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Biomedical subjects

A Doenicke

Publications and source records attributed to A Doenicke.

At least 91 records · Page 5Linked to original sources
PubMed1984

[The action of the benzodiazepine antagonist Ro 15-1788].

The benzodiazepine-receptors are close by the GABA-receptors. They are found in all areas of the brain, especially in the area of the cortex. The imidazo-benzodiazepine Ro 15-1788 has a high affinity to the receptor without showing any biological activity. The antagonist Ro 15-1788 cancels the sleeping effect, which was produced by benzodiazepines, within 30-60 s. Deep phases of sleep after 4 mg per 70 kg body weight lormetazepam, a dose which was not in clinical use up to now as well as the sleeping effect of 2 mg flunitrazepam per 70 kg body weight and 10-11 mg midazolam per 70 kg body weight are safely antagonized without adverse reactions. According to pharmacodynamic researches by means of EEG and psychometry the half-life period of the antagonist is shorter (1-2 h) than that of the agonist. The clinical application of the antagonist Ro 15-1788 (in patients) is at hand. The control of benzodiazepine-N2O/O2-anaesthesia seems to be guaranteed with the introduction of the antagonist for clinical use.

Anesthesia↗
PubMed1983

[Preoperative anxiolysis with lormetazepam. A model for measuring anxiety].

Lormetazepam significantly reduced anxiety during local anaesthesia when compared with a placebo control group. There were significantly fewer accompanying symptoms of spinal anaesthesia under lormetazepam than under placebo. This number fell in relation to the decrease in the patients' anxiety. Lormetazepam also proved to be significantly superior to placebo according to the physician's assessment of anxiety. There were no differences between the two groups with respect to side-effects. The results of the Erlanger Anxiety Scale--Situative (EAS-S) revealed: 1. Oral treatment with lormetazepam led to markedly lower anxiety values than treatment with placebo (p less than 0.1; t test, one-sided). - 2. Following additional, intravenous administration of lormetazepam an even greater difference between the two treatment groups became evident. - 3. The situative anxiety was lower under treatment with lormetazepam than with placebo, independent of the variables "sex", "trait anxiety" or "anxiety control mechanism" (dimension of sensitization-repression). - 4. Women attained higher actual anxiety values than did men. - 5. Patients with high basic anxiety expectedly attained higher situative anxiety scores than those with lower basic anxiety.

Adult↗
PubMed1982

Histamine release in anaesthesia and surgery. premedication with H1- and H2-receptor antagonists: indications, benefits and possible problems.

Our clinical and experimental studies have so far demonstrated, that the drugs used in anaesthesia; such as hypnotics, sedatives, narcotics or muscle relaxants, release histamine. The intravenous short acting anaesthetic etomidate has not shown either in experimental studies or in clinical use for 10 years any anaphylactoid reaction. The benzodiazepines are another group of drugs which appear not to release high amounts of histamine. Accurate studies on volunteers as well as on patients on the application of H1- and H2-receptor antagonists have demonstrated an effective inhibition of the anaphylactoid reaction. We suggest that in case of a history of allergy H1- and H2-receptor antagonists should be administered as a prophylactic premedication.

Adjuvants, Anesthesia↗
PubMed1982

Prophylaxis of anaphylactoid reactions to a polypeptidal plasma substitute by H1- plus H2-receptor antagonists: synopsis of three randomized controlled trials.

To demonstrate the efficacy of a premedication with H1- + H2-receptor antagonists against histamine-release responses in anaesthesia and surgery 3 randomized controlled trials were conducted in patients, volunteers and experimental animals (dogs). Cutaneous anaphylactoid reactions following infusion of polygeline (Haemaccel) in orthopedic patients were successfully abolished by premedication with 0.1 mg/kg dimethpyrindene (Fenistil) and 5 mg/kg cimetidine (Tagamet). Chlorpheniramine (Piriton) was also useful, but dimethpyrindene was more effective in the doses recommended and used. Side-effects of the premedication were not observed when the 2 drugs were slowly administered (2 min each). Systemic anaphylactoid reactions following infusion of polygeline were completely prevented in volunteers by the same premedication (0.1 mg/kg dimethpyrindene and 10 mg/kg cimetidine). Life-threatening reactions could not be tested in human subjects, but were elicited in experimental animals (dogs). In this species which resembles man in its sensitivity against histamine, in plasma histamine levels and in response to polygeline life-threatening reactions were prevented or in especially severe cases diminished to such an extent by the premedication with H1- + H2-blockers that this premedication was finally judged to be very effective against histamine-release responses of any grade of severity. To confirm this clinically very important hypothesis more clinical trials in patients at risk for anaphylactoid reactions to drugs are urgently needed.

Adult↗
PubMed1982

Histamine release and hypotensive reactions in dogs by solubilizing agents and fatty acids: analysis of various components in cremophor El and development of a compound with reduced toxicity.

Anaphylactoid reactions in man following administration of drugs solubilized with cremophor El (polyethylenglycolglycerol riconoleate) are a considerable clinical problem. Since these reactions occur in dogs on first exposure and in pigs on second exposure, the 'dog model' was used in this communication to analyse components and chemical modifications of cremophor El and its components for their clinical effects, their hypotensive actions and their histamine-releasing capacity. Two series of experiments in 1978 and 1980 were performed in 144 adult mongrel dogs of both sexes. In these studies histamine release was not related to the effect of the solubilizing agents as tensides and was elicited by rather low doses (about 10--100 mg/kg i.v.). The effect of these substances on blood pressure and on blood histamine levels was connected with distinct chemical features: the most potent compounds were oxethylated and additionally esterified unsaturated or hydroxylated fatty acids. Several phases in hypotensive reactions were observed, including an immediate response, a delayed blood pressure response and a late response about 15--20 min after injection. Only the delayed response was associated with histamine release. The combination of cardiovascular effects and histamine release was fatal on some occasions indicating that histamine release can be dangerous. Compared to cremophor El, the tenside effect was equal, but the toxicity was reduced in oxethylated 12-hydroxystearic acid. It is recommended that this solubilizer should be used in further extended studies in animals and - if these are successful - in clinical trials.

Animals↗
PubMed1982

Plasma concentration and E.E.G. after various regimens of etomidate.

Etomidate was injected i.v. within 10 or 60 s at various doses. After etomidate 0.3 mg kg-1 the plasma concentration was 1.6 micrograms ml-1 at 1 min after the end of injection. For about 7 min a good hypnotic effect (stages C0-D2) was observed on the e.e.g. recording. For surgical procedures, however, a combination with analgesic drugs appeared to be necessary. When the dose of etomidate was increased (0.1-0.4 mg kg-1) a linear increase in plasma concentration and slow e.e.g. activity was observed concomitantly. Anaesthesia could be prolonged with additional injections or with continuous infusion. Each additional injection produced a steep increase in concentration of short duration with marked deepening of hypnosis. The infusion induced only a moderate increase in plasma concentration, whereas the depth of sleep during the period of infusion remained nearly the same. E.e.g. changes induced by etomidate are similar to those after barbiturates and other i.v. anaesthetics.

Adult↗
PubMed1981

[Influence of domperidone and metoclopramide on serum gastrin levels and gastric acid secretion (author's transl)].

The influence of Domperidone and Metoclopramide on the Serum Gastrin Level and Gastric Acid Secretion was investigated in a crossed, randomized double blind study in 12 male subjects aged 29 years on the average and presenting a healthy stomach. Neither after Domperidone nor after Metoclopramide could a significant change in Gastrin Level and Acid Secretion be observed. Since both Domperidone and Metoclopramide exert a motility promoting but not secretagogue effect on the upper gastrointestinal tract, both drugs are suitable for the treatment of disordered motility and evacuation related to ulcer disease, as well as for the treatment of postoperative gastroatonia.

Adult↗
PubMed1981

[The antagonistic effect of physostigmine on sedation by lormetazepam (author's transl)].

The purpose of this study was to determine the arousal effect of physostigmine after lormetazepam sedation on the human EEG. 12 male volunteers received 2 mg/kg bm lormetazepam and 30 minutes later physostigmine 2 mg preceded by atropine 1 mg. Generally an arousal effect of physostigmine could be clinically observed and more objectively demonstrated by reduced sleep stages in the vigilosomnogram (p less than 0.05). 2 volunteers did not fall asleep. 9 volunteers were awake 5-12 minutes after termination of physostigmine injection. 1 volunteer did not show any effect. Resedation and parasympathetic side effects did not occur. In earlier studies deep sleep stages after lormetazepam 1 or 2 mg/70 kg bm lasted 70 to 120 minutes. Physostigmine is recommended to counteract undesirable benzodiazepine induced sedation.

Anti-Anxiety Agents↗
PubMed1981

[Intramuscular application of midazolam. Its effect upon CNS and respiration (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 benzodiazepine with a pronounced sleep-inducing effect. Deep-sleep stages and respiratory depressions were observed after 5 mg i.v. Whether and in what dosage midazolam can be safely, i.e., without continuous monitoring administered i.m. must be shown by the analysis of larger study populations. After i.m. injection, there is rapid onset of action leading to sleep stages which are comparable only with those hitherto observed after i.v. injection.

Anti-Anxiety Agents↗
PubMed1980

H1 + H2-receptor antagonists for premedication in anaesthesia and surgery: a critical view based on randomized clinical trials with Haemaccel and various antiallergic drugs.

Histamine release by drugs used in anaesthesia and surgery has been often demonstrated in human volunteers, but only occassionally in patients. Three questions arose from these studies. (1) Is the incidence of histamine release high in patients during routine anaesthesia and surgery? (2) Can the clinical effects of histamine release in man be prevented by H1 + H2-receptor antagonists? (3) Are there any side-effects of such a premedication? These problems were investigated in patients and volunteers by randomized controlled clinical trials using only one of the histamine-liberating drugs in man, the plasma substitute Haemaccel. This drug was chosen because it causes a reproducible histamine release in man and because its mechanism of action in man is largely known. (1) Out of 600 orthopaedic patients 30 (5%) showed anaphylactoid reactions following Haemaccel infusion. 26 of these had a histamine release of more than 1 ng histamine/ml plasma. Using predictive values this gives an efficiency of the test by nearly 98%. (2) In volunteers the combination of an H1-plus H2-receptor antagonist (dimethypyrindene and cimetidine) completely prevented the clinical effects of histamine release by Haemaccel (9 allergoid and anaphylactoid reactions in the control group, none in the H1 + H2-group). The incidence of histamine release, however, remained unchanged. (3) The premedication was found to release histamine itself. Cimetidine was effective when given alone but especially in combination with chlorpheniramine (4 events out of 7 applications). The clinical side-effects of these premedication were mild since apparently the free histamine was largely blocked at the receptor sites. It is concluded that premedication with a combination of H1- and H2-receptor antagonists is indicated due to the high incidence of histamine release during anaesthesia and surgery induced by various drugs and treatments. Such premedication is effective but associated with mild side-effects. For this reason more extended clinical trials with dimethpyrindene plus cimetidine in patients are necessary before this premedication can be generally recommended.

Adolescent↗