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PubMedDate not supplied

[Psychotropic properties of oxytocin].

Oxytocin neurotropic qualities were investigated in "reserpine depression" tests under ethanol and levomepromazine anesthesia, phenamine depression, haloperidol catatonia and swimming of experimental animals in the cylinder. Twenty seven patients with schizophrenia were treated with the hormone mentioned, injected intravenously and/or intranasally, using a double blind control test. The activating psychotropic oxytocin effects were revealed, allowing one to utilize it as a therapeutic means for psychosis treatment.

Adult↗

PubMedDate not supplied

Interactions of propranolol with some analgesics.

The duration of the analgesic effect of levomepromazine was prolonged in mice when associated with propranolol. The administration of morphine to animals treated with propranolol resulted in an increase of morphine toxicity with death of some animals.

Animals↗

PubMed1981

[Pharmacological influences on the brain level and transport of GABA. II) Effect of various psychoactive drugs on brain level and uptake of GABA].

The effects of some psychoactive drugs on the level and uptake of GABA in the mouse brain was studied using well standardized procedures, mainely the silica-gel cromatography for determining the GABA content and the brain slices for measuring GABA uptake. It was found that levomepromazine, sulpiride, haloperidol and amytryptiline were without effects on the cerebral level of GABA; it was also found that these drugs do not influence the rates of uptake of GABA by mouse brain slices. Such results do indicate that the psychoactive drugs studied are without effects on the level and uptake of GABA in the brain.

Amitriptyline↗

PubMed1995

Death due to asphyxia linked to antipsychotic drugs.

A 46-year-old man with schizophrenia, died in hospital. Autopsy revealed numerous facial injuries and the direct cause of death was apparently asphyxia as a large amount of coagulated blood was present in the lower part of the trachea and bronchi. The blood derived from a lacerated wound of the mouth. The question was raised as to why expectoration was impossible and a toxicological analysis was directed to the antipsychotic drugs allegedly prescribed by doctors at the hospital. Using gas chromatography and gas chromatography/mass spectrometry, four different antipsychotic drugs including chlorpromazine, levomepromazine, zotepine and haloperidol were identified in the whole blood and tissues with concentrations being 1.91, 0.75, 0.61 and 0.48 micrograms/g in the blood, respectively. These levels were toxic to the extent that he could not expectorate and blood accumulating in the airway led to asphyxia and death.

Antipsychotic Agents↗

PubMed1994

[A case of acute renal failure in neuroleptic malignant syndrome associated with rhabdomyolysis--possible contributing role of hyperreninemia].

A schizophrenic woman, aged 45, was admitted complaining of high fever, oliguria, blackish urine, muscle swelling and pain. She had been treated for the past 3 years with haloperidol (8 mg), levomepromazine (150 mg), chlorpromazine (75 mg), lithium carbonate (600 mg), bromocriptine mesilate (7.5 mg), etizolam (1 mg), and flunitrazepam (2 mg), Physical examination revealed her to be an obese and uncommunicatable woman with swelling and weakness of the extremities and abdominal distension without borborygmus. Urine was dark brown and (+) for protein and occult blood. Blood chemistry analysis revealed BUN 71 mg/dl, creatinine 6.8 mg/dl, CPK 143,850 IU and myoglobin 3,980 ng/ml. PRA on the 11th hospital day was 96 ng/ml/hour. This patient fulfilled the Levenson's diagnostic criteria for manifestations of neuroleptic malignant syndrome (NMS). High PRA did not decrease after cessation of the diuretics. After treatment with dantrolene sodium and 10 treatments with hemodialysis, azotemia disappeared with the start of diuresis. The PRA also decreased to the normal level. Characteristic acceleration of the central sympathetic stimuli in NMS seemed to have induced hyperreninemia, which together with rhabdomyolysis, might have contributed to the development of acute renal failure.

Acute Kidney Injury↗

PubMedDate not supplied

[Diagnostic difficulties and efficacy of electroconvulsive therapy in the treatment of lethal catatonia].

This publication presents a case of 38-year old woman suffering from schizophrenia, whose body temperature reached 41 degrees C after she had taken 1250 mg of levomepromazine during a suicide attempt. Initially, the dominant symptoms were quantitative and qualitative disturbances of consciousness and periodically increased psychomotor activity, negativism, hallucinations, delusions, schizophrenic disturbances of affect became prominent. When the patient was hospitalized on the internal diseases ward, only symptomatic treatment was conducted, while the cause of the patient's high temperature was still investigated. Only when acute lethal catatonia was diagnosed and ECT was used, did the patient recover. In the event of rapid onset of high temperature in a patient with a mental disorder, a possibility of acute lethal catatonia must be always considered. A differential diagnosis of this disorder with neuroleptic malignant syndrome is very important, as the treatment is quite different. Many M.D.s aren't aware that high body temperature may be a symptom of a mental disease.

Adult↗

PubMedDate not supplied

[Acute catatonia and neuroleptic malignant syndrome. A case of infantile psychosis].

Similar clinical and biological features in lethal catatonia (LC) and neuroleptic malignant syndrome (NMS) suggest a relationship between both affections and common physiopathologic mechanisms. Pharmacological effects of several drugs--dopaminergic agonists, benzodiazepines, carbamazepine--suggest an impairment of several systems of neurotransmitters. We report the case of a young woman with infantile psychosis who developed catatonic syndrome worsened by neuroleptic treatment, arising the problem of the chronology of both affections. The evolution with treatment may partially explain the physiopathology. A 18-year old woman with an history of infantile psychosis, experienced insomnia, anorexia, paradoxical agitation developed after affective traumatism (mother's hospitalization). Chlorazepate (150 mg) remained inefficient and hospitalization was necessary. The patient was dumb, prostate in bed. She presented negativism, rigidity of the four limbs, catalepsia and hyperpyrexia (38.5 degrees C). Hepatic transaminases were increased (SGOT: 71 UI/l; N < 30). After cumulated dose of levomepromazine (100 mg) profuse sudation, thermic and cardiovascular instability, alteration of consciousness, major rigidity of limbs appeared. (Blood) hepatic transaminases and muscular enzymes increased. Bacteriological samples, cerebrospinal fluid analysis, CT-scan and EEG were normal. Within 48 hours after rehydratation and bromocriptine (30 mg per day) alteration of consciousness and autonomic disorders decreased but hyperpyrexia (38 degrees C) persisted. Biological parameters were normalized 10 days later. Negativism and psychomotor inertia remained. Lorazepam (3 mg per day) failed to be clinically beneficial. On carbamazepine (600 mg per day) she started speaking and moving spontaneously. Catalepsia disappeared but rigidity and anorexia persisted. Electroconvulsivotherapy (ECT) was necessary. After 2 shocks she started standing up, walking, taking food and speaking fluently.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1994

[Emergency caesarean section for a patient with chronic schizophrenia].

A 39-year-old female with chronic schizophrenia underwent an emergency caesarean section under general anesthesia at her 39th week of gestation. A diagnosis of schizophrenia was made at 28 years of age and since then oral antipsychotic drugs, haloperidol and levomepromazine had been given orally. She had only taken haloperidol 4 mg per day between the 12th week of gestation and the day of surgery. At the 39th week of gestation, she developed a marked excitement which would have caused fetal distress. We decided to terminate her gestation. As the excitement was diagnosed as psychokinesis, we avoided using phenothiazine which might affect fetus and administered haloperidol 5 mg intramuscularly 210 and 30 minutes before emergency caesarean section. Anesthesia was induced with intravenous thiopental 300 mg and suxamethonium 60 mg. Pentazocine 30 mg in combination with nitrous oxide 70% in oxygen was given for the maintenance of anesthesia. During operation blood pressure was 160-180/80-90 mmHg, the heart rate was 90-100 beats.min-1. Hypertension and tachycardia might have been partially due to preoperative haloperidol. The induction-delivery time was 4 minutes 30 seconds. Plasma haloperidol levels were 23.8 ng.ml-1 in maternal venous blood and 8.8 ng.ml-1 in umbilical vein just after the delivery. The Apgar score was 7 at one minute and 8 at five minutes after delivery. The baby developed slight muscle weakness and poor sucking for two days after delivery and this was supposedly due to effect of preoperative haloperidol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Effects of the combination of ketoconazole and calmodulin inhibitors against Candida albicans in vitro. Short communication.

The susceptibility of 66 strains of Candida albicans from patients was tested against ketoconazole (Ktz), chlorpromazine (Chl) levomepromazine (Lev), haloperidol (Hal) and the combination of Ktz with these calmodulin inhibitors, using Sabouraud's broth. The minimal inhibitory concentrations (MICs) for 66 strains of C. albicans were as follows: Chl 192 +/- 11.4 micrograms/ml, Lev 306 +/- 16.4 micrograms/ml, Hal 464 +/- 13.8 micrograms/ml compared with Ktz 34.46 +/- 3.9 micrograms/ml. The combination of Ktz and calmodulin inhibitors in various ratios (1:1,1:2,2:1) was found to exert synergistic effect and the mean values of the combinations were: Ktz+Chl 3.45 +/- 0.35, 3.78 + 0.36, 5.58 + 0.4 micrograms/ml; Ktz+Lev 10.8 +/- 2.19, 9.7 +/- 2.23, 10.5 + 2 micrograms/ml; Ktz+Hal 6.4 +/- 1.7, 6.8 +/- 1.6, 7.28 +/- 1.5 micrograms/ml. These results were significantly different (p < 0.001) from those of ketoconazole. These findings indicate that some calmodulin inhibitors increase the antifungal activity of Ktz against C. albicans in vitro.

Calmodulin↗

PubMed1977

Influence of the antiparkinsonian drugs on the plasma level of neuroleptics.

The interaction between various neuroleptics and antiparkinsonian drugs was analyzed by measuring the neuroleptic plasma level before and after withdrawal of antiparkinsonian drugs. The population completing the study consisted of 32 chronic schizophrenics treated with chlorpromazine (8), levomepromazine (14), thioridazine (6), or haloperidol (4). Twenty-five were also receiving benztropine; 4, trihexyphenidyl; and 3, procyclidine. During the first 4 weeks patients remained on neuroleptics and antiparkinsonians, the latter being withdrawn during the 5th week, and the neuroleptics alone being administered during 16 following weeks. The plasma level of neuroleptics was assayed by gas liquid chromatography, once weekly in the morning at two different times. The analysis of variance showed a significant difference in neuroleptic plasma level when patients took neuroleptics only versus the period they had received neuroleptics and antiparkinsonians. The multiple comparison based on Studentized range Q0-05 revealed a significant progressive increase of neuroleptic plasma level during 12 weeks after withdrawal of antiparkinsonian drugs after which a plateau was reached. The hypothetical mechanisms of action of antiparkinsonians on neuroleptic plasma level are discussed.

Adult↗

PubMed1996

Screening of antipsychotic drugs by wide-bore capillary gas chromatography with nitrogen phosphorus detection--detection levels in plasma.

The detection levels of 12 antipsychotic drugs as ascertained from drug screening were examined in order to use the screening results effectively for treatment of patients or medico-legal examinations in cases of poisoning. Wide-bore capillary gas chromatography with nitrogen phosphorus detection was used for the analysis. The detection limits of drugs in plasma using 3 extraction procedures, single-solvent, 3-step solvent and solid-phase extractions were 50-100 ng/ml, 10-200 ng/ml and 5-50 ng/ml, respectively. The detection limits were compared with blood levels previously reported in the literature. Only 4 drugs were detected at the therapeutic level, thioridazine, floropipamide, sultopride and oxypertine using the single-solvent extraction procedure. Using the 3-step solvent extraction procedure, chlorpromazine, levomepromazine and zotepine in addition to the above 4 drugs were detected. Using the solid-phase extraction procedure, 8 of 12 drugs were able to be detected at the therapeutic level, with the exception of perphenazine, haloperidol, bromperidol and nemonapride. These data were proved to be useful for a rapid forensic diagnosis.

Antipsychotic Agents↗

PubMedDate not supplied

Therapeutic drug monitoring and drug-drug interactions: a pharmacoepidemiological perspective.

The present study investigates the potential of therapeutic drug monitoring databases to document co-medication as a possible risk factor for subtherapeutic or excessively high concentrations of psychotropic drugs. Exposure was defined with respect to co-medication including one of five agents known for their capacity to induce (phenytoin, phenobarbital and carbamazepine) or to inhibit (thioridazine and levomepromazine) the metabolism of psychotropic drugs. 87 patients exposed to such co-medication were matched by sex, age and monitored psychotropic medication with 87 patients randomly selected from a pool of subjects whose co-medication did not include any substance known to interact. Outcome was defined with respect to dose-normalized concentrations being below or above therapeutic range. When taking all psychotropic drugs together, the estimated relative risk to reach concentrations above the therapeutic range was 7.8 for patients exposed to phenothiazine co-medication. The relative risk to remain at subtherapeutic level was 2.7 for patients with inducers. When considering the different psychotropic drugs separately, a coherent picture was observed, with increased risk ratios for all substances.

Drug Interactions↗

PubMed1996

[A case of malignant neuroleptic syndrome. Case report].

We report on a woman patient with organophosphate poisoning resulting from a psychotically motivated suicide attempt. After detoxification and during treatment with haloperidol and levomepromazine, she developed acute malignant neuroleptic syndrome (MNS) in which dyspnea requiring assisted ventilation was the main symptom. Discontinuation of the neuroleptics was enough to effect sufficient recovery. With this case report, we would first like to emphasize that MNS can evolve within a very short time into a severe and life-threatening situation requiring intensive medical care, and secondly to illustrate the implications of organophosphate poisoning and the consequent cholinesterase blocking far the differential diagnosis of MNS.

Adult↗

PubMedDate not supplied

Trends in registered psychiatric morbidity and forecasting psychotropic drug needs in Bulgarian hospitals.

Registered psychiatric morbidity in Bulgaria as a whole and particularly in Plovdiv, the second largest region of the country, was assessed. Three aspects of psychotropic drug usage were analysed, namely, changes in registered psychotropic drugs, the prescribed daily dose (PDD) values for 2 years, and the preferred therapeutic schemes, and drug usage and needs in a psychiatric hospital with 365 beds. This was done by time series analysis for evaluation of psychiatric morbidity and drug consumption data, calculation of PDD for psychotropic medicines, and, based on a modification of the World Health Organization's morbidity method, assessment and prediction of drug use and needs in Plovdiv hospital. The results indicated that the registered morbidity had increased by 4% over the period 1989-93 to 2,427 psychiatric patients per 100,000 people. The increased consumption of especially benzodiazepines and sedative medicines was analyzed. Diazepam was prescribed the most often (91.1%), followed by levomepromazine (86.4%), haloperidol (82.7%), etc. Future drug consumption in Plovdiv hospital is expected to decrease because therapeutic practice in hospitals has been revised and improved on the basis of the World Health Organization's recommendations.

Bulgaria↗

PubMed1997

Effect of phenothiazines on activated macrophage-induced luminol-dependent chemiluminescence.

The inhibitory effect of some phenothiazine neuroleptics (chlorpromazine, levomepromazine, thioridazine, promethazine and trifluoperazine) on the ability of rat peritoneal macrophages to produce O2- during phagocytosis was investigated. The superoxide radical release was estimated by measuring the luminol-dependent chemiluminescence (CL). The effect of drugs was studied in the concentration range of 0.1-100 mumol/l. Additional experiments to determine the ability of the drugs to scavenge O2- were carried out. They included measuring the effect of phenothiazines on the luminol-dependent CL in systems with enzymatically (xanthine-xanthine oxidase) and non-enzymatically (KO2) generated O2-. The ability of phenothiazines to scavenge O2- was additionally tested by a "non-luminescence" method in which the superoxide concentration was determined spectrophotometrically by the reduction of nitro blue tetrazolium to formazan. All drugs tested decreased significantly CL of stimulated macrophages at concentrations greater than 1 mumol/l. The C50 values were between 0.45 and 1.74 mumol/l. Also phenothiazines were found to act as scavengers of O2-. However, this effect occurred at significantly higher drug concentrations. The C50 values for 50% scavenging of O2- in systems with different sources of O2- were in the concentration range of 5-160 mumol/l. These results suggested that phenothiazines predominantly affected the ability of macrophages to produce O2- during phagocytosis. The findings may provide some insight into the untoward effects of the drugs tested.

Animals↗

PubMed1998

[A survey of drug utilization in psychiatric hospitals in Japan: the basic analysis of the current status of prescription patterns].

Although concern about the prescription pattern of psychotropics is growing, there have been very few surveys in Japan. In this survey conducted in 1993, prescription data, patient characteristics, etc. were collected for 2,395 inpatients from 18 psychiatric hospitals. Their mean age was 48.4 (S.D. = 13.6). Of these patients, 1,818 (75.9%) were diagnosed with schizophrenia, 115 (4.8%) with mood disorder, and 102 (4.3%) with mental retardation. The results were as follows. 1) They were prescribed an average of 10.1 different drugs: of these, 5.6 were various psychotropics (2.6 neuroleptics, 1.2 antiparkinsonian drugs, 1.0 hypnotics). 2) The mean daily dose of antipsychotics was 1,082 mg of chlorpromazine equivalent. 3) The most commonly prescribed neuroleptic was haloperidol (53.2% of the total patients) followed by levomepromazine (48.7%), chlorpromazine (24.8%), bromperidol (18.7%), and zotepine (18.3%).

Drug Prescriptions↗

PubMedDate not supplied

[Phenothiazine drugs as photosensitizers and photoprotectors].

The photosensitizing properties of eight N-alkylated phenothiazine neuroleptic drugs were studied. The experiments were carried out in a model system based on photooxidative chemiluminescence of Gly-Trp peptide in aqueous solution. Under irradiation with light longer than 280 nm, all the studied phenothiazine derivatives decrease the chemiluminescence intensity at low concentrations and enhance it at high concentrations. Phenothiazine derivatives is likely to be due to superoxide and/or Gly-Trp free peroxide radicals. Photosensitization begins to dominate over protection at concentrations which are different for various phenothiazine derivatives compounds and lie in the range 10(-6)-10(-5) M. The photosensitizing efficiency decreases in the order: Thioproperazine, Trifluoperazine Hydrochloride, Alimezine, Thioridazine Hydrochloride, Levomepromazine Hydrochloride, Promethazine Hydrochloride, Periciazine, Chlorpromazine Hydrochloride. It was shown that photooxidation of Gly-Trp sensitized by phenothiazine derivatives occurs via singlet oxygen formation.

Light↗

PubMedDate not supplied

Stevens-Johnson syndrome from tetrazepam.

We present a case of a patient showing a cutaneous and systemic affectation compatible with the Stevens-Johnson syndrome due to the intake of tetrazepam as a muscular relaxant. The symptoms remitted after the suspension of the involved medicines and after treatment with systemic corticoids. Months later, a study with patch tests, with the standard battery and the medicines that she took (indapamide, tetrazepam, acetyl salicylic acid, botriozolam and levomepromazine) was carried out. She presented positivity to tetrazepam at 48 and 96 hours. The oral provocations with the other medicines, which she consumed, were negative. The study of cross reactivity with other benzodiazepines was negative. In the medical literature, different cutaneous affectations regarding benzodiazepine use (generalised drug eruptions, contact dermatitis, erythema multiforme, ...) have been described byt non Stevens-Johnson syndrome. The patch tests are useful in the diagnosis of this type of cutaneous reactions, avoiding in this way the achievement of oral provocations, with the potential risk for the patient that they imply. The absence of cross-reactions with other substances of the same group has to be pointed out, even with those with which keeps great structural similarity as the diazepam. In spite of the absence of cross reactions with the rest of benzodiazepines, faced with the seriousness of the case presented, it is advised to the patient to avoid this type of medicines.

Aged↗