RESUMEN
OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.
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Alanina , Bencidamina , Neoplasias de Cabeza y Cuello , Antisépticos Bucales , Quinolonas , Estomatitis , Humanos , Estomatitis/prevención & control , Estomatitis/etiología , Neoplasias de Cabeza y Cuello/radioterapia , Bencidamina/uso terapéutico , Masculino , Persona de Mediana Edad , Femenino , Quinolonas/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Antisépticos Bucales/uso terapéutico , Quimioradioterapia/efectos adversos , Traumatismos por Radiación/prevención & control , Anciano , AdultoRESUMEN
Benzydamine is an active pharmaceutical compound used in the oral care pharmaceutical preparation as NSAID. Beside from its anti-inflammatory action, benzydamine local application effectively reliefs pain showing analgesic and anaesthetic properties. Benzydamine mechanism of action has been characterized on inflammatory cell types and mediators highlighting its capacity to inhibit pro-inflammatory mediators' synthesis and release. On the other hand, the role of benzydamine as neuronal excitability modulator has not yet fully explored. Thus, we studied benzydamine's effect over primary cultured DRG nociceptors excitability and after acute and chronic inflammatory sensitization, as a model to evaluate relative nociceptive response. Benzydamine demonstrated to effectively inhibit neuronal basal excitability reducing its firing frequency and increasing rheobase and afterhyperpolarization amplitude. Its effect was time and dose-dependent. At higher doses, benzydamine induced changes in action potential wavelength, decreasing its height and slightly increasing its duration. Moreover, the compound reduced neuronal acute and chronic inflammatory sensitization. It inhibited neuronal excitability mediated either by an inflammatory cocktail, acidic pH or high external KCl. Notably, higher potency was evidenced under inflammatory sensitized conditions. This effect could be explained either by modulation of inflammatory and/or neuronal sensitizing signalling cascades or by direct modulation of proalgesic and action potential firing initiating ion channels. Apparently, the compound inhibited Nav1.8 channel but had no effect over Kv7.2, Kv7.3, TRPV1 and TRPA1. In conclusion, the obtained results strengthen the analgesic and anti-inflammatory effect of benzydamine, highlighting its mode of action on local pain and inflammatory signalling.
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Bencidamina , Humanos , Bencidamina/metabolismo , Bencidamina/farmacología , Bencidamina/uso terapéutico , Dolor/tratamiento farmacológico , Dolor/metabolismo , Nociceptores/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Antiinflamatorios/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos/metabolismoRESUMEN
Benzydamine hydrochloride (BZD) having analgesic, anesthetic, and anti-inflammatory effects is used orally or topically in the treatment of disorders such as joint inflammation and muscle pain. Within the scope of this study, sprayable thermosensitive BZD hydrogels were developed using thermoresponsive poloxamers to avoid systemic side effects and to provide better compliance for topical administration. Also, hydroxypropyl methyl cellulose (HPMC) was employed to improve the mechanical strength and bioadhesive properties of the hydrogel. The addition of BZD generally decreased the viscosity of the formulations (p < 0.05), while increasing the gelation temperature (p < 0.05). The formulations that did not have any clogs or leaks in the nozzle of the bottle during the spraying process were considered lead formulations. To spray the formulations easily, it was found that the viscosity at RT should be less than 200 mPa·s, and their gelation temperature should be between 26 and 34°C. Increasing HPMC and poloxamer improved bioadhesion. The amount of HPMC and poloxamers did not cause a significant change in the release characteristics of the formulations (p > 0.05); the release profiles of BZD from the formulations were similar according to model-independent kinetic (f2 > 50). HPMC and poloxamers had important roles in the accumulation of BZD in the skin. In vitro biological activity studies demonstrated that the formulations presented their anti-inflammatory activity with TNF-α inhibition but did not have any effect on the inhibition of COX enzymes as expected. As a result, thermosensitive hydrogels containing BZD might be an appropriate alternative, providing an advantage in terms of easier application compared to conventional gels.
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Bencidamina , Hidrogeles , Poloxámero , Geles , Temperatura , Antiinflamatorios/farmacología , Derivados de la Hipromelosa , ViscosidadRESUMEN
INTRODUCTION: Among the evidence-based agents outlined in the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) mucositis guidelines, benzydamine and morphine are advised for the management of oral mucositis (OM) in certain cancer patients. This study is aimed to collect information from a group of highly experienced healthcare professionals in the field of oral mucositis about their clinical experience with these agents. METHODS: A survey questionnaire about the clinical experience with topical benzydamine and morphine to manage oral mucositis and their related adverse effects (AEs) was electronically distributed to the members of the Mucositis Study Group of MASCC/ISOO. RESULTS: Eighty-eight entries were recorded (response rate 25%), and 54 entries submitted complete questionnaires about the drug-related AE (completion rate 65%) and were used for the data analysis. Of the respondents, 44% and 27.7% prescribed benzydamine and morphine to manage their patients' oral mucositis, respectively. Lack of availability in the respondent's country was the common reason for not prescribing benzydamine and morphine (18.9% and 5.4%, respectively); however, a large portion of the respondents indicated that 'another reason' stopped them from prescribing these agents (51.3% and 73%, respectively). AEs to benzydamine or morphine were observed by 25.9% and 12.9% of respondents, respectively, with mild numbness and tingling as the most common drug-related AE for both agents. CONCLUSION: The use of topical benzydamine and morphine for the management of OM varies between countries. While relatively common, the AEs related to these agents are mild. Mitigating the barriers for prescribing them may increase their use.
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Bencidamina , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Mucositis , Neoplasias , Estomatitis , Humanos , Bencidamina/efectos adversos , Morfina/efectos adversos , Estomatitis/inducido químicamente , Estomatitis/tratamiento farmacológicoRESUMEN
OBJECTIVES: To assess the effects of benzydamine and mouthwashes (MoWs) containing benzydamine on different stages of Candida albicans biofilm: adhesion, formation, persistence, and regrowth (if perturbed). MATERIALS AND METHODS: C. albicans CA1398, carrying the bioluminescence ACT1p-gLUC59 fusion product, was employed. Fungal cells were exposed for 1', 5', or 15' to 4 different benzydamine concentrations (0.075 to 0.6%) to 2 mouthwashes (MoWs) containing benzydamine and to a placebo MoW (without benzydamine). Treated cells were tested for adhesion (90 min) and biofilm formation (24-h assay). Next, 24- and 48-h-old biofilms were exposed to benzydamine and MoWs to assess regrowth and persistence, respectively. The effects of benzydamine, MoWs containing benzydamine, and placebo on different biofilm stages were quantified by bioluminescence assay and by the production of quorum sensing (QS) molecules. RESULTS: Benzydamine and MoWs containing benzydamine impaired C. albicans ability to adhere and form biofilm, counteracted C. albicans persistence and regrowth, and impaired a 48-h-old biofilm. Some of these effects paralleled with alterations in QS molecule secretion. CONCLUSIONS: Our results show for the first time that benzydamine and MoWs containing benzydamine impair C. albicans capacity to form biofilm and counteract biofilm persistence and regrowth. CLINICAL RELEVANCE: Benzydamine and MoWs containing benzydamine capacity to affect C. albicans biofilm provides an interesting tool to prevent and treat oral candidiasis. Likely, restraining C. albicans colonization through daily oral hygiene may counteract colonization and persistence by other critical oral pathogens, such as Streptococcus mutans, whose increased virulence has been linked to the presence of C. albicans biofilm.
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Bencidamina , Candida albicans , Bencidamina/farmacología , Biopelículas , Antisépticos Bucales/farmacología , Streptococcus mutansRESUMEN
THE AIM: Share with healthcare practitioners personal experience of using benzydamine spray (Oralsept) in pediatric practice; present a clinical case, which, according to the author, can help doctors optimize approaches to the treatment of patients with acute respiratory viral infections (including COVID-19), thereby improving the quality of life of pediatric patients.
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Bencidamina , COVID-19 , Infecciones del Sistema Respiratorio , Virosis , Humanos , Niño , Bencidamina/uso terapéutico , Calidad de Vida , Infecciones del Sistema Respiratorio/tratamiento farmacológicoRESUMEN
PURPOSE: To discuss the role of benzydamine in the prevention and treatment of radiation-induced oral mucositis (OM) in head and neck (H&N) cancer patients. This document represents an expert opinion paper on indications and key-role aspects in OM pathogenesis, prevention and treatment. ORAL MUCOSITIS: OM represents a common side effect of chemotherapy (CHT) and radiotherapy (RT). It consists in a painful erythema involving the oral cavity mucosa, which may progress to ulceration. Five biologically dynamic phases are considered crucial in mucositis: "initiation, signalling, amplification, ulceration and healing". Oral environment and microbiota are fundamental in mucositis development being involved in susceptibility to infections and in ulceration consequences. Different agents against mucositis have been studied and the use of benzydamine is strongly supported in literature. The Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO) guidelines recommend its use for the prevention of OM in H&N patients undergoing RT and RT/CHT. BENZYDAMINE: Benzydamine is a local anti-inflammatory drug with analgesic properties. It can decrease TNF-α, IL-1ß and prostaglandin synthesis, also inhibiting leukocyte-endothelial interactions, neutrophil degranulation, vasodilation and vascular permeability. Literature agrees on the beneficial effects of benzydamine in preventing and reducing oral mucositis severity in H&N cancer patients undergoing RT/CHT. CONCLUSIONS: Mucositis represents a major concern in H&N cancer patients and a clinical and economical issue. A multimodal and multidisciplinary approach is needed for its management. International guidelines recommend benzydamine for OM prevention and treatment in H&N cancer patients, but further "real world" trials should be designed.
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Bencidamina , Neoplasias de Cabeza y Cuello , Mucositis , Estomatitis , Bencidamina/uso terapéutico , Quimioradioterapia , Humanos , Mucositis/inducido químicamente , Mucositis/prevención & control , Estomatitis/inducido químicamente , Estomatitis/prevención & controlRESUMEN
BACKGROUND: Dental plaque is a major oral health problem with severe consequences. Oral antiseptics provide important means for controlling dental plaque formation and are widely used by the public. However, some of these antiseptics have been shown to have side effects on oral tissues. AIM: In this study, we aimed to investigate the time and dose-dependent cytotoxic effects of various antiseptics on primary human gingival fibroblasts (HGF). METHODS: HGF cells were obtained using primary culture techniques. The effects of various doses of 5 antiseptics containing Chlorhexidine-Gluconate (CHX), CHX with Benzydamine-Hydrochloride (Benzydamine-HCl), Povidone-Iodine (PVP-I), Benzydamine-HCl and Essential-Oil on HGFs were analyzed by using 2,3-bis (2-metoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide cell viability assay after 30, 60, and 180 s of exposure. Results: Cell viability analyses showed that cell death increased in an application time and dose-dependent manner. There was a statistically significant difference in the effects of each antiseptic on live-cell densities compared to the control group and each other (P < 0.001). Antiseptic containing 0.2% CHX showed the highest cytotoxicity on cells. The remaining viable cell density after administration of 0.2% CHX at a dose of 12.5% for 30 s is 35.19%. The high cytotoxic effect of 0.2% CHX was followed by 0.12% CHX with 0.15% Benzydamine-HCl, PVP-I and 0.15% Benzydamine-HCl groups. The lowest cytotoxic effect was observed for the Essential-Oil containing antiseptic solution. CONCLUSIONS: The results of this study show that these five antiseptic agents have variable effects on in vitro HGF proliferation. The doses and administration times of antiseptics should be controlled carefully during dental applications.
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Antiinfecciosos Locales , Antineoplásicos , Bencidamina , Antiinfecciosos Locales/toxicidad , Clorhexidina/toxicidad , Encía , Humanos , Povidona Yodada/toxicidadRESUMEN
Enterovirus infections are a group of acute infectious diseases caused by enteroviruses (including Coxsackie A and B viruses, ECHO viruses), which clinically present symptoms of damage to the central nervous system, cardiovascular system, gastrointestinal tract, muscular system, mucous membranes and skin, fever. This article presents a clinical case of patient L., 12 years old, who admitted to an otorhinolaryngologist with clinical manifestations of herpangina. The diagnosis was confirmed by PCR. The patient was prescribed, adequate rehydration, diet with the exclusion of salty, spicy and fried foods, restriction of physical activity, exclusion of thermal procedures, Benzydamine Spray (Oralsept) 0.255 mg/dose, 6 doses 3 times/day, topically, on demand and inosine pranobex (Groprinosin) in a daily dose of 50 mg/kg of body weight: 1 tablet 500 mg 4 times a day for 7 days (at the rate of 1 tablet of 500 mg per 10 kg of body weight; for a patient weighing 41 kg - 4 tablets per day). On the 10th day from the onset of the disease, the docter noted a complete regression of clinical symptoms and the patient was discharged with recovery.
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Infecciones por Enterovirus , Enterovirus , Herpangina , Niño , HumanosRESUMEN
BACKGROUND: Postoperative sore throat (POST) is a common, undesirable result of endotracheal intubation during general anaesthesia. This study aimed to evaluate the effectiveness of benzydamine hydrochloride (BH) spray in reducing the incidence of POST in paediatric patients. METHODS: This randomized, double-blind, prospective study included 142 children 6-12 years of age, who were randomly assigned to receive either BH spray or control. After induction of anaesthesia, direct laryngoscope was placed and BH spray was applied to the upper trachea and vocal cord in the BH group and intubation was performed using a cuffed tube lubricated with normal saline. Intubation in the control group was performed using a cuffed tube lubricated with normal saline without any intervention. The balloon was inflated to a pressure of 20 cmH2O. Patients were extubated after fully awakened and transferred to the post-anaesthetic care unit (PACU), where they were examined for the presence of POST and any adverse events 30 min after arrival to the PACU. Postoperative pain was evaluated using a smartphone application. RESULTS: Seventy-one patients were allocated to each group. The incidence of POST in the BH group did not differ from that in the control group (control: BH = 35 (49.3%): 42 (59.2%); P = 0.238); postoperative pain was also similar between the groups. Other complications, such as breath holding, secretions, coughing, laryngospasm and desaturation events, did not differ between the groups. CONCLUSIONS: Application of prophylactic BH spray to the vocal cords and upper trachea was not proven to reduce POST in paediatric patients. TRIAL REGISTRY: NCT03074968 (ClinicalTrials.gov, Feb 26, 2017).
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Bencidamina/administración & dosificación , Intubación Intratraqueal/efectos adversos , Faringitis/prevención & control , Complicaciones Posoperatorias/prevención & control , Extubación Traqueal/efectos adversos , Anestesia General , Antiinflamatorios/administración & dosificación , Niño , Método Doble Ciego , Femenino , Humanos , Incidencia , Masculino , Faringitis/epidemiología , Faringitis/etiología , Estudios ProspectivosRESUMEN
BACKGROUND: Endoscopic Retrograde Cholangiopancreatography (ERCP) is a complex endoscopic procedure that requires moderate to deep sedation. Propofol is the sedative agent of choice for sedation in ERCP due to its fast distribution and fast elimination time without a cumulative effect after infusion, resulting in shorter recovery time. Benzydamine hydrochloride is a topical non-steroidal anti-inflammatory drug that has analgesic, local anesthetic, and anti-inflammatory effects that have been known to be effective in reducing postoperative sore throat. Combination of propofol and topical analgesic may provide adequate sedation and reduce propofol consumption. This study aimed to determine the effectivity of benzydamine hydrochloride gargling in reducing propofol consumption in the ERCP procedure. METHODS: This study was a single-blind randomized controlled trial for patients undergoing ERCP procedures at Cipto Mangunkusumo Hospital from August to September 2018. A total of 72 subjects were recruited consecutively and randomly assigned into two groups. The first group received 15 mL of 0.15% benzydamine hydrochloride mouthwash prior to the procedure, whereas the second group received 15 mL of water mouthwash. Additional propofol was administered when patient moved or Ramsay Sedation Scale rose above 4. Cumulative propofol consumption per kg body weight per minute and incidence of postoperative sore throat were recorded in each group. Incidence of desaturation, postoperative nausea vomitting, and dysphagia were also recorded. Data analysis was performed with Statistical Package for the Social Sciences. RESULTS: Cumulative propofol consumption per minute per kg body weight in the benzydamine hydrochloride group was 152.7 (91.9-238.8) mcg/kg/minute, while in the control group was 200.05 (114.4-380.2) mcg/kg/ minute (p = < 0.001). The incidence of sore throat on the 0th, 2nd, and 4th hour for the benzydamine hydrochloride group was 11.4, 11.4, and 5.7%, while in the control group was 50, 52.8, and 36.1% (p = < 0.001, < 0.001, 0.003). Desaturation was found in control group whereas none in benzydamine hydrochloride group. Complaints of nausea and vomiting were comparable in both groups. CONCLUSION: Benzydamine hydrochloride gargling was effective in reducing cumulative propofol consumption in the ERCP procedure. TRIAL REGISTRATION: Study was registered retrospectively in ClinicalTrials.gov with NCT04167592 on November 8th 2019.
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Bencidamina/administración & dosificación , Colangiopancreatografia Retrógrada Endoscópica/métodos , Propofol/administración & dosificación , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antisépticos Bucales , Faringitis/epidemiología , Método Simple CiegoRESUMEN
BACKGROUND: Sufficient reference standards of drug metabolites are required in the drug discovery and development process. However, such drug standards are often expensive or not commercially available. Chemical synthesis of drug metabolite is often difficulty due to the highly regio- and stereo-chemically demanding. The present work aims to construct stable and efficient biocatalysts for the generation of drug metabolites in vitro. RESULT: In this work, using benzydamine as a model drug, two easy-to-perform approaches (whole cell catalysis and enzyme immobilization) were investigated for the synthesis of FMO3-generated drug metabolites. The whole cell catalysis was carried out by using cell suspensions of E. coli JM109 harboring FMO3 and E. coli BL21 harboring GDH (glucose dehydrogenase), giving 1.2 g/L benzydamine N-oxide within 9 h under the optimized conditions. While for another approach, two HisTrap HP columns respectively carrying His6-GDH and His6-FMO3 were connected in series used for the biocatalysis. In this case, 0.47 g/L benzydamine N-oxide was generated within 2.5 h under the optimized conditions. In addition, FMO3 immobilization at the C-terminal (membrane anchor region) significantly improved its enzymatic thermostability by more than 10 times. Moreover, the high efficiency of these two biocatalytic approaches was also confirmed by the N-oxidation of tamoxifen. CONCLUSIONS: The results presented in this work provides new possibilities for the drug-metabolizing enzymes-mediated biocatalysis.
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Bencidamina/metabolismo , Enzimas Inmovilizadas , Escherichia coli/metabolismo , Oxigenasas/metabolismo , Biocatálisis , Humanos , Oxidación-ReducciónRESUMEN
Benzydamine hydrochloride is a non-steroidal anti-inflammatory drug with analgesic and antipyretic effects. In those who use medicines containing this agent at high doses (500-3000 mg), some adverse effects such as hallucinosis, stimulant effects in the central nervous system, paranoia, and convulsions can be seen. The drug is vulnerable to abuse because of the stimulant effects on the central nervous system. In this paper, we present a young male patient with symptoms of psychosis due to benzydamine hydrochloride abuse. He was admitted to the psychiatry outpatient clinic with visual hallucinations, fear, and insomnia. His symptoms started after taking 10 tablets of benzydamine hydrochloride (500 mg) 6 months ago, which continued for 1-2 days and spontaneously resolved. The patient used high doses of the drug 3-4 times over a period of 3 months. Although his last drug intake was 3 months ago, his symptoms continued at the time of admission to the clinic. A neurologic examination and detailed laboratory tests of the patient revealed no evidence of a cause for psychotic symptoms. The patient was scheduled to undergo oral antipsychotic therapy. Although similar cases have been reported in the literature, this is the only case in which psychosis was still present despite discontinuation of the drug. Our aim was to contribute to the literature on the use of BH in causing chronic psychosis and to draw attention to the growing number of BH abuse cases.
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Bencidamina/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Trastornos Psicóticos/diagnóstico , Trastornos Relacionados con Sustancias/complicaciones , Humanos , Masculino , Adulto JovenRESUMEN
The expression of flavin-containing monooxygenase (FMO) varies extensively between human and commonly used preclinical species such as rat and mouse. The aim of this study was to investigate the pulmonary FMO activity in rat using benzydamine. Furthermore, the contribution of rat lung to the clearance of benzydamine was investigated using an in vivo pulmonary extraction model. Benzydamine N-oxygenation was observed in lung microsomes and lung slices. Thermal inactivation of FMO and CYP inhibition suggested that rat pulmonary N-oxygenation is predominantly FMO mediated while any contribution from CYPs is negligible. The predicted lung clearance (CLlung) estimated from microsomes and slices was 16 ± 0.6 and 2.1 ± 0.3 mL/min/kg, respectively. The results from in vivo pulmonary extraction indicated no pulmonary extraction following intravenous and intra-arterial dosing to rats. Interestingly, the predicted CLlung using rat lung microsomes corresponded to approximately 35% of rat CLliver suggesting that the lung makes a smaller contribution to the whole body clearance of benzydamine. Although benzydamine clearance in rat appears to be predominantly mediated by hepatic metabolism, the data suggest that the lung may also make a smaller contribution to its whole body clearance.
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Bencidamina/farmacocinética , Pulmón/enzimología , Microsomas/enzimología , Oxigenasas de Función Mixta/metabolismo , Animales , Bencidamina/farmacología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. METHODS: Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. RESULTS: The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. CONCLUSIONS: For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.
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Antiinflamatorios/uso terapéutico , Bencidamina/uso terapéutico , Traumatismos por Radiación/tratamiento farmacológico , Bicarbonato de Sodio/uso terapéutico , Estomatitis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Bencidamina/administración & dosificación , Bencidamina/farmacología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bicarbonato de Sodio/administración & dosificación , Bicarbonato de Sodio/farmacología , Adulto JovenRESUMEN
Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is known about the central pharmacological actions of BZY. Yet there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat self-administration paradigm. We found that BZY has a powerful reinforcing effect and that this effect is greatly facilitated in animals that already had substance experience, having previously self-administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse. We then assessed the effect of BZY on prelimbic cortex-to-nucleus accumbens glutamatergic transmission, using field recordings in rat parasagittal brain slices. BZY dose-dependently reduced both field excitatory post synaptic potential amplitude and paired pulse ratio, suggesting a presynaptic mechanism of action. Similarly to the in vivo paradigm, also the electrophysiological effects of BZY were potentiated in slices from animals that had undergone cocaine and heroin self-administration. Furthermore, BZY-induced Long Term Depression (LTD)-like responses in the prelimbic cortex-to-nucleus accumbens circuitry were significantly reduced in the presence of the CB1 receptor antagonist AM251. These findings provide firm evidence of the abuse liability of BZY and suggest a possible cannabinoidergic mechanism of action. Further research is needed in order to give insights into the molecular mechanism underlying BZY psychoactive and reinforcing effects, to better understand its abuse potential.
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Antiinflamatorios no Esteroideos/administración & dosificación , Bencidamina/administración & dosificación , Receptor Cannabinoide CB1/efectos de los fármacos , Administración Intravenosa , Animales , Antiinflamatorios no Esteroideos/farmacología , Conducta Animal , Bencidamina/farmacología , Cocaína/administración & dosificación , Inhibidores de Captación de Dopamina/administración & dosificación , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Ácido Glutámico/efectos de los fármacos , Ácido Glutámico/metabolismo , Heroína/administración & dosificación , Depresión Sináptica a Largo Plazo/efectos de los fármacos , Narcóticos/administración & dosificación , Vías Nerviosas , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Piperidinas/farmacología , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Pirazoles/farmacología , Ratas , Receptor Cannabinoide CB1/antagonistas & inhibidores , Receptor Cannabinoide CB1/metabolismo , Refuerzo en Psicología , Autoadministración , Transmisión Sináptica/efectos de los fármacosRESUMEN
Postoperative sore throat has a negative impact on patient satisfaction and recovery. Benzydamine hydrochloride is a non-steroidal anti-inflammatory drug available for topical use. We performed a systematic review and meta-analysis to assess the efficacy and safety of topical application of benzydamine to prevent postoperative sore throat in adults undergoing elective surgery under general anaesthesia. We searched PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials to identify relevant randomised controlled trials and pooled the data using a random effects model. The primary outcomes were the incidence and severity of sore throat 24 h after surgery/extubation, and adverse events. The quality of evidence was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) criteria. Thirteen randomised controlled trials involving 1842 patients were included. Compared with control patients who did not receive analgesia, benzydamine was associated with a decreased incidence of postoperative sore throat, with a risk ratio (95%CI) of 0.31 (0.20-0.47), but not with significantly reduced severity, the standardised mean difference (95%CI) being -0.27 (-0.63 to 0.08). There were no significant adverse events related to benzydamine. Benzydamine was also associated with a reduced incidence of postoperative sore throat when compared with lidocaine, with a risk ratio (95%CI) of 0.18 (0.07-0.43). We judged the evidence for the outcome 'incidence of postoperative sore throat' as high quality.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Bencidamina/uso terapéutico , Intubación Intratraqueal/efectos adversos , Faringitis/prevención & control , Complicaciones Posoperatorias/prevención & control , Administración Tópica , Anestesia General , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Bencidamina/administración & dosificación , Bencidamina/efectos adversos , Procedimientos Quirúrgicos Electivos/métodos , HumanosRESUMEN
The aim of this study was to develop benzydamine hydrochloride-loaded orodispersible films using the modification of a solvent casting method. An innovative approach was developed when the drying process of a small-scale production was used based on a heated inert base for casting the film. During this process, two types of film-forming maltodextrins for rapid drug delivery were used. They were plasticized with two different polyols (xylitol and sorbitol). Superdisintegrant Kollidon® CL-F was tested as an excipient that can induce faster disintegration of the prepared films. The influence of the formulation parameters (dextrose equivalent of film-forming maltodextrins, a type of plasticizer, and the presence of superdisintegrant) on the disintegration time, mechanical properties, and moisture content of films was statistically evaluated using a multivariate data analysis. Orodispersible films containing maltodextrin with lower dextrose equivalent value showed better mechanical properties (tensile strength ranged from 886.6 ± 30.2 to 1484.2 ± 226.9 N cm-2), lower moisture content (0.5 ± 0.0 to 1.2 ± 0.2%), and shorter disintegration time (17.6 ± 2.9 to 27.8 ± 2.8 s). Films plasticized with xylitol showed shorter disintegration time (17.6 ± 2.9 to 29.2 ± 3.8 s) than films containing sorbitol (23.8 ± 2.9 to 31.7 ± 3.9 s). With the addition of superdisintegrant Kollidon® CL-F, a significant influence on disintegration time was not observed. The modified solvent casting method shows great promise in a small-scale laboratory production of orodispersible films, e.g., in a pharmacy lab.
Asunto(s)
Bencidamina/química , Sistemas de Liberación de Medicamentos , Plastificantes/química , Polisacáridos/química , Povidona/química , Solventes/químicaRESUMEN
PURPOSE: Benzydamine is recommended for prophylaxis of oral mucositis (OM) in head and neck cancer (HNC) patients for radiation doses (<50 Gy). This study evaluates role of benzydamine for higher radiation doses (>50 Gy) with or without chemotherapy. METHODS: One hundred twenty patients of HNC with planned radiation doses of ≥60 Gy were randomized to group A (control radiotherapy alone), group B (study radiotherapy alone), group C (control chemoradiotherapy), or to group D (study chemoradiotherapy). Groups A and C were advised saline mouth rinses, and in groups B and D, additional benzydamine rinses (0.15%) were advised. Mucositis grading was done with both WHO (WHO-M) and CTCAE (CTC-M) version 4.0 (common terminology criteria for adverse events) weekly. RESULTS: Patient characteristics are presented in the table. Patients in group B had lesser grade 3 WHO-M and CTC-M as compared to group A, 62.1 vs. 36.4% (p = 0.038) and 51.7 vs. 27.3% (p = 0.043), respectively. The rates of Ryle's tube feeding (RTF), intravenous fluid supplementation (IVF), and hospitalization were also lesser in group B as compared to A, 34.5 vs. 21.2% (p = 0.18), 27.6 vs. 9.1% (p = 0.06), and 6.9 vs. 0% (p = 0.21), respectively. WHO-M and CTC-M in groups C and D were not statistically different, 64.3 vs. 43.3% (p = 0.091) and 53.6% vs. 43.3% (p = 0.30), respectively. The rates of RTF, IVF, and hospitalization were all lesser but p > 0.05. CONCLUSION: Benzydamine significantly reduces OM even at doses >50 Gy in HNC patients. Its role in patients receiving concurrent chemotherapy further needs to be evaluated.
Asunto(s)
Bencidamina/uso terapéutico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Traumatismos por Radiación/prevención & control , Estomatitis/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioradioterapia/efectos adversos , Relación Dosis-Respuesta en la Radiación , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Antisépticos Bucales/uso terapéutico , Estudios Prospectivos , Traumatismos por Radiación/etiología , Carcinoma de Células Escamosas de Cabeza y Cuello , Estomatitis/etiología , Adulto JovenRESUMEN
Liposomal vaginal drug delivery systems are important strategy in the treatment of both topical and systemic diseases. The aim of this study was to develop a vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes dispersed into mucoadhesive gels. The delivery system was also designed for a once a day dosage and to obtain controlled release of the BNZ. For this purpose BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M and Carbopol® 974P, which are composed of polymers that show promising potential as mucoadhesive vaginal delivery systems, were developed. In addition, a BNZ containing liposome formulation was developed for vaginal administration. To improve the vaginal retention time, liposome was incorporated in HPMC K100M and Carbopol® 974P gel formulations. This system is called lipogel. The developed BNZ liposomes have a slightly negative zeta potential (-1.50±0.16 mV), a 2.25±0.009 µm particle size and a 34% entrapment efficiency. These gels and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive value for vaginal administration. Lipogels were found to be the best formulations for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion obtained from liposomes was in the range of 0.027±0.045 and 0.030±0.017 mJ/cm2, while the value obtained from lipogels was between 0.176±0.037 and 0.243±0.53 mJ/cm2. N1 and N2 lipogel formulations diffused 57 and 67% of BNZ respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases drug residence time in comparison to liposomes, could improve BNZ efficacy. In conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising alternatives to traditional dosage forms for vaginal topical therapy.