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1.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281272

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with a highly variable phenotypic expression, ranging from asymptomatic to drug refractory heart failure (HF) presentation. Pharmacological therapy is the first line of treatment, but options are currently limited to nonspecific medication like betablockers or calcium channel inhibitors, with frequent suboptimal results. While being the gold standard practice for the management of drug refractory HCM patients, septal reduction therapy (SRT) remains an invasive procedure with associated surgical risks and it requires the expertise of the operating centre, thus limiting its accessibility. It is therefore with high interest that researchers look for pharmacological alternatives that could provide higher rates of success. With new data gathering these past years as well as the development of a new drug class showing promising results, this review provides an up-to-date focused synthesis of existing medical treatment options and future directions for HCM pharmacological treatment.


Assuntos
Cardiomiopatia Hipertrófica/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardiomiopatia Hipertrófica/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Humanos , Miosinas/antagonistas & inibidores , Bloqueadores dos Canais de Sódio/uso terapêutico , Espironolactona/uso terapêutico , Vasodilatadores/uso terapêutico
2.
J Clin Neurosci ; 89: 305-310, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34119285

RESUMO

INTRODUCTION: The efficacy of cilostazol administration to treat subarachnoid hemorrhage remains controversial. We conduct a systematic review and meta-analysis to explore the influence of cilostazol administration on treatment efficacy for subarachnoid hemorrhage. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2020 for randomized controlled trials (RCTs) assessing the effect of cilostazol administration in patients with subarachnoid hemorrhage. This meta-analysis is performed using the random-effect model. RESULTS: Four RCTs involving 405 patients were included in the meta-analysis. Overall, compared with control group for subarachnoid hemorrhage, cilostazol intervention can significantly reduce symptomatic vasospasm (OR = 0.35; 95% CI = 0.21 to 0.60; P = 0.0001) and cerebral infarction (OR = 0.40; 95% CI = 0.22 to 0.73; P = 0.003), as well as improve no or mild angiographic vasospasm (OR = 2.01; 95% CI = 1.19 to 3.42; P = 0.01) and mRS score ≤ 2 (OR = 2.70; 95% CI = 1.09 to 6.71; P = 0.03), but revealed no obvious influence on severe angiographic vasospasm (OR = 0.53; 95% CI = 0.27 to 1.02; P = 0.06). There were no increase in adverse events (OR = 1.17; 95% CI = 0.54 to 2.52; P = 0.69), hemorrhagic events (OR = 0.62; 95% CI = 0.06 to 6.27; P = 0.69) and cardiac events (OR = 2.14; 95% CI = 0.44 to 10.27; P = 0.34) after the cilostazol intervention than control intervention. CONCLUSIONS: Cilostazol treatment may be effective to treat subarachnoid hemorrhage in the terms of symptomatic vasospasm, cerebral infarction, no or mild angiographic vasospasm and mRS score ≤ 2.


Assuntos
Cilostazol/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Vasodilatadores/uso terapêutico , Cilostazol/administração & dosagem , Cilostazol/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Vasoconstrição , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos
4.
Medicine (Baltimore) ; 100(19): e25852, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106629

RESUMO

BACKGROUND: In recent years, the incidence rate of hypertensive nephropathy has been increasing quickly, which has been a major threat to people's health. Renin-angiotensin-aldosterone system blockers have certain curative effects. However, there are some patients having serious adverse reactions, and the benefit population is limited, so the treatment of hypertensive renal damage is necessary to have beneficial supplement. More and more clinical studies have shown that ginkgo leaf extract and dipyridamole injection (GDI) combined with antihypertensive drugs has achieved good results in the treatment of hypertensive renal damage. It is supposed to be a supplementary treatment in hypertensive nephropathy. OBJECTIVES: To systematically assess the efficacy and safety of GDI combined with antihypertensive drugs on hypertensive renal injury. METHODS: Seven databases including PubMed, Cochrane Library, Embase, Wanfang database, China biomedical literature service system (Sino Med), VIP Chinese Sci-tech journal database (VIP), and China national knowledge internet (CNKI) were retrieved to collect randomized controlled trials (RCTs) in the experimental group containing combined therapy of hypertensive nephropathy with GDI and antihypertensive drugs. The retrieval time was from the establishment of database to July 8, 2020. Two researchers independently selected literature, extracted data, and evaluated the risk of bias in the study. The methodological quality was evaluated with Cochrane handbook and meta-analysis was performed with Stata 14.0 software. RESULTS: Eight studies were included in this study which involved 556 patients. The meta-analyses indicated that, compared with using antihypertensive drugs alone, combined treatment of GDI with antihypertensive drugs can decrease 24-hour urinary total protein (weighted mean difference [WMD] -0.61, 95% confidence interval [CI]: -0.82, -0.39; k = 6, P ≤ .001), blood urea nitrogen (WMD -1.27, 95% CI: -2.45, -0.10; k = 6, P = .033, serum creatinine (WMD -29.50, 95% CI: -56.44, -2.56; number of estimates [k] = 6, P = .032). CONCLUSIONS: Our meta-analyses showed that GDI combined with antihypertensive drugs can improve the renal function of hypertensive patients with renal injury.


Assuntos
Anti-Hipertensivos/uso terapêutico , Dipiridamol/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão Renal/tratamento farmacológico , Nefrite/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vasodilatadores/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Dipiridamol/administração & dosagem , Dipiridamol/efeitos adversos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Testes Hematológicos , Humanos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Urinálise , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos
5.
Eur J Pediatr ; 180(8): 2379-2387, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091748

RESUMO

Persistent pulmonary hypertension of the neonate (PPHN) refractory to inhaled nitric oxide still represents a frequent clinical challenge with negative outcomes in neonatal critical care. Several pulmonary vasodilators have become available thanks to improved understanding of pulmonary hypertension pathobiology. These drugs are commonly used in adults and there are numerous case series and small studies describing their potential usefulness in neonates, as well. New vasodilators act on different pathways, some of them can have additive effects and all have different pharmacology features. This information has never been summarized so far and no comprehensive pathobiology-driven algorithm is available to guide the treatment of refractory PPHN.Conclusion: We offer a rational clinical algorithm to guide the treatment of refractory PPHN based on expert advice and the more recent pathobiology and pharmacology knowledge. What is Known: • Refractory PPHN occurs in 30-40% of iNO-treated neonates and represents a significant clinical problem. Several pulmonary vasodilators have become available thanks to a better understanding of pulmonary hypertension pathobiology. What is New: • Available vasodilators have different pharmacology, mechanisms of action and may provide additive effect. We provide a rational clinical algorithm to guide the treatment of refractory PPHN based on expert advice and the more recent pathobiology and pharmacology knowledge.


Assuntos
Hipertensão Pulmonar , Síndrome da Persistência do Padrão de Circulação Fetal , Administração por Inalação , Algoritmos , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Recém-Nascido , Óxido Nítrico/uso terapêutico , Síndrome da Persistência do Padrão de Circulação Fetal/tratamento farmacológico , Vasodilatadores/uso terapêutico
6.
Prog Urol ; 31(8-9): 495-502, 2021.
Artigo em Francês | MEDLINE | ID: mdl-33941462

RESUMO

OBJECTIVE: To assist urologists in the management of andrological and sexual medicine pathologies during the COVID-19 crisis. MATERIAL AND METHOD: Use of the formalized consensus method. RESULTS: The medical and surgical management of patients in andrology and sexual medicine must be adapted. Consultations should, as far as possible, be carried out by tele-consultation. For operative procedures, the delay between the operative decision and the date of (re)scheduling of the procedure will depend on: (1) the level of criticality of the clinical situation; (2) the type of intervention; (3) the functional and psychological repercussions, including quality of life while waiting for the procedure; (4) the notion of losing the chance of having an optimal outcome; (5) the risk of potential complications from delaying a procedure for too long; and (6) taking into account the patient's risk factors for severe forms of COVID-19. The protection of urologists from COVID-19 should be considered. Each urologist must make the best decision for the patient, taking into account the acceptable time frame and quality of life impact before surgical management, the COVID risk parameters, the technical and anesthetic feasibility and the structural possibility of the health care institution to ensure a specific dedicated pathway during the COVID-19 health crisis. CONCLUSION: The management of andrological and sexual medicine pathologies must be adapted to the COVID-19 crisis context. Some patients may require surgery, including in emergency. These recommendations are transitional and will end with the COVID-19 crisis.


Assuntos
Induração Peniana/diagnóstico , Induração Peniana/terapia , COVID-19 , Colagenases/uso terapêutico , Terapia Combinada , Disfunção Erétil/tratamento farmacológico , Humanos , Injeções , Masculino , Pandemias , Implante Peniano , Inibidores da Fosfodiesterase 5/uso terapêutico , Tração , Procedimentos Cirúrgicos Urológicos Masculinos , Vácuo , Vasodilatadores/uso terapêutico , Verapamil/uso terapêutico
7.
PLoS One ; 16(5): e0251048, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34033655

RESUMO

BACKGROUND: COVID-19 is a multisystemic disorder that frequently causes acute kidney injury (AKI). However, the precise clinical and biochemical variables associated with AKI progression in patients with severe COVID-19 remain unclear. METHODS: We performed a retrospective study on 278 hospitalized patients who were admitted to the ward and intensive care unit (ICU) with COVID-19 between March 2020 and June 2020, at the University Hospital, São Paulo, Brazil. Patients aged ≥ 18 years with COVID-19 confirmed on RT-PCR were included. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We evaluated the incidence of AKI, several clinical variables, medicines used, and outcomes in two sub-groups: COVID-19 patients with AKI (Cov-AKI), and COVID-19 patients without AKI (non-AKI). Univariate and multivariate analyses were performed. RESULTS: First, an elevated incidence of AKI (71.2%) was identified, distributed across different stages of the KDIGO criteria. We further observed higher levels of creatinine, C-reactive protein (CRP), leukocytes, neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) in the Cov-AKI group than in the non-AKI group, at hospital admission. On univariate analysis, Cov-AKI was associated with older age (>62 years), hypertension, CRP, MCV, leucocytes, neutrophils, NLR, combined hydroxychloroquine and azithromycin treatment, use of mechanical ventilation, and vasoactive drugs. Multivariate analysis showed that hypertension and the use of vasoactive drugs were independently associated with a risk of higher AKI in COVID-19 patients. Finally, we preferentially found an altered erythrocyte and leukocyte cellular profile in the Cov-AKI group compared to the non-AKI group, at hospital discharge. CONCLUSIONS: In our study, the development of AKI in patients with severe COVID-19 was related to inflammatory blood markers and therapy with hydroxychloroquine/azithromycin, with vasopressor requirement and hypertension considered potential risk factors. Thus, attention to the protocol, hypertension, and some blood markers may help assist doctors with decision-making for the management of COVID-19 patients with AKI.


Assuntos
Injúria Renal Aguda/diagnóstico , COVID-19/patologia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Azitromicina/uso terapêutico , Brasil/epidemiologia , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/virologia , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Vasodilatadores/efeitos adversos , Vasodilatadores/uso terapêutico , Adulto Jovem
8.
An. sist. sanit. Navar ; 44(1): 113-117, ene.-abr. 2021. ilus
Artigo em Espanhol | IBECS | ID: ibc-201853

RESUMO

Se describe el caso de una lactante de 41 días de vida con un hemangioma cráneo-facio-cervical izquierdo y subglótico con repercusión respiratoria. Aunque los hemangiomas infantiles son tumores vasculares benignos que se presentan predominantemente en piel y de forma aislada, un 1-2% de los pacientes pueden tener lesiones en la vía aérea que ocasionalmente provocan cuadros respiratorios potencialmente mortales. Se decidió iniciar inmediatamente el tratamiento con propranolol, sin esperar a completar el diagnóstico de extensión y sindrómico, con buena respuesta clínica y desaparición de la sintomatología respiratoria en las siguientes doce horas. En los niños con hemangiomas que por su localización produzcan síntomas o alteración funcional importante, es imprescindible iniciar el tratamiento betabloqueante de forma precoz y en algunos casos, urgentemente


We describe the case of a 41-day-old infant with a left craniofacial cervical and subglottic hemangioma with respiratory symptoms. Although infantile hemangiomas are occasional benign vascular tumors that appear predominantly on the skin, 1-2% of patients may have airway lesions that can sometimes cause potentially life-threatening respiratory conditions. The decision was made to immediately commence treatment with propranolol, without waiting to complete the extension and syndromic diagnoses. There was a positive clinical response and respiratory symptoms dissipated in twelve hours. Early treatment with beta-blockers is essential for children with hemangiomas whose location causes symptoms or significant functional changes: in some cases it may be a matter of urgency


Assuntos
Humanos , Feminino , Lactente , Hemangioma/diagnóstico , Hemangioma/tratamento farmacológico , Neoplasias Laríngeas/tratamento farmacológico , Propranolol/uso terapêutico , Vasodilatadores/uso terapêutico , Obstrução das Vias Respiratórias , Emissões Otoacústicas Espontâneas , Endoscopia , Laringoscopia
9.
Biomed Pharmacother ; 139: 111552, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33839495

RESUMO

Hesperetin (HSP) is a natural flavonoid that offers useful curative effects for cardiovascular diseases, but its effect on myocardial ischemia and its precise mechanism remains unclear. The aim of this study is to explore the potential cardioprotective mechanism of HSP on myocardial ischemia caused by isoproterenol (ISO). Adult male Kunming mice were randomly divided into five groups: control, ISO, low-dose HSP (L-HSP, 25 mg/kg/d), high-dose HSP (H-HSP, 50 mg/kg/d), and verapamil (VER) group. Treatment groups of mice received HSP or VER for seven days, and the groups other than the control group were injected with ISO (100 mg/kg/d) subcutaneously for two consecutive days to establish a model of myocardial ischemia. Electrocardiogram and heart-histology changes were used to assess changes in myocardial architecture. The activities and the content of oxidative stress markers and inflammatory cytokines were determined and assayed using kits respectively. The expressions of proteins associated with apoptosis and the Sirt1/Nrf2 pathway were evaluated by Western blotting. The results demonstrate that VER, L-HSP and H-HSP significantly reduced the J-point displacement, heart rate, cardiac pathomorphological changes, and the levels of creatine kinase, lactated dehydrogenase, malonaldehyde, interleukin-6, and tumor necrosis factor-α in serum while promoting the activation of superoxide dismutase, catalase, glutathione in serum in the ISO-treated animals. Furthermore, L-HSP and H-HSP also reversed the ISO-induced apoptosis and the changes in the Sirt1/Nrf2 signaling pathway, as evident from the levels of proteins Bax, Bcl-2, caspase-3, Sirt1, Nrf2, NQO-1, and HO-1. In conclusion, HSP plays a protective role in ISO-induced myocardial ischemia by modulating oxidative stress, inflammation, and apoptosis via Sirt1/Nrf2 pathway activation.


Assuntos
Apoptose/efeitos dos fármacos , Hesperidina/farmacologia , Inflamação/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Relação Dose-Resposta a Droga , Eletrocardiografia/efeitos dos fármacos , Testes de Função Cardíaca , Masculino , Camundongos , Miocárdio/patologia , Vasodilatadores/uso terapêutico , Verapamil/uso terapêutico
10.
Expert Rev Cardiovasc Ther ; 19(5): 457-464, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33823738

RESUMO

Background:Ranolazine and trimetazidine are piperazine derivatives used in antianginal therapy. There are data on the use of these drugs in the treatment of neuropathic pain. In this study, it was aimed to evaluate the antinociceptive effects of ranolazine and trimetazidine.Methods: Sixty patients who were started on trimetazidine or ranolazine treatment were included in the study. The patients were evaluated with Seattle Angina Questionnaire (SAQ), Visual Analog Scale (VAS) and State-Trait Anxiety Inventory (STAI) on the first day of treatment and at the first month follow-up.Results: The SAQ scores of the patients given ranolazine were statistically significantly higher than the patients given trimetazidine. The most significant increase was observed in terms of treatment satisfaction (53.03 ± 8.11 vs. 72.88 ± 5.29, p < 0.001) and quality of life (49.79 ± 8.62 vs. 68.01 ± 0.65, p = 0.016). The decrease in VAS (p = 0.001) and the decrease in STAI scores (p = 0.002) after treatment in the ranolazine group were significantly higher than in the trimetazidine group.Conclusions: Ranolazine and trimetazidine are two effective drugs in antianginal treatment. While both drugs are effective on general systemic musculoskeletal pain and anxiety, the efficacy of ranolazine is more pronounced.


Assuntos
Analgésicos/uso terapêutico , Ranolazina/uso terapêutico , Trimetazidina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Vasodilatadores/uso terapêutico
11.
J Stroke Cerebrovasc Dis ; 30(7): 105822, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33895426

RESUMO

There have been limited cases linking SARS-CoV-2 infection with the development of reversible cerebral vasoconstriction syndrome (RCVS). We hereby report a rare case of RCVS in the setting of mild SARS-CoV-2 respiratory infection successfully treated with nimodipine and aspirin. SARS-CoV-2 attacks the ACE2-receptors, which are expressed in various body organs including the lungs, kidneys, and blood vessels. Vasoconstriction can result from down-regulation of the ACE2-receptors that can lead to sympathetic hypertonia of the cerebral blood vessel walls and/or over-activation of the renin-angiotensin axis.


Assuntos
Aspirina/uso terapêutico , COVID-19/complicações , Artérias Cerebrais/efeitos dos fármacos , Nimodipina/uso terapêutico , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Vasoespasmo Intracraniano/tratamento farmacológico , Adulto , COVID-19/diagnóstico , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/fisiopatologia , Feminino , Humanos , Síndrome , Resultado do Tratamento , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/fisiopatologia
12.
JAMA ; 325(15): 1513-1523, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33877274

RESUMO

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.


Assuntos
Anemia Falciforme/tratamento farmacológico , Dor/tratamento farmacológico , Poloxâmero/uso terapêutico , Vasodilatadores/uso terapêutico , Adolescente , Adulto , Analgésicos Opioides/uso terapêutico , Anemia Falciforme/complicações , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Dor/etiologia , Placebos/efeitos adversos , Placebos/uso terapêutico , Poloxâmero/efeitos adversos , Vasodilatadores/efeitos adversos , Adulto Jovem
13.
CMAJ Open ; 9(1): E252-E260, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33731426

RESUMO

BACKGROUND: Topical nitroglycerin (TNG) ointment has been used for almost 3 decades to treat neonatal peripheral tissue ischemia, but this product is now no longer being produced by its Canadian manufacturer. Our aim was to investigate the efficacy and safety of TNG products in newborns in neonatal intensive care units. METHODS: In this systematic review we searched Embase, CINAHL, MEDLINE, PubMed and Web of Science from inception to April 2020 for studies on the use of TNG products (TNG ointment, TNG spray, glyceryl trinitrate [GTN] patch) for the treatment of neonatal tissue ischemia. We did not apply language or study design limitations. Animal studies and duplicate records were excluded. Two reviewers screened and extracted data. The Tool for Evaluating the Methodological Quality of Case Reports and Case Series was used to assess the risk of bias of individual studies. RESULTS: We included 23 articles (20 case reports, 2 case series and 1 retrospective audit) describing the use of TNG ointment, TNG spray or GTN patch in the treatment of 39 tissue ischemia events in 37 newborns. Twenty-three (62.2%), 12 (32.4%), 1 (2.7%) and 1 (2.7%) infants received TNG ointment, GTN patch, both TNG ointment and GTN patch, and TNG spray, respectively. Nineteen (76.0%) and 7 (53.8%) injuries treated with TNG ointment and GTN patch showed complete recovery, respectively. Two (16.7%) infants treated with GTN patch experienced adverse events (i.e., methemoglobinemia) requiring treatment discontinuation. INTERPRETATION: TNG ointment presents a safe therapeutic modality for salvage therapy of neonatal tissue ischemia. Engagement of stakeholders is essential to address its recent commercial inaccessibility in Canada.


Assuntos
Isquemia/tratamento farmacológico , Nitroglicerina/uso terapêutico , Terapia de Salvação , Vasodilatadores/uso terapêutico , Administração Cutânea , Cateterismo Periférico/efeitos adversos , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Isquemia/etiologia , Nitroglicerina/provisão & distribuição , Pomadas/provisão & distribuição , Vasodilatadores/provisão & distribuição
14.
Mayo Clin Proc ; 96(3): 708-719, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33673922

RESUMO

Multiple system atrophy (MSA) is a neurodegenerative disorder primarily characterized by autonomic failure plus parkinsonism or cerebellar ataxia. The diagnosis may be challenging and is usually made at a tertiary care center. The long-term management issues are equally challenging and frequently require collaboration with the patient's local care providers. Whereas there is currently no cure for MSA, treatment focuses on the most problematic symptoms experienced by the patient. Autonomic symptoms may include severe orthostatic hypotension with syncope, urinary symptoms culminating in incontinence, constipation, anhidrosis, and erectile dysfunction. Motor symptoms include parkinsonism, cerebellar ataxia, and falls. Although certain motor symptoms may respond partially to medications, some of these medications may exacerbate autonomic problems. In this manuscript, we seek to bridge the gap between tertiary care providers and the patient's local care providers to provide multidisciplinary care to the MSA patient. Patients are often best served by management of their chronic and evolving complex problems with a team approach involving their primary care providers and subspecialists. Treatment guidelines typically list myriad therapeutic options without clarifying the most efficacious and simplest treatment strategies. Herein, we provide a guideline based on what has worked in our MSA clinic, a clinic designed to provide care throughout the disease course with subspecialty integration with the goal of empowering a partnership with the patient's home primary care providers.


Assuntos
Pesquisa Interdisciplinar , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/tratamento farmacológico , Guias de Prática Clínica como Assunto , Sistema Nervoso Autônomo/fisiopatologia , Progressão da Doença , Humanos , Índice de Gravidade de Doença , Vasodilatadores/uso terapêutico
15.
Am J Cardiol ; 147: 122-128, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667439

RESUMO

In patients with pulmonary artery hypertension (PAH) associated with atrial septal defect (ASD), closure of ASD may carry significant risks. We aimed to evaluate the safety and efficacy of transcatheter closure of ASD in selected patients with PAH using a fenestrated device followed by pulmonary vasodilator therapy. During the 14.8-year period, 51 ASD patients (10 males, age 46 ± 18 years) with a mean pulmonary artery pressure (PAP) ≥ 35 mm Hg and/or systolic PAP ≥ 60 mm Hg, underwent closure with a fenestrated device. Of them, mean Qp/Qs ratio, systolic PAP and mean PAP were 2.6 ± 1.2, 73 ± 14 mm Hg, and 44 ± 8 mm Hg, respectively. A total of 35 patients received pulmonary vasodilator therapy. The New York Heart Association (NYHA) functional class improved at 3 to 6 months follow-up. (p < 0.001) Nineteen patients underwent repeated catheterization. A comparison of the hemodynamic parameters between baseline and repeated catheterization revealed significant decreases in both systolic and mean PAP (77 ± 11 vs 55 ± 14 mm Hg, p < 0.0001 & 48 ± 7 vs 37 ± 8 mm Hg, p = 0.001, respectively), pulmonary vascular resistance (PVR) (5.1 ± 2.3 vs 4.0 ± 1.7 WU, p = 0.011) and PVRi (7.7 ± 3.3 vs 6.2 ± 2.4 WU*m2, p = 0.024). After a follow-up period of 84 ± 45 months, 6 mortalities were noted in which 2 were due to cardiac causes. In conclusion, catheter closure of ASD in patients with PAH using a fenestrated device followed by vasodilator therapy is safe and effective.


Assuntos
Cateterismo Cardíaco/instrumentação , Comunicação Interatrial/complicações , Comunicação Interatrial/cirurgia , Hipertensão Arterial Pulmonar/complicações , Dispositivo para Oclusão Septal , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Comunicação Interatrial/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Vasodilatadores/uso terapêutico , Adulto Jovem
16.
Eur J Pharmacol ; 900: 174038, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33737008

RESUMO

Subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm leads to vasospasm resulting in delayed cerebral ischemia. Therapeutic options are currently limited to hemodynamic optimization and nimodipine, which have marginal clinical efficacy. Nitric oxide (NO) modulates cerebral blood flow through activation of the cGMP-Protein Kinase G (PKG) pathway. Our hypothesis is that SAH results in downregulation of signaling components in the NO-PKG pathway which could explain why treatments for vasospasm targeting this pathway lack efficacy and that treatment with a cell permeant phosphopeptide mimetic of downstream effector prevents delayed vasospasm after SAH. Using a rat endovascular perforation model, reduced levels of NO-PKG pathway molecules were confirmed. Additionally, it was determined that expression and phosphorylation of a PKG substrate: Vasodilator-stimulated phosphoprotein (VASP) was downregulated. A family of cell permeant phosphomimetic of VASP (VP) was wasdesigned and shown to have vasorelaxing property that is synergistic with nimodipine in intact vascular tissuesex vivo. Hence, treatment targeting the downstream effector of the NO signaling pathway, VASP, may bypass receptors and signaling elements leading to vasorelaxation and that treatment with VP can be explored as a therapeutic strategy for SAH induced vasospasm and ameliorate neurological deficits.


Assuntos
Fosfopeptídeos/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Vasodilatadores/uso terapêutico , Vasoespasmo Intracraniano/tratamento farmacológico , Animais , Moléculas de Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/efeitos dos fármacos , Regulação para Baixo , Desenho de Fármacos , Sinergismo Farmacológico , Proteínas dos Microfilamentos/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Mimetismo Molecular , Nimodipina/farmacologia , Óxido Nítrico/metabolismo , Fosfopeptídeos/farmacocinética , Fosfoproteínas/efeitos dos fármacos , Fosfoproteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Hemorragia Subaracnóidea/metabolismo , Suínos , Vasodilatadores/farmacocinética
17.
Transfusion ; 61(2): 537-545, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33616967

RESUMO

BACKGROUND: Therapeutic plasma exchange (TPE) is often used to decrease serum triglyceride levels in hypertriglyceridemic pancreatitis (HTGP), although there is a lack of high-quality data directly attributing improved clinical outcomes to TPE. There are currently no large studies evaluating the treatment of HTGP without TPE. STUDY DESIGN AND METHODS: This study retrospectively analyzes clinical and laboratory outcomes of 115 encounters at Massachusetts General Hospital (MGH) wherein a HTGP patient was treated without TPE and compares these outcomes to those of HTGP patients in the literature treated with TPE. RESULTS: After management without TPE, the median reduction in serum triglycerides was 48% (IQR 29%-63%) on day one and 74% (IQR 60%-84%) on day two in 115 episodes of acute HTGP. The reductions were comparable to those reported in several large published case series after a course of TPE (65.8% to 81% reduction). In 25 episodes among 24 patients, treatment included admission to an intensive care unit. There was no significant difference in mortality or rates of local complication, mechanical ventilation, or use of vasoactive medication or renal replacement therapy between this ICU subset and published cohorts (all P > .05). CONCLUSIONS: HTGP patients who do not receive TPE do not experience inferior outcomes compared to patients in the literature treated with TPE. The added value of TPE in HTGP, if any exists, needs to be demonstrated in controlled trials.


Assuntos
Heparina/uso terapêutico , Hipertrigliceridemia/complicações , Insulina/uso terapêutico , Pancreatite/tratamento farmacológico , Troca Plasmática , Adulto , Pré-Escolar , Cuidados Críticos , Quimioterapia Combinada , Feminino , Humanos , Hipertrigliceridemia/sangue , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Pancreatite/etiologia , Utilização de Procedimentos e Técnicas , Terapia de Substituição Renal/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Triglicerídeos/sangue , Vasodilatadores/uso terapêutico
18.
Curr Hypertens Rep ; 23(2): 11, 2021 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-33611627

RESUMO

PURPOSE OF REVIEW: To review the key clinical and research questions regarding blood pressure (BP) reduction with vasodilators in the early management of hypertensive acute heart failure (H-AHF). RECENT FINDINGS: Despite numerous AHF vasodilator clinical trials in the past two decades, virtually none has studied a population where vasoconstriction is the predominant physiology, and with the agents and doses most commonly used in contemporary practice. AHF patients are remarkably heterogenous by vascular tone, and this heterogeneity is not always discernible through BP or clinical exam. Emerging data suggest that diastolic BP may be a stronger correlate of vascular tone in AHF than systolic BP, despite the latter historically serving as a key inclusion criterion for vasodilator clinical trials. Existing data are limited. A clinical trial that evaluates vasodilators in a manner of use consistent with contemporary practice, specifically within the subpopulation of patients with true H-AHF, is greatly needed. Until then, observational data supports long-standing vasodilators such as nitroglycerin, administered by IV bolus, and with goal reduction of SBP ≤25% as a safe first-line approach for patients with severe H-AHF presentations.


Assuntos
Insuficiência Cardíaca , Hipertensão , Hipotensão , Doença Aguda , Pressão Sanguínea , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Vasodilatadores/uso terapêutico
19.
Medicine (Baltimore) ; 100(7): e24414, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607775

RESUMO

BACKGROUND: Coronary heart disease is a serious cardiovascular disease. There is coronary atherosclerosis, resulting in lumen stenosis, blockage, and then the symptoms of insufficient blood supply and hypoxia in the myocardium. Chronic heart failure is a kind of syndrome with abnormal ventricular filling and ejection function, which is the final stage of the development of coronary heart disease. At present, the treatment plan of Western medicine can significantly reduce the hospitalization rate, but it is still not satisfactory for the prognosis and mortality of patients. Shenfu injection has advantages in the treatment of heart failure in patients with coronary heart disease, but there is a lack of standard clinical studies to verify it, so the purpose of this randomized controlled study is to evaluate the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. The patients will be randomly divided into a treatment group and the control group according to 1:1, in which the treatment group is treated with Shenfu injection combined with sodium nitroprusside, and the control group is treated with sodium nitroprusside alone. Both groups will be treated with standard treatment for 7 days and followed up for 30 days to pay attention to their efficacy and safety indexes. The observation indexes include TCM syndrome score, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction, brain natriuretic peptide, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, stroke volume, adverse reactions and so on. We will use SPSS 25.0 software for data analysis. DISCUSSION: This study will evaluate the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. The results of this experiment will provide a clinical basis for Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in coronary heart disease. TRIAL REGISTRATION: DOI 10.17605/OSF.IO/4KNG3.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Nitroprussiato/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
J Stroke Cerebrovasc Dis ; 30(3): 105581, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33388632

RESUMO

OBJECTIVES: Cilostazol has promise as an alternative to aspirin for secondary stroke prevention given its vasodilatory and anti-inflammatory properties in addition to platelet aggregation inhibition. We aimed to conduct a systematic review and meta-analysis to estimate the efficacy and safety of cilostazol compared to aspirin for stroke prevention in patients with previous stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: We searched PubMed and the Cochrane Central Register of Controlled Trials from 1996 to 2019. Randomized clinical trials that compared cilostazol to aspirin and reported the endpoints of ischemic stroke, intracranial hemorrhage and any bleeding were included. A random-effects estimate was computed based on the Mantel-Haenszel method. The pooled risk estimates with 95% confidence intervals were compared between cilostazol and aspirin. RESULTS: The search identified 5 randomized clinical trials comparing cilostazol vs. aspirin for secondary stroke prevention that collectively enrolled 7240 patients, all from Asian countries (3615 received cilostazol and 3625 received aspirin). Pooled results from the random-effects model showed that cilostazol was associated with significantly lower risk of recurrent ischemic stroke (RR 0.68; 95% CI, 0.54 to 0.87), intracranial hemorrhage (RR 0.42; 95% CI, 0.27 to 0.65) and any bleeding (RR 0.71; 95% CI, 0.55 to 0.91). CONCLUSIONS: This meta-analysis suggests that cilostazol is more effective than aspirin in preventing recurrent ischemic stroke with lower risk of intracranial hemorrhage and other bleeding. Since all trials to date are from Asian countries, confirmatory trials of cilostazol for secondary stroke prevention in other populations are needed.


Assuntos
Aspirina/uso terapêutico , Cilostazol/uso terapêutico , AVC Isquêmico/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Prevenção Secundária , Idoso , Anti-Inflamatórios/uso terapêutico , Aspirina/efeitos adversos , Cilostazol/efeitos adversos , Feminino , Humanos , Hemorragias Intracranianas/induzido quimicamente , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Vasodilatadores/uso terapêutico
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