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Acta Clinica Croatica Apr 2023Physiological changes in pregnancy as part of biohumoral and morphological changes (hyperemia, edema, hypersecretion) influence the possible problems in obstetric... (Review)
Review
Physiological changes in pregnancy as part of biohumoral and morphological changes (hyperemia, edema, hypersecretion) influence the possible problems in obstetric anesthesia. These changes by themselves, and particularly aggravated by acute or chronic gestational or non-gestational comorbidity, increase the risk of aspiration of gastric contents, failed intubation, esophageal intubation, inadequate ventilation, and respiratory failure. The types of premedication, anesthesia and techniques of anesthesia are evident from medical historiography. Almost obligatory promethazine and atropine was given intravenously either in the delivery room or on the operating table immediately before the induction of anesthesia in a dose of 0.5 mg in partuients of average body weight. Atropine has been a favorite premedicant for decades, given its pharmacological properties, especially its antisialogenic effect and absence of a depressant effect on the fetoplacental unit, but today it is rarely used. Nasal decongestants before surgery are not recommended but in cases of severe rhinitis, atropine, promethazine, or topical decongestants may be used.
Topics: Humans; Female; Pregnancy; Anesthesia, Obstetrical; Obstetrics; Gynecology; Gynecologists; Obstetricians
PubMed: 38746603
DOI: 10.20471/acc.2023.62.s1.17 -
Medical Gas Research 2019
Topics: Child; Child, Preschool; Clinical Trials as Topic; Dental Anxiety; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Midazolam; Nitrous Oxide; Promethazine
PubMed: 31249260
DOI: 10.4103/2045-9912.260653 -
Mediators of Inflammation 2022Cerebral ischemia-reperfusion (I/R) incites neurologic damage through a myriad of complex pathophysiological mechanisms, most notably, inflammation and oxidative stress....
Cerebral ischemia-reperfusion (I/R) incites neurologic damage through a myriad of complex pathophysiological mechanisms, most notably, inflammation and oxidative stress. In I/R injury, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) produces reactive oxygen species (ROS), which promote inflammatory and apoptotic pathways, augmenting ROS production and promoting cell death. Inhibiting ischemia-induced oxidative stress would be beneficial for reducing neuroinflammation and promoting neuronal cell survival. Studies have demonstrated that chlorpromazine and promethazine (C+P) induce neuroprotection. This study investigated how C+P minimizes oxidative stress triggered by ischemic injury. Adult male Sprague-Dawley rats were subject to middle cerebral artery occlusion (MCAO) and subsequent reperfusion. 8 mg/kg of C+P was injected into the rats when reperfusion was initiated. Neurologic damage was evaluated using infarct volumes, neurological deficit scoring, and TUNEL assays. NOX enzymatic activity, ROS production, protein expression of NOX subunits, manganese superoxide dismutase (MnSOD), and phosphorylation of PKC- were assessed. Neural SHSY5Y cells underwent oxygen-glucose deprivation (OGD) and subsequent reoxygenation and C+P treatment. We also evaluated ROS levels and NOX protein subunit expression, MnSOD, and p-PKC-/PKC-. Additionally, we measured PKC- membrane translocation and the level of interaction between NOX subunit (p47) and PKC- via coimmunoprecipitation. As hypothesized, treatment with C+P therapy decreased levels of neurologic damage. ROS production, NOX subunit expression, NOX activity, and p-PKC-/PKC- were all significantly decreased in subjects treated with C+P. C+P decreased membrane translocation of PKC- and lowered the level of interaction between p47 and PKC-. This study suggests that C+P induces neuroprotective effects in ischemic stroke through inhibiting oxidative stress. Our findings also indicate that PKC-, NOX, and MnSOD are vital regulators of oxidative processes, suggesting that C+P may serve as an antioxidant.
Topics: Animals; Brain Injuries; Brain Ischemia; Chlorpromazine; Ischemic Stroke; Male; NADPH Oxidases; Oxidative Stress; Promethazine; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Stroke; Superoxide Dismutase
PubMed: 35873710
DOI: 10.1155/2022/6886752 -
Deutsches Arzteblatt International Jun 2019Psychomotor agitation and aggressiveness in the context of mental illnessare medical emergencies. In a survey of six German psychiatric hospitals, 1.7 to 5 aggressive... (Review)
Review
BACKGROUND
Psychomotor agitation and aggressiveness in the context of mental illnessare medical emergencies. In a survey of six German psychiatric hospitals, 1.7 to 5 aggressive attacks per patient-year were reported. If talking to the patient has no calming effect, intervention with drugs is required. In this article, we review the evidence on tranquilizing drugs and discuss clinically relevant ethical and practical questions, e.g., with respect to involuntary medication.
METHODS
This review is based on pertinent articles retrieved by a selective search in MEDLINE, supplemented by a reference search.
RESULTS
The evidence for the treatment of psychomotor agitation with antipsychotic drugs and benzodiazepines is relatively good. Randomized, controlled trials and a number of Cochrane reviews are available. These publications, however, contain data only on patients who were able to give informed consent. Their findings are often not applicable to real-life emergencies, e.g., when the patient is intoxicated with alcohol or suffers from a pre-existing disease. Haloperidol has a relatively weak effect on aggression when given alone and can also cause side effects such as early dyskinesia and epileptic seizures. It should, therefore, no longer be used as monotherapy. On the other hand, haloperidol combined with benzodiazepines or promethazine and monotherapy with lorazepam, olanzapine, ziprasidone, or aripiprazole intramuscular are effective options for the treatment of aggressive psychomotor agitation.
CONCLUSION
All of these drugs, if accepted by the patient, can also have an additional, beneficial placebo effect, with the patient calming down more rapidly than could be explained on pharmacological grounds alone. It is, therefore, important in emergencies (as at other times) for the patient to be involved in treatment decisions to the greatest possible extent.
Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Psychomotor Agitation; Psychotic Disorders
PubMed: 31431244
DOI: 10.3238/arztebl.2019.0445 -
Australian Family Physician Sep 2007Nausea and vomiting are common symptoms in early pregnancy. In most women the condition is mild and self limiting. A small percentage of women experience severe nausea... (Review)
Review
BACKGROUND
Nausea and vomiting are common symptoms in early pregnancy. In most women the condition is mild and self limiting. A small percentage of women experience severe nausea and vomiting. This is known as hyperemesis gravidarum. Outcomes have improved with intravenous rehydration therapy. Consequences include decreased quality of life, time off work and secondary depression.
OBJECTIVE
This article outlines the aetiology, outcomes, history and examination of women with hyperemesis gravidarum. Treatment modalities are discussed together with evidence regarding use.
DISCUSSION
It is important to exclude other causes of nausea and vomiting such as urinary tract infection and thyrotoxicosis. Assessment of severity by checking for ketones is important as severity determines management. Management will include rehydration (intravenous or oral). Evidence is lacking regarding dietary and lifestyle recommendations but some women find them useful. Pyridoxine and metoclopramide (category A) are first line in treatment of hyperemesis gravidarum followed by prochlorperazine (category C), prednisolone (category A), promethazine (category C) and ondansetron (category B1). Benefit has been reported with the use of ginger. Evidence is mixed regarding acupressure and acupuncture.
Topics: Antiemetics; Dehydration; Family Practice; Female; Fluid Therapy; Humans; Hyperemesis Gravidarum; Ketones; Life Style; Nausea; Pregnancy; Pregnancy Complications; Risk Factors
PubMed: 17885701
DOI: No ID Found -
Frontiers in Neurology 2021Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate...
Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-Like Effect in Stroke: Rationale, Design, and Protocol for a Prospective Randomized Controlled Trial.
Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate robust clinical efficacy. However, only a subset of these patients can benefit from these therapies due to their short treatment windows and potential complications. In addition, many patients despite successful reperfusion still have unfavorable outcomes. Thus, neuroprotection strategies are urgently needed for AIS patients. Chlorpromazine and promethazine (C+P) have been employed in clinical practice for antipsychotic and sedative purposes. A clinical study has also shown a neuroprotective effect of C+P on patients with cerebral hemorrhage and subarachnoid hemorrhage. The safety, feasibility, and preliminary efficacy of intravenous administration of C+P in AIS patients within 24 h of onset will be elucidated. A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to an intervention group and a control group with a 1:1 ratio ( = 30) and will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the intervention group will receive intravenous administration of C+P (chlorpromazine 50 mg and promethazine 50 mg) within 24 h of symptom onset. The primary outcome is safety (mainly hypotension), while the secondary outcomes include changes in functional outcome and infarction volume. This study on Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-like Effect in Stroke (RICHES) will be the first prospective randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of intravenous C+P as a neuroprotection strategy in AIS patients. These results will provide parameters for future studies, provide insights into treatment effects, and neuroprotection with phenothiazine in AIS. www.chictr.org.cn, identifier: ChiCTR2000038727.
PubMed: 33815250
DOI: 10.3389/fneur.2021.621476 -
The Cochrane Database of Systematic... Nov 2016Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such situations should ensure that the person becomes calm swiftly and safely.
OBJECTIVES
To examine whether haloperidol plus promethazine is an effective treatment for psychosis-induced aggression.
SEARCH METHODS
On 6 May 2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is compiled by systematic searches of major resources (including MEDLINE, EMBASE, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings.
SELECTION CRITERIA
All randomised clinical trials with useable data focusing on haloperidol plus promethazine for psychosis-induced aggression.
DATA COLLECTION AND ANALYSIS
We independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We found two new randomised controlled trials (RCTs) from the 2015 update searching. The review now includes six studies, randomising 1367 participants and presenting data relevant to six comparisons.When haloperidol plus promethazine was compared with haloperidol alone for psychosis-induced aggression for the outcome not tranquil or asleep at 30 minutes, the combination treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87, high-quality evidence). There were 10 occurrences of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.When haloperidol plus promethazine was compared with olanzapine, high-quality data showed both approaches to be tranquillising. It was suggested that the combination of haloperidol plus promethazine was more effective, but the difference between the two approaches did not reach conventional levels of statistical significance (n=300, 1 RCT, RR 0.60, 95% CI 0.22 to 1.61, high-quality evidence). Lower-quality data suggested that the risk of unwanted excessive sedation was less with the combination approach (n=116, 2 RCTs, RR 0.67, 95% CI 0.12 to 3.84).When haloperidol plus promethazine was compared with ziprasidone all data were of lesser quality. We identified no binary data for the outcome tranquil or asleep. The average sedation score (Ramsay Sedation Scale) was lower for the combination approach but not to conventional levels of statistical significance (n=60, 1 RCT, MD -0.1, 95% CI - 0.58 to 0.38). These data were of low quality and it is unclear what they mean in clinical terms. The haloperidol plus promethazine combination appeared to cause less excessive sedation but again the difference did not reach conventional levels of statistical significance (n=111, 2 RCTs, RR 0.30, 95% CI 0.06 to 1.43).We found few data for the comparison of haloperidol plus promethazine versus haloperidol plus midazolam. Average Ramsay Sedation Scale scores suggest the combination of haloperidol plus midazolam to be the most sedating (n=60, 1 RCT, MD - 0.6, 95% CI -1.13 to -0.07, low-quality evidence). The risk of excessive sedation was considerably less with haloperidol plus promethazine (n=117, 2 RCTs, RR 0.12, 95% CI 0.03 to 0.49, low-quality evidence). Haloperidol plus promethazine seemed to decrease the risk of needing restraints by around 12 hours (n=60, 1 RCT, RR 0.24, 95% CI 0.10 to 0.55, low-quality evidence). It may be that use of midazolam with haloperidol sedates swiftly, but this effect does not last long.When haloperidol plus promethazine was compared with lorazepam, haloperidol plus promethazine seemed to more effectively cause sedation or tranquillisation by 30 minutes (n=200, 1 RCT, RR 0.26, 95% CI 0.10 to 0.68, high-quality evidence). The secondary outcome of needing restraints or seclusion by 12 hours was not clearly different between groups, with about 10% in each group needing this intrusive intervention (moderate-quality evidence). Sedation data were not reported, however, the combination group did have less 'any serious adverse event' in 24-hour follow-up, but there were not clear differences between the groups and we are unsure exactly what the adverse effect was. There were no deaths.When haloperidol plus promethazine was compared with midazolam, there was clear evidence that midazolam is more swiftly tranquillising of an aggressive situation than haloperidol plus promethazine (n=301, 1 RCT, RR 2.90, 95% CI 1.75 to 4.8, high-quality evidence). On its own, midazolam seems to be swift and effective in tranquillising people who are aggressive due to psychosis. There was no difference in risk of serious adverse event overall (n=301, 1 RCT, RR 1.01, 95% CI 0.06 to 15.95, high-quality evidence). However, 1 in 150 participants allocated haloperidol plus promethazine had a swiftly reversed seizure, and 1 in 151 given midazolam had swiftly reversed respiratory arrest.
AUTHORS' CONCLUSIONS
Haloperidol plus promethazine is effective and safe, and its use is based on good evidence. Benzodiazepines work, with midazolam being particularly swift, but both midazolam and lorazepam cause respiratory depression. Olanzapine intramuscular and ziprasidone intramuscular do seem to be viable options and their action is swift, but resumption of aggression with subsequent need to re-inject was more likely than with haloperidol plus promethazine. Haloperidol used on its own without something to offset its frequent and serious adverse effects does seem difficult to justify.
Topics: Aggression; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Midazolam; Promethazine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic; Restraint, Physical
PubMed: 27885664
DOI: 10.1002/14651858.CD005146.pub3 -
Biomedicine & Pharmacotherapy =... Nov 2021To elucidate the potential effect of promethazine on colorectal cancer (CRC) cells and the underlying mechanism.
AIM
To elucidate the potential effect of promethazine on colorectal cancer (CRC) cells and the underlying mechanism.
MATERIALS AND METHODS
Targets of the drug promethazine (PMTZ) were identified by DrugBank and comparative toxicogenomic databases (CTD), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed with STRING software. The effects of PMTZ were predicted to be associated with the PI3K/AKT pathway. Cell Counting Kit 8 (CCK-8) assays were used to evaluate the effects of different concentrations of PMTZ on the proliferation of various types of CRC cells. Flow cytometry and Western blotting analyses were used to detect the degree of CRC cell apoptosis and the expression of the apoptosis-related proteins Bcl-2, Bax and caspase-3 after PMTZ treatment. The expression levels of PI3K/AKT pathway-related proteins [PI3K, AKT, phosphorylated (P)-PI3K and p-AKT] in CRC cells treated with PMTZ were analyzed by Western blotting.
RESULTS
PMTZ inhibited the proliferation and promoted the apoptosis of CRC cells and suppressed the activation of the PI3K/AKT signaling pathway in a dose-dependent manner.
DISCUSSION AND CONCLUSIONS
PMTZ may suppress the proliferation and induce the apoptosis of CRC cells by inhibiting the PI3K/ AKT signaling pathway. This study reported, for the first time, the function of PMTZ in CRC cells and the underlying mechanism and further confirmed the potential antitumor effects of phenothiazine. The combination of bioinformatics analyses and experiments provides informative evidence for the reuse of drugs and the development of new drugs.
Topics: Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Caco-2 Cells; Cell Proliferation; Colorectal Neoplasms; Databases, Genetic; Drug Repositioning; Gene Expression Regulation, Neoplastic; HCT116 Cells; HT29 Cells; Humans; Mitochondria; Phosphatidylinositol 3-Kinase; Promethazine; Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 34560542
DOI: 10.1016/j.biopha.2021.112174 -
Cureus May 2022Introduction In the present study, the combination of two tablets, one with Aspirin and Promethazine and the other with vitamin D3, C, and B3 along with zinc and...
Efficacy and Safety of Aspirin, Promethazine, and Micronutrients for Rapid Clinical Recovery in Mild to Moderate COVID-19 Patients: A Randomized Controlled Clinical Trial.
Introduction In the present study, the combination of two tablets, one with Aspirin and Promethazine and the other with vitamin D3, C, and B3 along with zinc and selenium supplementation was proposed as an intervention (APMV2020). The ingredients in the formulation represent a precise, tailored therapy for the symptoms of COVID-19, combined with natural constituents to help the body itself build immunity to recover from infection. The present study was conducted to clinically validate the safety and efficacy of the APMV2020 tablets. Trial design The present trial is a randomized, multicentric, controlled clinical trial involving 260 mild to moderate COVID-19 patients. The treatment duration was of 10 days. Methodology The subjects were randomized to receive either the control intervention (clinical management protocol for COVID-19 advocated by the Indian Council of Medical Research (ICMR) or the test intervention (treatment with APMV2020 tablets along with the standard control treatment. The assessment days were baseline, days five and 10. Results APMV2020 significantly (<0.05) improved symptoms of COVID-19 like cough, myalgia, headache, and anosmia as compared to the control group. APMV2020 treatment also reduced inflammatory markers like lactate dehydrogenase (LDH), ferritin, and C-reactive protein (CRP). Conclusion APMV2020 can prove as a good candidate to be integrated into the COVID-19 management protocol. As it can offer speedy clinical recovery to reduce the burden on healthcare infrastructure, second, the combination shows significant anti-inflammatory potential to improve prognosis, and lastly, the immunomodulatory properties offer long-term protection that can help in combating long COVID symptoms and complications.
PubMed: 35783877
DOI: 10.7759/cureus.25467 -
Cureus Nov 2019Acute agitation is a common presenting symptom in the emergency ward and is also dealt with on a routine basis in psychiatry. Usually a symptom of an underlying mental... (Review)
Review
Acute agitation is a common presenting symptom in the emergency ward and is also dealt with on a routine basis in psychiatry. Usually a symptom of an underlying mental illness, it is considered urgent and immediate treatment is indicated. The practice of treating agitation on an acute care basis is also referred to as rapid tranquilization. A variety of psychotropic drugs and combinations thereof can be used. The decision is usually made based on availability and the clinician's experience, with the typical antipsychotic haloperidol (alone or in combination with antihistaminergic and anticholinergic drugs such as promethazine), the benzodiazepines lorazepam, diazepam and midazolam as well as a variety of atypical antipsychotics being used for this purpose. Haloperidol is associated with extrapyramidal symptoms (which can be controlled by co-administration of promethazine) and may control agitation without inducing sedation, while benzodiazepines have a more pronounced sedating activity. The atypical antipsychotics aripiprazole and ziprasidone are better tolerated, while olanzapine is also a powerful sedative. Clinical trials evaluating the efficacy of different treatment options have been conducted but they are extremely heterogenous and most have numerous methodological flaws, leading to a poor overall quality of evidence upon which guidelines for the appropriate treatment could be based. The combination of haloperidol and promethazine, which combines the sedative properties of the antihistamine with the more selective calming action of haloperidol (with a reduced risk of extrapyramidal effects compared to haloperidol alone because of the anticholinergic properties of promethazine) may be the best choice based on empirical evidence.
PubMed: 31890361
DOI: 10.7759/cureus.6152