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The Cochrane Database of Systematic... Nov 2015Nausea and vomiting are common symptoms in patients with terminal, incurable illnesses. Both nausea and vomiting can be distressing. Haloperidol is commonly prescribed... (Review)
Review
BACKGROUND
Nausea and vomiting are common symptoms in patients with terminal, incurable illnesses. Both nausea and vomiting can be distressing. Haloperidol is commonly prescribed to relieve these symptoms. This is an updated version of the original Cochrane review published in Issue 2, 2009, of Haloperidol for the treatment of nausea and vomiting in palliative care patients.
OBJECTIVES
To evaluate the efficacy and adverse events associated with the use of haloperidol for the treatment of nausea and vomiting in palliative care patients.
SEARCH METHODS
For this updated review, we performed updated searches of CENTRAL, EMBASE and MEDLINE in November 2013 and in November 2014. We searched controlled trials registers in March 2015 to identify any ongoing or unpublished trials. We imposed no language restrictions. For the original review, we performed database searching in August 2007, including CENTRAL, MEDLINE, EMBASE, CINAHL and AMED, using relevant search terms and synonyms. Handsearching complemented the electronic searches (using reference lists of included studies, relevant chapters and review articles) for the original review.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) of haloperidol for the treatment of nausea or vomiting, or both, in any setting, for inclusion. The studies had to be conducted with adults receiving palliative care or suffering from an incurable progressive medical condition. We excluded studies where nausea or vomiting, or both, were thought to be secondary to pregnancy or surgery.
DATA COLLECTION AND ANALYSIS
We imported records from each of the electronic databases into a bibliographic package and merged them into a core database where we inspected titles, keywords and abstracts for relevance. If it was not possible to accept or reject an abstract with certainty, we obtained the full text of the article for further evaluation. The two review authors independently assessed studies in accordance with the inclusion criteria. There were no differences in opinion between the authors with regard to the assessment of studies.
MAIN RESULTS
We considered 27 studies from the 2007 search. In this update we considered a further 38 studies from the 2013 search, and two in the 2014 search. We identified one RCT of moderate quality with low risk of bias overall which met the inclusion criteria for this update, comparing ABH (Ativan®, Benadryl®, Haldol®) gel, applied to the wrist, with placebo for the relief of nausea in 22 participants. ABH gel includes haloperidol as well as diphenhydramine and lorazepam. The gel was not significantly better than placebo in this small study; however haloperidol is reported not to be absorbed significantly when applied topically, therefore the trial does not address the issue of whether haloperidol is effective or well-tolerated when administered by other routes (e.g. by mouth, subcutaneously or intravenously). We identified one ongoing trial of haloperidol for the management of nausea and vomiting in patients with cancer, with initial results published in a conference abstract suggesting that haloperidol is effective for 65% of patients. The trial had not been fully published at the time of our review. A further trial has opened, comparing oral haloperidol with oral methotrimeprazine (levomepromazine) for patients with cancer and nausea unrelated to their treatment, which we aim to include in the next review update.
AUTHORS' CONCLUSIONS
Since the last version of this review, we found one new study for inclusion but the conclusion remains unchanged. There is incomplete evidence from published RCTs to determine the effectiveness of haloperidol for nausea and vomiting in palliative care. Other than the trial of ABH gel vs placebo, we did not identify any fully published RCTs exploring the effectiveness of haloperidol for nausea and vomiting in palliative care patients for this update, but two trials are underway.
Topics: Antiemetics; Diphenhydramine; Gels; Haloperidol; Humans; Lorazepam; Nausea; Palliative Care; Randomized Controlled Trials as Topic; Vomiting
PubMed: 26524474
DOI: 10.1002/14651858.CD006271.pub3 -
Acta Cirurgica Brasileira 2008To compare two propofol infusion techniques in bitches subjected to ovary histerectomy by estimating the efficiency of the propofol target-dose, evaluating the... (Comparative Study)
Comparative Study
PURPOSE
To compare two propofol infusion techniques in bitches subjected to ovary histerectomy by estimating the efficiency of the propofol target-dose, evaluating the cardiorespiratory and hemogasimetric attributes, and the bispectral scale index (BIS) as well as the recovery period characteristics.
METHODS
Twenty anesthetized bitches were divided into two groups of 10 each (G1, G2). Animals of G1 were pre-treated with methotrimeprazine and anesthetized with target-controlled propofol infusion by means of a Harvard infusion pump combined to remifentanil through a syringe pump.
RESULTS
Bradycardia and light hypotension, hemogasimetric and respiratory stability besides a good myorelaxation, more evident during continuous infusion and good hypnosis.
CONCLUSIONS
Dosis used in both techniques, after methotrimeprazine pre-treatment and combined to the opioid, were efficient for the surgery. The target-controlled anesthesia required a smaller anesthetic consumption (propofol) with faster recovery periods.
Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Anesthesia, Intravenous; Anesthetics, Combined; Anesthetics, Intravenous; Animals; Dogs; Female; Heart Rate; Hypnotics and Sedatives; Infusion Pumps; Methotrimeprazine; Ovariectomy; Piperidines; Propofol; Random Allocation; Remifentanil; Respiration
PubMed: 18278395
DOI: 10.1590/s0102-86502008000100011 -
Acta Cirurgica Brasileira 2007To compare, by continuous infusion of ketamine or medetomidine combined to methotrimeprazine and buprenorphine, ketamine and midazolam, the degree of hypnosis,...
Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine.
PURPOSE
To compare, by continuous infusion of ketamine or medetomidine combined to methotrimeprazine and buprenorphine, ketamine and midazolam, the degree of hypnosis, myorelaxation, anesthetic quality and surgical feasibility through evaluation of possible parametric alterations and recovery quality.
METHODS
20 healthy adult females dogs, aged 3 to 5 years, body weight between 7 and 15 kg, were assigned randomly and homogenously to 2 groups of 10 animals each (n=10), group 1 (G1) and group 2 (G2), respectively. Animals of G1 were subjected to a pre-treatment with intravenous 1.0 mg/kg methotrimeprazine and or 3ì/kg. After 15 minutes, a 5.0 mg/kg ketamine and 0.2 mg/kg midazolam were intravenously injected. Immediately after induction, an anesthetic combination of 0.4 mg/kg/h midazolam, 20 mg/kg/h ketamine and 1.0 mg/kg/h xylazine, was continuously and intravenously administered for 30 minutes. The same techniques were used in G2 except for the substitution of xylazine for 30ìg/kg/h medetomidine.
RESULTS
In G1 there was a 1st and 2nd degree atrioventricular heart block, a longer recovery period and lower quality. In G2 a 1st degree atrioventricular heart block occurred but isolated and ephemeral.
CONCLUSIONS
The continuous infusion method, besides reducing drugs utilization, prevented collateral effects allowing a more tranquil recovery with no excitations, both protocols permitted the surgical procedure (ovary-hysterectomy) bringing about a reduction in hypnosis and an accentuated myorelaxation. Xylazine and medetomidine showed a similar pharmacodynamic behavior but with different clinical aspects. The electrocardiographic alterations observed in G2 and in a lower degree in G1 must be well studied. Describers: dogs, ketamine, methotrimeprazine, medetomidine, midazolam and xylazine.
Topics: Adrenergic alpha-Agonists; Analgesics, Opioid; Anesthetics, Combined; Anesthetics, Intravenous; Animals; Buprenorphine; Dogs; Dopamine Antagonists; Drug Evaluation, Preclinical; Female; Hypnotics and Sedatives; Hysterectomy; Infusion Pumps; Medetomidine; Methotrimeprazine; Midazolam; Models, Animal; Ovariectomy; Random Allocation; Xylazine
PubMed: 17625665
DOI: 10.1590/s0102-86502007000400008 -
Frontiers in Pharmacology 2020Drug repurposing is a rapid approach to identify therapeutics for the treatment of emerging infectious diseases such as COVID-19. To address the urgent need for...
Drug repurposing is a rapid approach to identify therapeutics for the treatment of emerging infectious diseases such as COVID-19. To address the urgent need for treatment options, we carried out a quantitative high-throughput screen using a SARS-CoV-2 cytopathic assay with a compound collection of 8,810 approved and investigational drugs, mechanism-based bioactive compounds, and natural products. Three hundred and nineteen compounds with anti-SARS-CoV-2 activities were identified and confirmed, including 91 approved drugs and 49 investigational drugs. The anti-SARS-CoV-2 activities of 230 of these confirmed compounds, of which 38 are approved drugs, have not been previously reported. Chlorprothixene, methotrimeprazine, and piperacetazine were the three most potent FDA-approved drugs with anti-SARS-CoV-2 activities. These three compounds have not been previously reported to have anti-SARS-CoV-2 activities, although their antiviral activities against SARS-CoV and Ebola virus have been reported. These results demonstrate that this comprehensive data set is a useful resource for drug repurposing efforts, including design of new drug combinations for clinical trials for SARS-CoV-2.
PubMed: 33708112
DOI: 10.3389/fphar.2020.592737 -
Molecules (Basel, Switzerland) Feb 2023Antipsychotics have narrow therapeutic windows, and their monitoring in biological fluids is therefore important; consequently, stability in those fluids must be...
Antipsychotics have narrow therapeutic windows, and their monitoring in biological fluids is therefore important; consequently, stability in those fluids must be investigated during method development and validation. This work evaluates the stability of chlorpromazine, levomepromazine, cyamemazine, clozapine, haloperidol, and quetiapine in oral fluid (OF) samples, using the dried saliva spots (DSS) sampling approach and gas chromatography coupled to tandem mass spectrometry. Since many parameters can influence the stability of the target analytes, design of experiments was adopted to check the crucial factors that affect that stability in a multivariate fashion. The studied parameters were the presence of preservatives at different concentrations, temperature, light, and time. It was possible to observe that antipsychotic stability improved when OF samples in DSS were stored at 4 °C, with a low ascorbic acid concentration, and in the absence of light. With these conditions, chlorpromazine and quetiapine were stable for 14 days, clozapine and haloperidol were stable for 28 days, levomepromazine remained stable for 44 days, and cyamemazine was stable for the entire monitored period (146 days). This is the first study that evaluates the stability of these antipsychotics in OF samples after application to DSS cards.
Topics: Antipsychotic Agents; Clozapine; Quetiapine Fumarate; Haloperidol; Chlorpromazine; Methotrimeprazine; Gas Chromatography-Mass Spectrometry
PubMed: 36903275
DOI: 10.3390/molecules28052030 -
JAMA Internal Medicine Oct 2022An increasing number of individuals fill antipsychotic prescriptions during pregnancy, and concerns have been raised about prenatal antipsychotic exposure on...
IMPORTANCE
An increasing number of individuals fill antipsychotic prescriptions during pregnancy, and concerns have been raised about prenatal antipsychotic exposure on neurodevelopmental outcomes.
OBJECTIVE
To examine whether maternal prescription fill for antipsychotics during pregnancy was associated with performance in standardized tests among schoolchildren.
DESIGN, SETTING, AND PARTICIPANTS
This register-based cohort study included 667 517 children born in Denmark from January 1, 1997, to December 31, 2009, and who were attending public primary and lower secondary school. All children had completed at least 1 language (Danish) or mathematics test as part of the Danish National School Test Program between 2010 and 2018. Data were analyzed from November 1, 2021, to March 31, 2022.
EXPOSURES
Antipsychotic prescriptions filled by pregnant individuals were obtained from the Danish National Prescription Register.
MAIN OUTCOMES AND MEASURES
Differences in standardized test scores (range, 1-100; higher scores indicate better test results) in language and mathematics between children of mothers with and without antipsychotic prescription fills during pregnancy were estimated using linear regression models. Seven sensitivity analyses, including a sibling-controlled analysis, were performed.
RESULTS
Of the 667 517 children included (51.2% males), 1442 (0.2%) children were born to mothers filling an antipsychotic prescription during pregnancy. The mean (SD) age of children at the time of testing spanned from 8.9 (0.4) years in grade 2 to 14.9 (0.4) years in grade 8. Maternal prescription fill for antipsychotics was not associated with performance in language (crude mean test score: 50.0 [95% CI, 49.1-50.9] for the exposed children vs 55.4 [95% CI, 55.4-55.5] for the unexposed children; adjusted difference, 0.5 [95% CI, -0.8 to 1.7]) or in mathematics (crude mean test score: 48.1 [95% CI, 47.0-49.3] for the exposed children vs 56.1 [95% CI, 56.1-56.2] for the unexposed children; adjusted difference, 0.4 [95% CI, -1.0 to 1.8]). There was no evidence that results were modified by the timing of filling prescriptions, classes (first-generation and second-generation) of antipsychotics, or the most commonly prescribed antipsychotic monotherapies, including chlorprotixene, flupentixol, olanzapine, zuclopenthixol, quetiapine, perphenazine, and methotrimeprazine. The results remained robust across sensitivity analyses, including sibling-controlled analyses, negative control exposures analyses, and probabilistic bias analyses.
CONCLUSIONS AND RELEVANCE
In this register-based cohort study, maternal prescription fill for antipsychotics during pregnancy did not appear to be associated with standardized test scores in the offspring. The findings provide further reassuring data on offspring neurodevelopmental outcomes associated with antipsychotic treatment during pregnancy.
Topics: Antipsychotic Agents; Child; Clopenthixol; Cohort Studies; Denmark; Female; Flupenthixol; Humans; Male; Methotrimeprazine; Olanzapine; Perphenazine; Pregnancy; Prescriptions; Quetiapine Fumarate
PubMed: 35969410
DOI: 10.1001/jamainternmed.2022.3388 -
BioRxiv : the Preprint Server For... Aug 2020Drug repurposing is a rapid approach to identifying therapeutics for the treatment of emerging infectious diseases such as COVID-19. To address the urgent need for...
Drug repurposing is a rapid approach to identifying therapeutics for the treatment of emerging infectious diseases such as COVID-19. To address the urgent need for treatment options, we carried out a quantitative high-throughput screen using a SARS-CoV-2 cytopathic assay with a compound collection of 8,810 approved and investigational drugs, mechanism-based bioactive compounds, and natural products. Three hundred and nineteen compounds with anti-SARS-CoV-2 activities were identified and confirmed, including 91 approved drug and 49 investigational drugs. Among these confirmed compounds, the anti-SARS-CoV-2 activities of 230 compounds, including 38 approved drugs, have not been previously reported. Chlorprothixene, methotrimeprazine, and piperacetazine were the three most potent FDA approved drugs with anti-SARS-CoV-2 activities. These three compounds have not been previously reported to have anti-SARS-CoV-2 activities, although their antiviral activities against SARS-CoV and Ebola virus have been reported. These results demonstrate that this comprehensive data set of drug repurposing screen for SARS-CoV-2 is useful for drug repurposing efforts including design of new drug combinations for clinical trials.
PubMed: 32839771
DOI: 10.1101/2020.08.18.255877 -
The Canadian Veterinary Journal = La... Jun 2000The aim of this study was to investigate the effect of several drug combinations (atropine, xylazine, romifidine, methotrimeprazine, midazolam, or fentanyl) with... (Clinical Trial)
Clinical Trial Comparative Study
The aim of this study was to investigate the effect of several drug combinations (atropine, xylazine, romifidine, methotrimeprazine, midazolam, or fentanyl) with ketamine for short term anesthesia in cats. Twelve cats were anesthetized 6 times by using a cross-over Latin square protocol: methotrimeprazine was combined with midazolam, ketamine, and fentanyl; midazolam and ketamine; romifidine and ketamine; and xylazine and ketamine. Atropine was combined with romifidine and ketamine, and xylazine and ketamine. Temperature, heart rate, and respiratory rate decreased in all groups. Apnea occurred in 1 cat treated with methotrimeprazine, romifidine, and ketamine, suggesting that ventilatory support may be necessary when this protocol is used. Emesis occurred in some cats treated with alpha 2-adrenoceptor agonists, and this side effect should be considered when these drugs are used.
Topics: Anesthesia, General; Anesthetics, Dissociative; Animals; Apnea; Cats; Drug Therapy, Combination; Female; Ketamine; Male; Vomiting
PubMed: 10857032
DOI: No ID Found -
Japanese Journal of Pharmacology Jun 1976A brief electrical stimulation of the substantia nigra induced a marked and long lasting inhibition of the somatosensory evoked potentials recorded from the centrum...
Inhibition of thalamic and hypothalamic somatosensory evoked potentials by stimulation of substantia nigra and its modification by morphine and methotrimeprazine (levomepromazine).
A brief electrical stimulation of the substantia nigra induced a marked and long lasting inhibition of the somatosensory evoked potentials recorded from the centrum medianum of the thalamus (CM) and posterior hypothalamic area (PHA) following sciatic stimulation in unanesthetized rabbits. The nigral inhibitory effect on CM was prolonged by the administration of morphine (4 mg/kg i.v.) but not influenced by that of methotrimeprazine (2-4 mg/kg i.v.). In contrast, the nigral inhibitory effect on PHA was enhanced by the injection of methotrimeprazine (2 mg/kg i.v.), but not changed by that of morphine (4 mg/kg i.v.). These results indicate that the inhibitory system originating from the substantia nigra operates on the somatosensory transmissions from the peripheral nerve to the thalamus and hypothalamus, and that morphine or methotrimeprazine in small doses induced a selective potentiation of the nigral inhibitory influence on the thalamus or hypothalamus, respectively.
Topics: Animals; Electric Stimulation; Evoked Potentials; Female; Hypothalamus; Male; Methotrimeprazine; Morphine; Rabbits; Sciatic Nerve; Substantia Nigra; Thalamus; Time Factors
PubMed: 978846
DOI: 10.1254/jjp.26.331 -
Levomepromazine and clozapine induce the main human cytochrome P450 drug metabolizing enzyme CYP3A4.Pharmacological Reports : PR Feb 2021Cytochrome P450 (CYP) enzymes are involved in the metabolism of many important endogenous substrates (steroids, melatonin), drugs and toxic xenobiotics. Their induction...
BACKGROUND
Cytochrome P450 (CYP) enzymes are involved in the metabolism of many important endogenous substrates (steroids, melatonin), drugs and toxic xenobiotics. Their induction accelerates drug metabolism and elimination. The present study aimed at examining the inducing abilities of two antipsychotic drugs levomepromazine and clozapine for the main CYPs.
METHODS
The experiments were performed using cryopreserved human hepatocytes. The hepatotoxicity of levomepromazine and clozapine was assessed after exposure to the neuroleptics (LDH test). CYP activities were measured in the incubation medium using the CYP-specific reactions: caffeine 3-N-demethylation (CYP1A1/2), diclofenac 4'-hydroxylation (CYP2C9), perazine N-demethylation (CYP2C19) and testosterone 6β-hydroxylation (CYP3A4). In parallel, CYP mRNA levels were measured in neuroleptic-treated hepatocytes.
RESULTS
The results indicate that levomepromazine and clozapine induce the expression of main CYP enzyme CYP3A4 in human hepatocytes. Levomepromazine and clozapine at concentrations of 2.5 and 10 µM, respectively, caused a significant increase in the mRNA level and activity of CYP3A4. Both neuroleptics did not produce any changes in CYP1A1/2, CYP2C9 and CYP2C19.
CONCLUSION
Levomepromazine and clozapine induce CYP3A4 in human hepatocytes in vitro. Further in vivo studies are advisable to confirm the CYP3A4 induction by levomepromazine and clozapine in the liver, and to assess the effect of these drugs on their own metabolism and on the biotransformation of other co-administered drugs which are the CYP3A4 substrates.
Topics: Antipsychotic Agents; Cells, Cultured; Clozapine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Enzyme Induction; Hepatocytes; Humans; Liver; Methotrimeprazine; RNA, Messenger
PubMed: 32888176
DOI: 10.1007/s43440-020-00157-4