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1.
J Photochem Photobiol B ; 202: 111674, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778953

RESUMO

The present work showed the preparation of gold (Au NPs) and silver nanoparticles (Ag NPs) using aqueous leaf extract of Clinacanthus nutans Lindau (C. Lindau). The prepared NPs were studied using various microscopic and spectroscopic techniques, which confirmed the formation of crystalline Ag NPs, Au NPs that are stabilized with C. Lindau extract polyphenols. The prepared Au NPs and Ag NPs are studied to assess their comparative analgesic and muscle relaxant activities conducted on BALB/c mice. The muscle relaxant studies displayed that Ag NPs were comparatively higher efficient than Au NPs and methanolic C. Lindau extract in traction examination. Additionally, the analgesic studies exhibited that Ag NPs, Au NPs showed maximum percentage reduction in acetic acid induced writhing at the concentrations of 50, 100 and 150 mg/kg body weight. Further, these results conclude that as prepared Au NPs and Ag NPs prepared from C. Lindau leaf extract demonstrated very good analgesic and muscle relaxant activities for the use of pain management in nursing care.


Assuntos
Acanthaceae/química , Analgésicos/síntese química , Ouro/química , Nanopartículas Metálicas/química , Prata/química , Acanthaceae/metabolismo , Ácido Acético/toxicidade , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Química Verde , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Relaxamento Muscular/efeitos dos fármacos , Cuidados de Enfermagem , Dor/induzido quimicamente , Dor/tratamento farmacológico , Manejo da Dor/métodos , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo
2.
J Photochem Photobiol B ; 202: 111716, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31821944

RESUMO

Though anesthetic drug delivery system and drug vehicles is generally applied for pain relief, there are have many difficulties and issues due to its short duration carrier and low biocompatibility, effectiveness at the conditions of inflammation at acidic pH. To resolve this issue, we have designed and developed the dual (pH and temperature) responsive bio-nanomaterial to improve the efficiency anesthetic drug delivery system. Chitosan is a unique class of biomaterials that is widely used in medical devices. The surface engineering of ZnFe2O4 nanoparticles was performed by coating with chitosan using simple precipitation method. Then, multi-active anesthetic drug (Lidocaine) was loaded into nano-ferrite to form a drug delivery vehicle. The prepared drug-vesicle was characterized by using XRD, FTIR, SEM, XPS and TGA analysis. XRD analysis proved the face center cubic structure of zinc nanoferrite. The sustained delivery of Lidocaine (LDC) from CS coated nanoferrite (CS/ZnFe2O4) was stimulated by pH and temperature responsive characteristics of vesicles. The in vitro cytotoxicity of the CS/ZnFe2O4 particles towards fibroblast cells was analyzed by using MTT assay. The drug loaded CS/ZnFe2O4 particles exhibit high biocompatibility and sustained drug release in the physiological pH environment (4.8, 5.5 and 7.4) and temperature responsive (25 and 37 °C) of normal tissues and also drug loading efficiency was measured.


Assuntos
Anestésicos/química , Quitosana/química , Portadores de Fármacos/química , Nanoestruturas/química , Anestésicos/metabolismo , Anestésicos/uso terapêutico , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Lidocaína/química , Lidocaína/metabolismo , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Nanoestruturas/toxicidade , Dor/tratamento farmacológico , Ratos , Temperatura Ambiente
3.
J Photochem Photobiol B ; 202: 111700, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810039

RESUMO

Zinc oxide (ZnO), an inorganic metal oxide established in the form of nanoparticles, has considerable biological properties. The current research uses Selaginella convolute (S. convolute) leaf extract to establish ZnO NPs and to assess their use in pain management. S. Convolute leaf extract mediated ZnO NPs were characterized by modern techniques and instruments such as Fourier transforms infrared spectroscopy (FTIR), electron microscopy, X-ray diffraction (XRD), and Ultraviolet-vis-spectroscopy (UV-vis), energy dispersive X-ray spectroscopy (EDX), indicating the emergence of spherical NPs of which is around 40 nm. The FTIR spectrum also signified that S. convolute plant extract polyphenols acted as a capping ligand for the fabricated ZnO NPs. Possessed ZnO NPs have shown important characteristics of muscle relaxing and antinociceptive. A concentration dependent acetic acid induced writhing effect was noted for both S. convolute extract and ZnO NPs. S. convolute plant extract and ZnO NPs are found to exhibit highest muscle relaxation effect in both traction and chimney tests and no sedative effect was shown by both ZnO NPs and plant extract. The present results showed that the S. convolute leaves extract is a very effective green reducing agent for the preparation of ZnO NPs and the prepared NPs can be used in pain management in emerging nursing care in future.


Assuntos
Nanopartículas Metálicas/química , Selaginellaceae/química , Óxido de Zinco/química , Ácido Acético/toxicidade , Animais , Química Verde , Locomoção/efeitos dos fármacos , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Relaxamento Muscular/efeitos dos fármacos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Manejo da Dor , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Selaginellaceae/metabolismo
4.
Fitoterapia ; 140: 104419, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705952

RESUMO

Despite advances in medicine and numerous agents that counteract pain, millions of patients continue to suffer. Attention has been given to identify novel botanical interventions that produce analgesia by interacting with nociceptive-transducing channels. The aim of this review is to provide an overview of the actual knowledge of Acmella oleracea (L.) and its activities, particularly those that are anti-inflammatory, anti-oxidant, and painkiller. These activities are attributed to numerous bioactive compounds, such as phytosterols, phenolic compounds and N-alkylamides (spilanthol, responsible for many activities, primarily anesthetic). This review includes 99 eligible studies to consider the anti-inflammatory, anti-oxidant, and painkiller of Acmella. Studies reported in this review confirmed anti-inflammatory and anti-oxidant activities of Acmella, postulating that transcription factors of the nuclear factor-κB family (NF-κB) trigger the transcription iNOS and COX-2 and several other pro-inflammatory mediators, such as IL-6, IL-1ß, and TNF-α. The antinociceptive effects has been demonstrated and have been related to different processes, including inhibition of prostaglandin synthesis, activation of opioidergic, serotoninergic and GABAergic systems, and anesthetic activity through blockage of voltage-gated Na Channels. acmella oleracea represents a promise for pain management, particularly in chronic degenerative diseases, where pain is a significant critical issue.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Asteraceae/química , Dor/tratamento farmacológico , Animais , Compostos Fitoquímicos/farmacologia
5.
J Photochem Photobiol B ; 202: 111668, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734435

RESUMO

Fraxinus rhynchophylla belongs to the family of Oleaceae and also called as Chinese ash wood possesses various pharmacological properties such as neuroprotective, antimicrobial, anti-inflammatory, etc. Therefore we synthesized ZnO nanoparticles using Fraxinus rhynchophylla wood extract as reducing and capping agent. The synthesized nanoparticles were characterized with the aid of UV-Spec, DLS, FT-IR and TEM analysis. Green synthesized ZnO nanoparticles were then assessed for anti-nociceptive property by using various nociception models such as thermal stress-induced, acetic acid, glutamate, capsaicin, and formalin-induced nociception. The sedative effect of synthesized ZnO nanoparticles was evaluated with an open field test. UV-Spectroscopic analysis confirms the formation of ZnO nanoparticles and the characterization studies DLS, FT-IR, and TEM analysis prove it has ideal nanoparticle can be used as a nano-drug. Results of both thermal stress-induced methods hot plate and tail immersion nociception test verified the synthesized ZnO nanoparticles are a potent antinociceptive drug. ZnO nanoparticles effectively reduced the abdominal writhes in acetic acid-induced nociception and it also significantly decreased the nociception activity in another glutamate, capsaicin, and formalin-induced nociception models. Open field experiment proved that synthesized ZnO nanoparticles are less sedative compared to the standard antinociceptive drug morphine. Overall our findings authentically confirm ZnO nanoparticles synthesized from Fraxinus rhynchophylla wood extract is a novel drug that persuasively reduces nociception in different nociceptive induced mice models and can be the best alternative for allopathic drugs which renders severe side effects.


Assuntos
Analgésicos/uso terapêutico , Fraxinus/química , Nanopartículas Metálicas/química , Dor/tratamento farmacológico , Óxido de Zinco/química , Analgésicos/síntese química , Analgésicos/química , Animais , Modelos Animais de Doenças , Formaldeído/toxicidade , Fraxinus/metabolismo , Química Verde , Temperatura Alta , Masculino , Nanopartículas Metálicas/uso terapêutico , Camundongos , Dor/induzido quimicamente , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química
6.
Food Chem Toxicol ; 135: 111053, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31857126

RESUMO

Chronic pain management has several adverse effects and research looking for new and effective pain management drugs posing lower undesirable effects is necessary. Given the above, the pharmacological investigation of medicinal plants significantly contributes to the dissemination of plant-derived therapeutics. The aim of this study was to evaluate the antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil (PBEO) and the participation of the opioid pathway in this effect in mice. Swiss Mus musculus male mice were tested using acute nociception models (acetic acid induced abdominal contortions, formalin, capsaicin and hot plate tests). The possible myorelaxant action of the PBEO was tested using the rotarod test. The essential oil reduced animal nociception in chemical and heat models, with this action being devoid of a myorelaxant effect. Naloxone (2 mg/kg, intraperitoneally - i.p.) partially antagonized the PBEO activity, possibly acting via opioid receptors. The results obtained provide evidence that the traditional Psidium brownianum use may be effective for pain treatment.


Assuntos
Analgésicos/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Psidium/química , Animais , Modelos Animais de Doenças , Dose Letal Mediana , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Teste de Desempenho do Rota-Rod
7.
Biochem Med (Zagreb) ; 30(1): 010802, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839727

RESUMO

Introduction: Hypoglycaemia has been reported as an unusual complication of tramadol use and in a few cases of tramadol poisoning, but the exact mechanism is not known. Case description: An ambulance crew was dispatched to an unconscious 46-year old man. A glucometer point-of-care measurement revealed a profound hypoglycaemia (1.9 mmol/L). Treatment with intravenous glucose was started and the patient was transported to the hospital. The patient had several episodes of pulseless electrical activity requiring cardiopulmonary resuscitation in the ambulance and upon arrival in the hospital. Despite continuous glucose infusion the hypoglycaemia was difficult to correct during the next few hours and the patient developed hypokalaemia. Further investigation to identify the cause of hypoglycaemia revealed that insulin and C-peptide were inappropriately raised. A toxicological investigation revealed the presence of tramadol and its metabolites in lethal concentrations. Also acetaminophen, ibuprofen and lormetazepam were present. Ethanol screening was negative (< 0.1 g/L) and no sulfonylurea were detected. The patient developed multiple organ failure, but eventually recovered. What happened: The hypoglycaemia was caused by inappropriate stimulation of insulin secretion in a patient intoxicated with tramadol. The sudden hypokalaemia was caused by a massive intracellular shift of potassium in response to the hyperinsulinemia, triggered by the intravenous administration of glucose. Main lesson: To our knowledge, we are the first to document a significant rise in endogenous insulin production in a hypoglycaemic patient presenting with tramadol intoxication. Our observation suggests that hyperinsulinemia could be the cause of the hypoglycaemia associated with tramadol use.


Assuntos
Analgésicos Opioides/efeitos adversos , Hipoglicemia/diagnóstico , Tramadol/efeitos adversos , Analgésicos Opioides/uso terapêutico , Glicemia/análise , Peptídeo C/sangue , Glucose/administração & dosagem , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/etiologia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Tramadol/uso terapêutico
8.
Equine Vet J ; 52(1): 13-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657050

RESUMO

Primary care guidelines provide a reference point to guide clinicians based on a systematic review of the literature, contextualised by expert clinical opinion. These guidelines develop a modification of the GRADE framework for assessment of research evidence (vetGRADE) and applied this to a range of clinical scenarios regarding use of analgesic agents. Key guidelines produced by the panel included recommendations that horses undergoing routine castration should receive intratesticular local anaesthesia irrespective of methods adopted and that horses should receive NSAIDs prior to surgery (overall certainty levels high). Butorphanol and buprenorphine should not be considered appropriate as sole analgesic for such procedures (high certainty). The panel recommend the continuation of analgesia for 3 days following castration (moderate certainty) and conclude that phenylbutazone provided superior analgesia to meloxicam and firocoxib for hoof pain/laminitis (moderate certainty), but that enhanced efficacy has not been demonstrated for joint pain. In horses with colic, flunixin and firocoxib are considered to provide more effective analgesia than meloxicam or phenylbutazone (moderate certainty). Given the risk of adverse events of all classes of analgesic, these agents should be used only under the control of a veterinary surgeon who has fully evaluated a horse and developed a therapeutic, analgesic plan that includes ongoing monitoring for such adverse events such as the development of right dorsal colitis with all classes of NSAID and spontaneous locomotor activity and potentially ileus with opiates. Finally, the panel call for the development of a single properly validated composite pain score for horses to allow accurate comparisons between medications in a robust manner.


Assuntos
Analgesia/veterinária , Doenças dos Cavalos/tratamento farmacológico , Dor/veterinária , Guias de Prática Clínica como Assunto , Sociedades Científicas/normas , Medicina Veterinária/normas , Animais , Cavalos , Dor/tratamento farmacológico , Reino Unido
9.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(10): 141-145, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31793556

RESUMO

Despite the variety of treatment options, pain syndromes are widespread in the population. Adjuvant methods, in particular vitamins and vitamin combinations, are widely used, along with nonsteroidal anti-inflammatory drugs, myorelaxants and anticonvulsants, by physicians of different specialties. In recent years, new drugs containing pyrimidine nucleotides (uridine monophosphate) were brought to market. The paper describes analgesic effects of uridine monophosphate and choline, possibilities of their simultaneous use in combination with vitamins to promote the recovery of damaged structured of the peripheral nervous system, including remyelination and neuroplasticity. It has been concluded that nucleotide complexes can be effectively used as adjuvant therapy of pain.


Assuntos
Nucleotídeos , Dor , Anti-Inflamatórios não Esteroides , Humanos , Nucleotídeos/uso terapêutico , Dor/tratamento farmacológico , Síndrome , Uridina Monofosfato
10.
J Craniomaxillofac Surg ; 47(12): 1922-1928, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810841

RESUMO

Non-surgical therapy has proved to be effective in chronic diffuse sclerosing osteomyelitis (DSO) of the mandible in children. Therefore we aimed to investigate the effect of non-surgical therapy in adult DSO patients. We included consecutive patients with DSO who received non-surgical therapy in our center. They all received occlusal splint therapy, counselling about the disease, and/or physiotherapy by a specialised team. The use of analgesics, preferably nonsteroidal anti-inflammatory drugs, was advised for symptomatic control during periods of exacerbation. Sixteen patients (11/5 female/male) aged 39.9 ± 15.0 years with DSO of the mandible were included. The mean duration of symptoms was 39.7 ± 26.3 months before referral to our center. Patients were treated with a broad range of treatments before referral. All patients underwent non-surgical treatment. In 12 patients this led to remission. Four patients still had complaints after 12 months of non-surgical therapy and started with intravenous bisphosphonate therapy. In our center, DSO of the mandible was successfully treated with non-surgical therapy, despite a long duration before referral and extensive pre-treatment. Considering this high success rate, we recommend this non-surgical approach as the first treatment option for DSO of the mandible. In case of persistence, alternative treatments such as bisphosphonates should be explored.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Tratamento Conservador/métodos , Difosfonatos/uso terapêutico , Doenças Mandibulares/terapia , Placas Oclusais , Osteomielite/terapia , Dor/tratamento farmacológico , Periostite/terapia , Adulto , Criança , Doença Crônica , Feminino , Humanos , Masculino , Mandíbula/patologia , Doenças Mandibulares/complicações , Pessoa de Meia-Idade , Osteomielite/complicações , Dor/etiologia , Periostite/complicações , Resultado do Tratamento , Adulto Jovem
11.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(12): 1159-1164, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874532

RESUMO

Objective: To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer. Methods: A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat-sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non-stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory(BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long-acting opioids were administered, which included sustained-release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ(2) test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non-stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two-tailed test was established as the alpha significance level. Result: A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty-two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non-stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non-stoma group located in other sites. Compared with non-stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non-stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non-stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)](χ(2)=10.023, P=0.002) in the non-stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI: 0.102-0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709-18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non-stoma group (49.3%, 35/71) (χ(2)=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123-0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033-6.687, P=0.045) were independent factors affecting the use of lactulose laxatives. Conclusions: Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.


Assuntos
Analgésicos/uso terapêutico , Enterostomia , Neoplasias Gastrointestinais/complicações , Dor/tratamento farmacológico , Analgésicos/administração & dosagem , Feminino , Neoplasias Gastrointestinais/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Estudos Retrospectivos
12.
J Med Life ; 12(3): 284-289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666832

RESUMO

Hysterosalpingography is one of the essential diagnostic methods for examining women who have difficulty becoming pregnant. This procedure is somehow invasive and is associated with numerous complications such as allergic sensitivity, pain, abdominal cramps and shock. Therefore, this study aimed to investigate the effect of evening primrose on cervical length and pain during and after hysterosalpingography. In this double-blind clinical trial, 66 candidates for hysterosalpingography were randomly divided into two groups. A group received 1000 mg of evening primrose orally for two days prior to hysterosalpingography, while the control group received a placebo drug similar in size to evening primrose three days prior to hysterosalpingography. The pain level was recorded based on the Visual Analogue Scale (VAS), during tenaculum placement but also immediately and four hours after hysterosalpingography. Finally, the data were analyzed using SPSS (version 20). There was a significant difference between the two groups in terms of pain during insertion of speculum and injection of the contrast medium (p <0.05). Less pain was reported in the evening primrose group compared to placebo. There was no significant difference between the two groups in terms of the length and diameter of the cervix (p <0.05). Given the fact that it is a medicinal plant with no complications and can reduce pain during speculum insertion and during contrast medium injection, evening primrose seems to be a good drug for managing pain during hysterosalpingography.


Assuntos
Colo do Útero/patologia , Histerossalpingografia/efeitos adversos , Oenothera biennis/química , Dor/tratamento farmacológico , Dor/etiologia , Extratos Vegetais/farmacologia , Adulto , Dilatação , Método Duplo-Cego , Feminino , Humanos , Medição da Dor , Placebos , Gravidez , Adulto Jovem
13.
Mayo Clin Proc ; 94(12): 2437-2443, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31685265

RESUMO

OBJECTIVE: To evaluate trends in the clinical development of new pain and reformulated pain medications given the ongoing opioid crisis and the public health burden of inadequately controlled pain. METHODS: We conducted a retrospective cohort study of new drugs starting clinical testing between January 1, 2000, and December 31, 2015. We searched two comprehensive commercial databases of global research and development activity. The primary outcomes were trends in new and reformulated pain drugs starting clinical testing, proportion of new pain drugs targeting a novel biological pathway, and rates and reasons for discontinuation of development. RESULTS: The proportion of new pain drugs entering phase 1 testing (relative to all new drug trials) declined from 2.5% between 2000 and 2002 to 1.7% between 2013 and 2015. No significant changes in the proportion of new pain drugs entering phase 2 or phase 3 trials were observed. Most new pain drugs failed to reach late-stage clinical development, with 52% of pain drugs successfully advancing from phase 1 to phase 2 and 11% advancing from phase 2 to phase 3 trials. The number of reformulated products starting clinical testing increased over the study period and was greater than that for new analgesics in 2012 and every year thereafter. CONCLUSION: Pain drug development activity has largely shifted from new therapeutics to reformulated ones. New policies, such as increased funding for basic pain research, may help address the urgent need for new therapies for pain.


Assuntos
Analgésicos Opioides/uso terapêutico , Desenvolvimento de Medicamentos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor/tratamento farmacológico , Humanos , Dor/diagnóstico , Dor/epidemiologia , Estudos Retrospectivos
14.
Harefuah ; 158(11): 711-715, 2019 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-31721512

RESUMO

INTRODUCTION: Burns are one of the most common and painful injuries among babies and children. The pain endured during and in between treatment can be minimized with sedation. These sedations, however, are not without side effects and risks. Given the potential complications, we devised a Burn Analgesic Treatment Protocol that incorporates safe analgesia during burn treatment and throughout the day, thus minimizing the necessity for sedations. AIMS: Assessment of the effectiveness of the analgesic protocol by quantification of overall number of sedations needed for burn treatment and by assessment of the overall experience of the treating medical team exposed to burn care before and after implementation of the protocol. METHODS: A retrospective analysis of analgesic treatment regimens among admitted pediatric burn patients both before and after the implementation of our analgesic protocol was performed. Furthermore, questionnaires were given to the nurses of the treating medical team in order to better assess overall experience with the new analgesic protocol. RESULTS: A total of 87 patients were treated with the new analgesic protocol and 46 patients served as the control group. A significantly lower number of sedations were performed in the group treated with the new protocol compared to the control group (18% vs 30%, p=0.057). The questionnaires filled out by the treating nurses revealed an average score of 4.5 (between 1 - 5), indicating high satisfaction with the protocol. CONCLUSIONS: Our new analgesic protocol allows for highly effective treatment of burn wounds while minimizing the necessity for sedations, thus increasing overall patient safety and reducing potential complications.


Assuntos
Analgésicos , Ansiedade , Queimaduras , Dor , Analgésicos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Queimaduras/complicações , Criança , Humanos , Dor/tratamento farmacológico , Dor/etiologia , Pacientes , Estudos Retrospectivos
15.
Expert Opin Ther Pat ; 29(12): 943-963, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31726893

RESUMO

Introduction: Purinergic P2X3-P2X2/3 receptors are placed in nociceptive neurons' strategic location and show unique desensitization properties; hence, they represent an attractive target for many pain-related diseases. Therefore, a broad interest from academic and pharmaceutical scientists has focused on the search for P2X3 and P2X2/3 receptor ligands and has led to the discovery of numerous new selective antagonists. Some of them have been studied in clinical trials for the treatment of pathological conditions such as bladder disorders, gastrointestinal and chronic obstructive pulmonary diseases.Areas covered: This review provides a summary of the patents concerning the discovery of P2X3 and/or P2X2/3 receptor antagonists published between 2015 and 2019 and their potential clinical use. Thus, the structures and biological data of the most representative molecules are reported.Expert opinion: The 2016 publication of the crystallographic structure of the human P2X3 receptor subtype gave an improvement of published patents in 2017. Hence, a great number of small molecules with dual antagonist activity on P2X3-P2X2/3 receptors, a favorable pharmacokinetic profile, and reasonable oral bioavailability was discovered. The most promising compounds are the phenoxy-diaminopyrimidines including gefapixant (AF-219), and the imidazo-pyridines like BLU-5937, which are in phase III and phase II clinical trials, respectively, for refractory chronic cough.


Assuntos
Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X2/efeitos dos fármacos , Receptores Purinérgicos P2X3/efeitos dos fármacos , Animais , Tosse/tratamento farmacológico , Tosse/patologia , Descoberta de Drogas , Humanos , Dor/tratamento farmacológico , Dor/patologia , Patentes como Assunto , Antagonistas do Receptor Purinérgico P2X/farmacocinética , Receptores Purinérgicos P2X2/metabolismo , Receptores Purinérgicos P2X3/metabolismo
16.
JAMA ; 322(19): 1887-1898, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742631

RESUMO

Importance: Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine. Objective: To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack. Design, Setting, and Participants: Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month. Interventions: Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity. Main Outcomes and Measures: Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication. Results: Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90% female); 1355 of 1465 (92.5%) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8%) in the ubrogepant 50-mg group, 90 of 435 (20.7%) in the ubrogepant 25-mg group, and 65 of 456 (14.3%) in the placebo group (absolute difference for 50 mg vs placebo, 7.5%; 95% CI, 2.6%-12.5%; P = .01; 25 mg vs placebo, 6.4%; 95% CI, 1.5%-11.5%; P = .03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9%) in the ubrogepant 50-mg group, 148 of 434 (34.1%) in the ubrogepant 25-mg group, and 125 of 456 (27.4%) in the placebo group (absolute difference for 50 mg vs placebo, 11.5%; 95% CI, 5.4%-17.5%; P = .01; 25 mg vs placebo, 6.7%; 95% CI, 0.6%-12.7%; P = .07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0%]; 25 mg, 12 of 478 [2.5%]; and placebo, 10 of 499 [2.0%]) and dizziness (50 mg, 7 of 488 [1.4%]; 25 mg, 10 of 478 [2.1%]; placebo, 8 of 499 [1.6%]). Conclusions and Relevance: Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02867709.


Assuntos
Analgésicos/administração & dosagem , Transtornos de Enxaqueca/tratamento farmacológico , Dor/tratamento farmacológico , Piridinas/administração & dosagem , Pirróis/administração & dosagem , Adulto , Idoso , Analgésicos/efeitos adversos , Tontura/induzido quimicamente , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Manejo da Dor , Piridinas/efeitos adversos , Pirróis/efeitos adversos , Adulto Jovem
17.
Life Sci ; 237: 116926, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31614148

RESUMO

Sex-related differences in pain and opioids has been the focus of many researches. It is demonstrated that women experience greater clinical pain, lower pain threshold and tolerance, more sensitivity and distress to experimentally induced pain compared to men. Sex differences in response to opioid treatment revealed inconsistent results. However, the etiology of these disparities is not fully elucidated. It is, therefore, conceivable now that this literature merits to be revisited comprehensively. Possible multifaceted factors seem to be associated. These include neuroanatomical, hormonal, neuroimmunological, psychological, social and cultural aspects and comorbidities. This review aims at providing an overview of the substantial literature documenting the sex differences in pain and analgesic response to opioids from animal and human studies within the context of the modulatory effects of the aforementioned factors. A detailed and critical discussion of the cellular and molecular signaling pathways underlying the modulatory actions of gonadal hormones in the sexual dimorphism in pain processing and opioid analgesia is extensively presented. It is indicated that sexual dimorphic activation of certain brain regions contributes to differential pain sensitivity between females and males. Plausible crosstalk between sex hormones and neuroimmunological signaling pertinent to toll-like and purinergic receptors is uncovered as causal cues underlying sexually dimorphic pain and opioid analgesia. Conceivably, a thorough understanding of these factors may aid in sex-related advancement in pain therapeutic management.


Assuntos
Analgésicos Opioides/administração & dosagem , Hormônios Gonadais/metabolismo , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Animais , Feminino , Humanos , Masculino , Nociceptividade/fisiologia , Dor/metabolismo , Caracteres Sexuais
18.
J Opioid Manag ; 15(4): 272-274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637679

RESUMO

OBJECTIVE: To determine the utility of the screener and opioid assessment for patients with pain-revised (SOAPP-R) for patients with cancer-related pain. DESIGN: The authors performed a retrospective analysis of cancer patients screened with the SOAPP-R. Opiate abuse was determined using a combination of urine drug screens and analysis of patients' electronic medical records. SETTING/PATIENTS: Patients who were seen at a palliative care clinic presenting with pain or needing an opioid prescription at an academic medical center with any type of cancer were screened using the SOAPP-R (N = 69). OUTCOME MEASURES: Aberrant opioid-related behavior was determined using a combination of provider notes and urine drug screens. RESULTS: A positive SOAPP-R score (⩾18) was observed in 27 participants (39.1 percent). The sensitivity and specificity of the SOAPP-R in the study population was 0.75 and 0.80, respectively. CONCLUSIONS: The SOAPP-R, in its current form, may have value in screening patients with cancer for substance abuse. Incorporation of the screening tool in palliative and oncology settings may help reduce opioid abuse in cancer patients.


Assuntos
Analgésicos Opioides , Neoplasias/complicações , Transtornos Relacionados ao Uso de Opioides , Dor/tratamento farmacológico , Inquéritos e Questionários/normas , Analgésicos Opioides/uso terapêutico , Humanos , Programas de Rastreamento/métodos , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Dor/etiologia , Manejo da Dor , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade
19.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2980-2986, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602843

RESUMO

Pain is one of the problems that seriously affect people's quality of life for thousands of years. The causes of pain are complex and varied,and long-term pain can also lead to depression. It has become a research hotspot to develop analgesic preparations with significant drug effects and small side effects. Recent studies have shown that certain alkaloid monomers have analgesic targets such as γ-aminobutyric acid,cannabinoids,and capsaicin. If their preparation is applied to the analgesic field,they can make up for the defects such as strong addiction and side effects of traditional opioid and non-steroidal analgesic drugs,but there is no relevant literature to summarize the research results in this field. This article first introduces the mechanism of pain production and the target of analgesia. Based on this,the application status of alkaloid monomer analgesic preparations approved by China Food and Drug Administration( CFDA)( number varieties,type of dosage form,drug description,analgesic mechanism and advantages) was analyzed,and the research dynamics of alkaloid monomer analgesic preparations( new formulation and new technology) were reviewed. Finally,some problems in this field were pointed out,such as imperfect medication information,inadequate transformation of research results,and too few kinds of analgesic components in developed alkaloids. The development direction was also pointed out for the above problems,with a view to provide reference for further development and in-depth research.


Assuntos
Alcaloides/farmacologia , Analgésicos/farmacologia , Dor/tratamento farmacológico , Analgesia , China , Humanos , Qualidade de Vida
20.
Clin Exp Rheumatol ; 37 Suppl 120(5): 124-129, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621576

RESUMO

Osteoarthritis (OA) is a debilitative, painful condition with significant global burden. Pharmacological options have limited analgesic efficacy and their side-effects often restrict their use. Novel pharmacological options are needed to relieve patient symptoms and their consequent disease impact. A variety of pharmacological options have been investigated in treating OA, including existing therapies previously used for treating other arthritides (such as colchicine and hydroxychloroquine) and new therapies targeting pain (including monoclonal antibodies to nerve growth factor and intra-articular trans-capsaicin). Extended-release triamcinolone may offer more persisting analgesic effects compared to immediate-release preparations. While most studies have been unsuccessful, pharmacological therapies targeting peripheral nociceptive pathways appear promising.


Assuntos
Osteoartrite , Dor/tratamento farmacológico , Analgésicos/uso terapêutico , Humanos , Osteoartrite/tratamento farmacológico , Manejo da Dor , Medição da Dor
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