebo controlled study. The mean maximal reduction in blood pressure was similar with both doses (35/20 mmHg supine, 38/20 mmHg standing), occurred on average within 6 h of tablet ingestion, and was not accompanied by any significant change in heart rate. Three patients experienced symptomatic hypotension. In one patient this was incapacitating after 10 mg and precluded exposure to 20 mg. This study shows that in hypertensive patients receiving treatment with diuretics, the addition of enalapril should be undertaken with caution. An optimal starting dose of enalapril in such patients remains to be confirmed.     

马来酸依那普利联合前列地尔治疗糖尿病肾病的临床疗效观察

目的观察马来酸依那普利联合前列地尔治疗糖尿病肾病患者的临床疗效。方法将68例糖尿病肾病患者随机分为观察组与对照组,每组各34例,对照组在常规糖尿病治疗基础上,给予马来酸依那普利10 mg,口服,1次/d;观察组在对照组治疗基础上,加用前列地尔注射液10μg,静脉滴注,1次/d;两组疗程均为4周。结果治疗结束后,观察组尿清蛋白排泄率(UAER)、血清肌酐(Scr)含量均较治疗前显著下降(P<0.05);观察组临床总有效率为91.18%,显著高于对照组的61.76%(P<0.05)。结论马来酸依那普利联合前列地尔治疗糖尿病肾病的疗效显著,值得推广使用。     

Chronopharmacology of enalapril in hypertensive patients

The pharmacokinetics and pharmacodynamics of enalapril, an angiotensin converting enzyme inhibitor, are reported to vary with the time of administration. The present study was undertaken to examine whether the effect of enalapril on plasma bradykinin (BK), substance P and prostaglandin E₂ (PGE₂), which are likely to be involved in the mechanism of enalaprilinduced cough, might also be affected by its time of administration. Enalapril 5 mg or placebo was given orally at 10:00 h (day trial) or 22:00 h (night trial) to 12 patients with essential hypertension. Serum concentrations of total drug (enalapril + enalaprilat, its active metabolite) during the day and night trials did not differ significantly at any time. However, serum enalaprilat tended to be higher and its maximum concentration greater in the day trial than in the night trial. Blood pressure 24 h after administration of enalapril was reduced at 22:00 h, but not at 10:00 h. Plasma BK tended to increase following enalapril administration at 10:00 h, but not at 22:00 h. Remarkable increases in plasma BK were observed in two patients in the day trial and one of them also complained of cough. However, no such increase in plasma BK or subsequent adverse effect were recorded in the night trial. Plasma substance P and PGE₂ did not change significantly following enalapril administration either in the day or night trial. The results suggest that the response of BK to enalapril is affected by the time of administration. In patients who complain of cough during treatment with enalapril during the daytime, this adverse effect might be dminished or eliminated by a switch to night-time administration.     

Effect of successful hypertension control by manidipine or lisinopril on albuminuria and left ventricular mass in diabetic hypertensive patients with microalbuminuria

Objective The aim of this open-labelled, randomised, parallel-group study was to evaluate the effect of long-term monotherapy with manidipine or lisinopril on albumin excretion rate (AER) and left ventricular mass index (LVMI) in hypertensive patients with type-2 diabetes and microalbuminuria.Methods After a 4-week wash-out period, 174 patients with essential hypertension [diastolic blood pressure (DBP) >80 mmHg and <100 mmHg], type-2 diabetes and microalbuminuria were randomised to manidipine 10 mg o.d. or lisinopril 10 mg o.d.; after 8 weeks, the dose was doubled in non-responders (DBP >80 mmHg); after 3 months, treatment was discontinued in the non-responder patients and in those complaining of side effects; the remaining 121 patients continued their therapy with manidipine or lisinopril, and 99 completed the 2-year study. At the end of the wash-out period, of the titration period and after 6, 12, 18 and 24 months of treatment, BP was measured, AER, creatinine clearance, glycosylated haemoglobin (HbA1c) and body mass index (BMI) were evaluated and an echocardiographic evaluation was performed.Results The 99 patients who completed the study were statistically analysed according to a per-protocol evaluation. Manidipine and lisinopril significantly reduced systolic blood pressure (SBP) and DBP levels (at 24 months, –22.3/15.5 mmHg, P<0.001 versus baseline and –21.4/15.7 mmHg, P<0.01 versus baseline, respectively). Both drugs provided a significant decrease in AER, but it was significantly more pronounced with lisinopril (at 24 weeks, –37.2 mg/24 h, P<0.001 versus baseline) than with manidipine (–29.9 mg/24 h, P<0.05 versus baseline) and became evident earlier in the lisinopril group (after 3 months versus 6 months of treatment). Manidipine produced a greater reduction of LVMI than lisinopril (–14.9 g/m² versus –10.8 g/m² at 24 months). The effect was more pronounced in patients with left ventricular hypertrophy at baseline (–19.8 g/m² versus –12.8 g/m², P<0.05).Conclusion These data suggest that, despite similar BP lowering, non-haemodynamic factors play an important role in the pharmacological reduction of AER and LVMI in diabetic hypertensive patients.     

Captopril and enalapril improve cognition and depressed mood in hypertensive patients

In this study, we evaluate the effects of two angiotensin converting enzyme inhibitors (ACEIs), captopril and enalapril given chronically as antihypertensive treatment, on certain cognitive and emotional processes in humans. Thirty-nine subjects with mild to moderate hypertension and fifteen normotensive controls were divided into four groups consisting of normotensive and hypertensive subjects taking captopril, enalapril, or no medication at all. The Rey Auditory Verbal Learning Test and the Wechsler Memory Scale were used to evaluate their cognitive functioning. Mood changes in all subjects were assessed using the Beck Depression Inventory and the Hopkins Symptom Check- list (HSC). Results: Untreated hypertensive patients scored lower than normotensive controls in cognitive tests and significantly worse in cumulative recall (P < 0.05) and paired words association (P < 0.01). When compared with normotensive subjects, untreated hypertensive patients also scored significantly higher on the depression with anxiety subscale in HSC (P < 0.05). No significant influence of hypertension was found in any other examined aspect of cognition and mood. In most cases captopril improved and enalapril reversed the adverse memory effects of hypertension. High arterial blood pressure is significantly associated with an impairment of cognition and the occurrence of depression with anxiety in humans. Enalapril and, to a lesser extent, captopril reversed these deficits.     

Antihypertensive efficacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study*

ABSTRACT

Objectives: Antihypertensive monotherapy rarely achieves blood pressure (BP) control. NATIVE (NATrilix SR use in combInation antihypertensiVe thErapy) evaluated indapamide sustained release (SR) in hypertensive patients receiving background therapy.

Research design and methods: Patients remaining hypertensive (systolic BP [SBP], 145–180?mmHg; diastolic BP [DBP], 95–105?mmHg) while receiving an angiotensin-converting enzyme (ACE) inhibitor (n = 709), β-blocker (n = 629), calcium-channel blocker (CCB; n = 493), angiotensin II type 1 receptor blocker (ARB; n = 75), α-blocker (n = 29) or other therapy (n = 6) were enrolled, recruited by physicians from 228 centres in Pakistan. Indapamide SR 1.5?mg was administered daily for 3 months with background therapy. BP was assessed every 2 weeks, and blood glucose and total cholesterol were evaluated at baseline and study end in a patient subgroup. Adverse events were also recorded.

Main outcome measures and results: Of 2073 enrolled patients (49% males; mean age 51 years), 1941 received indapamide SR and background therapy. SBP and DBP decreased significantly (SBP, 166 ± 16?mmHg at baseline vs. 132 ± 12?mmHg at 3 months; DBP, 102 ± 8?mmHg vs. 83 ± 6?mmHg; both p < 0.0001 vs. baseline). Patients uncontrolled with an ACE inhibitor, β-blocker, CCB or ARB achieved an SBP/DBP decrease of 34 ± 15/19 ± 9, 33 ± 17/19 ± 10, 33 ± 15/18 ± 8 or 35 ± 16/20 ± 12?mmHg, respectively (all p < 0.0001). In all, 84% of patients achieved target SBP (≤?140?mmHg) and 61% achieved BP normalisation (SBP <?140, DBP <?90?mmHg). The absence of placebo control may lead to an overestimation of the extent of the BP reduction achieved. Glucose and cholesterol levels were unaffected by indapamide SR. Four percent of patients experienced side-effects, which were mild-to-moderate in severity.

Conclusions: In patients with hypertension despite antihypertensive therapy, indapamide SR significantly reduced BP with a good acceptability profile. Indapamide SR may represent an effective additional therapy for patients who do not achieve BP goals with other antihypertensive agents.     

2型糖尿病合并高血压病的抗高血压药物治疗

糖尿病慢性并发症是糖尿病患者致死、致残的主要原因。在占临床糖尿病病例90％～95％以上的2型糖尿病患者中，最常见且危害最大的慢性并发症是心血管疾病，尤其是高血压病。因此，针对2型糖尿病患者合并的高血压病，早期、及时和达标治疗非常必要。由于糖尿病本身代谢紊乱和病理生理变化的影响，使得糖尿病合并的高血压病具有一些临床特点，临床医生在降压方案的确定和降压药物的选择时，应当注意这些特点。     

尼群地平、依那普利与牛磺酸合并应用对肾性高血压大鼠降压的协同研究

尼群地平１０ｍｇ·ｋｇ－１、依那普利１０ｍｇ·ｋｇ－１和牛磺酸５０ｍｇ·ｋｇ－１一次口服对肾性高血压大鼠均有降压作用，三者降压作用强度相当，最大降压百分率（给药后６ｈ）分别为３３、３６．６和２５．１，降压持续时间相似，给药后２４ｈ的降压百分率分别为１４．２、４．８和１３．７。尼群地平，依那普利分别与牛磺酸以及尼群地平与依那普利合用均有协同降压作用，Ｑ值分别为２．２１、２．６７和１．６４，且降压作用持久，给药后２４ｈ的降压百分率分别为３９．６、２６．８和３８．８，显著高于各药单用。     

血必净注射液联合依那普利、阿托伐他汀钙对高血压肾损害患者临床疗效及肾功能的影响

目的 探讨血必净注射液与马来酸依那普利片、阿托伐他汀钙片联合对高血压肾损害患者临床疗效及肾功能的影响。方法 选取2014年12月—2017年12月榆林市第二医院100例高血压肾损害患者为研究对象,根据入院单双号将入选者分为对照组和观察组,每组50例。对照组患者口服马来酸依那普利片10 mg/次,1次/d;阿托伐他汀钙片10 mg/次,1次/d。观察组患者在对照组治疗的基础上静脉滴注血必净注射液,将1.5 g加入到0.9%氯化钠溶液100 mL中,1次/d。两组均连续治疗6个月。观察两组患者的临床疗效,比较两组治疗前后的肾功能指标、D-二聚体（D-D）和炎性因子水平。结果 治疗后,观察组总有效率为92.00%,显著高于对照组的76.00%,两组比较差异具有统计学意义（P<0.05）。治疗后,两组肌酐（Cr）、尿微量白蛋白与肌酐比值（ACR）、尿微量白蛋白（mAlb）及尿β₂-微球蛋白（β₂-MG）水平均显著降低（P<0.05）;且观察组肾功能指标水平显著低于对照组（P<0.05）。治疗后,两组患者的D-D、白细胞介素-6（IL-6）、超敏C反应蛋白（hs-CRP）和肿瘤坏死因子-α（TNF-α）水平均显著降低（P<0.05）;且观察组D-D及各炎性因子水平显著低于对照组（P<0.05）。结论 血必净注射液联合马来酸依那普利片和阿托伐他汀钙片治疗高血压肾损害患者可有效改善肾功能,抑制机体炎性反应,疗效安全显著,值得临床推广使用。     

糖尿病合并高血压的降压治疗

目的探讨糖尿病合并高血压的降压治疗效果。方法将Ⅱ型糖尿病合并高血压患者23例随机分为A组8例、B组7例、C组8例。A组予硝苯地平缓释片;B组采用硝苯地平和缬沙坦联合给药方案;C组采用硝苯地平+吲哒帕胺联合方案。观察对比3组患者治疗前后的血压变化情况及不良反应。结果 3组患者在降压治疗后,其舒张压和收缩压均有显著下降(P<0.01)。其中,B组舒张压下降幅度最大,与其他2组比较差异有统计学意义(P<0.01);C组收缩压下降幅度最大,明显大于另外2组(P<0.01)。A组患者血压达标比率明显低于另外2组(P<0.01)。A组不良反应发生率高于B、C组,差异均有统计学意义(P<0.05)。结论硝苯地平联合血管紧张素转换酶抑制剂或利尿剂能取得较为满意的降压效果,且不良反应少。     

胺碘酮与依那普利联合治疗阵发性心房颤动的临床研究

目的评价胺碘酮与依那普利联合治疗阵发性心房颤动（房颤）的临床疗效。方法将129例阵发性房颤随机分为胺碘酮组（Ⅰ组,n=64）和胺碘酮联合依那普利组（Ⅱ组,n=65）,治疗随访时间为1年,研究终点为房颤发作。比较两组治疗前、治疗后的左心房内径。计算两组治疗后窦性心律维持率。结果两组患者治疗前后左心房内径比较：治疗前分别为（35．21±1．76）mm、（35．84±1．69）mm,治疗后分别为（38．76±2．14）mm、（36．27-I-1．91）mm,治疗后IⅠ组患者左房内径明显小于Ⅰ组。两组患者窦性心律维持率的比较：治疗结束时,Ⅰ组患者窦性心律维持率为62．3％,Ⅱ组患者窦性心律维持率80．6％,两组患者比较有显著性差异。结论胺碘酮与依那普利联合治疗阵发性房颤维持窦性心律的疗效优于单用胺碘酮,对延缓左心房扩大有一定作用。     

Antihypertensive and renal effects of enalapril and slow-release verapamil in essential hypertension

Summary The renal, metabolic and antihypertensive effects of enalapril (E) and slow-release verapamil (V) were compared in a 2-month double-blind crossover trial in 22 patients with newly discovered essential hypertension. The glomerular filtration rate and renal vascular resistance were unaltered; renal blood flow was slightly decreased by V Serum Ca²⁺ increased and Na⁺ excretion declined after V. Serum lipids, glucose, and erythrocyte electrolytes were unchanged. Blood pressure (BP) was lower with E after half the maximum dosage compared with V but similar BP reductions were obtained after 2 months with the maximum dosage.     

Cost of switching hypertensive patients from enalapril maleate to lisinopril.

The costs and potential savings associated with switching patients in a hypertension clinic from enalapril maleate to lisinopril were analyzed. Patients taking enalapril were randomized to receive lisinopril or to continue taking enalapril. For the 47 patients randomized, data were collected for 25 patients switched to an equal milligram dosage of lisinopril and for 21 patients who continued to receive a constant dosage of enalapril. To maintain blood pressure control, it was necessary to double the dosage of lisinopril in five patients (20%) and have it in one patient (4%), while the enalapril dosage was doubled in two patients (9.5%). The total direct cost of switching patients to lisinopril was $66.33 per patient. The annual drug cost savings per patient for switching to lisinopril would be $52.08, $46.80, and $120.24 for therapy with one 5-, 10-, and 20-mg tablet per day, respectively. A patient would have to receive 15, 17, or 7 months of therapy with 5-, 10-, or 20-mg tablets of lisinopril, respectively, before a net cost savings would be realized. In the evaluation of a less expensive therapeutic alternative, the total cost of switching must be considered.     

Antihypertensive and renal haemodynamic effects of atenolol and nadolol in elderly hypertensive patients.

As little is known of the antihypertensive efficacy or renal haemodynamic effects of beta-adrenoceptor blocking drugs in the elderly we studied two such drugs, atenolol and nadolol, in elderly hypertensive patients. Ten patients took part in a placebo-controlled double-blind study of atenolol and 10 received nadolol in a single-blind placebo-controlled study. Treatment phases lasted 12 weeks for atenolol or 10 weeks for nadolol. Blood pressure, effective renal blood flow and glomerular filtration rate data obtained at the end of each treatment phase were analysed. Atenolol lowered mean arterial pressure (mean +/- s.e. mean) from 129.9 +/- 1.5 to 108.2 +/- 2.3 mm Hg (P less than 0.01) while it increased mean effective renal blood flow 512.5 +/- 86.6 to 646.0 +/- 116.1 ml min-1 1.73 m-2 (P less than 0.05). Nadolol reduced mean arterial pressure from 133.2 +/- 2.0 to 113.5 +/- 3 mm Hg (P less than 0.001) but reduced mean effective renal blood flow from 558.8 +/- 32.2 to 446.0 +/- 26.9 ml min-1 1.73 m-2 (P less than 0.05). Glomerular filtration did not alter significantly with either drug. We conclude that beta-adrenoceptor blocking drugs are effective antihypertensive agents in the elderly but have disparate effects on effective renal blood flow perhaps because of differences in cardioselectivity. These data suggest that comparative studies with thiazide diuretics and beta-adrenoceptor blocking drugs are warranted in elderly hypertensives.     

Antihypertensive action and serotonin-induced platelet aggregation during long-term ketanserin treatment in hypertensive patients

Ketanserin (3 X 40 mg daily) was administered during 6 weeks in 14 patients with mild to moderate essential hypertension using a double-blind, placebo-controlled, crossover design. Ketanserin decreased (p less than 0.01) the recumbent blood pressure from 159/104 to 153/97 mm Hg and the recumbent heart rate from 75 to 72 beats/min. Platelet aggregation induced by 5-hydroxytryptamine (5-HT), whether or not amplified by threshold doses of collagen, was not inhibited; however, it was reduced in 10 normal volunteers after a single oral dose of 40 mg ketanserin. The results suggest that long-term treatment with ketanserin reduces blood pressure; whereas 5-HT receptor inhibition could not be demonstrated when assessed by platelet aggregation.