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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 -
The Medical Letter on Drugs and... Dec 2018
Review
Topics: Albuterol; Antitussive Agents; Codeine; Cough; Dextromethorphan; Humans
PubMed: 30625123
DOI: No ID Found -
Ugeskrift For Laeger Apr 2017
Topics: Aggression; Antipsychotic Agents; Drug Therapy, Combination; Haloperidol; Humans; Promethazine; Psychotic Disorders
PubMed: 28416057
DOI: No ID Found -
Toxicology Jun 2023The current review focuses on the effect of phenothiazine derivatives, tested in vitro, on necrosis and necroptosis, the latter constitutes one of the kinds of... (Review)
Review
The current review focuses on the effect of phenothiazine derivatives, tested in vitro, on necrosis and necroptosis, the latter constitutes one of the kinds of programmed cell death. Necroptosis is a necrotic and inflammatory type of programmed cell death. Phenothiazines are D1 and D2-like family receptor antagonists, which are used in the treatment of schizophrenia. Necroptosis begins from TNF-α, whose synthesis is stimulated by dopamine receptors, thus it can be concluded that phenothiazine derivatives may modulate necroptosis. We identified 19 papers reporting in vitro assays of necroptosis and necrosis in which phenothiazine derivatives, and both normal and cancer cell lines were used. Chlorpromazine, fluphenazine, levomepromazine, perphenazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate necroptosis and necrosis. The type of a drug, concentration and a cell line have an impact on the ultimate effect. Unfortunately, the authors confirmed both processes on the basis of TNF-α and ATP levels as well as the final steps of necrosis/necroptosis related to membrane permeability (PI staining, LDH release, and HMGB1 amount), which makes it impossible to understand the complete mechanism of phenothiazines impact on necroptosis and necrosis. Studies analyzing the effect of phenothiazines on RIPK1, RIPK3, or MLKL has not been performed yet. Only the analysis of the expression of those proteins as well as necrosis and necroptosis inhibitors can help us to comprehend how phenothiazine derivatives act, and how to improve their therapeutic potential.
Topics: Humans; Tumor Necrosis Factor-alpha; Necroptosis; Phenothiazines; Antipsychotic Agents; Necrosis
PubMed: 37127180
DOI: 10.1016/j.tox.2023.153528 -
Experimental Neurology Nov 2023Neuroprotective effects have been the main focus of new treatment modalities for ischemic stroke. Phenothiazines, or chlorpromazine plus promethazine (C + P), are...
BACKGROUND
Neuroprotective effects have been the main focus of new treatment modalities for ischemic stroke. Phenothiazines, or chlorpromazine plus promethazine (C + P), are known to prevent the generation of free radicals and uptake of Ca by plasma membrane; they have a potential as a treatment for acute ischemic stroke (AIS). This study aims to investigate the role of endoplasmic reticulum (ER) stress-associated PERK-eIF2α pathway underlying the phenothiazine-induced neuroprotective effects after cerebral ischemia/reperfusion (I/R) injury.
METHODS
A total of 49 male Sprague Dawley rats (280-320 g) were randomly divided into 4 groups (n = 7 per group): (1) sham, (2) I/R that received 2 h of middle cerebral artery occlusion (MCAO), followed by 6 or 24 h of reperfusion, (3) MCAO treated by C + P without temperature control and (4) MCAO treated by C + P with temperature control. Human neuroblastoma (SH-SY5Y) cells were used in 5 groups: (1) control, (2) oxygen-glucose deprivation (OGD) for 2 h followed by reoxygenation (OGD/R), (3) OGD/R with C + P; (4) OGD/R with PERK inhibitor, GSK2656157, and (5) OGD/R with C + P and GSK2656157. The molecules of ER stress, unfolded protein response (UPR) (Bip, PERK, p-PERK, p-PERK/PERK, eIF2α, p-eIF2α, p-eIF2α/eIF2α), autophagy (ATG12, LC3II/I), and apoptosis (BAX, Bcl-XL) were measured at mRNA levels by real time PCR and protein levels by Western blotting.
RESULTS
In ischemic rats followed by reperfusion, expression of Bip, p-PERK/PERK, p-eIF2α/eIF2α, ATG12, and LC3II/I, as well as BAX were all significantly increased. These markers were significantly reduced by C + P at both 6 and 24 h of reperfusion. Anti-apoptotic Bcl-XL expression was increased, while pro-apoptotic BAX expression was decreased by C + P. In SH-SY5Y cell lines, both C + P and GSK2656157 significantly reduced the level of autophagy and apoptosis after I/R, respectively. The combination of GSK2656157 and C + P did not promote the same effect, suggesting that C + P did not induce any neuroprotective effect by inhibiting autophagy and apoptosis through the PERK-eIF2α pathway when this pathway was already blocked by GSK2656157. In general, the reduction in body temperature by phenothiazines was associated with better neuroprotection but it did not reach significant levels.
CONCLUSION
The combined treatment of C + P plays a crucial role in stroke therapy by inhibiting ER stress-mediated autophagy, thereby leading to reduced apoptosis and increased neuroprotection. Our findings highlight the PERK-eIF2α pathway as a central mechanism through which C + P exerts its beneficial effects. The results from this study may pave the way for the development of more targeted and effective treatments for stroke patients.
Topics: Animals; Humans; Male; Rats; Apoptosis; Autophagy; bcl-2-Associated X Protein; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Infarction, Middle Cerebral Artery; Ischemic Stroke; Neuroblastoma; Neuroprotective Agents; Phenothiazines; Rats, Sprague-Dawley; Reperfusion Injury
PubMed: 37673390
DOI: 10.1016/j.expneurol.2023.114524 -
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 -
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 -
Cureus Aug 2023Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized... (Review)
Review
Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized approaches to managing opioid withdrawal symptoms, such as itching, jitteriness, anxiety, depression, craving, vomiting, diarrhea, insomnia, and anorexia. These symptoms pose substantial obstacles to the safe initiation of medications for OUD, maintenance of long-term sobriety, and prevention of relapse. In clinical practice, multiple medications (polypharmacy) are prescribed to manage these withdrawal symptoms, including ondansetron and promethazine for vomiting and nausea, loperamide and Lomotil for diarrhea, hydroxyzine and doxepin for pruritus, benzodiazepines, the Z-drugs, and melatonin for insomnia, and benzos, tricyclic antidepressants (TCAs), and various serotonergic agents for anxiety. This polypharmacy is associated with an increased risk of adverse drug-drug interactions and adverse drug events, increased medical costs, and increased odds of medication non-adherence and relapse. We propose an alternative single medication, mirtazapine, a noradrenergic and specific serotonergic receptor antagonist, that can be used for myriad symptoms of opioid withdrawal. Case series, clinical studies, and clinical trials have shown mirtazapine to be effective for treating nausea and vomiting resulting from multiple etiologies, including hyperemesis gravidarum and chemotherapy-induced emesis. Other evidence supports the salutary effects of mirtazapine on itching and craving. Research findings support mirtazapine's beneficial effects on diarrhea and anxiety, a consequence of its modulating effects on serotonergic receptors mediating mood and gastrointestinal symptoms. There is also evidence supporting its efficacy as a potent and non-addictive sleep aid, which presents itself as a solution for insomnia associated with opioid withdrawal. The current review presents evidence from extant literature supporting mirtazapine as a one-drug strategy to treat the variety of symptoms of opioid withdrawal. This one-drug strategy has much potential to decrease polypharmacy, adverse drug events, relapse, and healthcare cost and increase the likelihood of prolonged sobriety and better quality of life for people living with OUD.
PubMed: 37736438
DOI: 10.7759/cureus.43821 -
Brain Sciences Oct 2020Recently, a range of prescription and over-the-counter (OTC) drugs have emerged as being used recreationally, either on their own or in combination with other...
Recently, a range of prescription and over-the-counter (OTC) drugs have emerged as being used recreationally, either on their own or in combination with other substances, both licit and illicit, including new psychoactive substances (NPS). Among them, the misuse of prescription drugs involves not only traditionally recorded substances, such as benzodiazepines and opioid pain relievers, but also gabapentinoids (e.g., pregabalin and gabapentin); some antidepressants, e.g., bupropion and venlafaxine; some second-generation antipsychotics, e.g., quetiapine and olanzapine. Moreover, the use of some OTC for recreational purposes appears on the increase, especially in vulnerable categories such as young people/youths, including the use of high dosages of the antidiarrheal loperamide; first-generation antihistamines, e.g., promethazine, cyclizine, and diphenhydramine; cough and cold preparations containing dextromethorphan and/or codeine. In this context, the role of the Internet has rapidly increased, playing a significant role both in the diffusion of emerging trends of drug misuse among users and experimenters, and the marketing, sale, and distribution of drugs through online pharmacies. This phenomenon within the context of a rapidly modifying drug scenario is a globally recognized health problem, determining severe adverse consequences, including fatalities, and represents a challenge for clinicians in general, psychiatrists, public health, and drug-control policies.
PubMed: 33066476
DOI: 10.3390/brainsci10100736 -
Current Opinion in Psychiatry May 2022To provide updated guidance for the medication treatment of acute agitation in the setting of psychosis or mania on inpatient psychiatric units. (Review)
Review
PURPOSE OF REVIEW
To provide updated guidance for the medication treatment of acute agitation in the setting of psychosis or mania on inpatient psychiatric units.
RECENT FINDINGS
This topic presented challenges: studies are sparse, tend to be under-powered, and are difficult to compare. Though there have been few recent studies, there have been several recent meta-analyses, Cochrane reviews, and published guidelines that sift through the primarily older evidence as well as more recent trials. The reviewers often do not agree on what seems to have the best evidence for efficacy and safety.
SUMMARY
We conclude that the best approach is to summarize in some detail the evidence for each possible treatment and the interpretations published recently on each of those treatments, and then present recommendations for medication management in tiered rankings, based on the authors' qualitative review of the data and opinions. For oral treatment, the first-tier options are (alphabetically) haloperidol with lorazepam, lorazepam alone, and olanzapine. The second tier includes haloperidol with promethazine, loxapine inhaler, and risperidone alone. Tier 3 includes asenapine and quetiapine. For intramuscular treatment, the first-tier includes haloperidol plus promethazine, and olanzapine alone, and the second-tier includes haloperidol with lorazepam, and lorazepam alone.
Topics: Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Mania; Olanzapine; Promethazine; Psychomotor Agitation; Psychopharmacology; Psychotic Disorders
PubMed: 35579871
DOI: 10.1097/YCO.0000000000000787