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[PMID]:28450290
[Au] Autor:Doshi P; Godlee F
[Ti] Título:The wider role of regulatory scientists.
[So] Source:BMJ;357:j1991, 2017 04 27.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Tomada de Decisões/ética
Sociedades Científicas/legislação & jurisprudência
[Mh] Termos MeSH secundário: Celecoxib/farmacologia
Inibidores de Ciclo-Oxigenase 2/farmacologia
Acurácia dos Dados
Ética em Pesquisa
Seres Humanos
Lactonas/farmacologia
Paroxetina/farmacologia
Medição de Risco
Inibidores da Captação de Serotonina/farmacologia
Sociedades Científicas/normas
Sulfonas/farmacologia
Resultado do Tratamento
Estados Unidos
United States Food and Drug Administration/legislação & jurisprudência
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 (Cyclooxygenase 2 Inhibitors); 0 (Lactones); 0 (Serotonin Uptake Inhibitors); 0 (Sulfones); 0QTW8Z7MCR (rofecoxib); 41VRH5220H (Paroxetine); JCX84Q7J1L (Celecoxib)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.j1991


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[PMID]:28844482
[Au] Autor:Vichier-Guerre C; Parker M; Pomerantz Y; Finnell RH; Cabrera RM
[Ad] Endereço:Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX 78712, United States.
[Ti] Título:Impact of selective serotonin reuptake inhibitors on neural crest stem cell formation.
[So] Source:Toxicol Lett;281:20-25, 2017 Nov 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The use of antidepressants in pregnant women is rising, with rates up to 7.5% in the United States. Selective serotonin reuptake inhibitors (SSRIs) are currently the most common antidepressant prescribed to pregnant women. The teratogenic effects of SSRI exposure are debated because of discrepancies in epidemiological studies. As an alternative to epidemiological and animal studies, human embryonic stem cell research (hESC) provides a human-based experimental model to examine the risks of prenatal SSRI exposure. Neural crest stem cells (NCSCs) play an important role in craniofacial and cardiac development as precursors to craniofacial bones and heart septa. This study examines the effects of paroxetine (Paxil) and sertraline (Zoloft) exposure on proliferation, migration, and AP-2α protein expression of NCSC in vitro. hESCs were exposed to paroxetine and sertraline at three concentrations while undergoing directed differentiation into NCSCs. Our results indicate exposure to paroxetine significantly increased proliferation, migration, and AP-2α protein expression in NCSCs. Exposure to sertraline significantly decreased proliferation and significantly increased AP-2α protein expression in NCSC. This evidence suggests paroxetine and sertraline alter normal NCSC behavior and may thereby disrupt cardiac and craniofacial development.
[Mh] Termos MeSH primário: Antidepressivos/toxicidade
Células-Tronco Embrionárias/efeitos dos fármacos
Crista Neural/efeitos dos fármacos
Inibidores da Captação de Serotonina/toxicidade
[Mh] Termos MeSH secundário: Linhagem Celular
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células-Tronco Embrionárias/citologia
Regulação da Expressão Gênica
Seres Humanos
Crista Neural/citologia
Paroxetina/toxicidade
Sertralina/toxicidade
Fator de Transcrição AP-2/genética
Fator de Transcrição AP-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Serotonin Uptake Inhibitors); 0 (Transcription Factor AP-2); 41VRH5220H (Paroxetine); QUC7NX6WMB (Sertraline)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


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[PMID]:28708853
[Au] Autor:Westin AA; Brekke M; Molden E; Skogvoll E; Spigset O
[Ad] Endereço:Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway.
[Ti] Título:Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: Changes in drug disposition.
[So] Source:PLoS One;12(7):e0181082, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pregnancy may cause changes in drug disposition. The clinical consequences may be profound and even counterintuitive; in some cases pregnant women may need more than twice their usual drug dose in order to maintain therapeutic drug levels. For antidepressants, evidence on drug disposition in pregnancy is scarce. The aim of this study was to determine the effects of pregnancy on serum levels of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine in a large and naturalistic patient material, in order to provide tentative dose recommendations for pregnant women. METHODS: Using patient data from two routine therapeutic drug monitoring (TDM) services in Norway with linkage to the national birth registry, dose-adjusted serum drug concentrations of SSRIs and venlafaxine during pregnancy were compared to the women's own baseline (non-pregnant) values, using a linear mixed model. FINDINGS: Overall, the TDM databases contained 196,726 serum concentration measurements from 54,393 women. After data linkage and drug selection (SSRIs or venlafaxine only), we identified 367 analyses obtained from a total of 290 pregnancies in 281 women, and 420 baseline observations from the same women. Serum concentrations in the third trimester were significantly lower than baseline for paroxetine (-51%; 95% confidence interval [CI], -66%, -30%; p<0.001), fluvoxamine (-56%; CI, -75%, -23%; p = 0.004) and citalopram (-24%; CI, -38%, -7%; p = 0,007), and higher than baseline for sertraline (+68%; CI, +37%, +106%; p<0.001). For escitalopram, fluoxetine and venlafaxine concentrations did not change significantly. CONCLUSIONS: For paroxetine and fluvoxamine the pronounced decline in maternal drug serum concentrations in pregnancy may necessitate a dose increase of about 100% during the third trimester in order to maintain stable concentrations. For fluoxetine, venlafaxine, citalopram, escitalopram and sertraline, the present study indicates that dose adjustments are generally not necessary during pregnancy.
[Mh] Termos MeSH primário: Antidepressivos/sangue
Monitoramento de Medicamentos
Inibidores da Captação de Serotonina/sangue
Cloridrato de Venlafaxina/sangue
[Mh] Termos MeSH secundário: Adulto
Antidepressivos/uso terapêutico
Citalopram/sangue
Citalopram/uso terapêutico
Bases de Dados Factuais
Transtorno Depressivo/tratamento farmacológico
Feminino
Fluvoxamina/sangue
Fluvoxamina/uso terapêutico
Seres Humanos
Noruega
Paroxetina/sangue
Paroxetina/uso terapêutico
Gravidez
Terceiro Trimestre da Gravidez
Inibidores da Captação de Serotonina/uso terapêutico
Cloridrato de Venlafaxina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Serotonin Uptake Inhibitors); 0DHU5B8D6V (Citalopram); 41VRH5220H (Paroxetine); 7D7RX5A8MO (Venlafaxine Hydrochloride); O4L1XPO44W (Fluvoxamine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181082


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[PMID]:28674306
[Au] Autor:Shimoishi K; Anraku M; Uto A; Iohara D; Hirayama F; Kadowaki D; Zingami S; Maruyama T; Otagiri M
[Ad] Endereço:Department of Pharmacy, Japanese Red Cross Kumamoto Hospital.
[Ti] Título:A Comparison of the Phosphorus Content in Prescription Medications for Hemodialysis Patients in Japan.
[So] Source:Yakugaku Zasshi;137(7):903-908, 2017.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:A high dietary intake of phosphorus is considered to be a significant health threat for hemodialysis (HD) patients. Prescription medications, which might be a major source of phosphorus, is largely unrecognized in Japan. However, the amount of phosphorus indicated on the package label, is not quantified. In this study, the phosphorus content of 22 of the most widely prescribed medications that are used in conjunction with HD therapy were examined and differences between branded and generic prescription medications were compared. All samples were selected from medications that are typically prescribed for HD patients. The samples were ground prior to analysis. Phosphorus was measured using the Wako L-Type Phosphate method. All instruments used in the study were calibrated according to the manufacturers' specifications. Amlodipine (15 mg/tablet) and paroxetine (30.0 mg/tablet) were found to contain higher contents of phosphorus than the medications tested. Differences in phosphorus content between branded and generic drugs was also determined. The phosphorus content of all generic paroxetine preparations was significantly lower than the values for identical branded medications. On the other hand, the phosphorus content of several generic amlodipine preparations were significantly different from those of similar, branded preparations. Specific information regarding the phosphorus content of prescribed medications used by HD patient needs to be made available to the dialysis community.
[Mh] Termos MeSH primário: Fósforo/efeitos adversos
Fósforo/análise
Medicamentos sob Prescrição/química
Diálise Renal
[Mh] Termos MeSH secundário: Anlodipino/química
Medicamentos Genéricos/química
Seres Humanos
Japão
Paroxetina/química
Fósforo na Dieta/efeitos adversos
Fósforo na Dieta/análise
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drugs, Generic); 0 (Phosphorus, Dietary); 0 (Prescription Drugs); 1J444QC288 (Amlodipine); 27YLU75U4W (Phosphorus); 41VRH5220H (Paroxetine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00006


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[PMID]:28535332
[Au] Autor:Knapp P; Campbell Burton CA; Holmes J; Murray J; Gillespie D; Lightbody CE; Watkins CL; Chun HY; Lewis SR
[Ad] Endereço:Department of Health Sciences, University of York, York, UK, YO10 5DD.
[Ti] Título:Interventions for treating anxiety after stroke.
[So] Source:Cochrane Database Syst Rev;5:CD008860, 2017 05 23.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Approximately 20% of stroke patients experience clinically significant levels of anxiety at some point after stroke. Physicians can treat these patients with antidepressants or other anxiety-reducing drugs, or both, or they can provide psychological therapy. This review looks at available evidence for these interventions. This is an update of the review first published in October 2011. OBJECTIVES: The primary objective was to assess the effectiveness of pharmaceutical, psychological, complementary, or alternative therapeutic interventions in treating stroke patients with anxiety disorders or symptoms. The secondary objective was to identify whether any of these interventions for anxiety had an effect on quality of life, disability, depression, social participation, caregiver burden, or risk of death. SEARCH METHODS: We searched the trials register of the Cochrane Stroke Group (January 2017). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2017, Issue 1: searched January 2017); MEDLINE (1966 to January 2017) in Ovid; Embase (1980 to January 2017) in Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1937 to January 2017) in EBSCO; and PsycINFO (1800 to January 2017) in Ovid. We conducted backward citation searches of reviews identified through database searches and forward citation searches of included studies. We contacted researchers known to be involved in related trials, and we searched clinical trials registers for ongoing studies. SELECTION CRITERIA: We included randomised trials including participants with a diagnosis of both stroke and anxiety for which treatment was intended to reduce anxiety. Two review authors independently screened and selected titles and abstracts for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We performed a narrative review. We planned to do a meta-analysis but were unable to do so as included studies were not sufficiently comparable. MAIN RESULTS: We included three trials (four interventions) involving 196 participants with stroke and co-morbid anxiety. One trial (described as a 'pilot study') randomised 21 community-dwelling stroke survivors to four-week use of a relaxation CD or to wait list control. This trial assessed anxiety using the Hospital Anxiety and Depression Scale and reported a reduction in anxiety at three months among participants who had used the relaxation CD (mean (standard deviation (SD) 6.9 (± 4.9) and 11.0 (± 3.9)), Cohen's d = 0.926, P value = 0.001; 19 participants analysed).The second trial randomised 81 participants with co-morbid anxiety and depression to paroxetine, paroxetine plus psychotherapy, or standard care. Mean levels of anxiety severity scores based on the Hamilton Anxiety Scale (HAM-A) at follow-up were 5.4 (SD ± 1.7), 3.8 (SD ± 1.8), and 12.8 (SD ± 1.9), respectively (P value < 0.01).The third trial randomised 94 stroke patients, also with co-morbid anxiety and depression, to receive buspirone hydrochloride or standard care. At follow-up, the mean levels of anxiety based on the HAM-A were 6.5 (SD ± 3.1) and 12.6 (SD ± 3.4) in the two groups, respectively, which represents a significant difference (P value < 0.01). Half of the participants receiving paroxetine experienced adverse events that included nausea, vomiting, or dizziness; however, only 14% of those receiving buspirone experienced nausea or palpitations. Trial authors provided no information about the duration of symptoms associated with adverse events. The trial of relaxation therapy reported no adverse events.The quality of the evidence was very low. Each study included a small number of participants, particularly the study of relaxation therapy. Studies of pharmacological agents presented details too limited to allow judgement of selection, performance, and detection bias and lack of placebo treatment in control groups. Although the study of relaxation therapy had allocated participants to treatment using an adequate method of randomisation, study recruitment methods might have introduced bias, and drop-outs in the intervention group may have influenced results. AUTHORS' CONCLUSIONS: Evidence is insufficient to guide the treatment of anxiety after stroke. Further well-conducted randomised controlled trials (using placebo or attention controls) are required to assess pharmacological agents and psychological therapies.
[Mh] Termos MeSH primário: Ansiedade/terapia
Acidente Vascular Cerebral/psicologia
[Mh] Termos MeSH secundário: Ansiolíticos/uso terapêutico
Antidepressivos/efeitos adversos
Antidepressivos/uso terapêutico
Ansiedade/etiologia
Buspirona/uso terapêutico
Depressão/terapia
Seres Humanos
Meia-Idade
Paroxetina/efeitos adversos
Paroxetina/uso terapêutico
Projetos Piloto
Psicoterapia
Ensaios Clínicos Controlados Aleatórios como Assunto
Terapia de Relaxamento/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Antidepressive Agents); 41VRH5220H (Paroxetine); TK65WKS8HL (Buspirone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170524
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD008860.pub3


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[PMID]:28421837
[Au] Autor:Russell JL; Spiller HA; Chounthirath T; Casavant MJ
[Ad] Endereço:a Nationwide Children's Hospital , Columbus , OH , USA.
[Ti] Título:Pediatric ingestion of vilazodone compared to other selective serotonin reuptake inhibitor medications.
[So] Source:Clin Toxicol (Phila);55(5):352-356, 2017 Jun.
[Is] ISSN:1556-9519
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Unintentional ingestion of selective serotonin reuptake inhibitor (SSRI) medications is common amongst children <6 years of age. Current evidence-based management guidelines are based on a low incidence of significant medical outcomes in these children. OBJECTIVE: To describe and compare outcomes of pediatric exposures to vilazodone with other SSRIs. METHODS: A retrospective observational case series analysis of both single and polysubstance SSRI exposures amongst children <6 years old reported to the National Poison Data System (NPDS). RESULTS: 11,384 SSRI exposures in children <6 years of age reported to NPDS between January 2012 and June 2016 were assessed. Vilazodone only accounted for 5.9% of all exposures, but resulted in the highest proportion of health care facility admission compared to other SSRIs, both in single substance (165 of 531 (31.1%); OR 9.0 [7.3-11.2]) and polysubstance (57 of 107 (53.3%); OR 4.1 [2.7-6.2]) exposures. Children exposed to vilazodone also have higher odds of experiencing a major or moderate outcome in single (134 of 531 (25.2%); OR 20.5 [15.5-27.1]) and polysubstance (37 of 107 (35.6%); OR 5.9 [3.7-9.0]) exposures compared to other SSRIs. Several severe clinical outcomes, such as seizure and coma, were more common among the vilazodone exposures. CONCLUSIONS: Exposure to vilazodone in this age group results in an increased rate of hospitalization as well as more severe clinical effects as compared to other SSRIs. Current evidence-based SSRI exposure management guidelines may not be appropriate for the management of vilazodone ingestion in this age group.
[Mh] Termos MeSH primário: Inibidores da Captação de Serotonina/envenenamento
Cloridrato de Vilazodona/envenenamento
[Mh] Termos MeSH secundário: Criança
Pré-Escolar
Citalopram/envenenamento
Coma/induzido quimicamente
Coma/tratamento farmacológico
Relação Dose-Resposta a Droga
Medicina Baseada em Evidências
Feminino
Fluoxetina/envenenamento
Fluvoxamina/envenenamento
Seguimentos
Hospitalização
Seres Humanos
Lactente
Masculino
Paroxetina/envenenamento
Centros de Controle de Intoxicações
Estudos Retrospectivos
Convulsões/induzido quimicamente
Convulsões/tratamento farmacológico
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Serotonin Uptake Inhibitors); 01K63SUP8D (Fluoxetine); 0DHU5B8D6V (Citalopram); 41VRH5220H (Paroxetine); O4L1XPO44W (Fluvoxamine); U8HTX2GK8J (Vilazodone Hydrochloride)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170425
[Lr] Data última revisão:
170425
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1080/15563650.2017.1287375


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[PMID]:28349259
[Au] Autor:Lassen TR; Nielsen JM; Johnsen J; Ringgaard S; Bøtker HE; Kristiansen SB
[Ad] Endereço:Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark. thomasravnl@clin.au.dk.
[Ti] Título:Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction.
[So] Source:Basic Res Cardiol;112(3):26, 2017 May.
[Is] ISSN:1435-1803
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Left ventricular (LV) remodeling following a myocardial infarction (MI) involves formation of reactive oxygen species (ROS). Paroxetine, a selective serotonin reuptake inhibitor, has an antioxidant effect in the vascular wall. We investigated whether paroxetine reduces myocardial ROS formation and LV remodeling following a MI. In a total of 32 Wistar rats, MI was induced by a 30-min ligation of the left anterior descending artery followed by 7- or 28-day reperfusion. During the 28 days of reperfusion, LV remodeling was evaluated by magnetic resonance imaging (MRI) and echocardiography (n = 20). After 28 days of reperfusion, the susceptibility to ventricular tachycardia was evaluated prior to sacrifice and histological assessment of myocyte cross-sectional area, fibrosis, and presence of myofibroblasts. Myocardial ROS formation was measured with dihydroethidium after 7 days of reperfusion in separate groups (n = 12). Diastolic LV volume, evaluated by MRI (417 ± 60 vs. 511 ± 64 µL, p < 0.05), and echocardiography (515 ± 80 vs. 596 ± 83 µL, p < 0.05) as well as diastolic LV internal diameter evaluated with echocardiography (7.2 ± 0.6 vs. 8.1 ± 0.7 mm, p < 0.05) were lower in the paroxetine group than in controls. Furthermore, myocyte cross-sectional area was reduced in the paroxetine group compared with controls (277 ± 26 vs. 354 ± 23 mm , p < 0.05) and ROS formation was reduced in the remote myocardium (0.415 ± 0.19 normalized to controls, p < 0.05). However, no differences in the presence of fibrosis or myofibroblasts were observed. Finally, paroxetine reduced the susceptibility to ventricular tachycardia (induced in 2/11 vs. 6/8 rats, p < 0.05). Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Infarto do Miocárdio/patologia
Paroxetina/farmacologia
Remodelação Ventricular/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Ecocardiografia
Imagem por Ressonância Magnética
Masculino
Ratos
Ratos Wistar
Espécies Reativas de Oxigênio
Inibidores da Captação de Serotonina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Reactive Oxygen Species); 0 (Serotonin Uptake Inhibitors); 41VRH5220H (Paroxetine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.1007/s00395-017-0614-5


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[PMID]:28346565
[Au] Autor:Boccardi V; Baroni M; Paolacci L; Ercolani S; Longo A; Giordano M; Ruggiero C; Mecocci P
[Ad] Endereço:Dr Virginia Boccardi, Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, S. Andrea delle Fratte, 06156 Perugia, Italy. Phone number: +39 0755783524 Email address: virginia.boccardi@unipg.it.
[Ti] Título:Anticholinergic Burden and Functional Status in Older People with Cognitive Impairment: Results from the Regal Project.
[So] Source:J Nutr Health Aging;21(4):389-396, 2017.
[Is] ISSN:1760-4788
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The use of drugs with intrinsic anticholinergic properties is widespread among old age persons. A growing body of evidences suggest that a high anticholinergic burden is associated with physical and cognitive impairment. However, the association between anticholinergic drug use and functional status is still poorly investigated, particularly among subjects with initial cognitive impairment. DESIGN: Cross-sectional study examining the association between drug-related anticholinergic burden and functional status in cognitively healthy (CH) (n=691), mild cognitive impairment (MCI) (n=541) or mild Alzheimer's diseases (AD) (n=1127) subjects. SETTING: Data were gathered from the ReGAl project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large longitudinal Italian multicentric clinical-based study, promoted by the Italian Society of Gerontology and Geriatrics (SIGG). PARTICIPANTS: 2359 outpatients, older than 65 years, admitted to memory clinics. The total sample size, estimated according to a global effect size of 25% with type I error of 0.05 and a power of 95% is 2010 subjects. MEASUREMENT: Functional status was evaluated by the Katz Index of Independence in Activities of Daily Living (ADL) and the Lawton-Brody Instrumental Activities of Daily Living (IADL) scales. The drug-related anticholinergic burden was estimated by the Anticholinergic Risk Scale (ARS). RESULTS: The 15.9 % (n=375) of total population used at least one drug with anticholinergic properties. Such a drug use was associated with partially dependence in ADL (OR:1.42, CI95%: 1.10-1.83; p=0.006), independently of gender, number of drugs, comorbidity index, presence of clinically relevant neuropsychiatric symptoms and adjusted MMSE. Anticholinergic drug use was associated with un-ability at each IADL task only in male MCI subjects, with significant impairment in shopping (p=0.011), and drug management (p=0.05). CONCLUSIONS: The use of medications with anticholinergic properties is common among older persons cognitively health as well as with cognitive impairment. Our results suggest that the use of anticholinergic drugs is associated with functional impairment, especially in old age subjects with initial cognitive impairment. Minimizing anticholinergic burden should result in maintaining daily functioning, especially in a vulnerable population, such as MCI and mild AD.
[Mh] Termos MeSH primário: Atividades Cotidianas
Antagonistas Colinérgicos/efeitos adversos
Antagonistas Colinérgicos/uso terapêutico
Disfunção Cognitiva/induzido quimicamente
Memória/fisiologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/fisiopatologia
Estudos Transversais
Feminino
Hospitalização
Seres Humanos
Itália
Estudos Longitudinais
Masculino
Pacientes Ambulatoriais
Paroxetina/efeitos adversos
Paroxetina/uso terapêutico
Risperidona/efeitos adversos
Risperidona/uso terapêutico
Trazodona/efeitos adversos
Trazodona/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholinergic Antagonists); 41VRH5220H (Paroxetine); L6UH7ZF8HC (Risperidone); YBK48BXK30 (Trazodone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170328
[St] Status:MEDLINE
[do] DOI:10.1007/s12603-016-0787-x


  9 / 3756 MEDLINE  
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[PMID]:28323425
[Au] Autor:Waldschmidt HV; Homan KT; Cato MC; Cruz-Rodríguez O; Cannavo A; Wilson MW; Song J; Cheung JY; Koch WJ; Tesmer JJ; Larsen SD
[Ad] Endereço:Department of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
[Ti] Título:Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.
[So] Source:J Med Chem;60(7):3052-3069, 2017 Apr 13.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In heart failure, the ß-adrenergic receptors (ßARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing heart, making them desirable therapeutic targets. The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor. Utilizing a structure-based drug design approach, we modified paroxetine to generate a small compound library. Included in this series is a highly potent and selective GRK2 inhibitor, 14as, with an IC of 30 nM against GRK2 and greater than 230-fold selectivity over other GRKs and kinases. Furthermore, 14as showed a 100-fold improvement in cardiomyocyte contractility assays over paroxetine and a plasma concentration higher than its IC for over 7 h. Three of these inhibitors, including 14as, were additionally crystallized in complex with GRK2 to give insights into the structural determinants of potency and selectivity of these inhibitors.
[Mh] Termos MeSH primário: Desenho de Drogas
Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores
Paroxetina/análogos & derivados
Paroxetina/farmacologia
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Animais
Cristalografia por Raios X
Quinase 2 de Receptor Acoplado a Proteína G/química
Quinase 2 de Receptor Acoplado a Proteína G/metabolismo
Seres Humanos
Camundongos
Microssomos Hepáticos/metabolismo
Simulação de Acoplamento Molecular
Paroxetina/sangue
Paroxetina/metabolismo
Inibidores de Proteínas Quinases/sangue
Inibidores de Proteínas Quinases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); 41VRH5220H (Paroxetine); EC 2.7.11.16 (G-Protein-Coupled Receptor Kinase 2)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00112


  10 / 3756 MEDLINE  
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[PMID]:28253393
[Au] Autor:Mustian KM; Alfano CM; Heckler C; Kleckner AS; Kleckner IR; Leach CR; Mohr D; Palesh OG; Peppone LJ; Piper BF; Scarpato J; Smith T; Sprod LK; Miller SM
[Ad] Endereço:Department of Surgery, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.
[Ti] Título:Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis.
[So] Source:JAMA Oncol;3(7):961-968, 2017 Jul 01.
[Is] ISSN:2374-2445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Cancer-related fatigue (CRF) remains one of the most prevalent and troublesome adverse events experienced by patients with cancer during and after therapy. Objective: To perform a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the 4 most commonly recommended treatments for CRF-exercise, psychological, combined exercise and psychological, and pharmaceutical-and to identify independent variables associated with treatment effectiveness. Data Sources: PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane Library were searched from the inception of each database to May 31, 2016. Study Selection: Randomized clinical trials in adults with cancer were selected. Inclusion criteria consisted of CRF severity as an outcome and testing of exercise, psychological, exercise plus psychological, or pharmaceutical interventions. Data Extraction and Synthesis: Studies were independently reviewed by 12 raters in 3 groups using a systematic and blinded process for reconciling disagreement. Effect sizes (Cohen d) were calculated and inversely weighted by SE. Main Outcomes and Measures: Severity of CRF was the primary outcome. Study quality was assessed using a modified 12-item version of the Physiotherapy Evidence-Based Database scale (range, 0-12, with 12 indicating best quality). Results: From 17 033 references, 113 unique studies articles (11 525 unique participants; 78% female; mean age, 54 [range, 35-72] years) published from January 1, 1999, through May 31, 2016, had sufficient data. Studies were of good quality (mean Physiotherapy Evidence-Based Database scale score, 8.2; range, 5-12) with no evidence of publication bias. Exercise (WES, 0.30; 95% CI, 0.25-0.36; P < .001), psychological (WES, 0.27; 95% CI, 0.21-0.33; P < .001), and exercise plus psychological interventions (WES, 0.26; 95% CI, 0.13-0.38; P < .001) improved CRF during and after primary treatment, whereas pharmaceutical interventions did not (WES, 0.09; 95% CI, 0.00-0.19; P = .05). Results also suggest that CRF treatment effectiveness was associated with cancer stage, baseline treatment status, experimental treatment format, experimental treatment delivery mode, psychological mode, type of control condition, use of intention-to-treat analysis, and fatigue measures (WES range, -0.91 to 0.99). Results suggest that the effectiveness of behavioral interventions, specifically exercise and psychological interventions, is not attributable to time, attention, and education, and specific intervention modes may be more effective for treating CRF at different points in the cancer treatment trajectory (WES range, 0.09-0.22). Conclusions and Relevance: Exercise and psychological interventions are effective for reducing CRF during and after cancer treatment, and they are significantly better than the available pharmaceutical options. Clinicians should prescribe exercise or psychological interventions as first-line treatments for CRF.
[Mh] Termos MeSH primário: Estimulantes do Sistema Nervoso Central/uso terapêutico
Terapia Cognitiva
Terapia por Exercício
Fadiga/terapia
Glucocorticoides/uso terapêutico
Neoplasias/complicações
Inibidores da Captação de Serotonina/uso terapêutico
Promotores da Vigília/uso terapêutico
[Mh] Termos MeSH secundário: Compostos Benzidrílicos/uso terapêutico
Cloridrato de Dexmetilfenidato/uso terapêutico
Dextroanfetamina/uso terapêutico
Fadiga/etiologia
Seres Humanos
Metilfenidato/uso terapêutico
Metilprednisolona/uso terapêutico
Paroxetina/uso terapêutico
Psicoterapia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Benzhydryl Compounds); 0 (Central Nervous System Stimulants); 0 (Glucocorticoids); 0 (Serotonin Uptake Inhibitors); 0 (Wakefulness-Promoting Agents); 1678OK0E08 (Dexmethylphenidate Hydrochloride); 207ZZ9QZ49 (Methylphenidate); 41VRH5220H (Paroxetine); R3UK8X3U3D (modafinil); TZ47U051FI (Dextroamphetamine); V63XWA605I (armodafinil); X4W7ZR7023 (Methylprednisolone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170303
[St] Status:MEDLINE
[do] DOI:10.1001/jamaoncol.2016.6914



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