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Frontiers in Oncology 2023The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One... (Review)
Review
The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One promising avenue lies in the repurposing of existing drugs. This review explores the impact of phenothiazines, primarily used as antipsychotic agents, on key mechanisms driving tumor growth and metastasis. The cationic and amphiphilic nature of phenothiazines allows interaction with the lipid bilayer of cellular membranes, resulting in alterations in lipid composition, modulation of calcium channels, fluidity, thinning, and integrity of the plasma membrane. This is especially significant in the setting of increased metabolic activity, a higher proliferative rate, and the invasiveness of cancer cells, which often rely on plasma membrane repair. Therefore, properties of phenothiazines such as compromising plasma membrane integrity and repair, disturbing calcium regulation, inducing cytosolic K-RAS accumulation, and sphingomyelin accumulation in the plasma membrane might counteract multidrug resistance by sensitizing cancer cells to membrane damage and chemotherapy. This review outlines a comprehensive overview of the mechanisms driving the anticancer activities of phenothiazines derivates such as trifluoperazine, prochlorperazine, chlorpromazine, promethazine, thioridazine, and fluphenazine. The repurposing potential of phenothiazines paves the way for novel approaches to improve future cancer treatment.
PubMed: 38074670
DOI: 10.3389/fonc.2023.1320621 -
World Journal of Clinical Cases Nov 2023Tardive dyskinesia (TD) is a serious and disabling movement disorder; it impairs social function and quality of life and increases the mortality rate. TD is usually...
BACKGROUND
Tardive dyskinesia (TD) is a serious and disabling movement disorder; it impairs social function and quality of life and increases the mortality rate. TD is usually induced by the use of antipsychotic drugs; however, the underlying mechanism remains unclear. Pharmacotherapy of TD includes cholinergic drugs, benzodiazepines, ginkgo biloba extract (GBE), antioxidants, amantadine, propanolol, botulinum toxin, valbenazine, and deutetrabenazine, whereas the non-pharmacotherapy approach includes modified electroconvulsive therapy (MECT) and deep brain stimulation. We successfully treated a chronic schizophrenia patient with comorbid long-term severe TD using deutetrabenazine, clozapine, and MECT.
CASE SUMMARY
A 69-year-old woman who was diagnosed as having schizophrenia 16 years ago developed severe TD after 6-mo prescription of risperidone oral solution. Her TD symptoms did not resolve despite various treatments, such as GBE, vitamin E, trihexyphenidyl, promethazine, benzodiazepines, and switching to quetiapine and olanzapine. After admission, she was given deutetrabenazine 6 mg bid. Her buccal tremor was slightly resolved 3 d later; however, her tongue remained protruded and could not be retracted. Quetiapine was switched to clozapine on day 4, and the buccal tremor remarkably resolved, and the tongue could be retracted into the mouth from day 6 onward. After three sessions of MECT, the buccal tremor resolved further. Since then, she has been able to take a semifluid diet, and her quality of life improved remarkably during 6 mo of follow-up.
CONCLUSION
TD is a serious condition which could be caused by antipsychotic medications; however, the best strategy against TD is prevention and monitoring during using antipsychotics. For patients with TD caused by antipsychotic medication use, multiple measures should be considered like switching to clozapine, adjunction with deutetrabenazine, or even MECT.
PubMed: 38073685
DOI: 10.12998/wjcc.v11.i32.7895 -
West African Journal of Medicine Dec 2023Promethazine is a phenothiazine derivative that possesses antihistamine, anti-dopaminergic and anticholinergic properties. It is commonly used to treat motion sickness,...
INTRODUCTION
Promethazine is a phenothiazine derivative that possesses antihistamine, anti-dopaminergic and anticholinergic properties. It is commonly used to treat motion sickness, allergic conditions, nausea and vomiting, in addition to its use as a sedative. Promethazine has vesicant properties and is highly caustic to the intima of blood vessels and surrounding tissues. Intravenous administration may result in thrombophlebitis, unintentional intra-arterial administration, perivascular extravasation and tissue necrosis. To the best of our knowledge there is no previous published report of promethazine-induced thrombophlebitis from sub- Saharan Africa.
CASE REPORT
A 29-year-old Nigerian male was admitted at our hospital on account of malaria with acute gastroenteritis. Due to persistent vomiting, he was administered 25 mg of promethazine injection via a size 22G intravenous cannula which was inserted the previous day on the anteromedial aspect of his right forearm and maintained with continuous intravenous crystalloid infusion. Upon administration of promethazine, he experienced intense burning and erythema. The cannula was removed immediately, another cannula was inserted on the contralateral arm, and promethazine was replaced with ondansetron. Subsequently, he developed a tender, subcutaneous cord-like swelling extending from the middle-third of the anteromedial aspect of his right forearm, corresponding with the site of previous venous cannulation. Ultrasonography revealed a hypoechoic, non-compressible basilic vein, with no flow on colour Doppler interrogation, in keeping with superficial thrombophlebitis. He was treated with a topical anti-inflammatory agent, and the pain and redness subsided after four weeks.
CONCLUSION
The preferred parenteral route of administration of promethazine is deep intramuscular injection. Recommendations to prevent promethazine-induced thrombophlebitis include: use of large and patent veins, use of lower doses, drug dilution and slow administration, use of alternative therapies, and patient education. Promethazine-induced tissue injury is under-reported in this part of the world. Creating awareness through this case report would help reduce the morbidity following promethazine administration.
Topics: Humans; Male; Adult; Promethazine; Ondansetron; Vomiting; Nausea; Thrombophlebitis
PubMed: 38070188
DOI: No ID Found -
Drug Development and Industrial Pharmacy Jan 2024The present work aims to develop mucoadhesive thermosensitive nasal gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal...
OBJECTIVE
The present work aims to develop mucoadhesive thermosensitive nasal gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal mucociliary clearance (MCC) and increase residence of the drug on nasal mucosa. This might increase drug absorption to improve bioavailability of the drug as compared to oral dosage form.
SIGNIFICANCE
Promethazine hydrochloride is an antiemetic drug administered by oral, parenteral and rectal routes. These routes have poor patient compliance or low bioavailability. Nasal route is a better alternative as it has large surface area, high drug absorption rate and no first pass effect. Its only limitation is short drug retention time due to MCC. By formulating a mucoadhesive gel, the MCC can be reduced, and drug absorption will be prolonged. Thus, improving bioavailability.
METHOD
gel was prepared by cold method having material attributes as concentration of Poloxamer 407 (X) as gelling agent and hydroxypropyl methyl cellulose K4M (X) as mucoadhesive agent. Critical Quality Attributes (CQA) were gelation temperature, mucoadhesive force and diffusion. Central composite design (CCD) was adopted for optimization.
RESULT
Optimized formulation satisfied all the CQA significant for nasal administration. Moreover, the formulation was found to be stable in accelerated stability studies for 3 months.
CONCLUSION
It can be concluded that since the drug can easily permeate through nasal mucosa and can gain access directly in the brain without undergoing first pass metabolism along with increased residence due to mucoadhesion, mucoadhesive gel has potential to increase drug bioavailability.
Topics: Humans; Promethazine; Administration, Intranasal; Nasal Mucosa; Antiemetics; Excipients; Gels; Drug Delivery Systems
PubMed: 38054848
DOI: 10.1080/03639045.2023.2291463 -
Caspian Journal of Internal Medicine 2023The use of transcutaneous electrical nerve stimulation (TENS) to relieve labor pain remains controversial and existing evidence is neither strong nor consistent. This...
BACKGROUND
The use of transcutaneous electrical nerve stimulation (TENS) to relieve labor pain remains controversial and existing evidence is neither strong nor consistent. This research was designed to compare TENS' effect with the injection of pethidine and promethazine in labor pain reduction.
METHODS
In this trial, for 45 pregnant women in the active phase of labor, TENS electrodes were placed (two on both arms, and two over the participants' low back) continuously for 120 minutes; and for another group 45 pregnant women, 100 milligrams of pethidine and 250 micrograms of promethazine were injected intramuscularly which could be repeated once at least one hour later. Labor pain and duration, need for labor induction/augmentation/other pain control methods/ instrumental delivery, delivery type, and maternal and newborn complications were measured in both groups.
RESULTS
The baseline mean visual analog scale (VAS) score, in the TENS group was 8.51±0.62 and in the pethidine and promethazine groups was 8.37±0.61 (P=0.31). While in a 120min post-intervention, it was 6.29±1.50 and 5.73±1.46 in the TENS group and the pethidine and promethazine group, respectively with no statistically significant difference (P=0.07). The labor duration in the TENS group was 6.61±1.71 hours and in the pethidine and promethazine group was 6.17±2.07 hours, with no statistically significant difference (P=0.33). In addition, no complication was recorded neither in the mothers nor newborns.
CONCLUSION
This study showed that applying TENS in the active labor phase can reduce at least two scores in patient labor pain with no significant complications.
PubMed: 38024177
DOI: 10.22088/cjim.14.4.62 -
The Science of the Total Environment Feb 2024There is a growing concern about the presence of pharmaceuticals on the aquatic environment, while the marine environment has been much less investigated than in...
There is a growing concern about the presence of pharmaceuticals on the aquatic environment, while the marine environment has been much less investigated than in freshwater. Marine mammals are suitable sentinel species of the marine environment because they often feed at high trophic levels, have unique fat stores and long lifespan. Some small delphinids in particular serve as excellent sentinel species for contamination in the marine environment worldwide. To the best of our knowledge, no pharmaceuticals have been detected or reported in dolphins so far. In the present study, muscle, liver and blubber samples from three common dolphins (Delphinus delphis) and seven striped dolphins (Stenella coeruleoalba) stranded along the Basque Coast (northern Spain) were collected. A total of 95 pharmaceuticals based on detectability and predicted ability to bioaccumulate in fish were included in the liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. At least one pharmaceutical was found in 70 % of the individuals. Only three of the 95 monitored pharmaceuticals were detected in dolphin's tissues. Very low concentrations (<1 ng/g) of orphenadrine and pizotifen were found in liver and promethazine in blubber. Herein, the gap in the knowledge regarding the study organisms and marine environments with respect to pharmaceutical pollution, which demands further research to understand if pharmaceuticals are a threat for these apex predators, is highlighted and discussed.
Topics: Animals; Dolphins; Bays; Chromatography, Liquid; Tandem Mass Spectrometry; Stenella; Common Dolphins; Cetacea; Pharmaceutical Preparations
PubMed: 37979850
DOI: 10.1016/j.scitotenv.2023.168570 -
Frontiers in Pharmacology 2023Extrapontine myelinolysis (EPM) is a rare symmetrical demyelinating disease of the central nervous system, which is often accompanied with central pontine myelinolysis...
Extrapontine myelinolysis (EPM) is a rare symmetrical demyelinating disease of the central nervous system, which is often accompanied with central pontine myelinolysis (CPM) or can appear alone. A combination of flupentixol and melitracen is used as an antianxiety-antidepressant drug which may induce hyponatremia. Herein, we report a 46-year-old woman with depression who was treated with flupentixol and melitracen 0.5/10 mg once daily for 6 months. Later, the dosage increased to 0.5/10 mg twice daily. At the same time, she had complains of intermittent dizziness and fatigue. The laboratory test revealed hyponatremia (121 mmol/L). Dizziness was improved after sodium supplementation, with an increase in blood sodium to 133 mmol/L. Twenty days later, she had difficulty opening the mouth and swallowing, needing a gastric tube due to severe dysphagia. Head magnetic resonance imaging (MRI) showed a symmetric abnormal signal of caudate nucleus and lenticular nuclei. The symptoms were not relieved after active treatment, such as rehydration. However, her symptoms improved significantly after discontinuation of flupentixol and melitracen and switching to promethazine. Follow-up head MRI after 4 months revealed no abnormal signals. The patient who developed EPM had dysphagia, despite appropriate correction of hyponatremia. Flupentixol and melitracen can cause hyponatremia and dysphagia. This case highlights an unexpected association between EPM and flupentixol- and melitracen-induced dysphagia.
PubMed: 37920206
DOI: 10.3389/fphar.2023.1266296 -
Bioinformation 2023The use of antihistamine therapy in children for the management of upper respiratory tract infections remains a topic of debate. In this study, we focused on evaluating...
The use of antihistamine therapy in children for the management of upper respiratory tract infections remains a topic of debate. In this study, we focused on evaluating the effectiveness of promethazine (Phenergan), a first-generation H1 receptor antagonist and sedative, in addressing preoperative and intra-operative sequelae in cleft surgeries. A single-centered, parallel, randomized, double-blinded controlled clinical trial was conducted on 128 children aged 2 to 4 years undergoing cleft palate surgery under general anesthesia. The case group received Phenergan syrup orally twice a day for three days, while the control group received a placebo. Primary outcomes measured preoperative anxiety levels using a children's fear scale, while secondary outcomes assessed preoperative sleep quality and cough rate through objective scales. Intraoperative heart rate was monitored using an ECG connected to a monitor. The results demonstrated that the administration of promethazine resulted in a 34% reduction in anxiety levels, a 46% reduction in cold and cough, a 38% improvement in sleep score, and stable heart rates throughout the surgery compared to the control group. Based on these findings, promethazine is considered a safe premedication option for children undergoing cleft palate surgeries; given its benefits outweigh its adverse effects.
PubMed: 37885787
DOI: 10.6026/97320630019790 -
Food and Chemical Toxicology : An... Nov 2023Emesis is a complex physiological phenomenon that serves as a defense against numerous toxins, stressful situations, adverse medication responses, chemotherapy, and...
BACKGROUND
Emesis is a complex physiological phenomenon that serves as a defense against numerous toxins, stressful situations, adverse medication responses, chemotherapy, and movement. Nevertheless, preventing emesis during chemotherapy or other situations is a significant issue for researchers. Hence, the majority view contends that successfully combining therapy is the best course of action. In-vivo analysis offers a more comprehensive grasp of how compounds behave within a complex biological environment, whereas in-silico evaluation refers to the use of computational models to forecast biological interactions.
OBJECTIVES
The objectives of the present study were to evaluate the effects of Sclareol (SCL) on copper sulphate-induced emetic chicks and to investigate the combined effects of these compounds using a conventional co-treatment approach and in-silico study.
METHODS
SCL (5, 10, and 15 mg/kg) administered orally with or without pre-treatment with anti-emetic drugs (Ondansetron (ODN): 24 mg/kg, Domperidone (DOM): 80 mg/kg, Hyoscine butylbromide (HYS): 100 mg/kg, and Promethazine hydrochloride (PRO): 100 mg/kg) to illustrate the effects and the potential involvement with 5HT, D, M/ACh, H, or NK receptors by SCL. Furthermore, an in-silico analysis was conducted to forecast the role of these receptors in the emetic process.
RESULTS
The results suggest that SCL exerted a dose-dependent anti-emetic effect on the chicks. Pretreatment with SCL-10 significantly minimized the number of retches and lengthened the emesis tendency of the experimental animals. SCL-10 significantly increased the anti-emetic effects of ODN and DOM. However, compared to the ODN-treated group, (SCL-10 + ODN) group considerably (p < 0.0001) extended the latency duration (109.40 ± 1.03 s) and significantly (p < 0.01) decreased the number of retches (20.00 ± 0.70), indicating an anti-emetic effect on the test animals. In in-silico analysis, SCL exhibited promising binding affinities with suggesting receptors.
CONCLUSION
SCL-10 exerted an inhibitory-like effect on emetic chicks, probably through the interaction of the 5HT and D receptors. Further studies are highly appreciated to validate this study and determine the precise mechanism(s) behind the anti-emetic effects of SCL. We expect that SCL-10 may be utilized as an antiemetic treatment in a single dosage form or that it may function as a synergist with other traditional medicines.
Topics: Animals; Antiemetics; Serotonin; Emetics; Vomiting
PubMed: 37863383
DOI: 10.1016/j.fct.2023.114068 -
International Journal of Surgery Case... Oct 2023Baclofen is a γ -aminobutyric acid (GABA) agonist used to treat spasticity; however, it may be toxic at dosages above 200 mg. The psychological, nervous,...
INTRODUCTION
Baclofen is a γ -aminobutyric acid (GABA) agonist used to treat spasticity; however, it may be toxic at dosages above 200 mg. The psychological, nervous, cardiovascular, gastrointestinal, musculoskeletal, and respiratory systems are all affected. This report represents a case with the rare respiratory complications brought on by baclofen toxicity: atelectasis and pneumomediastinum.
PRESENTATION OF CASE
A 19-year-old female was admitted to the emergency department after attempting suicide by taking 20 baclofen tablets (500 mg). Imaging revealed pneumomediastinum, atelectasis, and a leftward displacement of mediastinal structures. Her therapy included a chest tube to relieve the pneumomediastinum and sodium valproate, promethazine, biperiden, and quetiapine for neurological symptoms. Four days after being admitted, she was successfully extubated without any complications.
DISCUSSION
Baclofen activates GABA-A and GABA-B receptors. High doses of baclofen may induce central nervous system and respiratory depression, requiring intensive care. GABA receptors may cause hallucinations, delusions, and agitation in baclofen overdose. High dosages of baclofen may cause bronchial and bronchiolar muscular spasms, leading to breathing problems and atelectasis. Recent animal studies on baclofen toxicity showed that increased alveolar pressure, circulatory abnormalities, edema, alveolar hemorrhages, and infiltration cause rupture and pneumomediastinum. Pneumomediastinum may need bed rest, oxygen, antitussives, and analgesics, but severe cases may necessitate a chest tube.
CONCLUSION
A high index of suspicion is required for early diagnosis of acute baclofen poisoning, which could manifest as respiratory complications, including pneumomediastinum and atelectasis. Since most cases are benign, it is still crucial for clinicians to detect complications early for further management.
PubMed: 37801962
DOI: 10.1016/j.ijscr.2023.108901