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[PMID]:29215340
[Au] Autor:Yakut K; Erdogan I; Varan B; Atar I
[Ad] Endereço:Department of Pediatric Cardiology, Baskent University Ankara Hospital, Ankara, Turkey.
[Ti] Título:A Report of Brugada Syndrome Presenting with Cardiac Arrest Triggered by Verapamil Intoxication.
[So] Source:Balkan Med J;34(6):576-579, 2017 12 01.
[Is] ISSN:2146-3131
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Brugada syndrome is a disease characterized by a specific electrocardiographic pattern and an increased risk of sudden cardiac death. We present this case with the updated literature to emphasise the need to consider the diagnosis of Brugada syndrome in patients admitted to the emergency ward with sudden cardiac arrest. CASE REPORT: A 16-year-old female patient was admitted to the emergency ward with complaints of weakness and abdominal pain, and she had four cardiac arrests during her evaluation period. She was referred to our clinic for permanent pacemaker implantation. She was on a temporary pace maker after having had C-reactive protein. Her physical exam was normal except for bilaterally decreased lung sounds. Lung x-ray and computed tomography, which were performed by another institution, revealed minimal pleural effusion and nothing else of significance. Blood and peritoneal fluid samples were sterile. Echocardiographic exam and cardiac enzymes were also in the normal ranges. Electrocardiographic showed incomplete right branch block in leads V1 and V2. An ajmaline test revealed specific electrocardiographic findings of the type I Brugada pattern. We proposed implanting an implantable cardioverter defibrillator to the patient as there were positive findings on the ajmaline test as well as a history of sudden cardiac arrest. After this treatment proposal, the patient's family admitted that she had taken a high dose of verapamil and thus, the encountered bradycardia was associated with verapamil overuse. The ajmaline test was repeated as it was contemplated that the previous positive ajmaline test had been associated with verapamil overuse. Implantable cardioverter defibrillator implantation was proposed again as there was a history of sudden cardiac arrest; however, the family did not consent to implantable cardioverter defibrillator, and the patient was discharged and followed up. CONCLUSION: Brugada syndrome should be considered for patients who are admitted to the emergency ward with sudden cardiac arrest though surface electrocardiographic is normal. If there is a suspicion of Brugada syndrome, repeated electrocardiographic should be performed on different occasions. Diagnosis can be clarified by upper costal electrocardiographic or by administering Na channel blockers during electrocardiographic performance.
[Mh] Termos MeSH primário: Antiarrítmicos/envenenamento
Síndrome de Brugada/induzido quimicamente
Parada Cardíaca/induzido quimicamente
Verapamil/envenenamento
[Mh] Termos MeSH secundário: Adolescente
Ajmalina/farmacologia
Síndrome de Brugada/diagnóstico
Síndrome de Brugada/fisiopatologia
Diagnóstico Diferencial
Eletrocardiografia
Feminino
Testes Genéticos
Parada Cardíaca/fisiopatologia
Seres Humanos
Fatores Desencadeantes
Bloqueadores dos Canais de Sódio/administração & dosagem
Tentativa de Suicídio
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Sodium Channel Blockers); 1PON08459R (Ajmaline); CJ0O37KU29 (Verapamil)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.4274/balkanmedj.2016.1301


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[PMID]:28954371
[Au] Autor:Ajima MNO; Pandey PK; Kumar K; Poojary N
[Ad] Endereço:Department of Fisheries and Aquaculture Technology, Federal University of Technology, Owerri, Nigeria. Electronic address: malajimo@gmail.com.
[Ti] Título:Alteration in DNA structure, molecular responses and Na -K -ATPase activities in the gill of Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) in response to sub-lethal verapamil.
[So] Source:Ecotoxicol Environ Saf;147:809-816, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The ecotoxicological consequences of residues from pharmaceutical drugs on aquatic biota have necessitated the development of sensitive and reliable techniques to assess the impact of these xenobiotics on aquatic organisms. This study investigated the alteration in DNA structure, molecular responses and the activities of Na -K -ATPase and antioxidant enzymes in the gill of Nile tilapia, Oreochromis niloticus, exposed to long-term effects at the concentrations (0.14, 0.28 and 0.57mgL ) of verapamil in static renewal system for 15, 30, 45 and 60 days. Evaluation of DNA structure, using single cell gel electrophoresis, revealed certain degree of DNA damages in the gill in a time and concentration-dependent relationship. Transcription of mRNA of superoxide dismutase (sod), catalase (cat) and heat shock protein (hsp70) genes in the gill of the fish showed the genes were up-regulated. Na -K -ATPase activity was inhibited in a concentration and time dependent manner. The indices of oxidative stress biomarkers (lipid peroxidation and carbonyl protein) as well as superoxide dismutase, glutathione peroxidase, glutathione-S-transferase were elevated in the treated fish in comparison to the control. Further, the level of reduced glutathione and catalase activity were inhibited at 0.28mgL after day 30. Long-term exposure to sub-lethal concentration of verapamil can cause DNA damages, molecular effects and oxidative stress in O. niloticus. The biomarkers analysed can be used as early warning signals in environmental biomonitoring and assessment of drug contamination in aquatic ecosystem.
[Mh] Termos MeSH primário: Ciclídeos/metabolismo
Dano ao DNA
Brânquias/efeitos dos fármacos
ATPase Trocadora de Sódio-Potássio/metabolismo
Verapamil/toxicidade
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Animais
Antioxidantes/metabolismo
Biomarcadores/metabolismo
Ciclídeos/genética
Relação Dose-Resposta a Droga
Monitoramento Ambiental/métodos
Brânquias/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Verapamil/metabolismo
Poluentes Químicos da Água/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Biomarkers); 0 (Water Pollutants, Chemical); CJ0O37KU29 (Verapamil); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170929
[St] Status:MEDLINE


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[PMID]:29442035
[Au] Autor:Incecayir T; Ilbasmis-Tamer S; Tirnaksiz F; Degim T
[Ti] Título:Assessment of the potential drug-drug interaction between carvedilol and clopidogrel mediated through intestinal P-glycoprotein.
[So] Source:Pharmazie;71(8):472-477, 2016 08 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The most widely prescribed oral antiplatelet agent, clopidogrel, shows high interindividual variability resulting in an increased risk of cardiovascular events in the patients with reduced platelet inhibition. The purpose of this study was to investigate the role of the P-glycoprotein (P-gp) efflux pump in limiting the intestinal permeability of clopidogrel and the effect of a ß-blocker, namely, carvedilol, on its intestinal transport. Effective permeabilities (Peff) of clopidogrel and carvedilol were investigated in the proximal jejunum and distal ileum of rats using an in situ intestinal perfusion model. Peff values of clopidogrel and carvedilol were found to be concentration dependent with decreased Peff values at the low perfusate concentrations. Coperfusion with the P-gp inhibitors verapamil (100 µM) and carvedilol (10 µM) significantly increased the Peff of clopidogrel in the jejunum (8.31±0.20 x 10-5 and 6.98±0.75 x 10-5 vs. 3.60±0.51 x 10-5, respectively) and ileum (9.08±2.19 x 10-5 and 8.35±1.58 x 10-5 vs. 3.85±0.15 x 10-5, respectively). However, at the highest concentration tested (30 µM), clopidogrel exhibited 3 and 1.4 times higher Peff than those of metoprolol, an FDA high permeability reference standard, in the jejunum and ileum, respectively. Overall, this study indicates that the efflux function appears not to have a significant impact on the in vivo intestinal absorption of clopidogrel due to the saturation of P-gp, suggesting no clinically relevant interaction between carvedilol and clopidogrel mediated through P-gp at intestinal level.
[Mh] Termos MeSH primário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos
Antagonistas Adrenérgicos beta/farmacologia
Carbazóis/farmacologia
Intestino Delgado/efeitos dos fármacos
Inibidores da Agregação de Plaquetas/farmacologia
Propanolaminas/farmacologia
Ticlopidina/análogos & derivados
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores
Animais
Interações Medicamentosas
Absorção Intestinal/efeitos dos fármacos
Intestino Delgado/metabolismo
Masculino
Metoprolol/farmacologia
Perfusão
Permeabilidade/efeitos dos fármacos
Ratos
Ratos Wistar
Ticlopidina/farmacologia
Verapamil/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Adrenergic beta-Antagonists); 0 (Carbazoles); 0 (Platelet Aggregation Inhibitors); 0 (Propanolamines); 0K47UL67F2 (carvedilol); A74586SNO7 (clopidogrel); CJ0O37KU29 (Verapamil); GEB06NHM23 (Metoprolol); OM90ZUW7M1 (Ticlopidine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6059


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[PMID]:27777258
[Au] Autor:Bibas L; Levi M; Essebag V
[Ad] Endereço:Division of Cardiology, McGill University Health Center, Montréal, Que.
[Ti] Título:Diagnosis and management of supraventricular tachycardias.
[So] Source:CMAJ;188(17-18):E466-E473, 2016 Dec 06.
[Is] ISSN:1488-2329
[Cp] País de publicação:Canada
[La] Idioma:eng
[Mh] Termos MeSH primário: Adenosina/uso terapêutico
Antagonistas Adrenérgicos beta/uso terapêutico
Antiarrítmicos/uso terapêutico
Bloqueadores dos Canais de Cálcio/uso terapêutico
Ablação por Cateter
Cardioversão Elétrica
Taquicardia Supraventricular/terapia
[Mh] Termos MeSH secundário: Diltiazem/uso terapêutico
Gerenciamento Clínico
Eletrocardiografia
Seres Humanos
Guias de Prática Clínica como Assunto
Taquicardia Supraventricular/diagnóstico
Verapamil/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Anti-Arrhythmia Agents); 0 (Calcium Channel Blockers); CJ0O37KU29 (Verapamil); EE92BBP03H (Diltiazem); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171206
[Lr] Data última revisão:
171206
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:28953988
[Au] Autor:Wang YH; Ke XM; Zhang CH; Yang RP
[Ad] Endereço:Chongqing Academy of Chinese Materia Medica, Chongqing, China.
[Ti] Título:Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method.
[So] Source:Braz J Med Biol Res;50(11):e6353, 2017 Sep 21.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.
[Mh] Termos MeSH primário: Adjuvantes Farmacêuticos/farmacologia
Curcumina/análogos & derivados
Curcumina/farmacocinética
Inibidores Enzimáticos/farmacocinética
Absorção Intestinal
Intestino Delgado/metabolismo
[Mh] Termos MeSH secundário: 2,4-Dinitrofenol/farmacocinética
Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores
Animais
Cromatografia Líquida de Alta Pressão/métodos
Curcumina/química
Emulsões
Feminino
Absorção Intestinal/efeitos dos fármacos
Intestino Delgado/efeitos dos fármacos
Masculino
Proteínas Associadas à Resistência a Múltiplos Medicamentos/análise
Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores
Imagem de Perfusão/métodos
Probenecid/farmacologia
Ratos Sprague-Dawley
Valores de Referência
Reprodutibilidade dos Testes
Fatores de Tempo
Desacopladores/farmacologia
Verapamil/farmacologia
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Abcc2 protein, rat); 0 (Adjuvants, Pharmaceutic); 0 (Emulsions); 0 (Enzyme Inhibitors); 0 (Multidrug Resistance-Associated Proteins); 0 (Uncoupling Agents); 2EFO1BP34R (bis(4-hydroxycinnamoyl)methane); 4AF605U6JN (multidrug resistance-associated protein 2); CJ0O37KU29 (Verapamil); IT942ZTH98 (Curcumin); PO572Z7917 (Probenecid); Q13SKS21MN (2,4-Dinitrophenol); W2F8059T80 (demethoxycurcumin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE


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[PMID]:28899749
[Au] Autor:Hammoud SH; Omar AG; Eid AA; El-Mas MM
[Ad] Endereço:Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Lebanon.
[Ti] Título:CYP4A/CYP2C modulation of the interaction of calcium channel blockers with cyclosporine on EDHF-mediated renal vasodilations in rats.
[So] Source:Toxicol Appl Pharmacol;334:110-119, 2017 Nov 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The endothelium-derived hyperpolarizing factor (EDHF) serves as a back-up mechanism that compensates for reduced nitric oxide (NO)/prostanoids bioavailability. Here we investigated whether (i) under conditions of vascular endothelium dysfunction, the immunosuppressant drug cyclosporine (CSA) upregulates EDHF-dependent renal vasodilations through altering CYP4A/CYP2C signaling, and (ii) calcium channel blockers modulate the CSA/EDHF/CYP interaction. Rats were treated with CSA, verapamil, nifedipine, or their combinations for 7days. Blood pressure (BP) was measured by tail-cuff plethysmography. Kidneys were then isolated, perfused with physiological solution containing L-NAME (NOS inhibitor) and diclofenac (cyclooxygenase inhibitor, DIC), and preconstricted with phenylephrine. CSA (25mgkg day for 7days) increased BP and augmented carbachol renal vasodilations. The co-treatment with verapamil (2mgkg day ) or nifedipine (3mgkg day ) abolished CSA hypertension and conversely affected carbachol vasodilations (increases vs. decreases). Infusion of MSPPOH (epoxyeicosatrienoic acids, EETs, inhibitor) reduced carbachol vasodilations in kidneys of all rat groups, suggesting the importance of EETs in these responses. By contrast, 20-Hydroxyeicosatetraenoic Acid (20-HETE) inhibition by HET0016 increased carbachol vasodilations in control rats, an effect that disappeared by CSA treatment, and reappeared in rats treated with CSA/verapamil or CSA/nifedipine. Renal protein expression of CYP2C and CYP4A as well as their vasoactive products (EETs/20-HETE) were increased in CSA-treated rats. Whereas the CYP2C/EETs effects of CSA were abolished by verapamil and intensified by nifedipine, the CYP4A/20-HETE effects were reduced by either CCB. Overall, nifedipine and verapamil blunts CSA hypertension but variably affected concomitantly enhanced EDHF-dependent renal vasodilations and alterations in CYP2C/CYP4A signaling.
[Mh] Termos MeSH primário: Fatores Biológicos/metabolismo
Bloqueadores dos Canais de Cálcio/farmacologia
Ciclosporina/farmacologia
Citocromo P-450 CYP4A/metabolismo
Sistema Enzimático do Citocromo P-450/metabolismo
Imunossupressores/farmacologia
[Mh] Termos MeSH secundário: Animais
Bloqueadores dos Canais de Cálcio/administração & dosagem
Ciclosporina/administração & dosagem
Citocromo P-450 CYP4A/genética
Sistema Enzimático do Citocromo P-450/genética
Interações Medicamentosas
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Imunossupressores/administração & dosagem
Rim/irrigação sanguínea
Masculino
Nifedipino/administração & dosagem
Nifedipino/farmacologia
Ratos
Ratos Sprague-Dawley
Vasodilatação/efeitos dos fármacos
Verapamil/administração & dosagem
Verapamil/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biological Factors); 0 (Calcium Channel Blockers); 0 (Immunosuppressive Agents); 0 (cytochrome P-450 CYP2C subfamily); 0 (endothelium-dependent hyperpolarization factor); 83HN0GTJ6D (Cyclosporine); 9035-51-2 (Cytochrome P-450 Enzyme System); CJ0O37KU29 (Verapamil); EC 1.14.15.3 (Cytochrome P-450 CYP4A); I9ZF7L6G2L (Nifedipine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE


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[PMID]:28717111
[Au] Autor:Watanabe H; Honda Y; Deguchi J; Yamada T; Bando K
[Ad] Endereço:Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd.
[Ti] Título:Usefulness of cardiotoxicity assessment using calcium transient in human induced pluripotent stem cell-derived cardiomyocytes.
[So] Source:J Toxicol Sci;42(4):519-527, 2017.
[Is] ISSN:1880-3989
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Monitoring dramatic changes in intracellular calcium ion levels during cardiac contraction and relaxation, known as calcium transient, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) would be an attractive strategy for assessing compounds on cardiac contractility. In addition, as arrhythmogenic compounds are known to induce characteristic waveform changes in hiPSC-CMs, it is expected that calcium transient would allow evaluation of not only compound-induced effects on cardiac contractility, but also compound arrhythmogenic potential. Using a combination of calcium transient in hiPSC-CMs and a fast kinetic fluorescence imaging detection system, we examined in this study changes in calcium transient waveforms induced by a series of 17 compounds that include positive/negative inotropic agents as well as cardiac ion channel activators/inhibitors. We found that all positive inotropic compounds induced an increase in peak frequency and/or peak amplitude. The effects of a negative inotropic compound could clearly be detected in the presence of a ß-adrenergic receptor agonist. Furthermore, most arrhythmogenic compounds raised the ratio of peak decay time to peak rise time (D/R ratio) in calcium transient waveforms. Compound concentrations at which these parameters exceeded cutoff values correlated well with systemic exposure levels at which arrhythmias were reported to be evoked. In conclusion, we believe that peak analysis of calcium transient and determination of D/R ratio are reliable methods for assessing compounds' cardiac contractility and arrhythmogenic potential, respectively. Using these approaches would allow selection of compounds with low cardiotoxic potential at the early stage of drug discovery.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Cardiotônicos/toxicidade
Células-Tronco Pluripotentes Induzidas/citologia
Miócitos Cardíacos/metabolismo
Testes de Toxicidade/métodos
[Mh] Termos MeSH secundário: Arritmias Cardíacas/induzido quimicamente
Astemizol/toxicidade
Bloqueadores dos Canais de Cálcio/toxicidade
Diferenciação Celular
Células Cultivadas
Digoxina/toxicidade
Relação Dose-Resposta a Droga
Descoberta de Drogas
Fluoroquinolonas/toxicidade
Isoproterenol/toxicidade
Contração Miocárdica/efeitos dos fármacos
Propranolol/toxicidade
Verapamil/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Blockers); 0 (Cardiotonic Agents); 0 (Fluoroquinolones); 73K4184T59 (Digoxin); 7HU6337315 (Astemizole); 9Y8NXQ24VQ (Propranolol); CJ0O37KU29 (Verapamil); L628TT009W (Isoproterenol); SY7Q814VUP (Calcium); U188XYD42P (moxifloxacin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.2131/jts.42.519


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[PMID]:28645473
[Au] Autor:Washam JB; Hellkamp AS; Lokhnygina Y; Piccini JP; Berkowitz SD; Nessel CC; Becker RC; Breithardt G; Fox KAA; Halperin JL; Hankey GJ; Mahaffey KW; Singer DE; Patel MR; ROCKET AF Steering Committee and Investigators
[Ad] Endereço:Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. Electronic address: jeff.washam@duke.edu.
[Ti] Título:Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial).
[So] Source:Am J Cardiol;120(4):588-594, 2017 Aug 15.
[Is] ISSN:1879-1913
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF.
[Mh] Termos MeSH primário: Fibrilação Atrial/tratamento farmacológico
Bloqueadores dos Canais de Cálcio/administração & dosagem
Rivaroxabana/administração & dosagem
Acidente Vascular Cerebral/prevenção & controle
Varfarina/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Idoso
Anticoagulantes/administração & dosagem
Fibrilação Atrial/complicações
Diltiazem/administração & dosagem
Relação Dose-Resposta a Droga
Método Duplo-Cego
Quimioterapia Combinada
Inibidores do Fator Xa/administração & dosagem
Feminino
Seres Humanos
Masculino
Fatores de Risco
Acidente Vascular Cerebral/etiologia
Resultado do Tratamento
Verapamil/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Calcium Channel Blockers); 0 (Factor Xa Inhibitors); 5Q7ZVV76EI (Warfarin); 9NDF7JZ4M3 (Rivaroxaban); CJ0O37KU29 (Verapamil); EE92BBP03H (Diltiazem)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE


  9 / 16301 MEDLINE  
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[PMID]:28603132
[Au] Autor:Alam F; Saqib QN; Shah AJ
[Ad] Endereço:Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
[Ti] Título:Airways and vascular smooth muscles relaxant activities of Gaultheria trichophylla.
[So] Source:Pak J Pharm Sci;30(1):199-203, 2017 Jan.
[Is] ISSN:1011-601X
[Cp] País de publicação:Pakistan
[La] Idioma:eng
[Ab] Resumo:The aim of this experimental work was to explore the potential pharmacological activities of Gaultheria trichophylla Royle in hyperactive respiratory and vascular conditions. Gaultheria trichophylla was extracted with solvents, phytochemical detection tests were performed, and rabbit trachea and aorta strips were used to evaluate its effects on airways and vascular smooth muscles. Qualitative phytochemical tests showed the presence of flavonoids, alkaloids, anthraquinones, saponins, terpenoids, and condensed tannins. The methanol extract caused inhibition (EC values of 3.12 mg/mL) of carbachol (1 µM) and partial relaxation of K (80 mM) caused contractions in tracheal strips. The chloroform extract was comparatively more potent against carbachol than K+ induced contraction with EC values of 0.64 and 2.26 mg/mL, respectively. However, the n-hexane extract showed more potency against K than cabachol induced contractions, as in case with verapamil, with EC values of 0.61 and 6.58 mg/mL, respectively. In isolated prepared trachea, the extracts displaced the carbachol concentration response curves and maximum response was suppressed. In rabbit aorta preparations, methanol and n-hexane extracts partially relaxed phenylephrine (1 µM) and K induced vasoconstrictions. However, the chloroform extract inhibited phenylephrine induced contractions and exhibited a vasoconstrictor effect at lower concentrations and a relaxant effect at higher concentrations against K precontractions. The data indicates that, in addition to others, the extracts of G .trichophylla possess verapamil like Ca channel blocking components which explain the possible role of this plant in respiratory and vascular conditions.
[Mh] Termos MeSH primário: Broncoconstrição/efeitos dos fármacos
Broncodilatadores/farmacologia
Bloqueadores dos Canais de Cálcio/farmacologia
Gaultheria/química
Músculo Liso Vascular/efeitos dos fármacos
Extratos Vegetais/farmacologia
Traqueia/efeitos dos fármacos
Vasodilatação/efeitos dos fármacos
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Animais
Aorta/efeitos dos fármacos
Aorta/metabolismo
Broncodilatadores/isolamento & purificação
Bloqueadores dos Canais de Cálcio/isolamento & purificação
Canais de Cálcio/efeitos dos fármacos
Canais de Cálcio/metabolismo
Clorofórmio/química
Relação Dose-Resposta a Droga
Feminino
Hexanos/química
Técnicas In Vitro
Masculino
Metanol/química
Músculo Liso Vascular/metabolismo
Compostos Fitoquímicos/isolamento & purificação
Compostos Fitoquímicos/farmacologia
Fitoterapia
Extratos Vegetais/isolamento & purificação
Plantas Medicinais
Coelhos
Solventes/química
Traqueia/metabolismo
Vasodilatadores/isolamento & purificação
Verapamil/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bronchodilator Agents); 0 (Calcium Channel Blockers); 0 (Calcium Channels); 0 (Hexanes); 0 (Phytochemicals); 0 (Plant Extracts); 0 (Solvents); 0 (Vasodilator Agents); 2DDG612ED8 (n-hexane); 7V31YC746X (Chloroform); CJ0O37KU29 (Verapamil); Y4S76JWI15 (Methanol)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE


  10 / 16301 MEDLINE  
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Texto completo
[PMID]:28533092
[Au] Autor:Loo TW; Clarke DM
[Ad] Endereço:Department of Medicine and Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
[Ti] Título:Thiol-reactive drug substrates of human P-glycoprotein label the same sites to activate ATPase activity in membranes or dodecyl maltoside detergent micelles.
[So] Source:Biochem Biophys Res Commun;488(4):573-577, 2017 Jul 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:P-glycoprotein (P-gp, ABCB1) is an ABC drug pump that is clinically important because it is involved in multidrug resistance. Many studies have used purified P-gp in detergent (n-dodecyl-ß-D-maltoside; DM) micelles to map the locations of the drug-binding sites. A potential problem is that DM could be a substrate and affect binding of drugs to P-gp. To test whether DM was a substrate of P-gp, we used an assay involving drug-rescue of the immature 150 kDa misprocessed P-gp mutant (L1260A) to show that DM is not substrate. By contrast, the detergents Triton X-100 or NP-35 were substrates because they rescued the L1260A P-gp mutant such that the major product was the mature 170 kDa protein. Cross-linking of mutant A80C/R741C in membranes can only be inhibited by the P-gp substrate tariquidar. We show that cross-linking A80C/R741C mutant was also inhibited by tariquidar in the presence of excess DM. This result suggests that the presence of DM did not affect the tariquidar-binding site. Similarly, the presence of DM did not alter the locations of other drug-binding sites since the thiol reactive forms of the substrates verapamil or rhodamine labeled the same sites in transmembrane segments 5 (I306C for verapamil) and 6 (F343C for rhodamine) whether P-gp was in native membranes or in detergent micelles. These results suggest that the presence of DM does not alter the locations of the P-gp drug-binding sites and that the detergent purified protein is suitable for mapping their locations using biochemical or structural assays.
[Mh] Termos MeSH primário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química
Adenosina Trifosfatases/metabolismo
Detergentes/química
Glucosídeos/química
Micelas
Quinolinas/farmacologia
Rodaminas/farmacologia
Verapamil/farmacologia
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética
Sítios de Ligação/efeitos dos fármacos
Membrana Celular/efeitos dos fármacos
Membrana Celular/enzimologia
Ativação Enzimática/efeitos dos fármacos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Detergents); 0 (Glucosides); 0 (Micelles); 0 (Quinolines); 0 (Rhodamines); 69227-93-6 (dodecyl maltoside); CJ0O37KU29 (Verapamil); EC 3.6.1.- (Adenosine Triphosphatases); J58862DTVD (tariquidar)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170524
[St] Status:MEDLINE



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