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Biomedical subjects

R Amrein

Publications and source records attributed to R Amrein.

At least 55 records · Page 3Linked to original sources
PubMed1981

[Relationship between clinical effects and pharmacokinetics of midazolam on i.m. and i.v. application to volunteers/1st comm.: Clinical aspects (author's transl)].

The onset of action of 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo [1,5-a] [1,4] benzodiazepine (midazolam, Ro 21-3981, Dormicum), after i.v. injection of 12.5 mg, occurs towards the end of the injection and reaches its maximum level in about 3 min. After i.m. injection, the first effects are generally seen about 5 min later. The maximum effect is reached in about 20 min. Psychometric tests tend to return to normal within 2 h after the injection and are completely normalized within 4 h. Although no objective effect was measurable, the subjects sometimes reported subjective effects lasting up to 6 h. These were mainly signs of mild residual fatigue. The objective and subjective symptoms disappeared after 6 h. General and local tolerance was excellent. A transient sensation (lasting a few minutes) of slight burning was mentioned by some subjects after i.m. injection. Midazolam is therefore a sleep-inducing agent distinguished by rapid and regular onset of action, relatively short duration of action and a low incidence of side effects.

Adult↗
PubMed1981

Evaluation of the efficacy and tolerance of orally administered midazolam as hypnotic agent compared with oxazepam in the treatment of insomnia of mild to moderate severity.

In a double-blind parallel study performed in 40 hospitalized patients, suffering from mild to moderate insomnia, the efficacy and tolerance of 15 mg of 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) administered p.o. were compared with those of 7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one (oxazepam) in the same dosage. The results show comparable values for the two drugs but with significantly better results for midazolam in the parameters: time taken to fall asleep and number of nocturnal awakenings.

Anti-Anxiety Agents↗
PubMed1981

[Pharmacokinetics of midazolam after i.v. administration (author's transl)].

8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a] [1,4] benzodiazepine (midazolam, Ro 21-3981, Dormicum) is a special type of benzodiazepine. Its salts are water-soluble and also stable in an aqueous solution. Following i.v. injection of the substance, the human body eliminates midazolam almost entirely by means of biotransformation. Following rapid i.v. injection of midazolam into 8 normal volunteers, the plasma concentration of the substance decreases to approximately 10% within 1 h owing to a rapid rate of distribution. The biological half-life in the terminal phase (beta) ranges between 1 1/2 and 2 1/2 h. In view of the non-dose-dependent clearance and the various phases of distribution, the pharmacokinetic behaviour of the drug can be described by means of a linear three-compartmental model. The portion of drug extracted by the liver ranges between 40 and 50%, which implies a liver first-pass effect of approximately 50% after oral administration. The total plasma clearance is 300-350 ml/min. The absorption rate after i.m. injection is extremely rapid, with complete absorption taking place.

Adult↗
PubMed1980

Pharmacokinetic and clinical observations on prolonged administration of flunitrazepam.

Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration of the tablet on days 4, 7, 11, 14, 18, 21 and 25. Clinically there were not changes during the trial period in the onset of sleep, duration of sleep, depth of sleep measured as number of spontaneous awakenings, or in the patients' condition on awakening. The time-course of the plasma concentration of flunitrazepam could be described by a three-compartment model, assuming that the rate constants remained unchanged during treatment. Maximal plasma concentrations of unchanged flunitrazepam, found two hours after intake, reached 10-15 ng/ml after the first and 15-20 ng/ml after the last dose. The beta-half-life was found to be between 20 and 36 h.

Adolescent↗
PubMed1979

Effect of intravenous glibornuride and tolbutamide on myocardial contractility.

The acute effects of therapeutic doses of intravenous tolbutamide and glibornuride on the systolic time intervals (QS2c, LVETc, PEPc and PEP/LVET) were examined in 5 healthy volunteers. Blood sugar was maintained constant throughout the study. No significant changes of these intervals as well as of heart rate and blood pressure were observed. Therefore, it is concluded that tolbutamide and glibornuride have no acute positive inotropic action.

Adult↗
PubMed1979

Effects of smoking and inhalation of carbon monoxide on systolic time intervals and blood pressure. Differences between two types of cigarettes and a cigar.

The effects of smoking and inhalation of carbon monoxide on the systolic time intervals and blood pressure were examined in ten healthy smokers with a mean age of 24.3 years. Each subject smoked a low-nicotine cigarette with a ventilated filter (0.1 mg nicotine, 1.1 vol percent CO), and a high-nicotine plain cigarette (2.6 mg nicotine, 4.5 vol percent CO), as well as a cigar in random sequence and in a standardized way. Cigar smoke was not inhaled. The product heart rate x blood pressure was increased and the left ventricular ejection time index (LVETc) prolonged following smoking the high-nicotine cigarette, whereas changes after smoking the low-nicotine cigarette and the cigar were not as pronounced. These changes are presumably caused by nicotine-induced catecholamine release. Inhalation of CO did not affect cardiac performance acutely as shown by unchanged systolic time intervals. When a high-nicotine cigarette was smoked after the subject received a beta blocker, a significant prolongation of the pre-ejection period index (PEPc) occurred as a result of the increased afterload. Thus, the effects of catecholamines on parameters of myocardial contractility (PEPc, PEP/LVET) were presumably offset by the increased afterload. We conclude that the acute hemodynamic changes of smoking in healthy subjects depend upon the amount of nicotine absorbed.

Adult↗
PubMed1979

Therapeutic effects of pindolol and nifedipine in patients with stable angina pectoris and asymptomatic resting ischemia.

A single blind randomized parallel study designed to assess the anti-anginal efficacy of pindolol and nifedipine was carried out in 42 ambulatory coronary patients with stable angina pectoris. Drug efficacy was assessed in terms of (a) pain, (b) frequency of anginal episodes, (c) nitroglycerin consumption, (d) exercise tolerance and (e) ST-segment changes. The effect of these drugs on asymptomatic resting myocardial ischemia was also assessed by means of 24-h dynamic electrocardiography (DCG). All patients were checked at weekly intervals. At the end of a 4-wk placebo period, the patients were randomly assigned either to the pindolol or nifedipine group. The treatment lasted for 45 days. During the placebo period, ischemic ECG changes and symptoms of coronary insufficiency were detected in all patients. Furthermore, 12 out of 42 patients had asymptomatic myocardial ischemia at rest. One patient from each group was dropped because of tolerance. At the end of the 45-day study, pindolol and nifedipine were equi-effective on spontaneous and effort-related angina. There were, however, some differences: increased tolerance to exercise appeared earlier with pindolol: the pindolol group showed a slightly reduced while the nifedipine group showed a slightly increased heart rate. Furthermore, nifedipine reduced or eliminated asymptomatic myocardial ischemia in 6 out of 7 patients while only 1 out of 5 improved in the pindolol group.

Adult↗
PubMed1979

The therapeutic value of clonidine in patients with coronary heart disease.

11 coronary patients, 8 with mild hypertension, were treated with clonidine, at a dose of 75 micrograms b.i.d. per os for a week. The effect of the drug on coronary heart disease was assessed by means of a symptom-limited multistage exercise test on the cycloergometer. Clonidine was effective in reducing the exercise-induced increases in blood pressure (by 15.5 +/- 6.1%), the double product (by 34.8 +/- 20.8%) and the electrocardiographic ischemic changes. In 2/4 patients, effort related ventricular extrasystoles were reduced by greater than 50% after clonidine. The drug worsened the anginal pain in 3 and relieved the pain in 3 patients. However, it reduced the exercise-induced ST-T segment downsloping in 7 patients. The tolerance was good, since only 3/11 patients reported slight dry mouth, sedation and pyrosis. In view of the electrocardiographic effect, further studies with clonidine on myocardial ischemia should be performed.

Angina Pectoris↗
PubMed1977

The antihypertensive effect of lexotan (bromazepam)- a new benzodiazepine derivative.

Clinical observations led to the assumption that there is an antihypertensive effect of bromazepam in patients suffering from mild benign hypertension. Because of this observation we studied the antihypertensive effect of bromazepam by means of a standardized simple submaximal ergometric load performed weekly over a 4-week period of observation. A control group of 68 hypertensive patients without any drug therapy but under active physical training combined with physiotherapy and medicinal baths showed only a slight decrease in systolic and diastolic blood pressure at rest (about 4%). Furthermore, the pulse frequency did not change. In contrast, there was a distinct and significant decrease in blood pressure at rest and during exercise after a 3-week period of additional treatment with bromazepam, especially in hypertensive patients. One group of 68 hypertensive patients receiving 9 mg bromazepam daily showed a mean reduction in blood pressure by 14.4% systolic and 12.7% diastolic at rest, and during exercise by 7.5% systolic and 6.8% diastolic. The heart remained practically unchanged. A somewhat slighter decrease of the blood pressure values was seen in an additional group of 31 hypertensive patients receiving 6 mg bromazepam per day and in a group of 30 normotensive patients receiving 9 mg bromazepam daily. The calculated indices such as the product of heart rate and mean systolic pressure and the tension time index in the groups receiving bromazepam pointed to a better economic work performance under reduced myocardial pressure effort and reduced oxygen demand on the myocardium. The possible action of bromazepam in reducing blood pressure will be discussed.

Anti-Anxiety Agents↗