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.     

应激状态下应用缓释维拉帕米及合用西拉普利的有益作用

目的 :探讨应激状态下缓释维拉帕米 (VerSR)及合用西拉普利 (Cil)的有益作用。方法 :5 4例原发性高血压病人 ,随机分为 3组 :VerSR组 19例(VerSR 2 4 0～ 36 0mg ,po ,qd) ,Cil组 14例 (Cil 2 .5～ 5mg ,po ,qd) ,VerSR +Cil组 2 1例 (VerSR 12 0～ 2 4 0mg ,po ,qd +Cil 2 .5～ 5mg ,po ,qd)。 (1)随访服药后 1,2和 4wk后坐位血压 (BP)及心率(HR) ;(2 )服药前及服药后 4wk做心算、冷压、握掌试验及运动激发试验 ,观察BP ,HR及血浆去甲肾上腺素 (NE) ,肾上腺素 (E) ,多巴胺 (DA)的变化。结果 :(1)VerSR组总有效率 93% ,Cil组总有效率77% ,VerSR +Cil组总有效率 10 0 % (P >0 .0 5 ) ;(2 )VerSR能明显降低心算试验后的BP(1.7± 0 .9/1.3± 0 .7)kPa(P <0 .0 1)、冷压试验后的BP(2 .5±1.4 /1.2± 0 .9)kPa(P <0 .0 1)及握掌试验后的收缩压 (SBP) (1.6± 1.4 )kPa(P <0 .0 1) ;Cil仅能降低握掌试验后的SBP ,(1.1± 1.4 )kPa(P <0 .0 5 ) ;VerSR +Cil则明显降低心算试验后的BP(3.0± 2 .9/2 .1± 1.1)kPa(P <0 .0 1)和HR(10± 9)次·min- 1(P <0 .0 1)、握掌试验后BP(1.8± 1.6 /1.8± 0 .9)kPa(P <0 .0 1)和HR(6± 7)次·min- 1(P <0 .0 5 )及冷压试验后的SBP(1.9± 1.8)kPa(P <0 .0 1)。Cil对运动激发试?     

缬沙坦氨氯地平对老年高危高血压患者的疗效及相关影响

目的研究缬沙坦氨氯地平复方制剂对老年高危高血压患者的降压疗效以及对血管内皮功能、氧化应激水平的影响。方法选取在我院就诊的84例老年高危高血压患者,随机分为缬沙坦氨氯地平组(A组,42例,服用缬沙坦氨氯地平复方制剂80/5mg,每日1次)、氨氯地平组(B组,42例,服用氨氯地平单药5mg,每日1次),观察16周,试验结束后比较各组的坐位静息血压水平、血压达标率、血清一氧化氮(NO)、内皮素-1(ET-1)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)的活性。结果治疗结束时,A、B 2组的血压降幅差异有统计学意义(P<0.05),A组的血压达标率与血清NO水平高于B组(P<0.05),ET-1水平低于B组(P<0.05)。A组的血清MDA水平低于B组(P<0.05),SOD活性水平高于B组(P<0.05)。结论对于老年高危高血压患者,应用缬沙坦氨氯地平复方制剂治疗血压达标率更高,能更好地减轻体内的氧化应激水平、保护血管内皮功能。     

维拉帕米缓释片与硝苯地平或维拉帕米治疗高血压病疗效比较

目的：比较维拉帕米缓释片与硝苯地平或维拉帕米治疗高血压的疗效。方法：维拉帕米缓释片（ＳＲＶＴ）组３４例（男性２１例，女性１３例，年龄５８±ｓ１１ａ），剂量１２０－２４０ｍｇ，ｐｏ，ｑｄ；硝苯地平（Ｎｉｆ）组３８例（男性２１例，女性１７例，年龄６０±１１ａ），剂量１０－２０ｍｇ，ｐｏ，ｔｉｄ；维拉帕米（Ｖｅｒ）组３６例（男性２２例，女性１４例，年龄５８±１１ａ），剂量４０－８０ｍｇ，ｐｏ，ｔｉｄ；３组疗程均为３０ｄ。结果：ＳＲＶＴ，Ｎｉｆ及Ｖｅｒ均有非常显著降压效果（Ｐ＜０．０１），总有效率依次为９４％，９５％及９４％。结论：３组降压疗效相似，但Ｎｉｆ组不良反应大于另２种药物。     

阿斯匹林与维拉帕米单用和合用对兔血液流变性的影响

观察阿斯匹林（Ａｓｐ）与维拉帕米（Ｖｅｒ）单用及合用对免血液流变性的影响。结果表明：ｉｖ生理盐水，Ａｓｐ１．２５ｍｇ·ｋｇ－１和Ｖｅｒ０．０５ｍｇ·ｋｇ－１对兔血液流变性各项指标均无明显影响；ｉｖＡｓｐ２．５、５ｍｇ·ｋｇ－１和Ｖｅｒ０．１、０．２ｍｇ·ｋｇ－１后，血液粘度（ＢＶ），血浆粘度（ＰＶ）和红细胞比积（ＨＣＴ）明显降低，红细胞电泳率（ＥＥＭ）显著提高，且呈明显量效关系；Ａｓｐ１．２５，２．５ｍｇ·ｋｇ－１和Ｖｅｒ０．０５，０．１ｍｇ·ｋｇ－１合用，呈明显协同效应。推测ＡｓＰ，Ｖｅｒ降低ＢＶ可能与ＰＶ，ＨＣＴ下降和ＥＥＭ提高有关。     

伊贝沙坦和缓释维拉帕米对高血压患者交感活性的影响

目的 用握力试验激活交感神经系统,评价服用伊贝沙坦和缓释维拉帕米8周后交感活性的变化。方法 48名轻中度高血压患者经2周安慰剂期后,随机分入伊贝沙坦组(n=24,150mg,每日1次)和缓释维拉帕米组(n=24,240mg,每日1次)。于安慰剂期末和药物治疗8周末各进行1次握力试验,并记录静息和负荷状态下的血压和心率。结果 伊贝沙坦组服药后静息收缩压和舒张压显著降低(P<0.01),下降幅度与缓释维拉帕米组无显著性差异(P>0.05)。握力试验中,服用伊贝沙坦后可使血压上升幅度从30.6±8.69/20.0±4.51mmHg降至15.2±5.90/14.3±4.26mmHg,疗效与缓释维拉帕米组相似。结论 服用伊贝沙坦不仅可降低静息血压,而且可降低负荷状态下的血压,其作用与缓释维拉帕米相似。     

氨氯地平对肾性高血压及肾功能不全的疗效

目的：观察氨氯地平治疗肾性高血压及保护肾功能的效果。方法：慢性肾脏疾病病人５０例（男性２９例，女性２１例，年龄４１±ｓ４ａ）用氨氯地平片５～１０ｍｇ，ｐｏ，ｑｄ，４ｗｋ为一个疗程。结果：降血压明显（Ｐ＜０．０１），２４ｈ尿蛋白量及血钾无变化，血肌酐下降（Ｐ＜０．０１），内生肌酐清除率上升（Ｐ＜０．０１）。结论：氨氯地平用于慢性肾脏疾病病人既可降低血压，也可以保护肾功能     

氨氯地平对稳定型心绞痛患者发生心血管意外的影响

目的:探讨苯磺酸左旋氨氯地平能否降低心绞痛患者发生心血管意外的风险。方法:对1 287例稳定型心绞痛患者,在用药2周后检测血压变化,比较长效氨氯地平和安慰剂的药效差异,并分析血压变化对药物和继发心血管病结果关系的影响。结果:服用氨氯地平后能明显减少心绞痛患者发生心血管意外的危险性,用药2周后收缩压的变化与心血意外事件的发生密切相关,但冠状动脉介入治疗和心脏搭桥手术与血压变化没有关系。对2周后收缩压变化进行校正后发现使用氨氯地平能使患者发生中风的风险从27%(P=0.03)降到20%(P=0.12),发生心力衰竭的风险从31%(P=0.03)降到21%(P=0.12),行冠状动脉介入治疗的比例降低26%(P=0.003),行冠状动脉搭桥手术的比例降低22%(P=0.01)。结论:氨氯地平能有效降低稳定型心绞痛患者心血管意外的风险,临床上为减少心绞痛患者发生心血管意外,要尽早应用药物降低血压。     

Single-pill combination of amlodipine and valsartan in the management of hypertension

Combination therapy is increasingly recommended for selected patients with hypertension to facilitate prompt attainment and maintenance of goal blood pressure (BP). Single-pill combination therapy simplifies treatment and optimizes long-term compliance. Amlodipine, a dihydropyridine calcium antagonist, and valsartan, an angiotensin receptor blocker, are well-established antihypertensive agents with complementary mechanisms of action. This combination lowers BP significantly more than either of its components, and valsartan reduces the incidence of dose-related amlodipine-induced edema. Rigorous clinical trial data have proven the BP-lowering efficacy and high tolerability of the amlodipine/valsartan combination in patients with moderate to severe hypertension as well as other difficult-to-treat populations. Amlodipine/valsartan is indicated as initial therapy in patients who are unlikely to be controlled with a single drug and as second-line therapy in patients not responding adequately to monotherapy.     

氨氯地平治疗肾性高血压的疗效和安全性

目的 :观察氨氯地平治疗肾性高血压的疗效和安全性。方法 :前瞻性研究。肾性高血压病人 96例 ,分 2组 ,氨氯地平单用组 5 4例 [男性 30例 ,女性2 4例 ;年龄 ( 38±s 19)a]给氨氯地平 10mg ,po ,qm ( 7∶0 0 )× 6wk(如治疗 2wk未达显效可剂量加倍 ) ;氨氯地平与依那普利合用组 42例 [男性 2 6例 ,女性 16例 ;年龄 ( 41± 2 0 )a]在原用依那普利 10mg ,po ,qd或bid基础上加用氨氯地平 (用法同上 )× 6wk。结果 :单用组总有效率 80 % ,合用组为98% (P <0 .0 1) (其中对重度高血压的有效率分别为 42 %和 80 % ,P >0 .0 5 ) ,不良反应均较少而轻。结论 :单用或合用氨氯地平治疗轻、中度肾性高血压疗效均较好 ,对重度高血压以加用依那普利的合用组似较好。     

Pharmacokinetics of verapamil in patients with hypertension

Summary Twelve hypertensive patients (WHO Stage I-II) were given oral verapamil (Isoptin) b.d. or t.d.s. as long-term treatment. The pharmacokinetics of verapamil and norverapamil were studied both after single and b.d. and t.d.s. doses of verapamil 240, 360 or 480 mg daily adjusted according to the blood pressure response. The apparent oral clearance of verapamil was decreased after both the twice and thrice daily dosage regimens (1.38 and 1.841/min, respectively) as compared to the single dose (4.39 l/min). The plasma half-life of verapamil was increased from 3.34 h (single dose) to 4.65 h (b.i.d.). Decreased elimination of norverapamil was also found after multiple doses of verapamil, as shown by an increase in the adjusted AUC of norverapamil (adjusted to a verapamil dose of 80 mg), namely from 574.9 h·ng·ml^–1 (single dose) to 1172 h·ng·ml^–1 (b.d.) and to 841 h·ng·ml^–1 (t.d.s.). The plasma half-life of norverapamil increase from 5.68 h to 7.34 h during twice daily dosing. During thrice daily verapamil, no increase in plasma half-life was found either for verapamil or norverapamil, probably due to the relatively short sampling time (6 h). The plasma concentration of verapamil and the reduction in supine systolic and diastolic blood pressure were correlated. The mean decrease in supine systolic blood pressure was 5.8 mm Hg per 100 ng verapamil/ml plasma, and for diastolic pressure 2.9 mm Hg per 100 ng verapamil/ml plasma. The mean steadystate plasma concentrations of verapamil were similar after twice and thrice daily dosing regimens, which agrees with the clinical observation that blood pressure control in hypertensive patients is as good after verapamil b.d. and t.d.s.     

乌拉地尔预防高血压病人气管插管时心血管反应的观察

目的 观察乌拉地尔（URA）预防高血压病人全麻气管插管期间心血管反应的效果。方法 40例确诊高血压病择期全麻手术病人,术前血压控制在21．3／13．3kPa以下。随机分成A组（URA组,n=20)和B组（对照组,n=20.A组于麻醉诱导前5分钟静注URA0．5mg/kg,B组静注生理盐水。两组均以芬太尼、安定、维库溴铵和丙泊酚静脉诱导后气管插管。记录诱导前、静注URA后5分钟、诱导后及插管后1分钟、3分钟、5分钟SBp、DBp、MAPey HR,并计算RRP。结果A组静注URA后5分钟SBp、DBp、及MAP显著下降（P＜0．01）,诱导插管期间SBp、DBp、MAP及RPP无明显变化,插管后1分钟HR显著加快（P＜0．05）。B组诱导后SBp、DBp及MAP显著下降（P＜0．01）;插管后1分钟、3分钟SBp、DBp、MAP及HR显著高于诱导前（P＜0．05,P＜0．01）,插管后1分钟、3分钟及5分钟RPP均显著升高（P＜0．01）,与A组同期比较差异有极显著意义（P＜0．01）。结论 应用URA能有效预防高血压病人气管插管时的心血管反应。     

氨氯地平与硝苯地平治疗老年原发性高血压的疗效比较

目的　探讨氨氯地平与硝苯地平治疗老年人原发性高血压的疗效比较。方法　老年人原发性高血压患者 80例 ,随机分成两组即A组 (氨氯地平组 )和B组 (硝苯地平组 )。A组 40例应用氨氯地平 5～ 10mg ,每日 1次 ,连服 4周。B组 40例应用硝苯地平 10～ 2 0mg ,每日 3次 ,连服 4周。两组均同时观察血压下降情况及不良反应。结果　氨氯地平降压总有效率 82 .5 % ,硝苯地平降压总有效率 70 %。结论　氨氯地平组的降压总有效率高于硝苯地平组 ,且不良反应少 ,安全性高 ,服用方便 ,是老年人原发性高血压有效的降压药。     

左旋氨氯地平和氨氯地平对高血压病人内皮功能及血清胆固醇影响

目的 :比较左旋氨氯地平及氨氯地平对原发性高血压 (EH)病人血管内皮功能及血清胆固醇的影响。方法 :将 6 0例EH病人随机分为 2组A组 ,用左旋氨氯地平 2 .5mg ,po ,qd ;B组用氨氯地平 5mg ,po ,qd。并设健康对照组 ,不用任何药物。6wk后测量结果 ,将 2药交叉继续用药 6wk复测各数值。对内皮功能与高血压危险分层进行相关分析。结果 :应用 2药 6wk ,2组肱动脉反应性充血时内径变化率 (FMD)较治疗前有明显改善 ,分别为(4±s 4 ) %vs (6± 7) % (P <0 .0 1) ,(3± 4 ) %vs(6± 8) % (P <0 .0 1) ,2组间比较无显著差异 (P >0 .0 5 ) ,2药交叉治疗后结果不变。 2组治疗后 12wk血清胆固醇水平下降。FMD(% )与病人高血压危险分层间呈负相关。结论 :左旋氨氯地平与氨氯地平均可改善高血压病人内皮功能 ,效果相似。 2药可轻度降低血清胆固醇。内皮功能随高血压危险分层增高而降低     

Pharmacokinetics of controlled-release verapamil in healthy volunteers and patients with hypertension or angina

AIMS: To study the dose-ranging population pharmacokinetics of controlled release verapamil in healthy subjects and patients with angina or hypertension. To characterize the pharmacodynamics of controlled-release verapamil in patients with hypertension. METHODS: Dose-ranging studies were conducted in healthy volunteers and patients with hypertension and angina. Subjects received doses of 120, 180, 360, or 540 mg racemic verapamil as an osmotic controlled-release formulation. A population pharmacokinetic model involving zero-order release of verapamil into the gastrointestinal tract with first-order absorption and elimination was used to describe the steady-state plasma concentration profile for R- and S-verapamil. A population sigmoid E(max) pharmacodynamic model was used to describe the effect of R- and S-verapamil on mean arterial blood pressure. RESULTS: S-verapamil had an approximate 4-fold greater apparent clearance than R-verapamil in both healthy volunteers and patients. The apparent plasma clearance of R- and S-verapamil in healthy volunteers decreased over the dose range of 120-540 mg. A similar dose-dependent decrease in apparent plasma clearance was also noted in patients. None of the patient demographic variables examined (age, total body weight, lean body weight, body mass index, and height) explained the variability in verapamil pharmacokinetics. The pharmacodynamic model describing the relationship between verapamil plasma concentration and mean arterial blood pressure indicated that the S-verapamil had a 3.6-fold lower estimated EC(50) compared to R-verapamil. CONCLUSIONS: The results from this dose-ranging pharmacokinetic investigation in healthy volunteers and patients are consistent with previous reports in healthy subjects. S-verapamil is cleared more rapidly than R-verapamil and the estimated EC(50) for S-verapamil was 3.6-fold lower than for R-verapamil. Estimated EC(50) values for R- and S-verapamil decreased with increasing age and decreasing weight.     

氨氯地平片在健康人和高血压患者中的药物动力学

采用反相高效液相色谱法测定了健康志愿者及高血压患者共３３名单剂量口服５ｍｇ苯磺酸氨氯地平片后的血清药物浓度，研究了该药在中国人体内的药物动力学。经ＰＫＢＰ－Ｎ１程序拟合表明，氨氯地平主要呈现二房室模型。其主要药动学参数分别为：健康人Ｔ１／２α＝０．６±０．５ｈ，Ｔ１／２β＝３５±９ｈ，Ｔｍａｘ＝８±４ｈ，Ｃｍａｘ＝２．４±０．８ｎｇ／ｍｌ；中青年高血压患者Ｔ１／２α＝０．６±０．４ｈ，Ｔ１／２β＝３６±９ｈ，Ｔｍａｘ＝１１±４ｈ，Ｃｍａｘ＝２．３±１．２ｎｇ／ｍｌ；老年高血压患者Ｔ１／２α＝０．４９±０．３３ｈ，Ｔ１／２β＝４２±１４ｈ，Ｔｍａｘ＝１０±４ｈ，Ｃｍａｘ＝２．８±１．４ｎｇ／ｍｌ。结果表明，中国人体内的氨氯地平药动学参数与报道的外国人相似。     

阿魏酸钠和维拉帕米对庆大霉素肾毒性的保护作用

目的研究中药阿魏酸钠（ＳＦ）和维拉帕米（Ｖｅｒ）对庆大霉素（ＧＭ）肾毒性的保护作用。方法采用原代近端肾小管上皮细胞培养技术制作体外ＧＭ损伤模型，观察细胞丙氨酸氨基转移酶（ＡＬＴ）、过氧化氢酶（Ｃａｔ）、ＮＡＧ酶活性、ＤＮＡ合成，细胞内游离钙浓度以及形态学变化，同时观察ＳＦ、Ｖｅｒ的防治作用。结果ＧＭ组表现为ＡＬＴ、Ｃａｔ活性下降，ＮＡＧ活性增加。同时细胞ＤＮＡ合成下降，细胞内游离钙浓度升高。光镜发现近端小管上皮细胞有大量空泡和溶酶体髓样体形成。给予ＳＦ能使上述异常指标明显改善，组织学损害也明显减轻。Ｖｅｒ仅能保护ＡＬＴ活性和降低细胞内游离钙浓度。结论ＳＦ能有效保护ＧＭ对肾小管上皮细胞的损害。     

缬沙坦氨氯地平片对高血压患者左室舒张功能和动脉顺应性影响的超声学评价

目的应用超声技术评价缬沙坦氨氯地平片（商品名：倍博特）对高血压左心室（LV）舒张功能及动脉顺应性的影响。方法选择90例原发性高血压患者分为LV构型异常组（42例）和LV构型正常组（48例）,均予缬沙坦氨氯地平片1片（含缬沙坦80mg,氨氯地平5mg）,po,qd。分别于给药前、给药3和6个月测量血压、脉压和体质量指数,应用超声心动图测定各受试者左房内径（LAD）、左室内径（LVDd及LVDs）、室壁厚度和相对室壁厚度（RWT）、左室质量指数（LVMI）、左室射血分数（LVEF）;运用多普勒超声和组织多普勒（TDI）分别记录二尖瓣口的血流频谱（E、A、E／A）和二尖瓣环的运动速度频谱（e’、a’）,计算E／e’、e’／a’;运用颈总动脉超声检查测左侧颈总动脉内中膜厚度（IMT）、最大径（Dmax）、最小径（Dmin）,计算颈动脉动脉顺应性（AC）、血管僵硬参数（β）和压力应变弹性系数（Ep）。结果原发性高血压LV构型异常组的e’／a’低于LV构型正常组（P〈0．05）,而E／e’β、Ep高于LV构型正常组（P〈0．05）。给予缬沙坦氨氯地平片治疗3和6个月,与用药前基线值相比,IMT以Ep、E／e’降低（P〈0．05）,AC、e’／a’增高（P〈0．05）,LV构型正常组干预6个月时恢复至正常值范围。LV构型异常组在干预3个月时左室舒张末期容积、每搏输出量恢复至正常值范围,6个月时LAD、RWT、LVMI恢复至正常值范围,但E／e’、e’／a’、β、Ep与LV构型异常组仍有差别（P〈0．05）。结论原发性高血压患者LV舒张功能、动脉弹性的减低,早于动脉结构及心脏构型的改变。缬沙坦氨氯地平片口服3和6个月,对LV构型正常的高血压患者可以改善心脏舒张功能和动脉弹性,对LV构型异常的高血压患者,逆转心脏的重构,形态结构恢复正常,但心脏舒张功能和动脉硬化的参数未完全正常。     

阿罗洛尔与氨氯地平治疗糖尿病高血压的随机对照研究

目的验证阿罗洛尔在治疗糖尿病合并高血压病人应用中临床有效性和安全性。方法18～75 a的糖尿病合并高血压者83例,随机分为阿罗洛尔组(n=41)和氨氯地平组(n=42),分别服用阿罗洛尔(5～15 mg,bid)或氨氯地平(5～10 mg,qd),观察12 wk。每4 wk随访一次,观察血压、空腹血糖,用药前后测定糖化血红蛋白(HbA1c)及各项安全性指标。结果治疗后,2组血压都明显下降,组间无明显差异(P>0.05)。高血压治疗前后,2组的空腹血糖及HhA1c均无统计学差异(P>0.05)。治疗12 wk后,阿罗洛尔组心率由(78±6)次·min~(-1)下降至(69±9)次·min~(-1),与氨氯地平组相比有统计学差异。阿罗洛尔组总有效率为85%,氨氯地平组为93%,无统计学差异(P>0.05)。结论阿罗洛尔能有效地降低糖尿病合并高血压痛病人的收缩压和舒张压,对糖代谢及脂代谢无不良影响,对糖尿病合并的高血压病人,尤其是对伴有交感神经兴奋者是一个安全有效的降压药物。     

氨氯地平剂量对高血压患者肾素-血管紧张素-醛固酮系统的影响

目的　观察不同剂量氨氯地平对高血压患者肾素-血管紧张素-醛固酮系统的影响。方法　坐位舒张压95~115mmHg的原发性高血压病人31例,经1周药物洗脱期, 2周安慰剂期后, 口服氨氯地平5mg,qd, 4周末坐位DBP≥90mmHg者剂量加倍×4周。测定安慰剂期后和治疗4, 8周后,立位血管紧张素原(AO)、血浆肾素活性(PRA)、血管紧张素II(AgII)和醛固酮水平(ALD)。结果　6例服氨氯地平每日5mg, 25例需加量至每日10mg。每日5mg氨氯地平使PRA无显著性变化[ (1. 75±3. 22)vs(2. 16±2. 89)ng·(mL·h)-1;P>0. 05],而每日10mg氨氯地平使PRA显著升高[ ( 2. 08±2. 01 ) vs( 4. 63±2. 01)ng·(mL·h)-1,P<0. 01]。2剂量均使AO显著升高(P<0. 01);AgII和ALD均无显著性变化(P>0. 05)。结论　原发性高血压患者服用氨氯地平每日5mg,对PRA无明显影响;而每日服10mg使PRA显著升高。但2剂量对AngⅡ和ALD水平影响均不明显。