抗高血压药物治疗依从性对高血压患者首发脑梗死的价值分析

目的抗高血压药物治疗依从性对高血压患者首发脑梗死的价值分析。方法针对高血压药物治疗的依从性,高血压患者因药物的依从性导致的突发脑梗死,采用临床治疗方法对于高血压患者进行治疗。结果经过临床治疗高血压患者,未出现并发症死亡,对于药物治疗高血压患者形成药物依赖性,导致脑梗死。结论根据高血压患者的自身情况制定药物治疗或是临床治疗。     

临床药师对1例高血压患者治疗用药的分析及给药方案调整

目的：总结临床药师参与高血压治疗用药的经验,提高其在治疗方案中调整药物的能力。方法：以临床药师参与1例高血压患者药物治疗为例,通过其对药物的选择和调整,协助医生拟定最佳治疗方案。结果：该例高血压患者临床症状明显改善,血压保持稳定。结论：临床药师参与高血压患者的药物治疗,可以协助临床医护人员提高药物治疗水平,促进临床合理用药。     

原发性高血压患者的临床疗效观察

目的观察原发性高血压患者治疗的临床疗效,总结临床防治原发性高血压的经验。方法对93例原发性高血压患者的临床治疗资料、治疗情况进行回顾性分析,对原发性高血压患者进行药物治疗与非药物治疗的综合措施治疗。结果患者经过治疗后,显效60例,有效24例,无效9例,总有效率90.32%。结论药物治疗、非药物干预是防治原发性高血压的主要方法,早诊断、早治疗对降低心脑血管疾病等并发症的发生率,减少病死率具有重大的积极意义。     

抗高血压药物的研究进展

目的为临床使用高血压病治疗药物提供参考。方法查阅近年来文献综合分析有关药物治疗高血压的进展资料。结果目前临床上治疗高血压有多种药物．并取得一定进展。结论高血压的药物治疗必须针对高血压不同类型综合进行,并通过循征医学不断探讨新的药物和治疗方法。     

轻度高血压的药物治疗

脑、心血管病变与血压升高有极密切的关系,利用抗高血压药的治疗来降低血压,减少脑、心、血管疾病的发病和死亡,迄今已有40余年的历史。药物治疗恶性高血压、重度及中重度高血压的临床重要性已为人们公认,而在轻度高血压的药物治疗方面,则存在较多的争议。本文就轻度高血压药物治疗的指征、药物治疗的目标及临床上常用于轻度高血压治疗的药物进行阐述和讨论。     

噻嗪类利尿药在高血压患者中的应用

利尿药是治疗高血压的重要药物,临床使用已经>50年,但目前临床使用中仍存在许多争议与问题。本文对噻嗪类利尿药治疗高血压的作用机制、药物分型与药代动力学、治疗高血压的循证证据、噻嗪类利尿药治疗高血压的临床地位和指南与共识推荐等进行综述。     

高血压治疗的研究进展

高血压是一种慢性病,也是一种不断进展的疾病,高血压的治疗贯穿在临床早期、疾病发展以及疾病终末期。高血压的治疗包括药物治疗和非药物治疗。     

联合抗高血压药物治疗应成为普遍适用临床策略

2007年<欧洲高血压治疗指南>再次强调了高血压患者必须降压达标.然而,目前临床上单用搞高血压药物治疗所获得降压达标率不足50%.已有的临床研究资料显示,超过60%的高血压患者需要至少两种以上搞高血压药物联合治疗才能使高血压控制达标.因此,联合搞高血压药物治疗应成为普遍适用的初始冶疗临床策略.     

高血压常见药物与治疗方法的研究进展

高血压是一种比较常见的心血管疾病,如果得不到及时治疗会给患者带来很大的痛苦,高血压的发病率逐年上升,而关于抗高血压药物的研究以及高血压治疗方法的研究也在不断的探索与实践中得到发展.很多学者都加大了对利尿剂、β受体阻滞剂、钙离子拮抗剂、血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体阻滞剂以及肾素抑制剂等治疗高血压药物的研究,越来越多的药物以及治疗方法被广泛应用于高血压的临床治疗上,并且取得了很好的疗效.主要介绍了高血压常见药物与治疗方法的研究进展,以供临床参考.     

浅谈抗高血压药物的选用

目的：通过对近年来抗高血压药物临床联合应用及某些特殊类型高血压或并发症选用药物原则的阐述,探讨抗高血压药物在临床上的选用。方法：通过查阅近年来文献资料对抗高血压药物的临床使用介绍,整理介绍抗高血压药物在某些特殊类型高血压中的合理选用和联合应用。结果：抗高血压药物的合理选用对于某些特殊类型高血压的有效治疗有积极的作用。     

Drug evaluation of clevidipine for acute hypertension

Background: Clevidipine is an investigational agent undergoing late-stage clinical development to evaluate its potential as a novel short-acting intravenous agent for treating acute hypertension, either in hypertensive emergencies encountered in the emergency department and intensive care units, or in the perioperative period. Method: Clevidipine has been evaluated in four Phase I studies, nine Phase II studies and six Phase III clinical studies. The patient populations studied include healthy volunteers, patients with essential hypertension, patients undergoing cardiac surgery, and patients presenting to the emergency department with hypertensive emergencies. Studies providing comparative data of clevidipine versus nitroglycerin, nicardipine or sodium nitroprusside are also available. Objective: This article reviews the results of clinical studies evaluating the pharmacological properties, clinical effects and safety profiles of clevidipine in various patient populations. Results/conclusion: Clevidipine is an effective agent for reducing acute elevation in blood pressure in various settings, including hypertensive emergencies and perioperative hypertension with a good safety profile.     

Clevidipine butyrate: a promising new drug for the management of acute hypertension

Clevidipine butyrate is an ultrashort-acting intravenous dihydropyridine calcium-channel blocker that has been approved by the FDA for the reduction of blood pressure when oral therapy is not feasible. Hypertension is a global disease that affects more than 1 billion people worldwide and 75 million people in the USA. There are multiple agents available for the management of hypertension. The acute setting is where the challenge arises for developing new agents that not only decrease, but more importantly, optimally control blood pressure. Many drugs lower blood pressure; however, only a few have the capacity to precisely control hypertension in the acute phase. Clevidipine has unique pharmacodynamic and pharmacokinetic properties that enable the fast, safe and adequate reduction of blood pressure in hypertensive emergencies, with unique precision necessary to maintain the target blood pressure range. Its use in different clinical settings has been evaluated in several Phase I, II and III clinical studies. It is easily administered and titrated with minimal side effects, achieves fast control with low doses, is highly successful as monotherapy and allows excellent transition to oral medication. Thus, clevidipine is a promising new agent for the management of acute hypertension in a variety of clinical settings.     

Clevidipine : a state-of-the-art antihypertensive drug under the scope

INTRODUCTION: Clevidipine butyrate is the first intravenous antihypertensive drug to be approved by the FDA over the last decade. This medication is approved for use in the USA, Australia and New Zealand, but is still pending for approval in Europe. It is a new agent that might change the current management for severe acute hypertension in the critical care, emergency and perioperative areas. AREAS COVERED: This systematic review summarizes the pharmacological and clinical characteristics of this third-generation dihydropyridine intravenous calcium channel blocker, and was done using the literature available from the first publication in 1999 up until now, including the pivotal trials that led to its approval. EXPERT OPINION: This agent is arterially selective, has an ultrashort half-life, with no CYP-mediated interactions with other medications and is easily titratable. These characteristics place it in a unique category compared with other commonly used antihypertensives. Clevidipine butyrate reaches target systolic blood pressure in more than 90% of patients, within 30 min. It has a low incidence of adverse reactions and is generally well tolerated. The main goal of this review is to provide healthcare providers with a comprehensive appraisal of this promising medication.     

Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81.

Clevidipine is a short-acting dihydropyridine calcium channel antagonist under development for treatment of perioperative hypertension. Patients treated with clevidipine are likely to be comedicated. Therefore, the potential for clevidipine and its major metabolite H152/81 to elicit drug interactions by induction or inhibition of cytochrome P450 was investigated. Induction of CYP1A2, CYP2C9, and CYP3A4 was examined in primary human hepatocytes treated with clevidipine at 1, 10, and 100 microM. Clevidipine was found to be an inducer of CYP3A4, but not of CYP1A2 or CYP2C9, at the 10 microM and 100 microM concentrations of clevidipine tested. Induction response for CYP3A4 to 100 microM clevidipine was approximately 20% of that of the positive control inducer rifampicin. The response of H152/81 was similar. Using cDNA-expressed enzymes, clevidipine inhibited CYP2C9, CYP2C19, and CYP3A4 activities with IC(50) values below 10 microM, whereas CYP1A2, CYP2D6, and CYP2E1 activities were not substantially inhibited (IC(50) values >70 microM). The K(i) values for CYP2C9 and CYP2C19 were 1.7 and 3.3 microM, respectively, and those for CYP3A4 were 8.3 and 2.9 microM, using two substrates, testosterone and midazolam, respectively. These values are at least 10 times higher than the highest clevidipine concentration typically seen in the clinic. Little or no inhibition by H152/81 was found for the enzyme activities mentioned above (IC(50) values >or= 69 microM). The present study demonstrates that it is highly unlikely for clevidipine or its major metabolite to cause cytochrome P450-related drug interactions when used in the dose range required to manage hypertension in humans.     

New therapeutic perspectives with clevidipine: an ultra-short-acting intravenous Ca2+ channel blocker

Intravenous antihypertensive agents are used in clinical situations in which the immediate, precise control of blood pressure is a clinical necessity. Clevidipine is a new, vascular-selective, dihyrdopyridine Ca(2+) channel blocker, which exerts its hemodynamic effects through selective arterial vasodilation without effects on the venous circulation. Because it is a potent coronary vasodilator, reduction in mean arterial pressure does not impair coronary perfusion. The unique properties of clevidipine include an ultra-short pharmacodynamic duration of action and a half-life after intravenous administration of approximately 2 min, resulting in very rapid onset and offset of antihypertensive effects. In clinical trials performed in patients undergoing cardiac surgery, clevidipine proved superior to nitroprusside and nitroglycerin in maintaining blood pressure within predetermined ranges during the perioperative period. Its safety profile is comparable to nicardipine and nitroglycerin and, in one study, was associated with reduced 30-day mortality compared with nitroprusside. Clevidipine constitutes a useful addition to available intravenous agents and could prove particularly valuable in circumstances that require the ability to rapidly terminate the blood pressure-lowering effects of administered agents.     

Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control

Clevidipine is an ultrashort-acting vasoselective calcium antagonist under development for short-term intravenous control of blood pressure. Studies in animals, healthy volunteers and patients have demonstrated the vascular selectivity and rapid onset and offset of antihypertensive action of clevidipine, a synthetic 1,4-dihydropyridine that inhibits L-type calcium channels. Clevidipine has a high clearance (0.05 L/min/kg) and is rapidly hydrolyzed to inactive metabolites by esterases in arterial blood. Its half-life in patients undergoing cardiac surgery is less than one min. Unlike sodium nitroprusside, a drug commonly used for the short-term control of blood pressure, which dilates both arterioles and veins, clevidipine reduces blood pressure through a selective effect on arterioles. As documented in animals and in cardiac surgical patients, clevidipine reduces peripheral resistance without any undesirable effect on cardiac filling pressure. It increases stroke volume and cardiac output. In anesthetized patients undergoing cardiac surgery clevidipine, unlike sodium nitroprusside, does not increase heart rate. In addition of having a favorable hemodynamic profile, suitable for rapid control of blood pressure, clevidipine protects against ischemia/reperfusion injuries, which are not uncommon during major surgery. In anesthetized pigs, clevidipine reduced infarct size after 45 min-long myocardial ischemia by 40%. In rats, renal function and splanchnic blood flow were better maintained when blood pressure was reduced with clevidipine than with sodium nitroprusside. Clevidipine was well tolerated in Phases I and II of clinical trials that included more than 300 individuals/patients. Since there are no known compounds with similar pharmacodynamic and pharmacokinetic properties in clinical development, it is anticipated that clevidipine, a compound tailored to the needs of anesthesiologists, has the potential to become a drug of choice for controlling blood pressure during surgical procedures.     

New therapeutic perspectives with clevidipine: an ultra-short-acting intravenous Ca2+ channel blocker

Intravenous antihypertensive agents are used in clinical situations in which the immediate, precise control of blood pressure is a clinical necessity. Clevidipine is a new, vascular-selective, dihyrdopyridine Ca²⁺ channel blocker, which exerts its hemodynamic effects through selective arterial vasodilation without effects on the venous circulation. Because it is a potent coronary vasodilator, reduction in mean arterial pressure does not impair coronary perfusion. The unique properties of clevidipine include an ultra-short pharmacodynamic duration of action and a half-life after intravenous administration of ～ 2 min, resulting in very rapid onset and offset of antihypertensive effects. In clinical trials performed in patients undergoing cardiac surgery, clevidipine proved superior to nitroprusside and nitroglycerin in maintaining blood pressure within predetermined ranges during the perioperative period. Its safety profile is comparable to nicardipine and nitroglycerin and, in one study, was associated with reduced 30-day mortality compared with nitroprusside. Clevidipine constitutes a useful addition to available intravenous agents and could prove particularly valuable in circumstances that require the ability to rapidly terminate the blood pressure-lowering effects of administered agents.     

Pharmacokinetics, pharmacodynamics, and safety of clevidipine after prolonged continuous infusion in subjects with mild to moderate essential hypertension

Purpose

Clevidipine is a rapidly-acting intravenous dihydropyridine antihypertensive acting via calcium channel blockade. This was a randomized, single-blind, parallel-design study of a 72-h continuous clevidipine infusion.

Method

Doses of 2, 4, 8, or 16.0?mg/h or placebo were evaluated in 61 subjects with mild to moderate essential hypertension. IV clevidipine or placebo was initiated at 2.0?mg/h and force-titrated in doubling increments every 3?min to target dose, then maintained for 72?h. Blood pressure and heart rate were measured during infusion, and for 4, 6 and 8?h after termination of infusion, although oral therapy could be restarted at 4?h. Clevidipine blood levels were obtained during infusion and for 1?hour after termination.

Results

Rapid onset of drug effect occurred at all clevidipine dose levels, with consistent pharmacokinetics and rapid offset after 72-h infusion. No evidence of tolerance to the clevidipine drug effect was observed at any dose level over the 72-h infusion. No evidence of rebound hypertension was found for either 4 or 6?h after termination of the clevidipine infusion. At 8?h following cessation of clevidipine, blood pressure was not significantly higher than at baseline. Placebo-treated subjects had blood pressures lower than baseline at 8?h following infusion termination; hence, placebo-adjusted blood pressures tended to be slightly higher than baseline.

Conclusion

This study supports the use of up to 72?h of IV clevidipine therapy for the management of blood pressure, with consistent pharmacokinetic/pharmacodynamic characteristics and context insensitive half-life across the dose ranges evaluated.     

氯维地平的合成

2,3-二氯苯甲醛、乙酰乙酸甲酯和浓氨水经闭环缩合、选择性水解得4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸单甲酯,再与正丁酸氯甲酯反应制得抗高血压药氯维地平,总收率约44%.     

Time-dependent cardioprotection with calcium antagonism and experimental studies with clevidipine in ischemic-reperfused pig hearts: part I

Clevidipine is a new ultrashort-acting dihydropyridine calcium antagonist developed for blood pressure regulation during cardiac surgery. When given locally to the ischemic and reperfused myocardium, clevidipine exerts a cardioprotective effect that varies depending on the timing of administration during ischemia. The current study explored the pharmacokinetics of clevidipine when administered locally into the coronary circulation. Pentobarbital-anesthetized pigs were randomly divided into four groups, of which three were subjected to myocardial ischemia through ligation of the left anterior descending coronary artery (LAD) for 15, 35, or 45 minutes (n = 4 in each group). The fourth group (n = 4) was not subjected to LAD occlusion and acted as nonischemic controls. Clevidipine (0.3 nmol/kg per minute) was infused over a period of 5 minutes through a catheter distal to the LAD ligation in the ischemic pigs, or at the corresponding site of the nonligated LAD in the nonischemic pigs. Following release of the LAD ligation, or in the nonligated group following the drug infusion, the pigs were subjected to 60 minutes of reperfusion. Simultaneous blood samples were obtained for analysis of clevidipine from the femoral artery and the coronary vein during reperfusion and during drug infusion in the nonischemic pigs. Blood samples for estimating the in vitro hydrolysis rate both in whole blood and in plasma were also obtained. In nonischemic hearts, clevidipine reached a steady state level in the coronary venous blood of about 30 nM during the infusion. The concentration declined almost to the detection limit (1 nM) within 3 minutes of the end of infusion. The mean blood clearance of clevidipine was calculated to be 0.17 l/min per kilogram, and the estimated half-life was 0.5 minute. In animals subjected to different periods of ischemia, very low levels of clevidipine were detected in the coronary venous blood only during the first 2 minutes of reperfusion. There were no detectable levels in the arterial blood at any time. Blood concentration profiles of clevidipine did not differ with the length of myocardial ischemia. The in vitro half-life in pig blood was 13 minutes, and the corresponding half-life in plasma was 111 minutes. At a dose known to exert cardioprotection when given as an intracoronary injection, the systemic concentration of clevidipine does not reach pharmacologically active levels. Clevidipine has an ultrashort blood half-life, and ischemic duration of up to 45 minutes does not seem to change the cardiac metabolism of this drug. Thus, it represents a pharmacological tool well suited for the study of time windows in cardioprotection. Moreover, considering the possibility of exerting myocardioprotection without any systemic effects, it could be an interesting compound to test in a clinical setting.