Effect of nicardipine on insulin secretion,glucose and lipid metabolism in hypertensive,non-insulin dependent diabetics

Summary Certain acute and chronic metabolic effects of nicardipine have been studied in 20 patients with non-insulin dependent diabetes (NIDD). An intravenous glucose tolerance test (i.v. GTT, glucose 0.33 g/kg as a bolus) and the corresponding insulin response were assessed at the end of a 4 week placebo period, after the first dose and on administration for 12 weeks of nicardipine 20 mg t.i.d.The glucose and insulin responses to the i.v. GTT, evaluated as incremental AUCs, did not change significantly (glucose 30.5 mg/dl·90 min on placebo, 33.1 mg/dl·90 min acutely and 31.4 mg/dl·90 min on chronic administration of nicardipine; insulin 2.08 µU/ml·90 min on placebo, 1.87 µU/ml·90 min acutely and 1.93 µU/ml·90 min after chronic nicardipine). Glucose removal rate (KG) following the i.v. GTT was 0.73%/min on placebo 0.75%/min on acute administration and 0.8%. min^–1 with chronic nicardipine.Active treatment produced a significant reduction of blood pressure (from 187/96 mm Hg on placebo to 166/89 mm Hg acutely and 152/83 mm Hg after 12 weeks of nicardipine treatment). It is concluded that the calcium antagonist nicardipine was an effective antihypertensive drug, and that it did not cause deterioration of metabolic control in hypertensive patients with NIDD.     

Comparison of nicardipine and propranolol in the treatment of mild and moderate hypertension

Summary In a double-blind controlled trial 22 patients with mild or moderate essential hypertension were treated with nicardipine 30 mg t.d.s. and 19 patients with propranolol 80 mg t.d.s. as monotherapy for 24 weeks. Blood pressure in both groups at the end of trial was equally and significantly reduced; systolic pressure 22.2 mmHg and diastolic pressure 15.5 mmHg in the supine position, and 24.4 mmHg and 18.4 mmHg, respectively, in the standing position in those on nicardipine, and by 23.7 and 16.2 mmHg and 28.0 and 19.2 mmHg, respectively, in the propranolol group. There was an initial increase in heart rate in the nicardipine group, but the rise was only moderate (3 beats/min supine p=0.3219, and 7 beats/min standing, p=0.0203) at the end of the 24 weeks. In the propranolol group heart rate was reduced markedly. Adverse effects occurred in 77% of patients on nicardipine and in 63% of those on propranolol, and there were no unexpected findings. The effects were mild in both groups and did not lead any patient to stop medication. One patient on propranolol was withdrawn from the trial because of poor blood pressure control and suspected angina pectoris after 5 weeks on active medication. There were no significant changes in blood chemistry, including lipoprotein classes. Overall, in comparison with propranolol, nicardipine was effective, well-tolerated and safe to use in the monotherapy of mild or moderate essential hypertension.     

Adrenergic system and carbohydrate metabolism. Effects of beta-receptor blockade on insulin secretion and peripheral insulin sensitivity in normoglycaemic patients

Summary The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique.Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment.The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin.     

Comparison of labetalol,propranolol and hydralazine in hypertensive out-patients

Summary In a randomised cross-over trial the combination labetalol/hydrochlorothiazide was compared with the combination of propranolol/hydralazine/hydrochlorothiazide in 34 uncomplicated hypertensive patients, who were not satisfactorily controlled with hydrochlorothiazide 50 mg alone. The elevated diastolic pressure (D.P.) in 27 patients responded satisfactorily to the labetalol schedule and in 28 patients to the propranolol/hydralazine schedule. No difference was found in the rate of decrease of D.P., nor in the disappearance of hypertension — related complaints. Although the duration of the washout between treatments was at least one month, treatment was significantly more efficacious during the second period. Labetalol pre-treatment especially seemed to enhance the effect of subsequent propranolol/hydralazine administration. Side effects due to therapy were rare and were not related to any particular treatment. The median daily dose of labetalol in responders was 600 mg and that of propranolol/hydralazine 120/60 mg (in both therapies hydrochlorothiazide 50 mg was given in addition). Patients showed a slight preference for the labetaol medication. It is concluded that labetalol/hydrochlorothiazide and propranolol/hydralazine/hydrochlorothiazide are equally satisfactory in the treatment of uncomplicated hypertension.     

The interaction between propranolol and the novel antimigraine agent zolmitriptan (311C90)

Aims Zolmitriptan (Zomig, formerly known as 311C90), a selective 5HT_1B/1D agonist is under development as an acute oral treatment for migraine. Despite the use of prophylactic medication, such as propranolol, breakthrough attacks often occur in patients. Consequently we investigated the effects of propranolol on the pharmacokinetics of, and cardiovascular responses to, zolmitriptan.
Methods A double-blind, randomized, crossover study of the effects of pre-treatment with propranolol 160  mg daily for 7 days or placebo on the pharmacokinetics and effects on blood pressure of a single 10  mg dose of zolmitriptan in 12 healthy volunteers.
Results Propranolol increased mean zolmitriptan C _max and AUC by 56% and 37% respectively; mean t _1/2 was prolonged from 3.1 to 4.0  h. Mean C _max and AUC of the pharmacologically active N -desmethyl metabolite were reduced by 24% and 11% respectively and the metabolite:parent AUC ratio (AUC_m/AUC_p ) fell from 0.46 to 0.26. Mean C _max and AUC for the inactive indole acetic acid metabolite were both reduced by 13% and AUC_m/AUC_p from 1.04 to 0.59. A small pressor effect of short duration was observed following zolmitriptan with mean peak rises of 13 and 11  mmHg in systolic and diastolic pressures respectively; propranolol had no effect on the pressor response.
Conclusions The results suggest that propranolol inhibits biotransformation of zolmitriptan but with no change in the small pressor response to zolmitriptan. It is therefore unlikely that the pharmacokinetic changes will lead to clinically important changes in pharmacological effects and dosage adjustment of zolmitriptan is not required in patients taking propranolol for migraine prophylaxis.     

Dose dependent changes in propranolol half life when used as an adjunct to neuroleptic treatment

Three investigations were made into the pharmacokinetics of propranolol when added to the existing phenothiazine regime of patients with schizophrenia.The plasma level was found to depart from a linear relation with dose range 80–1500 mg daily. The peak-to-trough half time was found to increase with increasing dose, and the half life of propranolol was also found to be dose-dependent.     

检测氯氮平对精神分裂症患者血糖的影响

目的检测氯氮平对精神分裂症患者血糖的影响。方法对已接受长期抗精神药物治疗的慢性精神分裂症患者,持续服用氯氮平80例的不同时点进行空腹血糖（FBG）及餐后2h血糖（2hBG）的测定。结果使用氯氮平治疗3个月末空腹血糖及餐后2h血糖无明显增高（P〉0.05）;治疗12个月末空腹血糖及餐后2h血糖增高,与基础值比较差异有统计学意义（P〈0.01）,氯氮平空腹血糖和餐后2h血糖异常（空腹血浆血糖≥6.1mmol/L,餐后2h血浆血糖≥11.1mmol/L）的发生率较高,（P〈0.05）。结论氯氮平影响慢性精神分裂症患者的血糖代谢较明显。     

A comparison of felodipine and propranolol as additions to hydrochlorothiazide in the treatment of hypertension

Summary Eighty one patients with uncomplicated hypertension who required additional antihypertensive medication (diastolic Phase V [dBP]95 mm Hg) after 4 weeks treatment with hydrochlorothiazide (HCTZ) 25 mg o.m. were randomized to receive felodipine 5 mg b.i.d. (n=40) or propranolol (n=41) 80 mg b.i.d. in addition to HCTZ 25 mg o.m. If the dBP measured about 12 h post-dose was not 90 mm Hg after 4 weeks, the dose of felodipine or propranolol was doubled. The double blind trial period was 8 weeks for all patients.Over the 8 week period, felodipine reduced the seated dBP from 100 to 83 mm Hg and propranolol from 101 to 86 mm Hg. The attained seated dBPs were significantly different in the two groups. About one third of patients in each group received the high dose of second-line therapy. After 8 weeks 91% of patients receiving HCTZ+felodipine and 84% receiving HCTZ+propranolol had a dBP 90 mm Hg. Both regimens were well-tolerated with an equal incidence but different pattern of adverse events (felodipine: flushing, headache and peripheral oedema; propranolol: dyspepsia, fatigue and vasospasm).In this 8-week study, felodipine and propranolol were safe and effective second-line antihypertensive drugs when added to hydrochlorothiazide. At the doses selected, felodipine was at least as effective as propranolol.     

药学服务对心肌梗死合并葡萄糖耐量异常病人用药依从性和血糖控制的影响

目的：探讨药学服务对心肌梗死合并糖耐量异常病人用药依从性和血糖控制的影响。方法：以292例有心肌梗死病史的病人为研究对象,对其中无糖尿病病史的病人行口服葡萄糖耐量（简称糖耐量）试验检查。通过筛查,入选糖耐量异常病人102例,采用随机双盲法分为试验组和对照组,每组各51例。对照组病人接受常规心肌梗死的治疗,试验组病人接受常规心肌梗死的治疗和药师提供的药学服务。两组病人随访时均接受了有关药学服务内容的问卷测试,将测试结果进行统计学分析,并分别记录干预前和干预1年后两组病人的用药依从性和生化指标。结果：干预前,试验组和对照组病人用药依从性和生化指标无统计学差异;干预1年后,试验组病人用药依从性显著高于对照组,空腹血糖、餐后2h血糖、糖化血红蛋白水平显著低于对照组（P〈0.05）。结论：药学服务能提高心肌梗死合并糖耐量异常病人的用药依从性,加强血糖控制。     

Effects of chlorpromazine on the disposition and beta-adrenergic blocking activity of propranolol in the dog

The effects of chlorpromazine (100mg p.o., 2hr before propranolol) on the disposition and beta-adrenergic blocking actions of both intravenous (6 mg) and oral (40 mg) propranolol were studied in the dog. Chlorpromazine pretreatment significantly reduced (69%) the oral clearance of propranolol, resulting in significant increases in propranolol bioavailability (159%), and in the total beta-adrenergic blocking activity (111%) after the oral dose. The increase in the total beta-adrenergic blocking activity of oral propranolol after chlorpromazine pretreatment was mostly due to an increased contribution from the parent compound; the apparent activity from active propranolol metabolites was not affected by chlorpromazine. Chlorpromazine pretreatment had no significant influence on the systemic clearance, elimination half-life, apparent volume of distribution, and plasma binding of propranolol, or on the apparent hepatic blood flow. After intravenous propranolol, chlorpromazine pretreatment had no effect on either the total amount of beta-adrenergic blocking activity or the amount of activity attributable to active metabolites. The decreased oral propranolol clearance by chlorpromazine was seen as a shift to the left in the propranolol dose vs. AUCrelationship, eliminating the apparent nonlinear kinetic behavior of oral propranolol, and reducing the apparent oral threshold dose. Chlorpromazine's major, if not only, effect on propranolol disposition was to reduce the presystemic elimination of propranolol, possibly through inhibition of its metabolism via a pathway other than ring oxidation.This work was supported by a US Public Health Grant No. HL-22718.     

Modulation of the effects of salbutamol by propranolol and atenolol

Summary Six healthy volunteers were given single oral doses of 8 mg salbutamol, 40 mg propranolol, 100 mg atenolol, 8 mg salbutamol plus 40 mg propranolol and 8 mg salbutamol plus 100 mg atenolol, in a placebo controlled study.Plasma potassium fell following salbutamol and rose following atenolol or propranolol, and the hypokalaemic effect of salbutamol was reversed more effectively by propranolol than by atenolol. Although blood glucose rose after salbutamol, it was unaffected by any of the other treatments. Lying and standing pulse rate rose after salbutamol and fell equally after either -adrenoceptor antagonist, and fell more after salbutamol plus propranolol than after salbutamol plus atenolol. Blood pressure rose after salbutamol and fell after each of the other treatments.Forty milligrams propranolol was thus more effective than 100 mg atenolol in reversing the metabolic effects of 8 mg salbutamol, and was as effective in reversing the cardiovascular effects. In cases of symptomatic salbutamol overdose, propranolol should be considered as an antidote provided the patient is not asthmatic.     

The Pharmacology of a New Hypoglycaemic Agent N-[4-(2-(2,3-dihydrobenzo (b) furan-7-carboxamido)-ethyl)- benzenesulphonyl]-N′-cyclohexylurea (NOVO CS 476). II. Pharmacological Studies on the Mechanism of Action

Abstract The new sulphonylurea CS 476 does not potentiate the effect of insulin on plasma glucose levels in diabetic dogs in which an oral glucose load does not cause insulin release. In normal dogs propranolol 0.3 mg/kg intravenously inhibites the insulin release and the hypoglycaemia due to CS 476 suggesting involvement of β-adrenergic receptors in its action on the pancreas. Pretreatment of dogs with phentolamine leads to an augmentation of the insulin response to CS 476.     

Metformin for obesity and glucose dysregulation in patients with schizophrenia receiving antipsychotic drugs

Antipsychotic drug-induced weight gain and glucose dysregulation add to the cardiovascular risk of patients with schizophrenia and contribute to their early mortality. The currently recommended interventions to address the metabolic complications of antipsychotic drug treatment are to switch the patient from an antipsychotic drug with high metabolic liability to one with a lower liability and to implement lifestyle changes. These interventions can be quite challenging to carry out. So far the progress in improving the metabolic and cardiovascular outcome of patients with major mental illness has been disappointing. We offer an overview of the literature on metformin for antipsychotic drug-induced weight gain and glucose dysregulation and pertinent literature from the Diabetes Prevention Program. We conclude that young adults with schizophrenia newly exposed to antipsychotic drugs, who show a pattern of rapid weight gain and/or glucose dysregulation, are prime candidates for metformin if switching the antipsychotic medication to one with a lower metabolic burden is not an option or does not curtail the weight gain and/or adverse metabolic effects. Metformin therapy should not preclude healthy lifestyle interventions.     

Clozapine, risperidone, olanzapine, and conventional antipsychotic drug effects on glucose, lipids, and leptin in schizophrenic patients

Some reports have indicated increased rates of diabetes and increased prevalence of glucose and lipid abnormalities during treatment with second-generation antipsychotics, with most concern raised about clozapine and olanzapine. Most of the findings have come from case reports, retrospective examination of laboratory values, and analysis of health-care claims databases. This study investigated fasting levels of glucose, lipids, and leptin in a non-randomized, cross- sectional study of 210 patients, with schizophrenic or schizoaffective disorder, treated with a single antipsychotic medication - clozapine, risperidone, olanzapine, or a conventional antipsychotic. Glucose tolerance tests (GTT), with a 75-g glucose load, were preformed in a subset of patients. In this sample most mean fasting glucose and lipid levels were within the normal range and were not significantly different across the four drug treatment groups. Patients treated with clozapine and olanzapine had higher triglyceride levels than risperidone patients. In patients receiving a GTT, risperidone-treated patients had higher glucose levels at 1 h than patients treated with olanzapine, and there were more patients on risperidone who met American Diabetes Association glucose metabolic criteria for diagnosis of diabetes. Although there were no significant differences in age or body mass index among the four drug groups, we cannot rule out some potential biasing factors we did not assess which could potentially influence our results. These include unknown physician preference in drug selection based on their beliefs about the weight-inducing or diabetes potential of different antipsychotics, differences in visceral fat, and differences in patients' antipsychotic drug history.     

Effect of chlorpromazine on blood glucose and plasma insulin in man

Summary In three groups of normal subjects and in one group of patients with latent diabetes mellitus a study has been made of the effects of chlorpromazine (CPZ) on blood glucose and plasma insulin. CPZ 75 mg/day for 7 days did not alter the plasma insulin response after oral glucose; nor did CPZ 50 mg/day for 7 days affect the glucose assimilation rate or insulin response to glucose injection. Infusion of CPZ 50 mg in 60 min slightly increased the basal blood glucose level but had no significant effect on basal plasma insulin. The insulin/glucose ratio after the end of the infusion was significantly higher than during the period of infusion of the drug. In latent diabetic patients CPZ infusion significantly diminished the insulin/glucose ratio during an intravenous glucose tolerance test. These results suggest that, whereas prolonged treatment with low doses of CPZ did not modify glucose tolerance and glucose-stimulated pancreatic response, higher acute doses of the drug may induce hyperglycaemia and can inhibit insulin secretion both in normal man and in patients with latent diabetes mellitus.     

Comparison of enalapril and propranolol in essential hypertension

Summary In 40 patients with essential hypertension, enalapril was compared with propranolol as an antihypertensive agent in a double-blind study. The patients were randomly given either enalapril 5–10–20 mg bid or propranolol 40–80–120 mg bid in a treatment consisting of step-by-step increases in dosage. When the diastolic blood pressure remained >90 mm Hg on the highest dosage, hydrochlorothiazide was added. Both enalapril and propranolol reduced blood pressure, although the patients tended to achieve lower blood pressures while on enalapril. More patients on propranolol required additional diuretic therapy than patients on enalapril.Propranolol reduced heart rate; with enalapril there were no changes in heart rate. Both drugs increased serum potassium and urea. Plasma renin substrate was reduced by enalapril, but raised by propranolol. Enalapril increased plasma renin activity and angiotensin I, while propranolol reduced both. Converting enzyme activity was lowered with enalapril but was unchanged with propranolol. Both drugs reduced angiotensin II. Plasma aldosterone concentration was more suppressed with propranolol than with enalapril.     

The phenomenon of β-adrenergic hypersensitivity following propranolol withdrawal studied in normal subjects

Summary A study was carried out to determine whether beta-adrenergic hypersensitivity occurs in normal subjects following the abrupt withdrawal of the beta-adrenoceptor antagonist propranolol. Sixteen normal subjects took propranolol, orally, 120 mg twice daily for one week. Heart rate and blood pressure were measured supine and standing as well as during exercise. Heart rate was measured during and following the Valsalva manoeuvre. Measurements were made on the last day of the treatment period and on two occasions during the six days following withdrawal. Three subjects were removed from the analysis because of failure to take medication and one more was excluded because of protocol variation. In the remaining twelve, propranolol treatment reduced all parameters measured. Following abrupt withdrawal of the drug, there was no measurable increase in any of the parameters above baseline or placebo values within six days of the withdrawal. These findings, from normal subjects, do not support the phenomenon of beta-adrenergic hypersensitivity following propranolol withdrawal.     

尼可地尔、普萘洛尔和地尔硫治疗心绞痛的血流动力学

31例(男24,女7;年龄55±11yr)慢性稳定型心绞痛患者分4组,其中10例口服尼可地尔30mg,bid;7例口服普萘洛尔80mg,bid和9例口服地尔硫(艹卓)120mg,bid;5例为口服安慰剂组。并于首次服药后2h及持续服药2wk后进行踏车运动试验,观察比较药物对心绞痛患者休息或运动峰时的血流动力学变化。发现3种药物都能延长运动时间,延长心电图ST段呈缺血性压低1mm所需时间和心绞痛发作时间。     

糖尿病社区干预对2型糖尿病患者血糖水平的影响

目的：探讨社区干预对2型糖尿病患者空腹血糖与餐后2 h血糖水平的影响。方法：收集2015年2型糖尿病患者100例,分为研究组和对照组各50例,对照组给予常规综合健康教育方式干预,研究组采取KTH糖尿病社区干预的健康教育模式,两组均干预3个月。比较干预前后空腹血糖与餐后2 h血糖水平以及患者的遵医行为变化。结果：在干预前两组空腹血糖、餐后2 h血糖差异无统计学意义（P＞0.05）。干预后,研究组空腹血糖、餐后2 h血糖显著低于对照组（P＜0.05）。两组干预前的按时复诊、规范服药、血糖自我检测、选择健康生活方式比较差异无统计学意义（P＞0.05）。干预后,研究组按时复诊、规范服药、血糖自我检测、选择健康生活方式的比例显著高于对照组（P＜0.05）。结论：KTH糖尿病社区干预有利于充分发挥健康教育在糖尿病治疗中的功能,值得社区推广应用。     

葛根素治疗过早搏动

本文用葛根素治疗早搏13例,与对照组普萘洛尔9例,葡萄糖12例相比,葛根素对早搏症状改善总有效率为53％,早搏次数明显减少,与普萘洛尔作用相似,说明葛根素治疗早搏有一定作用。此药尚具有减慢心率与降压作用,但无任何副作用,毒性极低。与普萘洛尔相比无明显心肌抑制作用,不易诱发心衰,是其优点。