Beta-blockers and psychic stress: a double-blind, placebo-controlled study of bopindolol vs lorazepam and butalbital in surgical patients.

One hundred patients scheduled for surgery participated in a randomized double-blind trial designed to evaluate the effects of acute treatment with two doses of bopindolol (1 mg:BP1;2 mg:BP2) in comparison with those of 2.5 mg lorazepam (LR), 75 mg butalbital (BT) and placebo (PL). Anxiety was evaluated by the STAI X1 questionnaire on the day before surgery, in the late afternoon (time 0: basal) and in the evening (time 1). At the same times patients were requested to play a game of manual skill called "Go Down". The next day, in the morning (time 2), the patients were given the same questionnaire and were asked a series of questions about their sleep and awakening. Mean anxiety scores were significantly increased over basal values at both time 1 and time 2 in the PL and LR groups and at time 2 in the BT group, but neither in the BP1 nor in the BP2 group. The time needed to perform the "Go Down" test was significantly shorter than the basal value for both BP groups and significantly longer for the BT group, while nonsignificant modifications occurred in the PL and LR groups. Positive effects were obtained in patients treated with BP, at both doses, on ease of "falling asleep", number of "night awakenings" and "reawakening mood" while LR and BT were mostly ineffective, except for BT on ease of "falling asleep". It was concluded that a beta-blocker such as bopindolol may be more effective than a benzodiazepine or a barbiturate for the prevention of anxiety symptoms induced by a clearly defined stress situation, such as awaiting a surgical operation.

A single blind comparison of dihydroergotoxine mesilate and clonidine for treatment of hypertensive emergencies.

The effectiveness and safety of dihydroergotoxine mesylate (DHT) and clonidine (CLO) as acute antihypertensive treatments were studied in a single-blind randomized controlled study of 28 patients hospitalized after abrupt increases in mean blood pressure (MAP) to more than 150 mmHg, with concomitant symptoms related to hypertensive status (16 patients). Intravenous infusion of 1.5 mg DHT significantly reduced both systolic (SBP) and diastolic (DBP) blood pressure from 227 +/- 2/128 +/- 2 mmHg to 160 +/- 4/94 +/- 2 mmHg by 1 hour after the onset of infusion (p less than 0.01). In patients given CLO, BP values fell from 221 +/- 3/123 +/- 3 mmHg to 166 +/- 5/95 +/- 3 mmHg after 150 minutes. After that BP values did not change significantly up to 6 hours after both treatments. One hour after the onset of infusion, mean heart-rate (HR) had decreased by 15 beats/min in the DHT group and by 10 beats/min in the CLO-group. Twenty-one per cent of the patients given DHT and 78% of the patients given CLO complained of mild or moderate side-effects. The results of this study showed that DHT is an effective and well tolerated agent for the treatment of hypertensive emergencies and can be used safely even when continuous monitoring of blood pressure cannot be carried out.

[Dihydroergotoxine mesylate in the treatment of senile cerebral insufficiency. Result of a long-term multicenter double-blind clinical trial with a placebo]. / Le mésylate de dihydroergotoxine dans le traitement de l'insuffisance cérébrale sénile. Résultat d'une étude clinique multicentrique en double aveugle contre placebo à long terme.

Many controlled double-blind clinical trials against placebo and other drugs have clearly demonstrated the activity of dihydroergotoxine mesylate (DHT) on some symptoms of chronic senile cerebral insufficiency (CSCI). In spite of this, there is still some controversy about the usefulness of DHT for treatment of CSCI, as it seems to be hard to transpose the results of these studies to treatment of a population with DHT. Trying to overcome this criticism, a multicenter double-blind, placebo-controlled long-term (1 year) clinical trial has been planned, using very simple criteria for patient selection and easy to use assessment devices. Fifty two centres distributed throughout Italy were invited and 40 took active part in the study. The present report deals with data collected for analysis on Aug. 31, 1982. On this date 559 patients entered the study and 458 were under treatment (229 on DHT 1.5 mg t.i.d. and 229 on placebo). 101 patients dropped out (48 on DHT and 53 on placebo). 388 patients (195 on DHT and 193 on placebo) had completed 6 months and 204 (111 on DHT and 93 on placebo) had completed 1 year of treatment. The data from patients who completed 6 and 12 months of treatment period were analyzed statistically using Student t tests for paired and unpaired data, the large number of patients being adequate protection against any non normality in the distribution of the data. Differences with 2P values of 0.01 or less were considered significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of effects of guanfacine and clonidine on blood pressure, heart rate, urinary catecholamines, and cyclic nucleotides during and after administration to patients with mild to moderate hypertension.

In a random trial, the effects of treatment and withdrawal of guanfacine were compared with those of clonidine in 20 uncomplicated hypertensive patients. Elevated blood pressure returned to normal or responded well in all the patients given either guanfacine once daily or clonidine thrice daily. The pulse rate was reduced comparably by both treatments after 12 weeks, but the effect of guanfacine developed more gradually. Both guanfacine and clonidine significantly inhibited urinary noradrenaline, dopamine, and cyclic nucleotide excretion, while urinary adrenaline levels were unaffected. Side effects occurred earlier during treatment with clonidine. After sudden withdrawal, all the parameters tended to increase gradually in the guanfacine group, reaching base line by days 4-6. In the clonidine group the increase was more rapid, with pretreatment values reached within the 2nd day, and sometimes these values were surpassed. After withdrawal of clonidine all the patients had one or more side effects, most of them occurring within 48 h, while only 60% of the patients in the guanfacine group reported the appearance of unwanted symptoms, on days 3-6. It is concluded that there are close similarities between the effects of guanfacine and clonidine on the parameters evaluated, except for dopamine excretion, which was significantly less affected by guanfacine. Marked differences were found after abrupt withdrawal, with guanfacine less likely to produce the "discontinuation syndrome," probably due to its long half-life.

Effects of pindolol and metoprolol on plasma lipids and lipoproteins.

1 The effects of two beta-adrenoceptor blocking drugs, pindolol and metoprolol, on plasma lipids and lipoproteins were studied in sixteen hypertensive patients (WHO I-I) by a cross-over design, with two active treatment periods of 12 weeks each. 2 Neither pindolol nor metoprolol had any effect on total plasma cholesterol (total-C), triglycerides (TG) or low-density lipoprotein cholesterol (LDL-C). 3 Pindolol significantly increased high-density lipoprotein cholesterol (HDL-C). After metoprolol, HDL-C levels remained similar to those in the placebo period. 4 The ratio of total-C to HDL-C was significantly reduced by pindolol only. 5 Compared with the placebo period, both pindolol and metoprolol significantly reduced heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure. The decreases in HR were significantly greater after metoprolol. No differences between the effects of the two drugs on SBP and/or DBP were observed.

Pirenzepine in duodenal ulcer. A multicentre double-blind controlled clinical trial, First of two parts.

Eighty-four patients with endoscopically-proved active duodenal ulcer were admitted to a multicentre double-blind trial with either pirenzepine tablets (25 mg three times per day for 1 week followed by 25 mg two times per day for 3 weeks) or placebo. Seventy-nine patients completed the trial, 44 treated with pirenzepine and 35 with placebo. After 4 weeks, complete healing had been achieved in 52% of the pirenzepine-treated patients and in 34% of the placebo-treated ones. Symptomatic responses were signigicantly better in those receiving pirenzepine than in those receiving placebo. In addition, the supplementary antacid consumption was significantly lesser in the pirenzepine group than in the placebo group. No important side-effects were observed in the two groups.

Pirenzepine (LS 519) in severe duodenal ulcer and in gastric ulcer. A double-blind clinical trial.

Duodenal ulcer. Forty-five of 49 adult outpatients with active, severe, endoscopically proven duodenal ulcers completed a 4-week double-blind trial comparing two doses of LS 519 (75 and 150 mg/day) with placebo. After 2 weeks, 1 of 15 patients given LS 75 mg and 4 of 15 given LS 150 mg/day had healed (P = 0.09). No patient given placebo had healed. After 4 weeks, 6 of 15 (40%) on placebo, 9 of 15 (60%) on LS 75 mg and 13 of 15 (86.7%) on LS 153 mg had healed (P less than 0.01). Patients given the highest dose of LS had significantly more pain-free days and nights and took fewer antacid tablets than those receiving the lowest dose of LS or placebo. Gastric ulcer. 19 of 20 adult outpatients with endoscopically proven active benign gastric ulcers completed a double-blind 4-week trial with either LS 519 (75 mg/day) or carbenoxolone (300 mg/day). Six of 10 (60%) given LS and 6 of 9 (66.7%) given carbenoxolone had healed after 4 weeks (N.S.). Symptomatic improvement was significantly faster in the LS group than in the carbenoxolone group. Hypokaliemia, increases in alkaline phosphatase and SGOT were observed in the carbenoxolone group.

Pirenzepine in peptic ulcer. Introduction to clinical trials reports.

The main pharmacodynamic characteristics of pirenzepine are briefly reported and the experimental plan of the clinical trial on pirenzepine in peptic ulcer is discussed.

Hypotensive action and side-effects of flutonidin in normal subjects. A double-blind controlled trial.

In a double blind study, planned as a 7 x 7 latin square, three oral doses of flutonidin (0.5, 1, 2 mg), of clonidine (0.0075, 0.150, 0.300 mg) and of a placebo were administered to 7 normal volunteers on 7 different treatment days, with an interval of 3 days. On each treatment day sitting blood pressure, heart rate and reaction time were measured, and sedation and dry mouth evaluated before the 1, 2, 3, 4, 6, and 8 h after administration. The placebo did not modify the basal value of any variable. Flutonidin and clonidine produced dose-related effects on blood pressure, heart rate, sedation and dry mouth, but did not influence reaction time. Analysis of the dose-response curves demonstrated that the effect of flutonidin was one-fifth to one-twelfth that of clonidine, depending on which variable was considered.