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PubMed1988

Antivasodepressor action of antihistaminics determined ex vivo in the leg blood vessels of anaphylactic mice and rats.

In anaphylactic mice and rats vasodepression determined ex vivo in the isolated perfused hindlegs can partly be prevented by pretreatment of the animals with promethazine, cyproheptadine, astemizole, clemastine, cimetidine, and some of their combinations. Astemizole and clemastine were most active. However, there was no complete protection against vasodepression, indicating vasodepression mediators others than histamine to be involved in the development of vasodepression.

Anaphylaxis↗
PubMed1978

[Induction of hepatic tyrosine transaminase in rats by phenothiazine derivatives and analogs].

We have showed induction of tyrosine-alpha-ketoglutarate transaminase in hepatic cytosol of Rats (Wistar strain) five hours after intraperitoneal administration of tricyclic compounds (phenothiazine, iminodibenzyl, thioxanthene, thiophenylpyridylamin, dibenzocycloheptadiene, dibenzoxepin derivatives). Chemical structure of these molecules is very important: sulfur atom (phenothiazine, thioxanthene), some substituants like chlorine (chlorpromazine, chlorprothixene) and 2'-dimethylaminopropyl chain (promethazine) increase this inductive effect.

Animals↗
PubMed1987

[Effects of parathyroid hormone on the cardiovascular system].

It has been well accepted that the bone and kidney are the principal organs of parathyroid hormone (PTH) actions, but there has been little work on the cardiovascular system. We evaluated the effect of PTH on the cardiovascular system of rats. In thiobutabarbital anesthetized rats, synthetic bovine parathyroid hormone, containing the amino acid (b-PTH 1-34) in dose of 0.1-10 micrograms/kg iv, caused dose related decrease in mean arterial blood pressure (MAP). On the other hand, there were significantly increase in heart rate (HR) and left ventricular contractile force. With the doses of 10 micrograms/kg, PTH decreased the MAP from 104.3 to 55.5 mmHg, left ventricular pressure (LVP) 122.1 to 96.4 mmHg, left ventricular end diastolic pressure (LVEDP) from 6.70 to 6.37 mmHg and LV dp/dt max 5,684 to 4,736 mmHg/sec. The HR, LV dp/dt/p and Vmax increase from 399.7 to 410.0 bpm, 95.5 to 108.4/sec, 98.2 to 107.4/sec, respectively. The propranolol, phentolamine, atropine and promethazine did not affect these actions of PTH. On the basis of these findings, we conclude that PTH has the directory vasodepressive action and the effect of augmentation of the left ventricular contractile force.

Animals↗
PubMed1988

Antiplasmid activity of tricyclic compounds.

Three representative groups of tricyclic psychopharmacons were shown to have antiplasmid activity. The first group, e.g., comprises promazine, chlorpromazine, promethazine, levo- and dextromepromazine, thioridazine, diethazine, thiethylperazine. There are two heteroatoms (S and N) in the ring system of these compounds. In the second group, which includes desipramine, imipramine, however, there is only one heteroatom N, or S in chlorprothixene, chlorpenthixols and in the third group amitriptyline, maprotiline contain no heteroatoms. The medical significance of plasmid elimination by tricyclic psychopharmacons and related compounds in vitro is that this opens up a new perspective in the struggle against bacterial resistance to antibiotics. This approach utilizes the beneficial side-effect of the plasmid curing ability of these psychopharmacons, and may serve as a guideline for drug design in the future, to develop related substances which are potent in eliminating the drug resistance-carrying plasmids of bacteria, but which have no other pharmacological effects. Here we propose a new mechanism for plasmid curing by tricyclic drugs.

Antidepressive Agents, Tricyclic↗
PubMed1988

[Myocardial metabolism as affected by propofol in geriatric patients. A comparison with etomidate].

This study was designed to compare the effects of propofol and etomidate on myocardial metabolism in elderly patients without clinical manifestations of heart failure or coronary artery disease. Twenty geriatric patients (age 65-82 years) scheduled to undergo elective major upper-abdominal surgery were studied and randomly allocated to two equal groups (propofol and etomidate). All patients were premedicated with piritramide, 7.5 mg, and promethazine, 25 mg, intramuscularly 1 h before arrival in the anesthesia room. Ten patients received propofol (1.5 mg/kg) for induction of anesthesia, followed by 10-min infusion of an induction dose; thereafter, anesthesia was maintained with a continuous infusion of 0.1 mg/kg per min. Ten patients received etomidate, 18 mg, for induction, followed by 2.4 mg/min for maintenance. Vecuronium was used for neuromuscular blockade. Cardiovascular dynamics were recorded while the patients were awake, 1-2 min after induction during apnoea, and 1, 5 and 30 min after tracheal intubation without surgical stimulation. Coronary blood flow (argon wash-in technique with sampling of blood from the coronary sinus), myocardial oxygen consumption and myocardial uptake of glucose, free fatty acids and lactate were determined in the awake state and 5 and 30 min after intubation. Arterial plasma concentrations of propofol (high-pressure liquid chromatography with fluorescence detection) and etomidate (gas chromatography) were measured every 5 min throughout the investigation period, which lasted 45 min. Overall mean plasma concentrations of propofol were 3.69 +/- 0.16 micrograms/ml and of etomidate 1.1 +/- 0.16 microgram/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Effect of extracellular Ca++ omission on isolated hepatocytes. I. Induction of oxidative stress and cell injury.

The effect of varying extracellular Ca++ concentration and various antioxidants and metal ion chelators on the viability of isolated rat hepatocytes incubated under 95% O2-5% CO2 was evaluated. Decreasing the extracellular Ca++ concentration from 2 mM to 50 microM or less resulted in a progressive increase in cell injury as determined by lactate dehydrogenase (LDH) leakage. The generation of an oxidative stress, indicated by malondialdehyde formation, occurred before and concomitant with LDH leakage. The antioxidants vitamin E, N,N'-diphenyl-p-phenyl-enediamine, chlorpromazine and promethazine, as well as the iron chelators desferrioxamine and EDTA, all prevented both malondialdehyde production and LDH leakage induced by the absence of extracellular Ca++. A marked loss of cytosolic and mitochondrial glutathione was observed in cells incubated without Ca++, which could be significantly prevented by antioxidants and iron chelators. Similar effects on hepatocyte vitamin E levels also were noted. Addition of the Ca++ chelator ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid to the incubation medium totally prevented LDH leakage and malondialdehyde production and partially ameliorated glutathione and vitamin E loss. Conversely, cell injury resulting from disrupted cellular Ca++ homeostasis after treatment with the Ca++ ionophore A23187 plus 2 mM Ca++ was only slightly inhibited by antioxidants and iron chelators. However, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid also prevented A23187-induced cell injury. These results indicate that a decrease in extracellular Ca++ generates an oxidative stress in hepatocytes which leads ultimately to severe cell injury. This oxidative stress appears to be a Ca++-dependent phenomenon, precipitating all toxicity by a mechanism distinct from that induced by A23187 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Effect of drugs on granulocyte motility].

The in-vitro influence of drugs on the chemokinesis and chemotaxis of neutrophils was investigated in order to prevent additional drug-induced motility impairment of cells in cases of already existing host defense disorders and for an eventual specific treatment of motility defects. Granulocyte motility is unimpaired by penicillin, ampicillin, carbenicillin, streptomycin, nystatin, and cyclophosphamide. The chemokinesis and chemotaxis of neutrophils are inhibited by erythromycin, oxytetracycline, doxycycline, chloramphenicol, hydrocortisone, g-strophanthin, digoxin, and digitoxin and in higher concentrations also by sulfonamides, gentamycin, prednisolone, methylprednisolone, dexamethasone, and phenylbutazone. Chemotaxis is selectively or rather more inhibited than chemokinesis by amphotericin B, griseofulvin, vinblastine++, trifluoperazine, and promethazine. Granulocyte motility is, however, stimulated by ascorbic acid, potassium thiocyanate, levamisole, lithium, and metofenazate.

Anthelmintics↗
PubMed1987

[Comparative clinical studies of the hemodynamic parameters by anesthesia combination with Nalbuphin (Nubain) and Fentanyl].

UNLABELLED: The narcotic agonist-antagonist nalbuphine is reported to act as a strong analgesic with only minor respiratory depressant side-effects. Even in the postoperative period, the pain-relieving properties of analgesic drugs are reported to continue if the respiratory side-effects are being antagonized by administering nalbuphine. It was the aim of this study to investigate the analgesic properties of nalbuphine as compared to those of fentanyl, in suppressing the hemodynamic responses due to endotracheal intubation and skin incision. Furthermore, we are interested in studying postoperative analgesia and respiratory depression after using the two drugs during anesthesia. PATIENTS AND METHODS: Forty-one patients undergoing general surgical procedures were randomly assigned to two groups in a double-blind study. The patients were between 18 and 70 years old and belonged to ASA classes I-III. Patients with chronic obstructive pulmonary disease, cerebral vascular disorders, hepatic or renal failure, or those treated with monoamine oxidase inhibitors and tricyclic antidepressants were excluded from the study, as were patients with a drug dependency. All patients were premedicated with 25-50 mg each promethazine and pethidine. Anesthesia was induced with either 60-70 mg nalbuphine or 0.3-0.35 mg fentanyl, 2 mg alcuronium, 0.01 mg/kg flunitrazepam, and 1-2 mg/kg thiopental. All patients were intubated following 1-2 mg/kg succinylcholine. Five minutes following intubation they received another 30-40 mg nalbuphine or 0.15-0.2 mg fentanyl intravenously. Anesthesia was maintained with N2O:O2 2:1, alcuronium, and either nalbuphine or fentanyl and enflurane up to 1 vol.% or halothane up to 0.5 vol.%. Blood pressure, pulse rate, and arterial blood gases were measured at certain intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

[Nitrous oxide in combination anesthesia. Quantitative aspects of the effect of nitrous oxide].

UNLABELLED: Minimal Alveolar Concentration (MAC) defines the anesthetic potency of nitrous oxide (N2O) combined with an inhalational anesthetic only for the moment of skin incision. For the complete operation, the proportional action of N2O is unknown. This prospective, randomized study reports the mean intraoperative concentration (MIC) of halothane with and without 70% N2O in combination with premedication, i.v. induction, and muscle relaxation for the duration of operation. METHODS: Forty ASA I-II patients scheduled for hysterectomies gave informed consent. All patients received atropine 0.5 mg, promethazine and pethidine 1 mg/kg i.m. 30-45 min prior to anesthesia, i.v. induction with thiopental, and neuromuscular blockade with alcuronium at the beginning of the operation. Post-induction, patients received randomized halothane in 30% O2/70% N2 (group 1, n = 20) or in 30% O2/70% N2O (group 2, n = 20). In the course of this observation (before induction and up to 15 min after extubation), the following parameters were measured (Table 1): arterial pressure (AP), heart rate (HR), plasma concentrations of growth hormone, prolactin, and cortisol in central venous blood, esophageal temperature, "train-of-four" ratio, and expiratory CO2 concentration. MIC had been computed from the integral of end-expiratory halothane concentration during the course of the operation. RESULTS: Biometric data and concomitant conditions were equivalent within the two groups (Table 2). MIC halothane was 0.72 +/- 0.014 vol% in group 1 (O2/N2) and 0.52 +/- 0.01 vol% in group 2 (O2/N2O).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1988

[Reaction of the sympathetic nervous system, cardiovascular parameters and endocrine stress response in disobliterating interventions of the carotid arteries. A comparison of isoflurane anesthesia and modified neurolepto-anesthesia].

In order to investigate whether the increases in mean arterial pressure (MAP) and HR during carotid endarterectomy are due to a systemic, sympathicotonic stress response and to compare two anesthetic regimens for this operation, 20 patients were randomly allocated to the following groups: (1) modified neuroleptanesthesia with midazolam, fentanyl, and vecuronium: and (2) isoflurane anesthesia with vecuronium relaxation. Premedication (pethidine, promethazine) and induction of anesthesia were similar in both groups. The plasma levels of epinephrine and norepinephrine (by HPLC/ECD), ADH, ACTH, and cortisol (by RIA), glucose, lactate, and free glycerol were determined before and after induction of anesthesia, 7 times during the operation, and 30 min after extubation. MAP and HR were measured continuously. Statistical evaluation was undertaken by analysis of variance with repeated measures on 1 factor, considering P values of less than 0.05 as significant. The endocrine parameters failed to show any remarkable increase during the entire operation period. After the end of the operation all hormones rose significantly (P less than 0.001). No correlation was found between plasma catecholamines and increases in MAP and HR. Group levels of norepinephrine and ADH were higher in the isoflurane group (P less than 0.04). It is concluded that cardiovascular reactions during carotid endarterectomy are not caused by systemic stress. Neuroleptanesthesia leads to better stress protection in the postoperative period, while isoflurane anesthesia has some advantages for the intraoperative control of arterial pressure.

Adult↗
PubMed1987

[Therapy of paradoxical reactions to midazolam in regional anesthesia].

Many patients fear being awake in the operating room, and the acceptance of regional anesthesia is often made dependent on the promise of adequate sedation. With the introduction of the short-acting benzodiazepine (bzdp) midazolam, it seemed possible to achieve induction and maintainance of sleep throughout an operative procedure. This substance may, however, occasionally result in a "paradoxical reaction" (PR) characterized by agitated excitement, mental confusion, and uncooperativeness. We have treated this condition successfully with physostigmine, as documented here in two case reports where a possible interaction between promethazine and midazolam may have been responsible for the PR. The symptoms resemble some of those seen in the central anticholinergic syndrome, as further implied by the therapeutic effect of physostigmine, but an etiological difference may exist. A direct anticholinergic effect of bzdp's is described only following excessive doses. An indirect effect may result from the impact on GABA-receptors, which have been identified as structurally related to the bzdp receptors. Physostigmine itself is not bound at the bzdp receptor, but has been shown to block the binding of bzdp's to their receptors and to reverse sedation from midazolam, perhaps through an indirect stimulatory effect. Previous case reports have indicated the effect of physostigmine in reversing PR following various bzdp's. Without treatment, a PR during regional anesthesia frequently makes general anesthesia necessary in order to immobilize the patient sufficiently to make surgery possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Mechanism of stimulation of duodenal contractions by the greater splanchnic nerve].

The mechanism of duodenal motor activity stimulation has been studied in dogs during irritation of the chest area of the greater splanchnic nerve. It has been established that a stimulating effect of the splanchnic nerve was not removed either by bilateral vagotomy or by separate and combined injections of bretylium tosylate and benzohexamethonium, but was removed by the blockade of M-serotoninergic receptors of the autonomic ganglia with atropine or by the blockade of D-serotoninergic receptors of the smooth muscles with promethazine hydrochloride. The data obtained demonstrate the presence of noncholinergic and nonadrenergic fibers in the chest area of the greater splanchnic nerve, having a potent stimulating effect on duodenal contractions. According to our functional and biochemical tests, they are mediated by serotonin.

Animals↗
PubMed1978

The interaction between alcohol, chlorpropamide and phenformin in a severe combined poisoning: case report.

A young non-diabetic woman ingested 2.5-3.7 g of chlorpropamide and 0.6-0.9 g of phenformin together with a large dose of alcohol, nitrofurantoin and promethazine in a suicidal attempt. She developed severe metabolic acidosis, hypokalemia, polyuria and prolonged hypoglycemia in the absence of typical hypoglycemic symptoms. These unusual clinical features were in part explained on the basis of the interactions between alcohol and the other drugs.

Adult↗
PubMed1986

[Preoperative increase in the plasma concentration of free fatty acids during minor elective interventions using a conventional anesthesia technic with enflurane].

Plasma concentrations of free fatty acids (FFApl) can be used as a parameter to measure stress. The present study aimed to evaluate the changes in the concentration of FFA during perioperative stress caused by minor elective surgery under a standard anaesthetic technique using enflurane. The premedication administered included heptabarbital on the preoperative night and morphine with promethazine prior to the transfer of the patient to the theatre. Blood samples for the analysis of FFA were obtained from 12 patients at the following times: 1 day preoperatively (control, c), prior to induction of anaesthesia (s1), following the administration of thiopentone (s2), following tracheal intubation (s3), 10 min after the commencement of enflurane administration (s4), following surgical incision (s5), intraoperatively (s6), following extubation (s7), 1 h after extubation (s8), and on the 1st postoperative day (s9). FFA were extracted from plasma with hexane and analysed in duplicate by a specific and sensitive gas-chromatographic assay with flame ionisation detection using pentadecanoic acid as the internal standard. All FFApl from the preoperative day (c) were within normal range. FFA concentrations at s1, s2, s3 and (to a lesser extent) at s4 were statistically significantly increased compared to control values. The maximum concentration of FFA in plasma occurred at s2. A decrease from this maximum was found in samples s4, s5 and s6 (the latter was the minimum intraoperative FFApl). The FFApl levels at s7, s8 and s9 were similar to control. A different response was found for each individual free fatty acid. The maximum increase ranged from 40% (stearic acid) to 300% (oleic acid).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Liquid chromatographic determination of organic nitrogenous bases in dosage forms: a progress report.

A liquid chromatographic (LC) method has been developed as a general procedure for the assay of the salts of organic nitrogenous bases in a variety of dosage forms. The method uses a nitrile-bonded reverse phase column, a methanol-0.003M ammonium acetate (90 + 10) mobile phase, and photometric detection at 254 nm. The sample is dissolved in the mobile phase and an aliquot is injected through a 20 microL injection loop. Average recovery values for duplicate assays were chlorpheniramine maleate injection 97.8%, chlorpheniramine maleate tablets 99.1%, cyclizine hydrochloride tablets 100.0%, doxylamine succinate tablets 103.3%, mesoridazine besylate tablets 100.4%, pentazocine hydrochloride tablets 103.0%, promethazine hydrochloride injection 98.4%, protriptyline hydrochloride tablets 101.2%, pyrilamine maleate tablets 97.8%, pyrimethamine tablets 100.0%, tripelennamine citrate elixir 100.0%, and tripelennamine hydrochloride tablets 97.2%. Results by this method were in good agreement with those obtained by the USP XX method. This study, which is being continued, will be expanded to include additional drugs.

Chromatography, Liquid↗
PubMed1985

Immunotoxicity screening of drugs and chemicals: value of contact hypersensitivity to picryl chloride in the mouse.

Contact hypersensitivity to picryl chloride in the mouse is proposed as a valuable tool for the in vivo immunotoxicological testing of new compounds. Reproducibility was found to be excellent. Results obtained in the present work with chlorpromazine, cyclophosphamide, diazepam, haloperidol, hydrocortisone, promethazine and lead acetate, nickel chloride and selenium were similar to those previously reported regarding the effects of these compounds on cell-mediated immunity.

Animals↗
PubMed1985

The effectiveness of antioxidants in reducing paracetamol-induced damage subsequent to paracetamol activation.

Paracetamol toxicity was studied in isolated mouse hepatocytes. This drug produced a concentration- and time-dependent loss of cell viability. Exposure to 5 mM paracetamol produced a rapid fall in intracellular reduced glutathione (GSH) followed by a decrease in plasma membrane integrity. The antioxidant, diphenyl-p-phenylenediamine (DPPD) had no effect on either the loss of GSH, the binding of 14C-paracetamol metabolites to protein or the loss of plasma membrane integrity when hepatocytes were incubated in 5 mM paracetamol. When hepatocytes were exposed to paracetamol for 1 hr they showed a loss of plasma membrane integrity during the subsequent 7 hr incubation. DPPD, alpha-tocopherol and promethazine reduced this effect when added after the paracetamol exposure. It appears that paracetamol exposure initiates toxic events subsequent to the generation of the reactive metabolite but prior to cell death and that the progression of these events can be interrupted by compounds with antioxidant properties.

Acetaminophen↗
PubMed1985

The protective effect of different drugs in rats poisoned by sulfur and nitrogen mustards.

Based on the recent pathognomic accomplishment in the mechanisms of toxic actions, the favorable degree of protection was achieved by several drugs in acute poisoning of rats with sulfur and nitrogen mustards. It has been established that dexamethasone, promethazine, vitamin E, heparin, and sodium thiosulfate (a) prolonged the survival time in animals poisoned by 3 LD50s of toxic agents, (b) diminished the lethalty (with the protective indices ranging from 1.5 to 2.7), (c) antagonized the decrease of body weight, and (d) lessened the degree of pathological organ changes. The simultaneous administration of two or three of the drugs mentioned, of which sodium thiosulfate as chemical inactivator of the toxic agents was basic and consonant component, led to the further increase in effectiveness. It is concluded that satisfactory results obtained in this study speak in favor of the basic pathological effects of mustard gases, as well as possible causes and their possible ways of action as postulated by Dannenberg (1983).

Animals↗