肾素-血管紧张素系统抑制药和糖尿病

血管紧张素转换酶抑制药(ACEI)和血管紧张素Ⅱ受体1拮抗药(ARB)是目前抑制肾素-血管紧张素系统的主要药物大量研究结果表明ACEI和ARB不仅可降低糖尿病的发生率、延迟糖尿病的进展,而且可降低糖尿病患者心血管事件的发生率和心血管死亡率。本文对其作用及机制进行探讨     

某院中心药房2011年~2013年口服抗高血压药物使用情况的分析

目的调查本院中心药房口服抗高血压药物使用规律。方法对本院中心药房2011²013年口服抗高血压药物使用频度进行统计分析。结果血管紧张素转换酶抑制药、血管紧张素Ⅱ受体拮抗药、钙通道阻滞药及β受体拮抗药每月总DDDs的年变化趋势基本一致,各月份增长环比基本一致。结论本院中心药房口服抗高血压药物使用频度于2011年2013年口服抗高血压药物使用频度进行统计分析。结果血管紧张素转换酶抑制药、血管紧张素Ⅱ受体拮抗药、钙通道阻滞药及β受体拮抗药每月总DDDs的年变化趋势基本一致,各月份增长环比基本一致。结论本院中心药房口服抗高血压药物使用频度于2011年²013年存在使用规律,可应用于该类药物领入量的调节和库存管理。     

糖尿病肾病药物治疗的研究

糖尿病肾病是糖尿病重要的慢性微血管并发症,长期理想控制血糖、血压和血脂等是其基本的防治措施,但近来一些有关糖尿病肾病防治的基础和临床研究表明不少药物如噻唑烷二酮类药物、血管紧张素转换酶抑制药、血管紧张素Ⅱ受体拮抗药、醛固酮受体拮抗药和他汀类药物等存在上述作用之外的肾脏保护作用,受到大家关注。     

几种肾素—血管紧张素—醛固酮抑制药的合理应用

肾素 血管紧张素 醛固酮系统 (ＲＡＡＳ)是由血管紧张素原(Ａｎｇ)、肾素、血管紧张素Ⅰ (ＡｎｇⅠ )、血管紧张素Ⅰ转化酶(ＡＣＥ)、血管紧张素Ⅱ (ＡｎｇⅡ )、血管紧张素Ⅱ受体和醛固酮等组成的具有多元生物活性的系统。ＲＡＡＳ抑制药按其作用部位可分为肾素抑制药、血管紧张素Ⅰ转化酶抑制药 (ＡＣＥＩ)、血管紧张素ⅡＡＴ1受体抑制药 (ＡＲＢ)、醛固酮抑制药[1] 。1　肾素抑制药当肾交感神经兴奋时 ,其末稍释放的去甲肾上腺素可激活近球细胞的β 肾上腺素受体 ,从而使肾素释放增加 ,而肾素抑制药为 β 受体阻断药如普萘洛尔等则使肾素…     

血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体拮抗剂在慢性肾脏疾病治疗中的应用

血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体拮抗剂是目前广泛使用的降压药。对肾脏疾病患者,这两类药物还有独立于降压作用之外的减少蛋白尿的作用,在保护肾功能、延缓肾脏疾病的进展方面起到了极其重要的作用。但使用血管紧张素转化酶抑制剂或血管紧张素Ⅱ受体拮抗剂也可能导致产生高钾血症、急性肾损伤等不良反应,妊娠、双侧肾动脉狭窄或容量不足等患者禁用,老年人或肾功能明显减退患者慎用。一般不建议联合使用血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体拮抗剂。     

他索沙坦的药理作用与临床应用

血管紧张素转化酶抑制药 (ＡＣＥＩ)是常用的抗高血压药物之一 ,但 1 5 %～ 39%的患者发生干咳 ,大部分需停药。阻抑肾素 血管紧张素系统的替代方法是阻滞血管紧张素Ⅱ受体。他索沙坦 (ｔａｓｏｓａｒｔａｎ)是美国家用产品公司研制的新型吡啶并 [2 ,3 ｄ]嘧啶类血管紧张素Ⅱ受体拮抗药 ,动物实验和临床研究均表明可有效降压。1　药理作用该药能特异性地结合血管紧张素Ⅱ的ＡＴ1 受体 ,抑制其活性 ,可口服用于高血压治疗。它是在洛沙坦的化学结构的基础上进行修饰 ,对大鼠肾上腺皮质细胞膜上ＡＴ1 受体的亲和力是洛沙坦的 3倍 ,结合是可饱和…     

血管紧张素Ⅱ受体拮抗剂减轻糖尿病肾间质巨噬细胞的浸润

目的探讨血管紧张素Ⅱ受体拮抗剂对糖尿病肾脏的保护作用。方法 STZ尾静脉注射建立大鼠糖尿病模型。用免疫组化方法检测大鼠肾脏巨噬细胞的表达。比较血管紧张素Ⅱ受体拮抗剂治疗组与非治疗组肾脏CD68+巨噬细胞的表达。结果糖尿病成模后,巨噬细胞在肾间质的表达明显增加。血管紧张素Ⅱ受体拮抗剂治疗组较非治疗组肾间质巨噬细胞的浸润减少加(P<0.01),伴随蛋白尿的减轻。结论血管紧张素Ⅱ受体拮抗剂可减轻糖尿病大鼠肾脏炎症浸润。     

新型血管紧张素Ⅱ受体拮抗药：衣普沙坦

衣普沙坦 (ｅｐｒｏｓａｒｔａｎ ,商品名Ｔｅｖｅｔｏｎ ,代号ＳＫＦ10 85 6 6 )是继氯沙坦 (ｌｏｓａｒｔａｎ)、缬沙坦 (ｖａｌｓａｒｔａｎ)、伊贝沙坦 (ｉｒｂｅｓａｒｔａｎ)之后又一种血管紧张素Ⅱ受体拮抗药。本文就其药理作用、药代动力学及临床应用综述如下。1　药理作用1.1　对血管紧张素Ⅱ受体的拮抗作用　肾素 血管紧张素 醛固酮系统 (ＲＡＳ)在原发性高血压和慢性充血性心力衰竭的发生过程中起着十分重要的作用 ,血管紧张素转化酶抑制药 (ＡＣＥＩ)已广泛应用于高血压的临床治疗。但主要的不足之处是 :①不能完全阻断血管紧…     

2002~2004年杭州地区抗高血压药用药分析

目的考察杭州地区2002~2004年抗高血压药使用情况及趋势。方法采用购药金额排序法,对临床常用的几类抗高血压药在杭州地区的使用情况进行分析。结果近三年来,杭州地区抗高血压药的用药金额呈上升趋势,用量前十位的抗高血压药物金额在抗高血压药总金额中的比例也逐年增加;其中2004年钙通道拮抗剂的用药金额占总金额的50%左右,血管紧张素转换酶抑制药约占16%,血管紧张素Ⅱ受体拮抗药约占19%。结论钙通道阻滞药、血管紧张素转换酶抑制药和血管紧张素Ⅱ受体拮抗药成为临床用药金额最大的3类抗高血压药,血管紧张素Ⅱ受体拮抗药的临床使用正日益广泛。     

原发性高血压治疗的药物选择

对肾素－血管紧张素系统在原发性高血压发病的作用进行简略阐述,介绍血管紧张素Ⅱ家族和最近合成的血管紧张素Ⅱ非肽同类物,由此将血管紧张素Ⅱ受体分为AT1和AT2两亚型。血管紧张素AT1受体拮抗剂,如氯沙坦（Losartan）等在治疗原发性高血压、充血性、力衰竭、保护肾功能、预防脑卒中和脑血管疾病方面,都有很好作用,而且耐受性好,不良反应少。其效能甚至超过血管紧张素转换酶抑制剂（如卡托普利）。     

血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂在慢性心力衰竭治疗中的应用

心力衰竭是多种心脏病的最终死亡原因,阻断肾素-血管紧张素-醛固酮系统(renin angiotensin aldosterone system,RAAS)是减慢心力衰竭病变进展的主要策略。血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitors,ACEI)和血管紧张素受体拮抗剂(angiotensin receptor blockers,ARB)是目前最常用的阻断RAAS的药物。本文对慢性心力衰竭评估,以及ACEI和ARB在慢性心力衰竭治疗中的应用进行综述。     

Angiotensin II Type 1 receptor antagonists in chronic heart failure

Angiotensin II Type 1 receptor antagonists share most but not all of their pharmacological actions with angiotensin-converting enzyme inhibitors. The latter belong to standard heart failure therapy, with proven benefit in terms of morbidity and mortality. Promising data have been provided for angiotensin II Type 1 receptor antagonists in experimental models of heart failure. In patients with hypertension and those with diabetic nephropathy, favourable results have been observed with regards to blood pressure control, reversibility of structural changes or prevention of progression of disease. The currently available clinical trials in heart failure patients with angiotensin II Type 1 receptor antagonists suggest that they may be equivalent to angiotensin-converting enzyme inhibitors, but superiority has not been proven. There is no doubt about their effectiveness with regards to symptoms; however, their effect on hospitalisation and mortality is not unequivocally demonstrated. Further trials are warranted, particularly to define their role in comparison with and in addition to angiotensin-converting enzyme inhibitors and to further characterise heart failure patient populations who derive benefit from angiotensin II Type 1 receptor blockers above and beyond angiotensin-converting enzyme inhibitors, β-blockers and spironolactone.     

某院2010～2012年抗高血压药的应用分析

目的了解我院抗高血压药的利用情况与趋势。方法对我院2010至2012年抗高血压药的种类、销售金额、用药频度等进行统计、分析。结果我院抗高血压药的销售金额呈逐年上升趋势。钙通道阻滞剂在三年中始终排在销售金额第一位,其次是血管紧张素Ⅱ受体阻滞剂和血管紧张素转换酶抑制剂。结论我院抗高血压药以钙通道阻滞剂、血管紧张素Ⅱ受体阻滞剂、血管紧张素转换酶抑制剂、β受体阻滞剂和利尿药为主,与国内外用药基本相符。钙通道阻滞剂、血管紧张素Ⅱ受体阻滞剂、血管紧张素转换酶抑制剂有广阔的用药前景。     

Valsartan Effective for Malignant Hypertension after Aortic Dissection with Renal Artery Involvement

When aortic dissections extend to the renal arteries, reductions in renal blood flow can cause marked increases in renin production. The resultant rise in angiotensin II can lead to difficult‐to‐control blood pressure, despite normal postdissection antihypertensive agents. We highlight a case of a postdissection patient with malignant hypertension refractory to eight different enteral antihypertensives. Angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers had been held due to postoperative acute kidney injury. A single dose of valsartan, administered on day 12, produced a marked drop in blood pressure, alleviation of encephalopathy, and allowed for cancellation of a planned tracheostomy. A serum renin level was found to be 50 times the normal upper limit. In patients with aortic dissection and renal artery involvement, angiotensin‐modifying agents may warrant earlier administration to combat this unique cause of hypertension.     

Hypotension induced by inhibition of angiotensin-converting enzyme in pentobarbital-anesthetized dogs.

The mechanism of the hypotensive response produced by inhibition of the angiotensin converting enzyme was studied in pentobarbital anesthetized dogs. A recently developed potent inhibitor of the converting enzyme, SQ 14,225 (D-3-mercapto-2-methyl propanoyl-L-proline), administered i.v. to intact dogs resulted in a rapid marked decrease in blood pressure. In nephrectomized dogs, SQ 14,225 retained significant hypotensive activity, although the absolute magnitude of the decreases in blood pressure were less than had been observed in dogs with intact kidneys. SQ 14,225 also lowered blood pressure when administered to intact dogs in which angiotensin II receptors had been blocked with the receptor antagonist Sar1,Ala8-angiotensin II. This apparent ability of SQ 14,225 to decrease blood pressure in the absence of a functional renin angiotensin system was shared by a structurally dissimilar, nonapeptide, angiotensin converting enzyme inhibitor, SQ 20,881 (Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro). SQ 20,881 also produced significant decreases in blood pressure in nephrectomized dogs. These findings indicate that the angiotensin converting enzyme inhibitors, SQ 14,225 and SQ 20,881 may lower blood pressure in anesthetized normotensive dogs via a mechanism unrelated to either the renin angiotensin system or the renal kinin system.     

New advances in the pharmacological management of chronic heart failure

The management of heart failure has evolved in parallel with advances in the understanding of the disease process. Inotropes and diuretics are used to combat pump failure and fluid overload. While no convincing data has emerged regarding the long-term safety of inotropes, new exciting data concerning the role of diuretics, especially aldactone, has led to a renewed interest in this class of drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were noted to not only affect symptomatology but also decrease mortality by interfering with the renin-angiotensin-aldosterone system. Recent research has focused on more complete blockade of the renin-angiotensin system than that achieved with ACE inhibitors alone with the addition of direct angiotensin II receptor blockers. This new class of drugs may become not only a reasonable alternative to ACE inhibitors in patients intolerant of the drug but also a possible addition to ACE inhibitors in the battle to prevent progression of remodelling and disease. β-blockers are the most exciting new class of drugs used to combat heart failure. They appear not only to combat the remodelling process that occurs in the progression of disease but also other pathological events such as apoptosis and cellular oxidation. New medical therapies currently being investigated include novel agents such as endothelin antagonists, natriuretic peptides, vasopressin antagonists and anticytokine agents - all part of a new era in drug management of heart failure that has evolved with continued advances in the understanding of chronic heart failure (CHF).     

Vascular benefits of angiotensin receptor blockers

There is convincing evidence that angiotensin II, through activation of the angiotensin II type 1 (AT1) receptor, is involved in the atherosclerotic process. Similarly, angiotensin receptor blockers decrease vascular inflammation, hypertrophy and thrombosis, which are the key components of the progression of atherosclerosis. In addition, in several animal models, angiotensin receptor blockade was able to inhibit atherosclerosis. However, the effects of angiotensin receptor blockers on clinical outcome in cardiovascular patients remains to be established. Contradictory results have been found on the reduction of the risk on myocardial infarctions and in-stent restenosis, although there is solid evidence for cerebroprotective effects of these receptor blockers. These differences may be related to the role of the AT2 receptor. This review discusses the role of angiotensin II and angiotensin receptor blockers in the atherosclerotic process and its translation into clinical practice.     

SAR1-LEU8-ANGIOTENSIN II REVERSES THE EFFECTS OF CAPTOPRIL ON RENAL FUNCTION IN RATS

In Inactin-anaesthetized rats inhibition of angiotensin converting enzyme by captopril resulted in a small decrease in mean arterial blood pressure accompanied by increases in the rates of glomerular filtration, water and electrolyte excretion. Infusion (100 pmol/min) of sar1-leu8-angiotensin II (sar1-leu8-AII) during continuing converting enzyme blockade reversed these changes in renal function but had no effect on arterial blood pressure. The data indicate that sar1-leu8-AII has partial agonist activity in the kidney although it acts as an antagonist of AII in the systemic circulation. This supports the proposal that angiotensin receptors within the kidney differ from those in the peripheral circulation.