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ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng flowers, which are the buds of the traditional Chinese medicinal herb Sanqi, are widely used in China for their cough-ameliorating properties, with demonstrated therapeutic effects in the treatment of both acute and chronic coughs. However, both the antitussive mechanism and active compound basis of P. notoginseng flowers remain poorly understood. AIM OF THE STUDY: We investigated the antitussive effects of P. notoginseng flowers, identified the bioactive constituents responsible for alleviating cough symptoms, and elucidated the underlying pharmacological mechanisms. MATERIALS AND METHODS: We analyzed the major chemical constituents of aqueous extracts of P. notoginseng flowers using liquid chromatography-mass spectrometry and quantitatively analyzed the key component, 20S-ginsenoside Rh2, using high-performance liquid chromatography. Using a cough reflex model in healthy mice and an ovalbumin-induced, highly sensitive guinea pig cough model, we verified the suppressive effects of P. notoginseng flowers and their saponin constituents on coughing. Furthermore, we explored the mechanisms of action of the key ion channels, NaV1.7 and TRPV1, using whole-cell patch-clamp techniques and molecular docking. Finally, the therapeutic mechanisms of P. notoginseng flowers on pathological cough were revealed using hematoxylin and eosin staining, immunohistochemistry, and western blotting. RESULTS: The active components of P. notoginseng flowers were primarily protopanaxadiol-type saponins, among which 20S-ginsenoside Rh2 had the highest content (51.46 mg/g). In the mouse model, P. notoginseng flowers exhibited antitussive effects comparable to those of pentoxyverine citrate. Although its main saponin component, 20S-ginsenoside Rh2, showed slightly weaker effects, it still demonstrated concentration-dependent inhibition of channel activity. The whole-cell patch-clamp technique and virtual molecular docking showed that Rh2 might exert its effects by directly binding to the NaV1.7 and TRPV1 channels. In the guinea pig model, P. notoginseng flowers and their saponin components not only reduced cough frequency and prolonged the latency period before cough onset, but also significantly inhibited tracheal and pulmonary inflammation and the overexpression of TRPV1. CONCLUSIONS: 20S-Ginsenoside Rh2, the major bioactive saponin in P. notoginseng flowers, exhibits potent antitussive effects. The potential mechanism of action of 20S-Ginsenoside Rh2 in the treatment of cough may involve inhibiting NaV1.7 and TRPV1 channel currents through direct binding to core protein active sites and downregulating TRPV1 expression.
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Antitusígenos , Tos , Regulación hacia Abajo , Flores , Ginsenósidos , Canal de Sodio Activado por Voltaje NAV1.7 , Panax notoginseng , Canales Catiónicos TRPV , Animales , Canales Catiónicos TRPV/metabolismo , Cobayas , Flores/química , Tos/tratamiento farmacológico , Ginsenósidos/farmacología , Antitusígenos/farmacología , Masculino , Ratones , Panax notoginseng/química , Regulación hacia Abajo/efectos de los fármacos , Humanos , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Canal de Sodio Activado por Voltaje NAV1.7/efectos de los fármacos , Células HEK293 , Simulación del Acoplamiento Molecular , Cricetulus , Modelos Animales de Enfermedad , Células CHO , Saponinas/farmacología , OvalbúminaRESUMEN
Codeine was microinjected into the area of the Kölliker-Fuse nucleus and the adjacent lateral parabrachial nucleus, within the pontine respiratory group in 8 anesthetized cats. Electromyograms (EMGs) of the diaphragm (DIA) and abdominal muscles (ABD), esophageal pressures (EP), and blood pressure were recorded and analyzed during mechanically induced tracheobronchial cough. Unilateral microinjections of 3.3â¯mM codeine (3 injections, each 37 ± 1.2â¯nl) had no significant effect on the cough number. However, the amplitudes of the cough ABD EMG, expiratory EP and, to a lesser extent, DIA EMG were significantly reduced. There were no significant changes in the temporal parameters of the cough. Control microinjections of artificial cerebrospinal fluid in 6 cats did not show a significant effect on cough data compared to those after codeine microinjections. Codeine-sensitive neurons in the rostral dorsolateral pons contribute to controlling cough motor output, likely through the central pattern generator of cough.
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Codeína , Tos , Electromiografía , Animales , Gatos , Tos/tratamiento farmacológico , Tos/fisiopatología , Codeína/farmacología , Codeína/administración & dosificación , Microinyecciones , Masculino , Puente/efectos de los fármacos , Antitusígenos/farmacología , Antitusígenos/administración & dosificación , Femenino , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Núcleo de Kölliker-Fuse/efectos de los fármacos , Núcleo de Kölliker-Fuse/fisiología , Diafragma/efectos de los fármacos , Diafragma/fisiopatología , Núcleos Parabraquiales/efectos de los fármacos , Núcleos Parabraquiales/fisiología , Músculos Abdominales/efectos de los fármacosRESUMEN
OBJECTIVE: This retrospective longitudinal cohort study aimed to explore the best therapeutic regimen and treatment duration of cough variant asthma (CVA) in children. METHODS: A total of 314 children with CVA were divided into receive inhaled corticosteroids (ICS) combined with long-acting beta2-agonist (LABA) group, ICS combined with leukotriene receptor antagonists (LTRA) group, ICS monotherapy group and LTRA monotherapy group. All clinical data were statistically analyzed. Logistic regression model was used to compare the advantages and disadvantages of different treatment schemes at each follow-up time point and the best treatment scheme. The Cox proportional hazard regression model based on inverse probability weighting was used to compare the effects of different medication regimens on adverse outcomes with asthma recurrence or progression as the end point. RESULTS: (1) After comprehensive analysis, ICS + LABA group was the preferred control regimen for CVA within 8 weeks. After 8 weeks of diagnosis, the efficacy of ICS group or LTRA group was comparable to that of ICS + LABA group and ICS + LTRA group. (2) The ICS + LABA group showed a significant improvement in cough at an early stage, particularly at 4 weeks; the symptoms of ICS + LTRA and ICS groups were significantly improved at 36 weeks. The LTRA group alone showed significant improvement at 20 weeks. CONCLUSION: ICS + LABA, ICS + LTRA, ICS alone and LTRA alone can effectively treat CVA. ICS + LABA could improve the symptoms most quickly within 8 weeks after CVA diagnosis, followed by ICS + LATR group. After 8 weeks, it can be reduced to ICS alone to control CVA for at least 36 weeks based on the remission of symptoms in children.
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Corticoesteroides , Antiasmáticos , Asma , Tos , Quimioterapia Combinada , Antagonistas de Leucotrieno , Humanos , Asma/tratamiento farmacológico , Tos/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Masculino , Niño , Resultado del Tratamiento , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Administración por Inhalación , Antagonistas de Leucotrieno/uso terapéutico , Antagonistas de Leucotrieno/administración & dosificación , Preescolar , Antiasmáticos/uso terapéutico , Antiasmáticos/administración & dosificación , Estudios Longitudinales , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Adolescente , Asma Variante con TosRESUMEN
AIM: To study the efficacy and safety of Eladis® in comparison with placebo in patients with non-productive cough. MATERIALS AND METHODS: A phase III clinical trial enrolled 250 patients aged 18-65 years with acute respiratory viral infection with upper respiratory tract involvement or acute bronchitis. Patients were randomized into 2 groups of 125 subjects: group 1 received Eladis® (40 mg tablets), group 2 received a matching placebo. The patients received the study drugs 1 tablet BID for 7-14 days. After the treatment, patients were followed up (day 7±2) to assess the effect of therapy on the frequency of coughing attacks, the frequency and severity of daytime and nocturnal cough, the severity of cough, the duration of clinical cough cure, and the effect on the severity of the main acute respiratory viral infection symptoms. RESULTS AND CONCLUSION: The results of the study demonstrate the overall efficacy and statistically significant superiority of Eladis® over placebo: there were significant differences between the study groups in the proportion of patients who decreased the coughing attack frequency by ≥50% by day 5 (p<0.0001). In addition, the clinical cure of cough in the Eladis® group occurred 2 days earlier: the median time was 6 days, vs 8 days in placebo group. There was a decrease in the frequency of cough attacks and a decrease in its severity by more than 3.5 points by day 5 of treatment. All the effects were associated with high safety of the drug.
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Tos , Infecciones del Sistema Respiratorio , Humanos , Tos/tratamiento farmacológico , Tos/etiología , Masculino , Adulto , Femenino , Persona de Mediana Edad , Método Doble Ciego , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Resultado del Tratamiento , Adulto Joven , Antitusígenos/administración & dosificación , Antitusígenos/uso terapéutico , Adolescente , Virosis/tratamiento farmacológico , AncianoRESUMEN
BACKGROUND: Chronic cough (persisting for ≥8 weeks) is a common disorder affecting approximately 5 to 10% of adults worldwide that is sometimes refractory to treatment (refractory chronic cough [RCC]) or has no identifiable cause (unexplained chronic cough [UCC]). There is minimal information on the patient's experience of RCC/UCC in Canada. The aim of this study was to evaluate the patient journey and perceptions related to RCC/UCC management in Canada. METHODS: Our exploratory study included Canadians in the Leger Opinion Panel and focused on individuals with RCC or UCC. Key entry criteria were: age ≥18 years, cough on most days for ≥8 weeks, no smoking within 1 year, no serious respiratory disease or lung cancer, and not taking angiotensin-converting enzyme inhibitors. Individuals who met entry criteria were invited to complete an approximately 30-minute online survey with questions on demographic characteristics, healthcare professional (HCP) interactions, diagnosis of underlying conditions, current treatments, and satisfaction with HCPs and chronic cough therapies. RESULTS: A total of 49,076 individuals completed the chronic cough screening questionnaire (July 30, 2021 to September 1, 2021): 1,620 (3.3%) met entry criteria for RCC or UCC, and 1,046 (2.1%) completed the online survey (mean age of 45 years, 61% female). Most respondents (58%) reported their chronic cough was managed by a general practitioner (GP). Forty-four percent of respondents did not have a diagnosis of an underlying condition for their cough. Breathing tests (39%) and chest imaging (34%) were the most common diagnostic tests. Cough suppressants (18%) were the most frequent current treatment. Respondents were moderately satisfied with their HCPs, but more than half considered their treatment ineffective and 34% had considered no longer seeking medical attention because of a lack of treatment success. CONCLUSIONS: Individuals with RCC/UCC in Canada are largely unsatisfied with the effectiveness of treatment. Additional HCP education and new treatment options are needed to improve patient satisfaction.
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Tos , Satisfacción del Paciente , Humanos , Tos/tratamiento farmacológico , Canadá/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Enfermedad Crónica , Adulto , Encuestas y Cuestionarios , Anciano , Tos CrónicaRESUMEN
INTRODUCTION: Neurogenic cough (NC) is thought to be related to sensory neuropathy in the hypopharynx and larynx. Defined as a cough persisting longer than 8 weeks refractory to standard therapy, it is a diagnosis of exclusion when other common etiologies (asthma, gastroesophageal reflux disease (GERD), medication side effects) are ruled out. It affects roughly 11 % of Americans and can negatively impact quality of life. METHODS: Following institutional review board approval, we evaluated the medical records of adult patients seen at the University of Arizona's tertiary laryngology center from 2018 to 2023. Patients were included if their cough persisted for >8 weeks, and they either did not respond to prior proton pump inhibitor and asthma therapy or had GERD and asthma ruled out. These patients underwent a progressive escalation of therapy, which included neuromodulators with or without cough suppression therapy, superior laryngeal nerve (SLN) block, and laryngeal botulinum toxin injections. The primary outcome was patient-reported improvement in cough symptoms rated on a 1-5 scale: 1 = no response, 2 = mild improvement, 3 = moderate improvement, 4 = significant improvement, 5 = complete resolution. RESULTS: A total of 56 patients were included. Mean (SD) age was 64.6 (14.8) years, and 66 % were female. Overall, 42 patients (75.0 %) responded to treatment. Among responders, 7 (16.7 %) experienced mild improvement, 14 (33.3 %) experienced moderate improvement, 17 (40.5 %) experienced significant improvement, and 4 (9.5 %) experienced complete resolution of their cough. 33 patients (58.9 %) were managed exclusively with neuromodulators ± cough suppression therapy; 27 responded, with an average response rating of 3.0 (SD = 1.2). 11 patients (19.6 %) failed medical therapy and underwent SLN block without subsequent botox treatment; 7 responded, with an average response rating of 2.5 (SD = 1.4). 9 patients (16.1 %) failed all previous therapies and underwent laryngeal botulinum toxin injections; 6 responded with an average response rating of 2.4 (SD = 1.3). The remaining 3 patients underwent cough suppression therapy alone, with 2 responding and an average response rating of 3.3 (SD = 1.7). CONCLUSIONS: Neurogenic cough can be effectively treated with a stepwise multimodal approach, including neuromodulators, cough suppression therapy, SLN block, and laryngeal botulinum toxin injections.
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Tos , Humanos , Tos/etiología , Tos/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Nervios Laríngeos , Bloqueo Nervioso/métodos , Toxinas Botulínicas Tipo A/administración & dosificación , Calidad de VidaRESUMEN
PURPOSE: Cough is a prevalent symptom driving patients to seek medical attention in general practice. Despite its widespread use, the clinical efficacy of oxomemazine, the second most reimbursed molecule in France for symptomatic cough treatment, remains uncertain. This study aims to systematically evaluate the clinical efficacy of oxomemazine in cough. METHODS: A systematic literature review with meta-analysis of randomized controlled trials (RCTs) was conducted according to the Rebuild the Evidence Base (REB) protocol. Clinical trials comparing the efficacy of oxomemazine versus placebo or active comparator in cough were searched for. Trials with insufficient data were excluded. Searches were conducted across major databases (Medline, Cochrane Central Register of Controlled Trials, and Embase) and trial registries (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov). RCTs comparing oxomemazine versus placebo or active comparators in cough were sought. Risk of bias was assessed using the Cochrane Collaboration's RoB2 tool. The protocol was preregistered on PROSPERO under the number CRD42022345496 (15). This study received no funding. RESULTS: No RCTs were at low risk of bias. Therefore, no meta-analysis was conducted, in accordance to the pre-specified protocol. CONCLUSIONS: This systematic review highlights the lack of evidence regarding the efficacy of oxomemazine in cough treatment and underscores the need for further well-designed clinical trials to inform its clinical utility in primary care settings.
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Tos , Humanos , Tos/tratamiento farmacológico , Antitusígenos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVES: Farfarae Flos has the effect of cough suppression and phlegm elimination, with cough suppression as the main function. Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect, and some components have been confirmed to have cough suppressant activity. However, the antitussive material basis of Farfarae Flos has not been systematically elucidated. This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography (HPLC) fingerprint of Farfarae Flos extract with its cough suppressant activity. METHODS: HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data. Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract. SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups, a positive control group, and a blank control group (12 groups in total), with 10 guinea pigs in each group. The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10 (4 g/kg), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days. The guinea pigs were placed in 5 L closed wide-mouth bottles, and 17.5% citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes. The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig. Grey relational analysis (GRA) and partial least squares regression (PLSR) were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data, and predict the group of active ingredients in Farfarae Flos with antitussive activity. The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity: SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group, an active ingredient group, a positive control group, and a blank control group (4 groups in total), with 10 guinea pigs in each group. The S9 group was administered Farfarae Flos extract S9 (4 g/kg), the active ingredient group was administered the predicted combination of antitussive active ingredients (dose equivalent to 4 g/kg of Farfarae Flos extract S9), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days, and animal modeling and observation of efficacy indicators were the same as above. RESULTS: The HPLC fingerprint of 10 batches of Farfarae Flos extract was established, and the peak area data of 14 main common peaks were obtained. The antitussive effect data of 10 batches of Farfarae Flos extract were obtained. Compared with the blank control group, the cough latence in the positive control group and S1, S2, S3, S4, S6, S7, S8, S9, S10 groups was prolonged (all P<0.01), while the cough frequency in 5 minutes in the positive control group and S1, S2, S4, S6, S8, S9, S10 groups was decreased (all P<0.05). The analysis of spectrum-effect relationship revealed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercitrin, and rutin had high contribution to the antitussive effect of Farfarae Flos, and the 6 components were predicted to be the antitussive component group of Farfarae Flos. The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P>0.05), which confirmed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercetin, and rutin were the antitussive component group of Farfarae Flos. CONCLUSIONS: The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos. The antitussive effect of Farfarae Flos is the result of the joint action of many components.
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Antitusígenos , Tos , Medicamentos Herbarios Chinos , Flores , Animales , Antitusígenos/uso terapéutico , Antitusígenos/farmacología , Cobayas , Flores/química , Masculino , Tos/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Cordyceps/químicaRESUMEN
BACKGROUND: Cough is a common clinical complaint in small animal practice with limited treatment options for chronic underlying conditions. OBJECTIVES: The present study aimed to evaluate the efficacy of three antitussive drugs in a novel, minimally invasive canine acute cough model. METHODS: Five clinically healthy Beagles were used to create an acute cough model by administering sterile saline via a transtracheally placed central venous catheter. Single-dose antitussive effects of butorphanol, maropitant and Danpron were assessed. Cough frequency was measured before and at hourly intervals up to 3 h post-administration of each drug, with a linear mixed model used for statistical analysis. RESULTS: Butorphanol (0.3 m/kg, IM) significantly reduced cough frequency at 1 and 3 h post-administration. Danpron (0.1 mL/kg, IM) also significantly reduced cough frequency 1 h post-administration; however, this effect was not sustained at 3 h. Maropitant (1 mg/kg, IM) did not significantly reduce cough frequency. The cough induction method was effective and minimally invasive, with no adverse effects. CONCLUSION: The present study demonstrated that butorphanol has a potent and prolonged antitussive effect in an acute canine cough model, whereas Danpron shows a transient effect. These findings provide valuable insights into the comparative efficacy of commonly used antitussive drugs in dogs.
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Antitusígenos , Butorfanol , Tos , Enfermedades de los Perros , Animales , Perros , Tos/veterinaria , Tos/tratamiento farmacológico , Tos/etiología , Antitusígenos/uso terapéutico , Antitusígenos/farmacología , Antitusígenos/administración & dosificación , Enfermedades de los Perros/tratamiento farmacológico , Butorfanol/administración & dosificación , Butorfanol/uso terapéutico , Quinuclidinas/uso terapéutico , Quinuclidinas/farmacología , Quinuclidinas/administración & dosificación , Masculino , Femenino , Modelos Animales de Enfermedad , Enfermedad AgudaAsunto(s)
Tos , Humanos , Tos/tratamiento farmacológico , Administración por Inhalación , Enfermedad Crónica , Tos CrónicaRESUMEN
Herbal medicines, particularly traditional Chinese medicines (TCMs), are a rich source of natural products with significant therapeutic potential. However, understanding their mechanisms of action is challenging due to the complexity of their multi-ingredient compositions. We introduced Herb-CMap, a multimodal fusion framework leveraging protein-protein interactions and herb-perturbed gene expression signatures. Utilizing a network-based heat diffusion algorithm, Herb-CMap creates a connectivity map linking herb perturbations to their therapeutic targets, thereby facilitating the prioritization of active ingredients. As a case study, we applied Herb-CMap to Suhuang antitussive capsule (Suhuang), a TCM formula used for treating cough variant asthma (CVA). Using in vivo rat models, our analysis established the transcriptomic signatures of Suhuang and identified its key compounds, such as quercetin and luteolin, and their target genes, including IL17A, PIK3CB, PIK3CD, AKT1, and TNF. These drug-target interactions inhibit the IL-17 signaling pathway and deactivate PI3K, AKT, and NF-κB, effectively reducing lung inflammation and alleviating CVA. The study demonstrates the efficacy of Herb-CMap in elucidating the molecular mechanisms of herbal medicines, offering valuable insights for advancing drug discovery in TCM.
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Antitusígenos , Medicamentos Herbarios Chinos , Medicina Tradicional China , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China/métodos , Ratas , Antitusígenos/farmacología , Antitusígenos/uso terapéutico , Mapas de Interacción de Proteínas/efectos de los fármacos , Asma/tratamiento farmacológico , Asma/metabolismo , Asma/genética , Transducción de Señal/efectos de los fármacos , Tos/tratamiento farmacológico , Transcriptoma , HumanosRESUMEN
Refractory chronic cough is a disabling disease with very limited therapeutic options. A better understanding of cough pathophysiology has led to the development of emerging drugs targeting cough receptors. Recent strides have illuminated novel therapeutic avenues, notably centred on modulating transient receptor potential (TRP) channels, purinergic receptors, and neurokinin receptors. By modulating these receptors, the goal is to intervene in the sensory pathways that trigger cough reflexes, thereby providing relief without compromising vital protective mechanisms. These innovative pharmacotherapies hold promise for improvement of refractory chronic cough by offering improved efficacy and potentially mitigating adverse effects associated with current recommended treatments. A deeper comprehension of their precise mechanisms of action and clinical viability is imperative for optimising therapeutic interventions and elevating patient care standards in respiratory health. This review delineates the evolving landscape of drug development in this domain, emphasising the significance of these advancements in reshaping the paradigm of cough management.
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Antitusígenos , Tos , Tos/tratamiento farmacológico , Humanos , Antitusígenos/uso terapéutico , Antitusígenos/farmacología , Enfermedad Crónica , Canales de Potencial de Receptor Transitorio/antagonistas & inhibidores , Canales de Potencial de Receptor Transitorio/metabolismo , Receptores Purinérgicos/metabolismo , Tos CrónicaRESUMEN
Purpose: This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery. Patients and Methods: A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 µg·kg-1 (Group LN), and high-dose nalmefene 0.25 µg·kg-1 (Group HN). Sufentanil 0.5 µg·kg-1 was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery. Results: Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; P < 0.001), but no significant difference was observed between the two groups (P=0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181-0.735, P=0.008) in Group LN and by 75.9% (95% CI=0.432-0.898, P=0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C (P < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups. Conclusion: Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity.
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Anestesia General , Tos , Naltrexona , Sufentanilo , Humanos , Sufentanilo/administración & dosificación , Sufentanilo/efectos adversos , Anestesia General/efectos adversos , Tos/tratamiento farmacológico , Tos/inducido químicamente , Femenino , Naltrexona/análogos & derivados , Naltrexona/administración & dosificación , Naltrexona/farmacología , Método Doble Ciego , Persona de Mediana Edad , Adulto , Mama/cirugía , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Relación Dosis-Respuesta a DrogaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Bronchitis is a respiratory disease characterized by a productive cough. Polygala tenuifolia Willd., commonly known as Yuan zhi, is a traditional Chinese herbal medicine used for relieving cough and removing phlegm. Despite its historical use, studies are lacking on the effectiveness of P. tenuifolia in treating bronchitis. Furthermore, the molecular mechanisms underlying the action of its bioactive compounds remain unknown. AIM OF THE STUDY: This study aims to identify the main bioactive compounds responsible for the effects of P. tenuifolia liquid extract (PLE) in treating bronchitis and to elucidate the associated molecular mechanisms. MATERIALS AND METHODS: The main chemical compounds in PLE were identified and determined using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The antitussive, expectorant and anti-inflammatory activities of PLE were evaluated in an ammonia-induced mouse cough model, a tracheal phenol red excretion mouse model, and a xylene-induced ear swelling mouse model, respectively. A network pharmacology analysis was conducted to investigate the associated gene targets, gene ontology, and KEGG pathways related to the main bioactives in PLE targeting bronchitis. PLE and its five bioactive compounds were assessed for their potential anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Western blot analysis was conducted to elucidate the associated molecular mechanisms. RESULTS: Thirty-seven compounds in PLE were identified, and twelve main compounds were further quantified in PLE using UPLC-MS/MS. PLE oral gavage administrations (0.6 and 0.12 mg/kg) for 7 days markedly reduced cough frequency, prolonged latency period of cough, reduced phlegm and inflammation in mice. The network pharmacology analysis identified 57 gene targets of PLE against bronchitis. The PI3K/AKT and MAPK signalling pathways were the top two modulated pathways. In RAW264.7 cells, PLE (12.5-50 µg/mL) significantly reduced cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. PLE downregulated LPS-elevated protein targets in both PI3K/AKT and MAPK signaling pathways. In PLE, tenuifolin, polygalaxanthone â â â , polygalasaponin ⠩⠩⠤⠢, tenuifoliside B, and 3,6'-Disinapoyl sucrose, were identified as the top five core components responsible for treating bronchitis. These compounds were also found to modulate the protein targets in the PI3K/AKT and MAPK signalling pathways. CONCLUSIONS: This study demonstrated the potential therapeutic effects of PLE on bronchitis by reducing cough, phlegm and inflammation. The anti-inflammatory action and molecular mechanisms of the 5 main bioactive compounds in PLE were partly validated through the in vitro assays. The findings provide valuable insights into the mechanisms underlying the traditional use of PLE for bronchitis.
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Antiinflamatorios , Bronquitis , Tos , Farmacología en Red , Extractos Vegetales , Raíces de Plantas , Polygala , Espectrometría de Masas en Tándem , Animales , Polygala/química , Espectrometría de Masas en Tándem/métodos , Ratones , Tos/tratamiento farmacológico , Células RAW 264.7 , Antiinflamatorios/farmacología , Cromatografía Líquida de Alta Presión/métodos , Masculino , Raíces de Plantas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Bronquitis/tratamiento farmacológico , Fitoquímicos/farmacología , Fitoquímicos/análisis , Antitusígenos/farmacología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Modelos Animales de Enfermedad , Xilenos , Amoníaco , Cromatografía Líquida con Espectrometría de MasasRESUMEN
The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300â mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300â mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.
Asunto(s)
Antipiréticos , Antitusígenos , Etanol , Expectorantes , Momordica charantia , Extractos Vegetales , Hojas de la Planta , Animales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Ratones , Antitusígenos/farmacología , Antitusígenos/química , Antitusígenos/aislamiento & purificación , Hojas de la Planta/química , Ratas , Etanol/química , Antipiréticos/farmacología , Antipiréticos/química , Antipiréticos/aislamiento & purificación , Masculino , Momordica charantia/química , Expectorantes/farmacología , Expectorantes/aislamiento & purificación , Expectorantes/química , Tos/tratamiento farmacológico , Ratas Wistar , Relación Dosis-Respuesta a Droga , Saccharomyces cerevisiae/efectos de los fármacos , Fiebre/tratamiento farmacológicoRESUMEN
Aspiration pneumonia is the leading cause of death in patients with Parkinson's disease. The incidence of silent aspiration is high in such patients owing to decreased pharyngeal and laryngeal sensation; thus, interventions for this condition may help prevent pneumonia. In this single-arm, open-label study, we used a cervical percutaneous interferential current stimulation device to activate pharyngeal and laryngeal sensory nerves. We evaluated its effectiveness in patients with Hoehn-Yahr stages 2-4 Parkinson's disease. The primary endpoint was the proportion of patients with a normal cough reflex after consuming 1% citric acid at the end of the intervention compared with baseline measurements. In total, 25 patients received neck percutaneous interferential current stimulation for 20 min twice weekly for 8 weeks. Afterward, the proportion of patients with a normal cough reflex after 1% citric acid consumption increased significantly (p = 0.001), whereas other indicators, such as tongue pressure, peak expiratory flow, and penetration or aspiration during videofluoroscopic examination, remained unchanged. A longer duration of illness, higher Unified Parkinson's Disease Rating Scale total scores, and higher levodopa equivalent daily doses were significantly associated with improved cough test outcomes. Hence, cervical percutaneous interferential current stimulation significantly improved cough reflexes and may improve silent aspiration. Trial Registration: Japan Registry of Clinical Trials, jRCTs062220013, first registered 09/05/2022.
Asunto(s)
Ácido Cítrico , Tos , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/fisiopatología , Femenino , Masculino , Anciano , Tos/tratamiento farmacológico , Persona de Mediana Edad , Neumonía por Aspiración/etiología , Neumonía por Aspiración/prevención & control , Terapia por Estimulación Eléctrica/métodosRESUMEN
Zhi-Ke-Bao pills (ZKB), a traditional Chinese medicine preparation composed of 13 herbs, is generally used to treat cough caused by external wind cold, phlegm, etc in clinical applications, and it plays a core role in relieving cough caused by COVID-19 and influenza in China. Till now, the understanding of its chemical constituents was dramatically limited due to its chemical complexity, restricting its clinical application or development. In this work, a developed ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) method, a targeted and non-targeted strategy and network pharmacology were used to comprehensively characterize the chemical compositions in ZKB and predict its mechanism against cough. A total of 164 compounds (148 targeted compounds and 16 non-targeted ones) were identified or tentatively characterized in ZKB, including 65 flavonoids, 25 alkaloids, 19 organic acids, 41 saponins, 9 coumarins, 2 phenylpropanoids, 2 anthraquinones, and 1 other types. Among them, 37 compounds were unambiguously identified by comparison to reference standards. Meanwhile, the fragmentation behaviors of five main chemical structure types were also summarized. 309 targets and two core signaling pathways of ZKB against cough were predicted by network pharmacology, including MAPK and PI3K-Akt signaling pathways. It was the first time to characterize the chemical compounds of ZKB and reveal its potential mechanism against cough, providing the material basis for further quality control or pharmacodynamic evaluation of ZKB.
Asunto(s)
Tos , Medicamentos Herbarios Chinos , Farmacología en Red , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión/métodos , Tos/tratamiento farmacológico , Humanos , Espectrometría de Masas/métodos , Medicina Tradicional China/métodos , Antitusígenos/farmacología , Antitusígenos/química , Antitusígenos/análisis , Tratamiento Farmacológico de COVID-19 , Alcaloides/análisis , Alcaloides/química , Alcaloides/farmacologíaRESUMEN
This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15-0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29-1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17-1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in ß-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.
Asunto(s)
Antibacterianos , Proteína C-Reactiva , Tos , Humanos , Antibacterianos/uso terapéutico , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Masculino , Femenino , Persona de Mediana Edad , Tos/tratamiento farmacológico , Adulto , Comunicación , Enfermedad Aguda , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano , Atención Primaria de Salud/métodos , COVID-19/complicaciones , España , Pruebas en el Punto de AtenciónAsunto(s)
Corticoesteroides , Tos , Óxido Nítrico , Humanos , Administración por Inhalación , Tos/tratamiento farmacológico , Enfermedad Crónica , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Óxido Nítrico/administración & dosificación , Resultado del Tratamiento , Tos CrónicaRESUMEN
This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.