Relationship between plasma concentrations and pharmacological effects of labetalol

Summary In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the administered dose of labetalol. Labetalol was rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occurred two hours after oral administration. There was a linear correlation (r=0.84) between the logarithm of the plasma concentration and the maximum inhibition of exercise tachycardia at two hours. After intravenous administration there was an immediate reduction in systolic and diastolic blood pressure with a concomitant small increase in heart rate. There was a rapid decline in the associated plasma concentration but the pharmacological effects were maintained in excess of two hours. Our findings are consistent with those of others who have studied the relationship between pharmacological events and plasma concentrations after single doses of other adrenoceptor blocking drugs.     

Adrenoceptor blocking hemodynamic and coronary effects of YM-09538, a new combined alpha- and beta-adrenoceptor blocking drug, in anesthetized dogs

In anesthetized dogs. YM-09538, a new sulfonamide-substituted phenylethylamine, competitively antagonised the phenylephrine-induced vasopressor response with a DR10 of 0.50 mg/kg i.v. and the isoproterenol-induced positive chronotropic response with a DR10 of 0.66 mg/kg i.v., indicating that YM-09538 blocks both alpha 1- and beta 1-adrenoceptors and almost to the same extent. YM-09538 was 4 times more potent than phentolamine in blocking alpha 1-adrenoceptors and 3 times less potent than propranolol in blocking beta 1-adrenoceptors. YM-09538 non-selectively blocked cardiac beta 1- and vascular beta 2-receptors and was devoid of intrinsic beta-sympathomimetic and local anesthetic activities. In anesthetized closed-chest dogs, YM-09538 resembled propranolol in reducing heart rate, cardiac output, max. dLVP/dt and left ventricular cardiac work but differed from propranolol in decreasing total peripheral resistance, in increasing femoral blood flow, in causing larger falls in arterial blood pressure and in decreasing pulmonary arterial pressure. In anesthetized open-chest dogs, YM-09538 reduced heart rate, myocardial contractile force and arterial blood pressure. In non-ischemic myocardium, transmural flow and coronary vascular resistance were respectively strongly increased and decreased and the endo/epi flow ratio was slightly but not significantly reduced. In ischemic myocardium, YM-09538 also increased transmural flow and since endocardial and epicardial flows were augmented to the same extent, the endo/epi flow ratio remained unchanged. All these hemodynamic and coronary effects of YM-09538 can be accounted for the drug's combined alpha- and beta-adrenoceptors blocking properties.     

拉贝洛尔、酚妥拉明联合硫酸镁治疗 早发型重度子痫前期的疗效

〔摘 要〕 目的：观察拉贝洛尔、酚妥拉明联合硫酸镁治疗早发型重度子痫前期（EOSP）的疗效。 方法：选取泉州市中 医院 2017 年 12 月至 2020 年 12 月期间接收的 82 例 EOSP 患者,基于患者意愿给予不同治疗方案分为对照组与观察组,各 41 例。其中对照组给予酚妥拉明联合硫酸镁治疗,观察组在对照组的基础上给予拉贝洛尔治疗,观察比较两组患者分娩结 局以及治疗前后血压状况〔舒张压（DBP）、收缩压（SBP）〕、凝血指标〔纤维蛋白原（FIB）、D– 二聚体（D–D）、凝 血活酶时间（TT）、凝血酶原时间（PT）〕。 结果：治疗前两组患者的 DBP、SBP 比较,差异无统计学意义（P ＞ 0.05）; 治疗后观察组患者的 SBP、DBP 低于对照组,差异具有统计学意义（P ＜ 0.05）。治疗前两组患者的 PT、TT、FIB、D–D 比较,差异无统计学意义（P ＞ 0.05）;治疗后观察组患者的 PT、TT 高于对照组,FIB、D–D 低于对照组,差异具有统计 学意义（P ＜ 0.05）。观察组的新生儿窒息率、产后出血率、剖宫产率均低于对照组,差异具有统计学意义（P ＜ 0.05）。 结论：拉贝洛尔、酚妥拉明联合硫酸镁治疗 EOSP 患者时,可下调血压,改善凝血功能,减少不良分娩结局发生率。     

参芎注射液联合硫酸镁和拉贝洛尔治疗妊娠期高血压的临床疗效观察

目的:探究参芎注射液联合硫酸镁和拉贝洛尔治疗妊娠期高血压的临床疗效及其相关机制。方法:选取2017年6月至2018年6月武警北京总队医院产科收治的妊娠期高血压患者156例作为研究对象,按随机数字表法随机分为对照组和观察组,每组78例。对照组给予常规治疗+硫酸镁+拉贝洛尔,观察组在对照组治疗的基础上加用参芎注射液,连续治疗2周。观察2组患者的临床疗效及其血管内皮功能指标(PGI2、TXA2、ET-1、NO)、氧化应激指标(LPO、GSH-PX、SOD、MDA)、血清炎性反应因子(IL-6、TNF-α、CRP)、血压水平变化情况。结果:治疗后,2组患者ET-1、TXA2、LPO、MDA水平明显降低,PGI2、NO、GSH-PX、SOD水平明显升高,观察组上述指标变化更明显,差异有统计学意义(P<0.05)。治疗后,2组患者IL-6、TNF-α、CRP、收缩压、舒张压、S/D比值、阻力指数水平明显降低,观察组上述指标变化更明显,差异有统计学意义(P<0.05)。观察组治疗后的总有效率(93.59%)明显高于对照组(80.77%),差异有统计学意义(P<0.05)。结论:参芎注射液联合硫酸镁、拉贝洛尔治疗妊娠期高血压病可通过抗炎、抑制氧化应激反应、保护血管内皮功能,提高妊娠期高血压患者的临床治疗效果。     

硫酸镁联合拉贝洛尔治疗重度妊娠高血压综合征临床疗效观察

目的探讨硫酸镁联合拉贝洛尔治疗重度妊娠高血压综合征(PIH)的临床疗效。方法选择笔者所在医院2009年1月～2011年2月收治的重度PIH孕妇86例,随机分为对照组和治疗组各43例,对照组给予硫酸镁常规解痉降压,观察组则在硫酸镁基础上,应用拉贝洛尔针加入5%葡萄糖注射液中静脉点滴。结果两组患者治疗后血压控制有效率观察组明显优于对照组,差异有统计学意义(P<0.05);并发症发生率上,两组患者在宫颈裂伤、子宫过度刺激、产后出血的发生率均有显著性差异(P<0.05)。结论硫酸镁联合拉贝洛尔治疗重度PIH效果确切,能有效降低患者平均动脉血压,改善母婴结局,具有广阔的临床应用前景。     

硫酸镁联合拉贝洛尔治疗妊娠期高血压疾病临床疗效观察

目的探讨硫酸镁联合拉贝洛尔治疗妊娠期高血压疾病的临床疗效。方法选择2009年1月至2010年12月收治的妊娠期高血压疾病孕妇86例,随机分为对照组和治疗组各43例。对照组给予硫酸镁常规解痉降压,观察组则在硫酸镁基础上,应用拉贝洛尔针加入5%葡萄糖注射液中静脉点滴。结果两组患者治疗后血压控制效果观察组明显优于对照组,差异有统计学意义(P<0.05);两组患者宫颈裂伤、子宫过度刺激、产后出血等的发生率均有显著性差异(P<0.05)。结论硫酸镁联合拉贝洛尔治疗妊娠期高血压疾病效果确切,能有效降低患者平均动脉血压,具有广阔的临床应用前景。     

Changes in fetal and maternal Doppler parameters observed during acute severe hypertension treatment with hydralazine or labetalol: a randomized controlled trial

We evaluated 16 pregnant women with gestational age between 20 and 32 weeks in acute severe hypertension which were randomly allocated to receive either hydralazine or labetalol. Blood pressure and Doppler ultrasound parameters from maternal uterine and fetal middle cerebral and umbilical arteries were assessed during acute severe hypertension and after treatment. A significant reduction in systolic and diastolic blood pressure was observed in both groups. A significant change in Doppler parameters was observed only in pregnant women who received hydralazine: an increase in uterine arteries resistance index. We concluded that both drugs were highly effective in reducing blood pressure in these women. Despite the observed increase in resistance index of uterine arteries associated with hydralazine, the use of hydralazine and labetalol were not related to any significant changes in fetal Doppler, which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy. (E-mail: wpmartins@gmail.com)     

硫酸镁联合拉贝洛尔治疗78例孕妇妊娠期高血压的随机对照研究

目的：研究硫酸镁联合拉贝洛尔治疗妊娠期高血压对孕妇血压、新生儿Apgar评分的影响,并探讨其作用机制。方法：选取2012年3月至2013年12月在我院妇产科住院的156例妊娠期高血压孕妇,采用随机数字表法分为试验组和对照组各78例。试验组给予硫酸镁联合拉贝洛尔治疗,对照组仅给予同等剂量的硫酸镁治疗。用药结束后比较两组孕妇血压的下降情况,并比较两组新生儿Apgar评分情况。结果：治疗前两组孕妇收缩压和舒张压比较差异均无统计学意义（P均〉0.05）;治疗后试验组孕妇的收缩压和舒张压分别下降了19.7%和18.4%（P均〈0.01）,而对照组分别下降了10.0%和12.3%（P均〈0.01）,且试验组孕妇的收缩压和舒张压比对照组下降更明显（P均〈0.01）。试验组新生儿Apgar评分≥7分者67例（85.90%）,平均评分（9.42±0.57）分;对照组新生儿评分≥7分者54例（69.23%）,平均评分（8.36±0.49）分,两组比较差异均有统计学意义（P均〈0.05）。结论：硫酸镁联合拉贝洛尔治疗妊娠期高血压,能有效降低孕妇血压（包括收缩压和舒张压）,有利于提高妊娠期高血压孕妇的新生儿的Apgar评分,其远期安全性有待进一步多中心大样本的研究及对不良反应的长期监测。     

Labetalol (‘Trandate’) in hypertension: A multicentre study in general practice

Summary

A study was carried out in 1286 hypertensive patients seen in general practice to evaluate the effectiveness of labetalol given for periods of up to 24 months. Initial dosage was 300?mg per day. The results showed that blood pressure was readily controlled and maintained by labetalol alone in the majority of patients. Pulse rate, vision andfundi were unchanged. There was little difference between the supine and upright blood pressures, confirming the clinical finding that postural hypotension was not a problem. The incidence of side-effects leading to withdrawal was small (7.2%), most side-effects being minor and transient. No drug interactions with concomitant therapy were apparent and the incidence of bronchospasm was very low. The incidence of myocardial infarction and cerebrovascular accident in the population studied was lower than expected.