美托洛尔用于老年COPD合并冠心病史治疗的临床疗效观察

目的:探讨美托洛尔(β1受体阻滞剂)用于老年COPD合并冠心病史治疗的临床疗效。方法:选取2018年6月—2019年6月在我院接受治疗的60岁以上(包括60岁)COPD合并冠心病史老年患者,分为对照组与观察组。对照组给予接受布地奈德福莫特罗粉吸入剂治疗,观察组在使用布地奈德福莫特罗粉吸入剂治疗的基础上口服琥珀酸美托洛尔缓释片治疗,观察对比两组治疗效果。结果:观察组临床治疗效果优于对照组,观察组住院时长以及并发症的发生率低于对照组(P<0.05),差异具有统计学意义。结论:老年COPD合并冠心病史接受美托洛尔治疗,可有效缩短住院时长、用药效果明显、有效提升用药安全性,值得临床推广。     

静脉注射美托洛尔、地尔硫卓治疗快速心房纤颤的临床疗效观察

目的:观察美托洛尔注射液和地尔硫卓注射液治疗快速房颤的有效性和安全性。方法:105例符合入选标准的快速房颤患者被随机分为3组,美托洛尔组39例:5mg美托洛尔缓慢静脉注射,观察5min,如无效重复一次,连续用药3次,总量15mg;地尔硫卓35例:地尔硫卓15mg稀释后静脉注射,观察15min,如无效重复1次,继以15mg/h维持。西地兰组31例:西地兰0.2～0.4mg稀释后静脉注射,观察10min,如无效追加0.2～0.4mg,连续用药3次;总量0.6～1.0mg。记录用药前、后心室率和血压变化,并比较在各观察时间点上的有效率。结果:与西地兰相比,美托洛尔和地尔硫卓起效更快[(36.9±11.6)min∶(8.2±4.5)min∶(9.1±3.8)min,P<0.05],心室率下降幅度更明显(25.22%∶33.32%∶37.50%,P<0.05),治疗有效率更高(71.0%∶89.7%∶91.4%,P<0.05)。而美托洛尔组和地尔硫卓组之间无显著性差异。三组均无严重不良反应发生。结论:美托洛尔注射液和地尔硫卓注射液均能快速、安全、有效控制快速房颤的心室率。     

美托洛尔预防老年围拔管期心血管反应的临床观察

目的探讨美托洛尔用于预防老年患者围拔管期心血管反应的方法。方法40例全身麻醉行择期手术的老年患者随机分为A组20例,B组20例,A组围拔管期分次静注美托洛尔0.06~0.1 m g/kg,B组以生理盐水分次静注。观察手术结束时、拔管前5分钟、拔管时、拔管后5、20分钟的心率(HR)、收缩压(SBP)、舒张压(DBP)及心率收缩压乘积(RPP)的变化。结果A组拔管时、拔管后5、20分钟的HR、RPP与手术结束时比较,差异无统计学意义,用药后最慢心率53次/m in,围拔管期血压维持平稳,RPP保持在较低值;B组拔管前5分钟、拔管时、拔管后5分钟的各参数与手术结束时比较明显升高(P<0.01);两组间比较,B组拔管前5分钟、拔管时、拔管后5分钟的HR、SBP、RPP明显高于A组(P<0.01)。结论老年患者小剂量分次静注美托洛尔可以安全地预防围拔管期心血管反应。     

卡维地洛与美多心安对高血压患者治疗效果的比较研究

目的　评价国产卡维地洛的降压效应与安全性。方法　 90例原发性高血压患者随机分为观察组与对照组 ,分别口服国产卡维地洛 1片 (10mg)或美多心安 1片 (2 5mg) ,2次 /d ,4周为 1疗程。 结果　卡维地洛组服药 4周后收缩压 (SBP)及舒张压 (DBP)与治疗前比较分别下降 (18.92± 11.5 8)、(12 .34± 7.2 5 )mmHg(P <0 .0 1) ,美多心安组与治疗前比较分别下降 (19.13± 9.70 )、(13.5 0± 7.4 6 )mmHg(P <0 .0 1) ;观察组与对照组总有效率分别为 89.4 8%与 80 .4 3% ,两组比较无显著差异 (P >0 .0 5 )。两药的不良反应均轻微 ,发生率分别为 2 .7%和 4 .4 %。结论　卡维地洛是一种安全有效的抗高血压药物     

美托洛尔对急性心肌梗死早期QT离散度的影响

目的 :探讨急性心肌梗死早期应用美托洛尔对QT离散度 (QTd)的影响。方法 :选择符合条件的 14 2例急性心肌梗死 (AMI)患者 ,男 95例 ,女 47例 ,平均年龄 5 7± 12 3岁 ,随机分为治疗组 78例 ,对照组 64例 ,两组病例性别、年龄等基本情况相似。在AMI常规治疗的基础上 ,治疗组给予美托洛尔 6 2 5～ 5 0mg口服 ,2次 /d ;对照组仅常规治疗。治疗前及治疗 1周后同步记录体表常规 12导联心电图 ,每一导联连续测量 3个Q -T间期 ,取其均值。最大QT间期 (QTmax)与最小QT间期 (QTmin)之差为QTd。结果 :治疗组在常规治疗基础上早期给予美托洛尔后 ,QTd、QTcd显著缩小 (P <0 0 1) ,QTmax无明显改变 (P >0 0 5 ) ,QTmin显著延长 (P <0 0 5 ) ,心率显著减慢 (P <0 0 1)。而对照组QTd、QTcd、QTmax、QTmin、HR均无明显变化 (P >0 0 5 )。结论 :AMI早期应用 β1 受体阻滞剂美托洛尔治疗 ,可显著延长正常心肌的复极过程 ,从而防治早期恶性心律失常 ,降低猝死率。     

琥珀酸美托洛尔HPMC骨架片释放影响因素研究

以羟丙基甲基纤维素（HPMC）为骨架材料，乙基纤维素（EC）为阻滞剂，采用湿颗粒压片法制备琥珀酸美托洛尔亲水凝胶骨架片，考察HPMC用量、HPMC黏度、EC用量、制备方法、压片压力、释放介质及转速对琥珀酸美托洛尔（MS）骨架片体外释药的影响。结果表明，MS骨架片体外释药符合Higuchi方程，药物释放机制是骨架溶蚀和药物扩散的综合效应；HPMC用量与黏度、阻滞剂用量、制备方法、压片压力对释放速率均有显著性影响；释放介质的pH值及转速对释放速率无显著性影响。     

倍他乐克逆转高血压左室肥厚的临床观察

目的　比较 2药对高血压左室肥厚患者的疗效及运动后对心率、血压的影响。方法　采用随机分组法将 80例高血压左室肥厚的病人分成两组 ,倍他乐克组和硝苯地平组 ,治疗前后查超声心动图 ,测定IVST、PWT及LVMI ,心率及血压。结果　① 2药降压效果无明显差异。② 2组患者IVST、PWT、LVMI的下降幅度相同。③中度体力活动后 ,倍他乐克组心率增快 9± 2次 ,收缩压、舒张压上升均小于 3kPa(7 5mmHg) ,硝苯地平组心率增快 2 0± 4次 ,2组相比P <0 0 1,具有显著意义 ;收缩压、舒张压上升幅度均为 3 4± 1 2kPa(2 6±9mmHg) ,明显大于倍他乐克组。④结论　 2药对高血压患者的左心室肥厚有相似的逆转作用 ,但倍他乐克可减少体力活动时血压及心率的上升 ,对心脏更具有保护作用。     

Beta-adrenergic drugs do not affect phrenic nerve afterdischarge

Summary In anesthetized cats, a carotid sinus nerve was stimulated electrically. After this stimulation the time course of the afterdischarge in the phrenic nerve activity was studied in the control situation, during infusion of isoprenalin and after administration of metoprolol. The time courses were identical in all situations.It is concluded that in spite of the fact that the beta-adrenergic drugs change the steady state phrenic nerve activity, the afterdischarge is unchanged and therefore probably mediated by a separate mechanism. A comparison is made with analogous findings in patients with a hyperventilation syndrome.     

Receptor binding assays in analysing the bioavailability and pharmacodynamic bioequivalence of active drug moieties

The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its ₁-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung ₁-and rat reticulocyte ₂-adrenoceptors.The formulations differed markedly in their kinetic characteristics: the peak plasma concentration (C_max) of R,S-metoprolol after administration of the conventional formulation was 140 ng·ml^–1, (n=7) and it was approximately one-third of that after the sustained-release formulation, 49 ng·ml^–1, (n=6); the AUC_{0–24 h}-values for the formulations were 700 and 310 ng·h·ml^–1, respectively. The C_max for the ₁-adrenoceptor binding component of metoprolol was 180 ng·ml^–1 (n=7) after administration of the conventional, and 74 ng·ml^–1 after administration of the sustained-release formulation. The corresponding AUC_{0–24 h}-values for the receptor binding component were 920 and 470 ng·h·ml^–1 (n=7).Thus, the kinetic differences between R,S-metoprolol and the ₁-receptor binding component were considerable and they were affected by the type of formulation. In general, after administration of the sustained-release formulation, the percentage ₁- and ₂-adrenoceptor occupancy of metoprolol in plasma was 5–15% less than after administration of the conventional formulation. At 0.5–1.5 h after drug intake the average ₁-adrenoceptor occupancy of the conventional formulation varied between 80–90% and that of the sustained release formulation between 20–76%. At these times the differences in receptor occupancy were significant; at 0.5–2 h after drug intake the average ₂-adrenoceptor occupancy of the conventional formulation varied from 20–30%, and that of the sustained-release formulation was 2–17%. At other times the difference in receptor occupancy between the formulations was not significant.The results demonstrate that plasma concentration-kinetics were more discriminating than -adrenoceptor-binding in analysing bioequivalence. It was possible to determine the bioavailability of the active ingredient of metoprolol and to study pharmacodynamic bioequivalence by using receptor binding assays.     

Behavioral and autonomic responses to intermittent social stress: differential protection by clonidine and metoprolol

The present study investigated physiological and pharmacological characteristics of socially stressed animals. Specifically, we examined (1) to what degree autonomic and behavioral stress reactions during intermittent confrontations between an intruder male adult Long-Evans rat with an aggressive resident undergo habituation, and (2) to what extent the defeat-experienced animal can be protected against these stress reactions with clonidine or metoprolol, two adrenergic agents with clinical anxiolytic effects. We developed an acute social stress situation that consisted of initially placing an experimental rat as an intruder into the homecage of a resident while the resident was not present, thereafter permitting brief physical agonistic interactions with the reintroduced resident until the intruder was forced into a submissive supine posture and emitted ultrasonic vocalizations (USV), and eventually exposing the intruder to the resident's threats for one hour, while being shielded from potentially injurious attacks (threat encounter). Over the course of the initial 4-weekly threat encounters the acute tachycardia but not the hyperthermic stress responses decreased in magnitude. Following the first three threat encounters core temperature (T_c) was significantly elevated for at least 3 h. The T_c was already elevated when the repeatedly defeated intruder was confronted with the olfactory cues of the resident's cage. This conditioned anticipatory hyperthermia developed in the course of the first three confrontations and was paralleled by a decrease in exploratory and motor behavior and by an increase in defensive behaviors and in both types of USV emitted in the low (20–30 kHz) and the high (31–70 kHz) frequency range. Clonidine (0.01–0.1 mg/kg, IP), an ₂-adrenergic agonist and metoprolol, a -adrenergic blocker (1.0–10.0 mg/kg, IP), dose-dependently prevented the tachycardic response to stress. Only clonidine, but not metoprolol, also attenuated the rise in T₀ during the 1-h agonistic interaction. Clonidine decreased those aspects of motor behavior (e.g. rearing, walking) that are of lesser cost for the individual but maintained high levels of defensive reactions and increased the duration of low USV. The high doses of clonidine (0.06, 0.1 mg/kg) attenuated the homeostatic regulation and sedated the intruder while exposed to threats during a social confrontation. The absence of attenuation of the high level of defensive behavior and the prolonged low USV suggest a stress intensification by the higher doses of clonidine. In conclusion, after the fourth encounter, the autonomic, behavioral and vocal response pattern prior to and during repeated weekly confrontations show no evidence for habituation for the following 6 weeks. Moreover, adrenergic therapeutic agents that are applied to treat symptoms of anxiety block the tachycardic response but may actually intensify defensive behavior and certain stress vocalizations.