The effect of arsenic trioxide on QT interval prolongation during APL therapy

Objective To investigate the cardiac effect of QT interval prolongation in the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (As2O3), and the relationship between QT and serum arsenic concentration.Methods Blood serum arsenic concentrations of thirty APL patients were determined at 2 hours, 4 hours, 8 hours, and 24 hours after As2O3 injection using atomic fluorophotometry. Cardiac functions were measured simultaneously using a 12-lead body-surface electrocardiogram (ECG). Q-T intervals were manually measured, and then corrected using Bazett’s formula (QTc). QT dispersion (QTd) was also calculated. In order to assess the effects of arsenic on the symptoms of anemia, twenty-four anemia patients were divided into two groups on the basis hemoglobin concentration: Group1 (Hb≥90 g/L), and Group 2 (60 g/L≤Hb＜90 g/L). QTc and QTd of these patients were also manually measured.Results All QT intervals of APL patients treated with As2O3 injection were prolonged ［32.2 ms (27, 41 ms); P< 0.05］, but the changes of QTd were not prominent ［3 ms (－8, 7 ms), P> 0.05］. There was a delay of 2 hours in maximum QTc following peaks in serum arsenic concentration. Changes in QTc and QTd of the two anemic groups were not prominent.Conclusions As2O3 can prolong QTc intervals in APL patients, but the effects are delayed compared to peak serum arsenic concentrations. As2O3 has no prolongation effect on QTd. Mild and moderate anemia do not effect QTc and QTd.     

体检人群中代谢综合征与QTc间期延长的相关性研究

目的 探讨代谢综合征(MS)与校正的QT(QTc)间期延长的关系.方法 选取2015年6月至2016年6月该院18岁以上体检行心电图检查者1 260例,根据有无MS分为MS组与Non-MS组.按照Bazett公式计算QTc间期.建立Logistic回归模型,分析MS与QTc间期延长的关系.结果 MS组QTc间期延长者63例,Non-MS组40例(P＜0.01).在未调整模型中,MS是QTc间期延长的危险因素[OR=6.36,95％CI(2.34,8.67),P＜0.01].进一步调整混杂因素后,MS与QTc间期延长仍密切相关[OR=4.11,95％CI(2.09,7.13),P＜0.01].在MS各组分别与QTc间期延长的关系研究中,调整混杂因素后,仅腹型肥胖[OR=2.76,95％CI(1.43,7.56),P＜0.01]及高三酰甘油血症[OR=1.75,95％CI(1.22,4.31),P=0.013]与QTc间期延长密切相关.结论 MS是QTc间期延长的独立危险因素,应加强对MS患者血脂及腹围的管理.     

普罗帕酮对“犬”的起搏阈值影响的实验研究

【目的】观察逐步加大普罗帕酮剂量后对起搏阈值、感知和电极阻抗的影响。【方法】动物（犬,n=12）麻醉后,维持自主呼吸。放置心房和心室起搏电极后,静脉给予不同剂量的普罗帕酮,比较用药前后起搏阈值、感知和电极阻抗以及血压、心率等参数的变化。普罗帕酮剂量依次是3．1、3．1、4．65、4．65m异,kg和6．2mg／kg。每次用药后5min测定上述指标,并采用高效液相色谱法测定普罗帕酮的血清浓度。【结果】普罗帕酮剂量增至6．2mg／kg时,心房起搏阈值从（0．98±0．36）V增加至（8．25±1．92）V（P〈0．01）,增加幅度与普罗帕酮血清浓度呈正相关,r=0．826,P=0．029。心室起搏阈值从（0．55±0．35）V增加至（2．30±1．78）V（P〈0．01）,增加幅度与普罗帕酮血清浓度无明显相关,r=0．375,P=0．265。P波振幅从（4．8±1．3）mV降至（1．6±0．7）mV（P〈0．01）,R波振幅从20mV降至（18．3±2．2）mV,（P〈0．05）。平均动脉压（MBP）从（142±11）mmHg降至（67±12）mmHg,心率从（163±13）降至（90±10）次／min,（均为P〈0．01）。PR间期从（98±10）船延长至（159±28）ms,QRS间期从（40±5）ms至（102±22）ins,QTc间期从（315±32）ms至（366±18）ms,（均为P〈0．01）。【结论】随着普罗帕酮剂量逐渐增加,起搏阈值明显增加,心房起搏阈值尤其明显。     

Verapamil modulating arsenic trioxide-induced QT interval rolongation in guinea pig

Objective To investigate therapeutic action of verapamil on QT prolongation induced by arsenic trioxide (As2O3) in guinea pig and to further explore its possible mechanism. Methods Different doses of As2 O3 was infused intravenously to observe the changes of QT interval on the electrocardiogram (ECG) at different times in guinea pig. Patchclamp technique and laser scanning confocal microscopy were utilized to study the action of As2 O3 on action potential duration (APD),L-type calcium current (ICa-L ), rapid delayed rectifier potassium current (IKr) and intracellular calcium concentration ([Ca2+]i) of guinea pig myocytes. At the same time, verapamil was applied preliminarily to evaluate effects of verapamil on changes of the above index induced by As2O3. Results Intravenous administration of As2 O3 at the dose of 1.6mg/kg and 0.8mg/kg prolonged QT interval on ECG obviously in guinea pig hearts dose dependently and time dependently. QTc (corrected QT interval) was progressively prolonged in the 2-hour period of intravenous infusion of 1.6mg/kg As2O3 from (328.5 ± 30.9)ms of control to (388.4 ± 31.3)ms at 2h following As2O3 ( P ＜ 0.01) .When verapamil was pretreated for 5min, then 1.6mg/kg As2 O3 was added, the results showed that QTe was shorter in verapamil-treatment group (357.3±21.4)ms than that in As2O3 group (388.4±31.3)ms (P＜0.05) at 2h. Confocal experiments showed that in normal Tyrode solution, As2 O3 (1μmol/L and 10μmol/L) had no obvious effects on resting [Ca2+]i (P＞0.05) in guinea pig cardiomyocytes, however, 10μmol/L As2 O3 could markedly enhance [Ca2+]i increase induced by KCl 60mmol/L and the peak value increased from 903.4±369.4 to 1674.6±563.2 ( P＜0.05). The action of elevating [Ca2+]icould be blocked by 10μmol/L verapamil incompletely. The patch-clamp studies indicated that As2 O3 at concentration of 10μmol/L prolonged APD50 from (263.6 -±75.2)ms to (523.9±47.8)ms (P＜0.01) and APD90 from (277.5 ± 77.5)ms to (536.3 ±49.6)ms (P ＜0.01) ,and increased ICa-L from (- 6.0±1.5)pA/pF to (-8.7±2.0)pA/pF (P＜0.01) at 0mV and also reduced IKr from (6.7±1.8)pA/pF to (4.5±1.8)pA/pF (P＜0.05). However, 10μmol/L verapamil could modulate prolonging APD50 from (523.9 ± 47.8) ms to (340.4±83.8) ms ( P＜0.01) and APD90 from (536.3 ±49.6)ms to (348.9 ± 85.5)ms (P＜0.01) and correct increasing Ica-L induced by 10μmol/L As2O3 from (-8.7±2.0)pA/pF to ( - 6.6±1.4)pA/pF (P＜0.05) at 0mV. Conclusion As2O3 could induce prolongation of the QT interval on the ECG in guinea pig hearts and the ionic mechanism is associated with increasing Ica-L and inhibiting IKr/HERG. Verapamil may be useful in normalizing QT prolongation during As2 O3 therapy by decreasing Ica-L and [Ca2+]iof ventricular myocytes in guinea pig.     

Verapamil modulating arsenic trioxide-induced QT interval prolongation in guinea pig

Objective To investigate therapeutic action of verapamil on QT prolongation induced by arsenic trioxide （As2O3） in guinea pig and to further explore its possible mechanism. Methods Different doses of As2O3 was infused intravenously to observe the changes of QT interval on the electrocardiogram （ECG） at different times in guinea pig. Patchclamp technique and laser scanning confocal microscopy were utilized to study the action of As2O3 on action potential duration （APD）,     

不同剂量阿托伐他汀对老年糖尿病患者冠状动脉介入治疗术后对比剂肾病的影响

目的 研究不同剂量阿托伐他汀对老年糖尿病患者冠状动脉(冠脉)介入治疗术后对比剂肾病的影响.方法 将80例行冠脉介入检查和治疗的老年糖尿病患者随机分为大剂量组( 80 mg/d,n =40)和常规剂量组(20 mg/d,n-40),分别于冠脉介入治疗前2～3d开始每晚顿服阿托伐他汀80 mg及20 mg.所有患者分别于冠脉介入治疗前1天、检查后第1天、第3天、第5天测定血尿素氮(Bun)、血肌酐(Scr)、尿β2-微球蛋白及尿白蛋白的改变.并根据Cockcroft-Gault公式计算出内生肌酐清除率(Ccr).结果 ①小剂量组:与冠脉介入治疗前相比,治疗后第1～3天Scr尿β 2-微球蛋白均有显著升高(P＜0.01),Ccr显著降低(P＜0.01);检查后第5天Scr、Ccr、尿2-微球蛋白、白蛋白均无显著变化(P＞0.05).(②大剂量组:与治疗前比较,治疗后第1～3天Scr、尿β2-微球蛋白均升高(P＜0.05),Ccr降低(P＜0.05),检查后第5天Scr、Ccr、尿β2-微球蛋白、白蛋白均无显著变化(P＞0.05).③与常规剂量组相比:大剂量组检查后第1～3天Scr、尿β2-微球蛋白、尿白蛋白显著降低(P＜0.01),Ccr显著升高(P＜0.01);检查后第5天尿β2微球蛋白、尿白蛋白、Scr、Ccr差异均无统计学意义(P＞0.05).两组治疗前后BUN均无明显的变化(P＞0.05).结论 阿托伐他汀对老年糖尿病患者冠脉介入治疗术后对比剂肾病有预防作用,并且使用大剂量(80 mg/d)的阿托伐他汀可能对对比剂肾病的发生有更好的预防作用.     

齐拉西酮导致精神分裂症患者QTc间期延长的对照研究

目的：探讨齐拉西酮对精神分裂症患者QTc间期延长的影响。方法：将97例精神分裂症患者分为研究组及对照组，分别使用齐拉西酮及利培酮治疗，在用药前及用药后第1、2、4、8周分别检查心电图，比较两组的QTc间期。结果：（1）齐拉西酮组与利培酮组用药后的QTc间期都较基线有所延长，齐拉西酮显著高于基线（P〈0．01），而利培酮则无统计学意义（P〉0．05），反映出齐拉西酮对QTc延长的影响强于利培酮；（2）两组内部用药后复查4次心电图，QTc结果之间的差异均无统计学意义（P〉0．05），反映出两种药物对QTc间期的影响与疗程关系并不明显；（3）两组QR间期均无达到异常标准的病例。结论：齐拉西酮使心电图QTc延长强于利培酮，虽然QTc延长的程度在正常参考值范围内，仍需临床医生给予关注。     

Ketanserin in essential hypertension: a double-blind, placebo-controlled study

The antihypertensive effect of the selective serotonin antagonist ketanserin was examined in a double-blind, placebo-controlled, parallel group study in 20 patients with essential hypertension. After 7 weeks treatment with ketanserin (mean dose 71 mg/d) there was a significant fall of both systolic and diastolic blood pressure, as compared to placebo, with a peak effect of 19.1/9.1 mmHg lying (P less than 0.01/P less than 0.01), and 16.5/11.3 mmHg standing (P less than 0.01/P less than 0.01); twice daily dosage appeared satisfactory. Subjective side effects were similar in the ketanserin and placebo groups. Ketanserin is an effective antihypertensive drug of moderate potency when given twice daily, with no orthostatic effect.     

Efficacy of atenolol and oxprenolol in the treatment of arterial hypertension. A comparison.

Twenty-seven patients with mild to moderate arterial hypertension were treated "double-blind" with either atenolol of oxprenolol. Placebo was given for four weeks before the beta-blocking drugs were administered. Atenolol was given in doses of either 50 mg twice a day, 100 mg twice a day or 100 mg once a day for periods of four weeks. Oxprenolol was given in doses of either 80 mg or 160 mg twice a day for the same duration. Patients were assessed at the end of each four-week period. The mean blood pressure and pulse rate did not vary significantly for the two different dose regimens at which each drug was administered. There was no statistical difference between the reduction of systolic blood pressure produced by the two drugs, but there was a significant difference in the reduction in diastolic blood pressure in favour of atenolol (P less than 0.05 supine; P less than 0.01 erect). A single, 100-mg daily dose of atenolol was just as effective as 50 mg or 100 mg twice a day. Similarly, an 80 mg twice a day dose of oxprenolol was just as effective as that of 160 mg twice a day. Side effects for each drug were not statistically different from those recorded with placebo.     

肝硬化患者Q-T间期延长的临床观察

目的探讨肝硬化患者心电图Q-T间期（Q-Tc）延长与肝硬化的严重程度及预后的相互关系。方法对126例肝硬化患者及126例健康对照的心电图Q-Tc进行比较;肝硬化患者按Child—Pugh分级后,观察各级间心电图Q—Tc、凝血酶原时间（胛）、血清白蛋白（ALB）、血清总胆红素（TBIL）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、1谷氨酰转移酶（GGT）、碱性磷酸酶（ALP）、血清钾、血清钙等指标;观察20例肝硬化晚期行肝移植手术患者手术前后的心电图Q．Tc及上述生化指标。结果肝硬化患者的Q—Tc较健康对照明显延长（P〈0．01）;肝硬化患者各级间Q—Tc随Child分级呈现逐渐增高趋势,A级与B、C级Q-Tc差异有统计学意义（均P〈0．01）,B、C级之间差异无统计学意义;直线相关分析Q-Tc与Child积分呈正相关（r=0．56,P〈0．05）;20例术前Q-T延长的肝移植患者术后17例患者Q—Tc恢复正常,3例患者明显较术前缩短。结论肝硬化患者存在Q-Tc延长,且随着病情的严重程度增加,Q-Tc异常率增高。肝移植后往往恢复正常。Q—Tc延长在判定肝硬化患者病情程度及预后上有重要的临床意义。     

老年人睡眠质量及睡眠时长与动态心电图校正的QT间期的关联分析

背景　睡眠对于维持人体健康至关重要,睡眠质量和睡眠时长与多种疾病发生相关。既往职业人群研究表明,睡眠剥夺与QT间期延长相关。但关于一般人群中睡眠质量、睡眠时长与校正的QT间期（QTc）关联的研究较少。目的　探讨中国老年人群睡眠质量及睡眠时长与QTc的关联。方法　选取2017年11-12月如皋市长寿和衰老队列（RuLAS）的睡眠和心电图数据,并根据匹兹堡睡眠质量指数量表（PSQI）评分将老年人分为睡眠正常组（n=776）、睡眠质量轻度下降组（n=214例）、睡眠质量下降组（n=152例）;通过静息心电图（ECG）仪的解读程序收集ECG参数〔QTc、心率（HR）、P波、QRS间期、PR间期、V5导联的R波（RV5）、V1导联的S波（SV1）〕。采用多重线性回归分析探讨PSQI评分与QTc的影响因素。结果　老年人PSQI评分为（4.6±2.6）分,夜间睡眠时长为（9.2±1.8）h。3组间性别、受教育程度、饮酒情况、糖尿病患病情况、认知功能评分、体力活动评分、QTc、RV5比较,差异均有统计学意义（P<0.05）。校正多种混杂因素后,多重线性回归分析显示,PSQI评分〔β=1.63,95%CI（0.23,3.04）,P=0.023〕,≤6 h〔β=21.22,95%CI（6.28,36.16）,P=0.005〕的睡眠时长、>10 h〔β=8.81,95%CI（0.24,17.39）,P=0.044〕的睡眠时长是QTc的影响因素。结论　中国老年人群睡眠质量差、睡眠时长过长或过短与QTc相关,提示睡眠质量及时长可能是QTc的影响因素之一,改善睡眠可能预防QTc延长,从而预防心源性死亡。     

不同剂量卡维地洛防治大鼠急性心肌梗死左室重构的研究

目的对比观察不同剂量卡维地洛对大鼠急性心肌梗死(AMI)左室重构(LVRM)的防治作用。方法雌性SD大鼠AMI术后成活142只,分为AMI对照组(n=35),和卡维地洛大剂量(10mg·kg-1·d-1,n=37),中剂量(1mg·kg-1·d-1,n=35),及小剂量(0.1mg·kg-1·d-1,n=35)四组。另设假手术组对照。直接灌胃给药4周后行血流动力学测定、心脏标本固定及病理分析。去除梗死面积＜35％或＞55％者,最终58只大鼠资料完整。结果AMI各组间梗死面积均无显著差异(44.5％～46.3％,P均＞0.05)。与假手术组相比,AMI组的左室舒张末压(LVEDP)、容积(LVV)、实际左心室重量(LVAW)及相对重量(LVRW)均显著增加(P均＜0.01),左室球形指数和左室内压最大上升和下降速率(±dp/dt)及其校正值(±dp/dt/LVSP)均显著降低(P均＜0.01)。与AMI组相比,卡维地洛大、中、小剂量组的LVEDP、LVV、LVAW和LVRW均呈剂量相关性显著降低(LVEDP7.7mmHg±1.9mmHg,12.1mmHg±2.0mmHg,14.5mmHg±4.6mmHg对24.5mmHg±5.3mmHg;LVV0.72ml±0.10ml,0.79ml±0.08ml,0.82ml±0.10ml对0.92ml±0.11ml;LVAW589mg±57mg,622mg±70mg,666mg±57mg对730mg±79mg;P＜0.05～0.001),±dp/dt及±dp/dt/LVSP均显著增加(P＜0.05～0.01),但各剂量组间均无显著差异,左室球形指数仅在大剂量组显著改善(P＜0.05)。结论卡维地洛大、中、小剂量均能有效地防止大鼠AMI左室重构,改善血流动力学和左室功能;小剂量有效,大剂量更好。     

红霉素对Langendorff灌流豚鼠心脏电活动的影响

目的研究红霉素对langendorff灌流豚鼠心脏电活动的影响。方法常规心电图记录法,观察红霉素对豚鼠离体心电图的作用。结果红霉素可延长豚鼠心电图PR间期、QT间期,增大QTc,减慢心率。0．3mmol／L红霉素可使PR间期从（66．1±3．2）ms延长到（92．3±10．7）m8（P〈0．05）;R波从（16．1±1．2）ms增宽至（18．1±3．7）ms（P〈0．05）;QT间期和QTc分别从（184．3±13．8）mS和（10．6±0．6）ms增加到（250．7±27．6）ms和（13．1±1．7）ms,（P〈0．01,P％0．01）;RR间期延长22．5％;心率减慢17．1％。较高浓度红霉素作用下,可出现室上性期前收缩。结论红霉素可减慢兴奋在心脏的传导,诱发室上性期前收缩等心律失常。     

Cardiac autonomic dysfunction in sickle cell anaemia and its correlation with QT parameters

Background:

Abnormalities of QT parameters together with cardiac autonomic neuropathy (CAN) confer significant risks of cardiac morbidity and mortality in patients with diabetes mellitus. We questioned whether or not CAN influences occurrence of QT interval prolongation and dispersion in patients with sickle cell anaemia (SCA).

Materials and Methods:

Forty stable adult sickle cell patients with 44 healthy haemoglobin AA controls were studied. Baseline electrocardiograms were obtained and cardiovascular autonomic function tests were performed using standard protocols.

Results:

Mean corrected QT (QTc) in sickle cell patients was significantly higher (P = 0.001) than the mean of controls. Similarly, mean QT dispersion (QTcd) was higher (P = 0.001) in the former than in the latter. Mean QTc in patients with CAN was longer than patients with normal autonomic function (461 ± 26 ms versus 411 ± 23 ms), P = 0.001 (OR of 17.1, CI 3.48–83.71). Similarly, QTcd was higher (P = 0.001) in patients with CAN than those with normal cardiac autonomic function. Positive correlations were found between CAN with QTc and QTcd (r = 0.604, P = 0.001, r = 0.523, P = 0.001, respectively).

Conclusion:

CAN is a risk factor for abnormalities of QT parameters in SCA and both may be harbinger for cardiac death.     

索他洛尔与普罗帕酮平行对照治疗阵发性心房颤动

目的：评价索他洛尔与普罗帕酮平行对照治疗阵发性心房颤动的临床疗效和安全性。方法：本研究为随机、平行对照研究。138例阵发性心房颤动患者经2周洗脱期后,随机分为索他洛尔组（每日2次,剂量从40 mg/d开始,根据具体情况,适量渐增,最大剂量320 mg/d。n=68）和普罗帕酮组（每日3次,剂量从450 mg/d开始,根据具体情况,适量渐增,最大剂量不超过800 mg/d。n=70）,治疗12周末评价两组疗效。结果：随机、平行对照治疗12周末的总有效率,索他洛尔组为72.06%;普罗帕酮组为62.86%。两组组间比较均有统计学意义（P〈0.01）。索他洛尔组与普罗帕酮组的不良反应发生率分别为8.82%和18.57%（P〈0.01）。结论：索他洛尔治疗阵发性心房颤动患者的疗效明显优于普罗帕酮,且有良好的安全性。     

四种非典型抗精神病药长期治疗老年慢性精神分裂症对QTc间期的影响

目的评价利培酮、喹硫平、奥氮平和氯氮平四种非经典抗精神病药对老年慢性精神分裂症患者QTc间期的影响。方法将北京市海淀区精神卫生防治院2010年1月～2013年1月收治的80例老年慢性精神分裂症患者分为利培酮组（n=20）、奥氮平组（n=20）、喹硫平组（n=20）和氯氮平组（n=20）,接受单一药物治疗,随访1年。基线和治疗每月末分别检查心电图和血清钾钠氯水平。结果治疗12个月末,利培酮组、奥氮平组、喹硫平组和氯氮平组QTc间期分别延长了21.5、15.5、27.5、13.5 ms,四组QTc间期变化比较差异无统计学意义（F=2.18,P=0.097）。治疗1年内,四组精神分裂症患者均未达到QTc间期延长的诊断标准（男性〉470 ms,女性〉480 ms）,无任何患者QTc间期在原基础上增加超过60 ms。结论利培酮、奥氮平、奎刘平和氯氮平均具有延长QTc间期的作用,并且程度不同,但它们总体对QTc间期的影响有限,比较适合在老年慢性精神分裂症患者中使用。     

瑞芬太尼预防异丙酚注射痛的最佳剂量研究

目的探讨瑞芬太尼预防异丙酚静脉注射痛的最佳剂量。方法全麻下行择期手术患者200例,ASAⅠ-Ⅱ级,随机分为5组：R1组（瑞芬太尼0.01mg,n=40）、R2组（瑞芬太尼0.02mg,n=40）、R3组（瑞芬太尼0.03mg,n=40）、L组（利多卡因40mg,n=40）和S组（0.9％氯化钠注射液2ml,n=40）。所研究的阿片类药物均稀释成2ml溶液。药物注入外周静脉30s后以0.5ml／s的速度注射异丙酚（1％得普利麻）50mg。立即观察和询问注射处有无疼痛,疼痛评分采用四分法。结果R1组、R2组、R3组和L组较S组明显降低异丙酚注射痛发生率和程度（P〈0.05）。R2组、R3组和L组较R1组更有效降低异丙酚注射痛（P〈0.05）,R2和R3组之间异丙酚注射痛发生率和程度差异无统计学意义（P〉0.05）。结论瑞芬太尼同利多卡因一样,都可有效降低异丙酚注射痛。随着瑞芬太尼剂量的增加,异丙酚注射痛发生率并无明显减少,瑞芬太尼0.02mg是预防异丙酚注射痛较好剂量。     

Diazepam tolerance: effect of age, regular sedation, and alcohol

The dose of intravenous diazepam required for sedation was estimated in a series of 78 patients aged 17-85 years given the drug for dental and endoscopic procedures. Multiple regression analysis showed a significant correlation (r = 0.71; p less than 0.001) between dose and age, body weight, the taking of regular sedation, and the taking of more than 40 g alcohol daily, but there were no differences in the doses required between men and women, smokers and non-smokers, inpatients and outpatients, or dental and endoscopy patients. Patients aged 80 required an average dose of 10 mg and patients aged 20 an average dose of 30 mg, and the dose required was much higher in those receiving regular sedation or having a high alcohol intake. Plasma total and free diazepam concentrations were measured in the second half of the series of patients (n = 37). Plasma concentrations required for sedation fell twofold to threefold between the ages of 20 and 80 and were significantly higher in those taking regular sedation or alcohol. Differences in the acute response to diazepam appeared to be due to differences in the sensitivity of the central nervous system (pharmacodynamic tolerance) rather than to differences in pharmacokinetic factors.     

Hypnotic accumulation and hangover in elderly inpatients: a controlled double-blind study of temazepam and nitrazepam

The hypnotic and residual sedative effects of the first and seventh of seven regular night-time doses of nitrazepam 5 mg, temazepam 20 mg, and placebo were studied in 58 elderly inpatients. Plasma temazepam and nitrazepam concentrations rose by about 50% and 113% respectively between the mornings of day 1 and day 7. Patients reported sleeping well more often after the first dose of either hypnotic (p less than 0.05), but there was no difference after the seventh dose. Reaction time was unchanged on the morning after the first dose but was significantly prolonged after the seventh dose of both hypnotics (p less than 0.01). The time taken to eliminate the letter E from a page of prose tended to be prolonged after the first dose of both drugs (temazepam v placebo, p less than 0.05; nitrazepam v placebo, not significant) and was further prolonged on the morning after the seventh dose of nitrazepam (nitrazepam v placebo, p less than 0.05). Thus plasma accumulation of the drug was associated with a deterioration in daytime performance. This change in performance did not correlate with age, cerebral blood flow, or plasma concentration, but patients of low intelligence tended to be more severely affected.     

Absorption of isophane (NPH) insulin and its clinical implications

Absorption of 125I-NPH insulin (125I-isophane insulin) (40 IU/ml) was studied in eight diabetics given 50% and 150% of their normal daily dose of insulin. Insulin absorption correlated with plasma insulin (r = 0.97, p less than 0.001) and blood glucose (r = -0.87, p less than 0.01) concentrations. Absorption was slower at higher doses, so that trebling the insulin dose only doubled the amount absorbed over the first 24 hours. The plasma elimination half time (t12) of insulin was about five minutes. Thus, the disappearance of radiolabelled insulin is a reliable and quantitative index of insulin absorption; subcutaneous degradation, if present, is minimal and constant. Changes in dise of intermediate-acting insulin further increases the large variation in insulin absorption. This implies that minor adjustments of intermediate insulin dosage are probably futile.