RESUMO
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.
Assuntos
Antitussígenos , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Ratos , Antitussígenos/farmacologia , Antitussígenos/uso terapêutico , Mapas de Interação de Proteínas/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/metabolismo , Asma/genética , Transdução de Sinais/efeitos dos fármacos , Tosse/tratamento farmacológico , Transcriptoma , HumanosRESUMO
In recent years, there has been a substantial increase in the development of antitussive therapies and the first new therapy, gefapixant has been licenced in Europe. This review describes current unlicenced treatments for chronic cough and details treatments currently in development for refractory chronic cough and cough in idiopathic pulmonary fibrosis, as well as compounds previously explored.
Assuntos
Antitussígenos , Tosse Crônica , Humanos , Doença Crônica , Tosse/tratamento farmacológico , Tosse/etiologia , Antitussígenos/uso terapêutico , Europa (Continente)RESUMO
PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.
Assuntos
Antitussígenos , Codeína , Humanos , Codeína/uso terapêutico , Antitussígenos/uso terapêutico , Estudos Prospectivos , Tosse Crônica , Estudos de Coortes , Tosse/tratamento farmacológico , Tosse/etiologiaRESUMO
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.
Assuntos
Tosse , Infecções Respiratórias , Humanos , Tosse/tratamento farmacológico , Tosse/etiologia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , Infecções Respiratórias/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem , Antitussígenos/administração & dosagem , Antitussígenos/uso terapêutico , Adolescente , Viroses/tratamento farmacológico , IdosoRESUMO
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.
Assuntos
Antitussígenos , Tosse , Medicamentos de Ervas Chinesas , Flores , Animais , Antitussígenos/uso terapêutico , Antitussígenos/farmacologia , Cobaias , Flores/química , Masculino , Tosse/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Cordyceps/químicaAssuntos
Tosse , Humanos , Tosse/terapia , Tosse/fisiopatologia , Doença Crônica , Efeito Placebo , Placebos , Antitussígenos/uso terapêutico , Tosse CrônicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xingbei antitussive granules (XB) is a classic Chinese Medicine prescription for treating post-infectious cough(PIC), based on the Sanao Decoction from Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and Jiegeng decoction from Essentials of the Golden Chamber in the Han Dynasty. However, the therapeutic effects and pharmacological mechanisms are still ambiguous. In the present study, we endeavored to elucidate these underlying mechanisms. AIMS OF THE STUDY: This study aimed to explore the potential impact and mechanism of XB on PIC, and provide a scientific basis for its clinical application. MATERIALS AND METHODS: Cigarette smoking (CS) combined with lipopolysaccharide (LPS) nasal drops were administered to induce the PIC guinea pig with cough hypersensitivity status. Subsequently, the model guinea pigs were treated with XB and the cough frequency was observed by the capsaicin cough provocation test. The pathological changes of lung tissue were assessed by HE staining, and the levels of inflammatory mediators, mast cell degranulating substances, and neuropeptides were detected. The protein and mRNA expression of transient receptor potential vanilloid type 1(TRPV1), proteinase-activated receptor2(PAR2), and protein kinase C (PKC) were measured by Immunohistochemical staining, Western blot, and RT-qPCR. Changes in the abundance and composition of respiratory bacterial microbiota were determined by 16S rRNA sequencing. RESULTS: After XB treatment, the model guinea pigs showed a dose-dependent decrease in cough frequency, along with a significant alleviation in inflammatory infiltration of lung tissue and a reduction in inflammatory mediators. In addition, XB high-dose treatment significantly decreased the levels of mast cell Tryptase as well as ß-hexosaminidase (ß-Hex) and downregulated the expression of TRPV1, PAR2, and p-PKC. Simultaneously, levels of neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and nerve growth factor (NGF) were improved. Besides, XB also can modulate the structure of respiratory bacterial microbiota and restore homeostasis. CONCLUSION: XB treatment alleviates cough hypersensitivity and inflammatory responses, inhibits the degranulation of mast cells, and ameliorates neurogenic inflammation in PIC guinea pigs whose mechanism may be associated with the inhibition of Tryptase/PAR2/PKC/TRPV1 and the recovery of respiratory bacterial microbiota.
Assuntos
Antitussígenos , Doenças Transmissíveis , Humanos , Cobaias , Animais , Suínos , Antitussígenos/farmacologia , Antitussígenos/uso terapêutico , Tosse/tratamento farmacológico , Triptases , RNA Ribossômico 16S , Mediadores da Inflamação , Canais de Cátion TRPVRESUMO
BACKGROUND: Chronic cough (CC) affects about 10% of adults, but opioid use in CC is not well understood. OBJECTIVES: To determine the use of opioid-containing cough suppressant (OCCS) prescriptions in patients with CC using electronic health records. DESIGN: Retrospective cohort study. METHODS: Through retrospective analysis of Midwestern U.S. electronic health records, diagnoses, prescriptions, and natural language processing identified CC - at least three medical encounters with cough, with 56-120 days between first and last encounter - and a 'non-chronic cohort'. Student's t-test, Pearson's chi-square, and zero-inflated Poisson models were used. RESULTS: About 20% of 23,210 patients with CC were prescribed OCCS; odds of an OCCS prescription were twice as great in CC. In CC, OCCS drugs were ordered in 38% with Medicaid insurance and 15% with commercial insurance. CONCLUSION: Findings identify an important role for opioids in CC, and opportunity to learn more about the drugs' effectiveness.
Assuntos
Analgésicos Opioides , Tosse Crônica , Registros Eletrônicos de Saúde , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Antitussígenos/administração & dosagem , Antitussígenos/uso terapêutico , Tosse Crônica/tratamento farmacológico , Doença Crônica , Estudos de Coortes , Prescrições de Medicamentos/estatística & dados numéricos , Medicaid , Meio-Oeste dos Estados Unidos , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Estados UnidosRESUMO
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.
Assuntos
Antitussígenos , Tosse , Tosse/tratamento farmacológico , Humanos , Antitussígenos/uso terapêutico , Antitussígenos/farmacologia , Doença Crônica , Canais de Potencial de Receptor Transitório/antagonistas & inibidores , Canais de Potencial de Receptor Transitório/metabolismo , Receptores Purinérgicos/metabolismo , Tosse CrônicaRESUMO
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.
Assuntos
Antitussígenos , Butorfanol , Tosse , Doenças do Cão , Animais , Cães , Tosse/veterinária , Tosse/tratamento farmacológico , Tosse/etiologia , Antitussígenos/uso terapêutico , Antitussígenos/farmacologia , Antitussígenos/administração & dosagem , Doenças do Cão/tratamento farmacológico , Butorfanol/administração & dosagem , Butorfanol/uso terapêutico , Quinuclidinas/uso terapêutico , Quinuclidinas/farmacologia , Quinuclidinas/administração & dosagem , Masculino , Feminino , Modelos Animais de Doenças , Doença AgudaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.
Assuntos
Antipiréticos , Antitussígenos , Nymphaea , Ratos , Camundongos , Animais , Antipiréticos/farmacologia , Antipiréticos/uso terapêutico , Antipiréticos/química , Carragenina , Antitussígenos/uso terapêutico , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Fator de Necrose Tumoral alfa , Saccharomyces cerevisiae , Interleucina-6 , Ciclo-Oxigenase 2 , Dinoprostona , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Anti-Inflamatórios/efeitos adversos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/química , Dor/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Acetatos , Tosse/tratamento farmacológico , Granuloma/tratamento farmacológico , Superóxido DismutaseRESUMO
In this issue of NEJM Evidence, Maher et al.1 report the results of a randomized, controlled, 22-day treatment crossover trial comparing the antitussive effect of extended-release nalbuphine, an opioid agonist-antagonist, with placebo in a cohort of patients with definite or probable idiopathic pulmonary fibrosis (IPF). In this small, short-term trial of 38 evaluable patients, the active drug was associated with a 75.1% reduction in daytime objective cough frequency (the primary outcome) compared with a 22.6% reduction in placebo-treated patients, yielding a substantial and statistically significant 52.5 percentage point placebo-adjusted change from baseline.
Assuntos
Antitussígenos , Fibrose Pulmonar Idiopática , Nalbufina , Humanos , Analgésicos Opioides/uso terapêutico , Antitussígenos/uso terapêutico , Tosse Crônica , Fibrose Pulmonar Idiopática/complicações , Nalbufina/uso terapêuticoRESUMO
A partir de una consulta en la central de emergencias de un niño con tos aguda, el autor del artículo realiza una búsqueda bibliográfica para revisar la evidencia sobre el uso de la miel para aliviar este síntoma. Luego de la lectura crítica de una revisión sistemática, el autor concluye que ésta podría ser una alternativa elegible frente a los jarabes para la tos, por su perfil de seguridad y su posible beneficio en el alivio de la tos. (AU)
Based on a consultation at the emergency room of a child with acute cough, the author of this article performs a bibliographic search to review the evidence on the use of honey to alleviate this symptom. After the critical appraisal of a systematic review, the author concludes that honey could be an eligible alternative to cough syrups, due to its safety profile and its possible benefit in cough relief. (AU)
Assuntos
Humanos , Masculino , Criança , Adolescente , Tosse/terapia , Mel , Antitussígenos/uso terapêutico , Infecções Respiratórias/terapia , Tosse/classificação , Tosse/fisiopatologia , Tosse/tratamento farmacológico , Dextrometorfano/uso terapêutico , Difenidramina/uso terapêutico , Febre , Assistência Ambulatorial/métodos , Revisões Sistemáticas como AssuntoAssuntos
Humanos , Criança , Adolescente , Antitussígenos/efeitos adversos , Descongestionantes Nasais/efeitos adversos , Resfriado Comum/tratamento farmacológico , Tosse/tratamento farmacológico , Antitussígenos/uso terapêutico , Simpatomiméticos/efeitos adversos , Simpatomiméticos/uso terapêutico , Descongestionantes Nasais/uso terapêutico , Combinação de Medicamentos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Analgésicos/efeitos adversos , Analgésicos/uso terapêuticoRESUMO
A CYP2D6 é uma enzima metabólica e sua atividade varia entre indivíduos em função de fatores genéticos, ambientais, presença de doenças e/ou comedicações. A fenotipagem de CYP2D6 com dextrometorfano (DXM) é uma abordagem útil para a determinação da atividade metabólica individual de CYP2D6 e seu procedimento envolve o uso de um método analítico adequado. O uso de matrizes alternativas como a saliva pode tornar a fenotipagem mais simples, e favorecer sua aplicação na rotina clínica. O objetivo desse estudo foi desenvolver e validar um método analítico em CL-EM/EM para a quantificação de DXM e dextrorfano (DTF) em saliva humana. Foi necessária uma alíquota de 200 μl de amostras de saliva, processadas utilizando-se a precipitação de proteínas com metanol. (...) Os valores de razão metabólica (RM DXM/DTF) foram calculados individualmente para a classificação fenotípica e variaram de 4 a 383, sendo todas as pacientes classificadas como metabolizadoras extensivas. O presente método é adequado para a quantificação de DTF e DXM em saliva e pode ser aplicado na rotina clínica para a fenotipagem de CYP2D6. (AU)
CYP2D6 is a metabolic enzyme and its activity varies according to factors like environment, genetic, drug interactions and disease determinants. CYP2D6 phenotyping with dextromethorphan (DXM) is a useful approach to determine an individual metabolic activity and its procedure involves the use of an appropriate analytical method. The use of alternative matrices such as saliva can make phenotyping simpler, and favor its application in the clinical routine. The aim of this study was to develop and validate an analytical method in LC-MS/MS for DXM and dextrorphan (DX) quantification in human saliva. Aliquots of 200 μl of saliva were required for analysis and samples were processed with methanol for protein precipitation. (...) The metabolic ratio (MR DXM/DX) values were individually calculated for phenotype classification and ranged from 4 to 383, all patients being classified as extensive metabolizers. The present method is suitable for the quantification of DX and DXM in saliva and may be applied in clinical routine for CYP2D6 phenotyping. (AU)
Assuntos
Dextrometorfano , Dextrorfano , Citocromo P-450 CYP2D6 , Preparações Farmacêuticas , Stents , Tamoxifeno/uso terapêutico , Antitussígenos/uso terapêutico , Polimorfismo Genético , /métodosRESUMO
Introdução: A tosse é o sintoma respiratório mais comum em crianças e adultos. Objetivo: Apresentar uma revisão sobre a neurofisiologia e os métodos para estudo do reflexo da tosse, bem como a farmacoterapia e terapia fonoaudiológica da tosse, baseada nos trabalhos publicados entre 2005 e 2010 e indexados nas bases Medline, Lilacs e Biblioteca Cochrane sob os unitermos "tosse" ou "antitussígenos". Síntese dos dados: O reflexo da tosse envolve ativação de múltiplos receptores vagais nas vias aéreas e de projeções neurais do núcleo do trato solitário para outras estruturas do sistema nervoso central. Técnicas experimentais permitem estudar o reflexo da tosse ao nível celular e molecular para desenvolver novos agentes antitussígenos. Não há evidências de que antitussígenos isentos de prescrição médica tenham eficácia superior à do placebo para o alívio da tosse. A terapia fonoaudiológica pode beneficiar pacientes com tosse crônica refratária ao tratamento farmacológico, sobretudo quando coexiste movimento paradoxal das pregas vocais. Comentários Finais: A abordagem multidisciplinar tem papel fundamental no diagnóstico etiológico e tratamento da tosse. O otorrinolaringologista deve informar os pacientes sobre os riscos dos antitussígenos de venda livre a fim de prevenir intoxicações e efeitos adversos, especialmente em crianças...
Introduction: The cough is the more common respiratory symptom in children and adults. Objective: To present a revision on the neurophysiology and the methods for study of the consequence of the cough, as well as the pharmacotherapy and phonoaudiology therapy of the cough, based on the works published between 2005 and 2010 and indexed in the bases Medline, Lilacs and Library Cochrane under them to keywords "cough" or "anti-cough". Synthesis of the data: The consequence of the cough involves activation of receiving multiples becomes vacant in the aerial ways and of neural projections of the nucleus of the solitary treatment for other structures of the central nervous system. Experimental techniques allow studying the consequence of the cough to the cellular and molecular level to develop new anti-cough agents. It does not have evidences of that anti-cough exempt of medical lapsing they have superior effectiveness to the one of placebo for the relief of the cough. The phonoaudiology therapy can benefit patients with refractory chronic cough to the pharmacological treatment, over all when paradoxical movement of the vocal folds coexists. Final Comments: The boarding to multidiscipline has basic paper in the etiological diagnosis and treatment of the cough. The otolaryngologist must inform the patients on the risks of the anti-cough of free sales in order to prevent adverse poisonings and effect, especially in children...
Assuntos
Antitussígenos/uso terapêutico , Codeína/uso terapêutico , Dextrometorfano , Expectorantes/uso terapêutico , Fonoaudiologia , Tosse/tratamento farmacológico , Tosse/terapiaRESUMO
Avaliaram-se os efeitos antitussígenos-expectorantes de duas formulações fitoterápicas utilizando-se três modelos biológicos diferentes. Foram utilizados ratos Wistar no modelo da secreção das vias aéreas, cobaias no modelo de tosse induzido por ácido cítrico e codornas japonesas na determinação da velocidade de transporte mucociliar. Os animais foram distribuídos em grupos e tratados por via oral com as formulações, com doses equivalentes a 10 vezes a terapêutica recomendada, 9ml.kg-1. O grupo-controle negativo de cada espécie foi tratado com solução fisiológica, 10ml.kg-1. O grupo-controle positivo no modelo de tosse induzida pelo ácido cítrico foi tratado com morfina, 1mg.kg-1, por via subcutânea. No modelo em que foram utilizados ratos e codornas, o grupo-controle positivo recebeu erdosteína por via oral, 600mg.kg-1. Os resultados mostraram que as duas formulações fitoterápicas foram eficazes no reflexo da tosse em cobaias, causando 36,4 por cento e 27,3 por cento, respectivamente, de redução. Nos modelos de secreção das vias aéreas e determinação da velocidade de transporte mucociliar, ambas as formulações não apresentaram eficácia significativa.
The antitussive-expectorant effects of two phytotherapic formulations available in the Brazilian market were evaluated using three different biological models. Each phytotherapic formulation, with different composition, had the same batch number and fabrication date. The trade names of the phytotherapics were: Gripalplus Solução® and Melagrião®. Wistar rats were used in the airway secretion model, guinea pigs in the citric acid-induced cough model and japanese quails in the mucociliary transport rate determination. The animals (one group/formulation) were divided in the two phytotherapic groups and orally treated with the equivalent to ten told the therapeutic recommended dose, which was 9ml.kg-1. Animals of negative control group of each specie were orally treated with 10ml.kg-1 of saline. Positive guinea-pigs citric acid-induced cough model was subcutaneously treated with 1mg.kg-1 of morphine. In the rats airway secretion model and japanese quails mucociliary transport rate, a positive control orally received 600mg.kg-1 of erdosteine. The results showed that both phytotherapic formulations were able to inhibit the guinea pig cough reflex induced by citric acid, being 36.4 percent of reduction in the Gripalplus Solução® group and 27.3 percent in the Melagrião® group. The rats airway secretion and the mucociliary transport rate were not significantly affected by the two phytotherapic formulations.
Assuntos
Animais , Cobaias , Ratos , Expectorantes/administração & dosagem , Medicamento Fitoterápico , Resultado do Tratamento , Antitussígenos/administração & dosagem , Antitussígenos/uso terapêutico , Coturnix , Fitoterapia/veterinária , Cobaias , Ratos WistarRESUMO
Revisao sucinta de farmacos utilizados no tratamento de doencas que acometem o aparelho respiratorio,a saber:antitussigenos,expectorantes,farmacos para o resfriado comum,antiasmaticos e tensoativos pulmonares.