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1.
Ann Rheum Dis ; 79(6): 778-786, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32381564

RESUMO

OBJECTIVE: To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA). METHODS: This is a systematic literature research of 2015-2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case-control studies and long-term extensions (LTEs) were analysed. RESULTS: 56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case-control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies. CONCLUSION: Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Humanos , Interleucina-17/antagonistas & inibidores , Subunidade p19 da Interleucina-23/antagonistas & inibidores , Terapia de Alvo Molecular , Medicamentos Sintéticos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
2.
Ann Rheum Dis ; 79(6): 700-712, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32434812

RESUMO

OBJECTIVE: To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA). METHODS: According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined. RESULTS: The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed. CONCLUSION: These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Glucocorticoides/uso terapêutico , Sociedades Médicas , Consenso , Conferências de Consenso como Assunto , Tomada de Decisão Compartilhada , Europa (Continente) , Humanos , Interleucina-12/antagonistas & inibidores , Interleucina-17/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Medicamentos Sintéticos/uso terapêutico , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
3.
Ann Rheum Dis ; 79(6): 744-759, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32033937

RESUMO

OBJECTIVES: To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA). METHODS: A systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019. RESULTS: 234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products. CONCLUSION: This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Substituição de Medicamentos , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Humanos , Inibidores de Janus Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicamentos Sintéticos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
4.
Biochem Biophys Res Commun ; 524(3): 772-783, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037088

RESUMO

This review is devoted to comparative pharmacological analysis of synthetic drugs such as memantine and its isomers, as well as tacrine, velnacrine, rivastigmine, and donepezil, with natural alkaloids, terpenoids, and triterpenoid peroxides, which are used to treat dementia, Alzheimer's and Parkinson's diseases, myasthenia gravis and other neurodegenerative diseases. Recently discovered by French scientists from Marseille triterpenoid hydroperoxides demonstrate high activity as potential therapeutic agents for the treatment of dementia. The information presented in this review is of great interest to pharmacologists, medical chemists, physiologists, neurologists and doctors, as well as for the pharmaceutical industry.


Assuntos
Produtos Biológicos/uso terapêutico , Demência/tratamento farmacológico , Medicamentos Sintéticos/uso terapêutico , Alcaloides/química , Alcaloides/uso terapêutico , Animais , Produtos Biológicos/química , Demência/prevenção & controle , Humanos , Medicamentos Sintéticos/química , Terpenos/química , Terpenos/uso terapêutico
6.
Medicina (Kaunas) ; 56(1)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936616

RESUMO

Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography-mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome.


Assuntos
Canabinoides/uso terapêutico , Avaliação Pré-Clínica de Medicamentos/tendências , Manejo da Dor/tendências , Pesquisa/tendências , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Canabinoides/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Manejo da Dor/métodos , Medicamentos Sintéticos/farmacologia , Medicamentos Sintéticos/uso terapêutico
7.
Ann Rheum Dis ; 79(6): 685-699, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31969328

RESUMO

OBJECTIVES: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. METHODS: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Sociedades Médicas , Medicamentos Sintéticos/uso terapêutico , Antirreumáticos/economia , Produtos Biológicos/economia , Consenso , Quimioterapia Combinada , Europa (Continente) , Humanos , Inibidores de Janus Quinases/uso terapêutico , Medicamentos Sintéticos/economia , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
8.
Curr Diabetes Rev ; 16(4): 340-356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31438829

RESUMO

BACKGROUND: Diabetes is a multifactorial disease and a major cause for many microvascular and macrovascular complications. The disease will ultimately lead to high rate mortality if it is not managed properly. Treatment of diabetes without any side effects has always remained a major challenge for health care practitioners. INTRODUCTION: The current review discusses the various conventional drugs, herbal drugs, combination therapy and the use of nutraceuticals for the effective management of diabetes mellitus. The biotechnological aspects of various antidiabetic drugs are also discussed. METHODS: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was sorted in terms of various approaches that are used for the treatment of diabetes. RESULTS: More than 170 papers including both research and review articles, were included in this review in order to produce a comprehensive and easily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose, mechanism of action and possible side effects. The article also focuses on combination therapies containing synthetic as well as herbal drugs to treat the disease. The role of pre and probiotics in the management of diabetes is also highlighted. CONCLUSION: Oral antihyperglycemics which are used to treat diabetes can cause many adverse effects and if given in combination, can lead to drug-drug interactions. The combination of various phytochemicals with synthetic drugs can overcome the challenge faced by the synthetic drug treatment. Herbal and nutraceuticals therapy and the use of probiotics and prebiotics are a more holistic therapy due to their natural origin and traditional use.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fitoterapia , Medicamentos Sintéticos/uso terapêutico , Administração Oral , Suplementos Nutricionais , Interações Medicamentosas , Quimioterapia Combinada , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Probióticos/uso terapêutico , Medicamentos Sintéticos/administração & dosagem , Medicamentos Sintéticos/efeitos adversos
9.
J Clin Endocrinol Metab ; 105(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585006

RESUMO

CONTEXT: Antenatal synthetic glucocorticoid (sGC) treatment constitutes a potent programming factor of the hypothalamic-pituitary-adrenal (HPA) axis. Previous findings from our group revealed long-term changes in cortisol stress reactivity following antenatal sGC therapy. However, the few prior studies exclusively relied on spot measurements of phasic HPA axis activity, which may not adequately capture cortisol output over prolonged periods of time. OBJECTIVE: To address this gap, the current study utilized hair steroid concentrations, a valid marker of integrated long-term HPA-axis activity, to investigate endocrine changes in individuals treated with antenatal sGC. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study comprised 76 term-born children (7-12 years) and 58 adolescents (14-18 years). Cumulated hormonal secretion in scalp hair over a 3-month period was determined for different biomarkers of tonic HPA axis activity by liquid chromatography coupled with tandem mass spectrometry. Hair steroid levels were compared between participants with antenatal sGC therapy (dexamethasone or betamethasone) and different control groups. RESULTS: Findings from this study provide no evidence for a significant effect of antenatal sGCs on long-term hair steroid concentrations. Participants treated with antenatal sGC exhibited comparable levels of hair cortisol, cortisone, dehydroepiandrosterone, and cortisol/dehydroepiandrosterone ratios compared to those of mothers who had been admitted to hospital for pregnancy complications but had never received sGC therapy and controls from physiological pregnancies. CONCLUSION: In conjunction with data from previous studies, it is thus tempting to speculate that sGC may affect the capacity of dynamic changes and flexible adaption of an individual's HPA axis rather than changes in tonic steroid output.


Assuntos
Glucocorticoides/uso terapêutico , Cabelo/química , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Esteroides/análise , Adolescente , Betametasona/análise , Betametasona/uso terapêutico , Criança , Cortisona/análise , Estudos Transversais , Dexametasona/análise , Dexametasona/uso terapêutico , Feminino , Glucocorticoides/análise , Humanos , Hidrocortisona/análise , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Recém-Nascido , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Medicamentos Sintéticos/análise , Medicamentos Sintéticos/uso terapêutico
10.
FASEB J ; 33(10): 10889-10901, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31266358

RESUMO

Synthetic biologic drugs are highly successful for induction therapy in transplantation, but the development of novel biologics is limited because of the high cost of synthesis and purification. In this study, we developed a novel strategy for the production of synthetic protein drugs in vivo by the host itself. We utilized minicircle (MC) technology, which can robustly express a target molecule and secrete it from cells, as an indirect method to produce a protein of interest in vivo. We designed an MC vector containing the sequences of basiliximab (anti-CD25 mAb) and IL-10. We verified the substantial production of the anti-CD25/IL-10 protein from the MC in vitro and in vivo. The therapeutic effect of MC-derived anti-CD25/IL-10 was evaluated in a skin allograft mouse model by single intravenous infusion. Mice treated with the MC encoding anti-CD25/IL-10 exhibited prolonged skin allograft survival times accompanied by improved histologic changes and immunologic regulation. These findings indicate that the anti-CD25/IL-10 protein drug obtained by MC technology is functionally active and relevant for reducing allograft rejection. This self-reproducible strategy for synthetic protein drugs using MCs is a promising tool for transplantation.-Lim, S. W., Shin, Y. J., Luo, K., Quan, Y., Ko, E. J., Chung, B. H., Yang, C. W. Host cell in vivo production of the synthetic drug anti-CD25/IL-10 using minicircle vector.


Assuntos
Vetores Genéticos/genética , Interleucina-10/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Plasmídeos/genética , Animais , Vetores Genéticos/metabolismo , Rejeição de Enxerto/tratamento farmacológico , Células HEK293 , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Injeções Intravenosas , Interleucina-10/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos/metabolismo , Transplante de Pele/efeitos adversos , Medicamentos Sintéticos/administração & dosagem , Medicamentos Sintéticos/uso terapêutico
11.
Med Decis Making ; 39(4): 359-369, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30896330

RESUMO

Research reveals a biased preference for natural v. synthetic drugs; however, this research is based on self-report and has not examined ways to reduce the bias. We examined these issues in 5 studies involving 1125 participants. In a pilot study (N = 110), participants rated the term natural to be more positive than the term synthetic, which reveals a default natural-is-better belief. In studies 1 (N = 109) and 2 (N = 100), after a supposed personality study, participants were offered a thank you "gift" of a natural or synthetic pain reliever. Approximately 86% (study 1) and 93% (study 2) of participants chose the natural v. synthetic pain reliever, which provides a behavioral choice confirmation of the natural drug bias. In studies 3 (N = 350) and 4 (N = 356), participants were randomly assigned to a control or experimental condition and were asked to consider a scenario in which they had a medical issue requiring a natural v. synthetic drug. The experimental condition included a stronger (study 3) or weaker (study 4) rational appeal about the natural drug bias and a statement suggesting that natural and synthetic drugs can be good or bad depending on the context. In both studies, the natural bias was reduced in the experimental condition, and perceived safety and effectiveness mediated this effect. Overall, these data indicate a bias for natural over synthetic drugs in preferences and behavioral choices, which might be reduced with a rational appeal.


Assuntos
Viés , Produtos Biológicos/normas , Comportamento de Escolha , Medicamentos sob Prescrição/classificação , Medicamentos Sintéticos/normas , Produtos Biológicos/uso terapêutico , Humanos , Medicamentos sob Prescrição/normas , Opinião Pública , Medicamentos Sintéticos/uso terapêutico
12.
PLoS One ; 14(3): e0213219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30822348

RESUMO

The treatment of rheumatoid arthritis (RA) has evolved rapidly in recent years. Nonetheless, conventional synthetic disease-modifying drugs (csDMARDs) remain the gold standard for RA treatment. The treatment for RA is expensive and this has a negative impact on public health. Given the low cost of csDMARDs compared to those of other treatment strategies, it is important to manage this type of treatment properly. Information on the duration of use of each drug and the reasons for their discontinuation is relevant to medical practitioners as it could improve the information available regarding side effects and their proper management. Moreover, data from clinical practice in the population can provide health care managers with information for resource allocation and optimization of csDMARD use with a consequent cost reduction in the treatment of RA. In this cross-sectional study, we aimed to describe the use of csDMARDs in public health services in Brazil, emphasizing on the duration of use and reasons for discontinuation of each drug. This study is a part of the REAL, a multicenter project that evaluated Brazilian patients with RA from eleven rheumatology services from August to October 2015. Patients were examined clinically, and an analysis of complementary exams and medical records was performed. A total of 1125 patients were included. 98.5% were women with a median age of 55.6 years. 36% and 90.84% patients were using biological disease-modifying drugs (bDMARDs) and csDMARDs, respectively. The duration of use and doses of each medication and the causes of suspension were analyzed. Most of the patients analyzed in this study were using csDMARDs for prolonged periods and methotrexate showed the longest duration of use. Interruption indexes due to ineffectiveness and side effects were analyzed. The knowledge of common adverse effects may alert attending physicians to the proper management of effective and low-cost therapeutic groups.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Sintéticos/uso terapêutico , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/patologia , Artrite Reumatoide/psicologia , Brasil , Estudos Transversais , Feminino , Humanos , Leflunomida/efeitos adversos , Leflunomida/uso terapêutico , Masculino , Adesão à Medicação , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Medicamentos Sintéticos/efeitos adversos , Falha de Tratamento
13.
Rheumatol Int ; 39(1): 47-58, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30421105

RESUMO

The aim of this study is to compare the efficacy and safety of biological therapy with cyclosporin A (CsA), azathioprine (AZA), or placebo in uveitis flares and other ocular outcomes in patients with Behçet disease. A comprehensive and sensitive search in MEDLINE, EMBASE, and the Cochrane Library was performed. We selected articles including: (1) adult patients with Behçet's and uveitis; (2) on biological therapies; (3) placebo or active control with CsA or AZA; (4) analyzing efficacy (number of uveitis flares, macular edema, etc.) and/or safety outcomes. Meta-analyses, systematic reviews, clinical trials, and observational studies with > 10 patients were included. The selection, data collection and quality assessment (Oxford scale) was carried out by 2 reviewers independently. Nine articles of moderate quality were included (6 randomized clinical trials and 3 retrospective studies) involving 378 patients. Most of them, apart from the study drugs received systemic corticosteroids and other immunosuppressant drugs. Infliximab was more effective than CsA in reducing short-term uveitis flares and severe complications of retinal vasculitis in the long term. Rituximab was similar to a combination of cytotoxic drugs in improving inflammatory activity. In patients with active uveitis adalimumab was associated with a lower risk of uveitic flare or visual impairment, and in patients with inactive uveitis to a significantly lowered the risk of flare upon corticosteroid withdrawal. Secukinumab and daclizumab were not superior to placebo in reducing uveitis flares, like interferonα compared to other drugs. Our results highlight the need for better designed comparative studies on Behçet's uveitis.


Assuntos
Síndrome de Behçet/complicações , Produtos Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Medicamentos Sintéticos/uso terapêutico , Uveíte/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Medicamentos Sintéticos/efeitos adversos , Resultado do Tratamento , Uveíte/etiologia
14.
J Diet Suppl ; 16(6): 699-713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29985715

RESUMO

Osteoporosis is one of the major health problems worldwide. It is characterized by increased bone fragility and loss of bone matter due to the action of osteoclast cells, which are associated with modified hormone levels and factors such as aging. Bisphosphonates are the primary treatment for osteoporosis. Apart from bisphosphonates, hormone therapy, calcitonin treatment, selective estrogen receptor modulators (SERMs), and strontium ranelate (SR) are some of the other treatments available for osteoporosis. However, these treatments have some side effects, such as oily skin, fluid retention, nausea, long-term toxicity, and even prostate cancer in males, and thus natural therapies that incur fewer side effects are sought. Phytochemicals, antioxidants, and other plant-based bioactives are important in the human diet. They are abundant in fruits and help against various chronic diseases, including bone disorders. Other providers of these important compounds are the medicinal plant parts. In this article, we highlight the various species of plants and herbs that are useful for the treatment of osteoporosis. The prospect of using these plant-based bioactives in amelioration of osteoporosis as an alternative to hormonal and synthetic drug-based therapy is also discussed.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Fitoterapia/métodos , Plantas Medicinais , Idoso , Difosfonatos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Medicamentos Sintéticos/uso terapêutico , Tiofenos/uso terapêutico
15.
Arthritis Res Ther ; 20(1): 285, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30587248

RESUMO

BACKGROUND: The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden. METHODS: Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available. RESULTS: Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1-6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor-negative polyarthritis (range of 24.6-29.9%). Methotrexate (61-84%) and etanercept (24%-61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7-42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4-30.1%) followed by gastrointestinal disorders (11.5-19.6%). The most frequent ESIs were infections (75.3-89%). CONCLUSIONS: This article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA. REGISTRY REGISTRATION: The Pharmachild registry is registered at ClinicalTrials.gov ( NCT01399281 ) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) ( http://www.encepp.eu/encepp/viewResource.htm?id=19362 ). The BiKeR registry is registered at ENCePP ( http://www.encepp.eu/encepp/viewResource.htm?id=20591 ).


Assuntos
Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Farmacovigilância , Sistema de Registros/estatística & dados numéricos , Medicamentos Sintéticos/uso terapêutico , Adolescente , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Juvenil/diagnóstico , Produtos Biológicos/efeitos adversos , Criança , Pré-Escolar , Monitoramento de Medicamentos , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Feminino , Humanos , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Medicamentos Sintéticos/efeitos adversos , Resultado do Tratamento
16.
Hist. ciênc. saúde-Manguinhos ; 25(4): 979-998, Oct.-Dec. 2018. graf
Artigo em Português | LILACS | ID: biblio-975441

RESUMO

Resumo O artigo reflete sobre o processo de medicalização do parto, tendo como foco específico o desenvolvimento da ocitocina sintética em 1953. Investiga a vida social da ocitocina, isto é, sua sintetização, estabilização e uso em obstetrícia para acelerar o trabalho de parto. Por meio do levantamento em dois periódicos brasileiros de obstetrícia da época, é analisado o início do uso da ocitocina sintética no Brasil, a partir do final da década de 1950, e os argumentos dos obstetras acerca da recomendação ou não desse uso. É observada, nesse período, a centralidade cada vez maior do obstetra no parto, bem como a recomendação do uso encadeado de diferentes intervenções - com destaque para a ocitocina - visando menor tempo de trabalho de parto.


Abstract This article reflects on the medicalization of childbirth, focusing on the development of synthetic oxytocin in 1953. Specifically addressed is the social life of oxytocin; in other words, its synthesis, stabilization, and use in obstetrics to hasten labor. Two Brazilian obstetrics journals of this era were surveyed to analyze the early use of synthetic oxytocin in Brazil in the late 1950s, along with obstetric arguments for or against its use. Notable in this period is the increasingly central role of the obstetrician in childbirth, as well as the recommendation to use different interventions linked together (particularly oxytocin) to shorten labor.


Assuntos
Humanos , Feminino , Gravidez , História do Século XX , Ocitócicos/história , Ocitocina/história , Medicamentos Sintéticos/história , Trabalho de Parto Induzido/história , Obstetrícia/história , Publicações Periódicas como Assunto/história , Brasil , Parto , Medicalização/história , Medicamentos Sintéticos/uso terapêutico
17.
Clin Ther ; 40(9): 1457-1466, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30180974

RESUMO

Cannabis sativa has a long history of use for medical purposes despite marijuana's addictive potential. The discovery of the endogenous cannabinoid system as a neuromodulatory system composed of receptors, endogenous ligands (endocannabinoids), and enzymes responsible for their synthesis and degradation, together with recent advancements in the elucidation of cannabinoid pharmacology, has renewed interest in medicines acting on the endocannabinoid system. Synthetic cannabinoid agonists have been developed and used for treatment of different human pathologic conditions, and promising potent cannabinoid antagonists are currently under clinical evaluation. During the last decade, new generations of synthetic cannabinoids appeared on the global drug market, proposed as marijuana-like compounds and sold as herbal mixture also known as spice drugs or legal highs. Because activation of cannabinoid receptors may induce central and peripheral beneficial effects, the newest synthetic cannabinoids having full agonistic activity and high potency at cannabinoid type 1 and type 2 receptors might have therapeutic potential too. However, case reports of acute and fatal intoxications are accumulating and revealing that this is not the case because adverse effects of the latest generation of synthetic cannabinoids far exceed the desired ones.


Assuntos
Canabinoides/uso terapêutico , Endocanabinoides/metabolismo , Maconha Medicinal/uso terapêutico , Medicamentos Sintéticos/uso terapêutico , Animais , Agonistas de Receptores de Canabinoides/uso terapêutico , Humanos , Ligantes , Maconha Medicinal/efeitos adversos , Receptores de Canabinoides/metabolismo , Medicamentos Sintéticos/efeitos adversos
18.
Epidemiol Infect ; 146(14): 1746-1749, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30081970

RESUMO

Leprosy is a granulomatous disease, infectious and transmissible, which affects the skin and peripheral nerves, having Mycobacterium leprae as causative agent. The manifestation of this disease causes cutaneous lesions, peripheral neuropathies and, in more extreme cases, may generate deformities and disabilities in affected individuals. Patents were identified using the descriptor 'leprosy' and code A61K of the international patent classification, which indicates only products that meet human needs. The analysis was made using the WIPO, ESPACENET and USPTO databases, until the month of September 2016. Through this review, we found a variety of in vitro, pre-clinical and clinical studies relating to the treatment of leprosy with different types of compounds and forms of administration. New treatment proposals should include pain reduction capabilities, prevention or limitation of the appearance of cutaneous lesions, as well as prevention of the progression of the disease to more severe stages that may lead to loss of function or potentiate the individual's immune response to the M. leprae bacillus in order to prevent bacterial spread. We concluded that any patents developed with natural products were not found in the treatment of leprosy. All the deposited products were synthetic origin, mostly tested in humans and of varied forms of administration.


Assuntos
Desenvolvimento de Medicamentos , Hanseníase/tratamento farmacológico , Patentes como Assunto , Antibacterianos/uso terapêutico , Anticorpos/uso terapêutico , Humanos , Peptídeos/uso terapêutico , Medicamentos Sintéticos/uso terapêutico
19.
Hist Cienc Saude Manguinhos ; 25(4): 979-998, 2018.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30624476

RESUMO

This article reflects on the medicalization of childbirth, focusing on the development of synthetic oxytocin in 1953. Specifically addressed is the social life of oxytocin; in other words, its synthesis, stabilization, and use in obstetrics to hasten labor. Two Brazilian obstetrics journals of this era were surveyed to analyze the early use of synthetic oxytocin in Brazil in the late 1950s, along with obstetric arguments for or against its use. Notable in this period is the increasingly central role of the obstetrician in childbirth, as well as the recommendation to use different interventions linked together (particularly oxytocin) to shorten labor.


Assuntos
Trabalho de Parto Induzido/história , Obstetrícia/história , Ocitócicos/história , Ocitocina/história , Medicamentos Sintéticos/história , Brasil , Feminino , História do Século XX , Humanos , Medicalização/história , Parto , Publicações Periódicas como Assunto/história , Gravidez , Medicamentos Sintéticos/uso terapêutico
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