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1.
Respir Res ; 24(1): 1, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600234

RESUMO

BACKGROUND: Almitrine, a selective pulmonary vasoconstrictor in hypoxic area, improves oxygenation in mechanically ventilated patients with COVID-19 but its effects in spontaneously breathing patients with COVID-19 remain to be determined. METHODS: We prospectively studied the effects of almitrine (16 µg/kg/min over 30 min followed by continuous administration in responders only) in 62 patients (66% of male, 63 [53-69] years old) with COVID-19 treated with high-flow nasal cannula oxygen therapy (HFNO) and with persistent hypoxemia, defined as a PaO2/FiO2 ratio < 100 with FiO2 > 80% after a single awake prone positioning session. Patients with an increase in PaO2/FiO2 ratio > 20% were considered as responders. RESULTS: Overall, almitrine increased the PaO2/FiO2 ratio by 50% (p < 0.01), decreased the partial arterial pressure of carbon dioxide by 7% (p = 0.01) whereas the respiratory rate remained unchanged and 46 (74%) patients were responders. No patient experienced right ventricular dysfunction or acute cor pulmonale. The proportion of responders was similar regardless of the CT-Scan radiological pattern: 71% for the pattern with predominant ground-glass opacities and 76% for the pattern with predominant consolidations (p = 0.65). Responders had lower intubation rate (33 vs. 88%, p < 0.01), higher ventilator-free days at 28-day (28 [20-28 ] vs. 19 [2-24] days, p < 0.01) and shorter ICU length of stay (5 [3-10] vs.12 [7-30] days, p < 0.01) than non-responders. CONCLUSIONS: Almitrine could be an interesting therapy in spontaneously breathing patients with COVID-19 treated with HFNO and with persistent hypoxemia, given its effects on oxygenation without serious adverse effects regardless of the CT-Scan pattern, and potentially on intubation rate. These preliminary results need to be confirmed by further randomized studies.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Almitrina , COVID-19/terapia , Cânula , Síndrome do Desconforto Respiratório/terapia , Hipóxia/diagnóstico , Hipóxia/terapia , Oxigênio
2.
Crit Care Med ; 49(2): e191-e198, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33093279

RESUMO

OBJECTIVES: Treating acute respiratory failure in patients with coronavirus disease 2019 is challenging due to the lack of knowledge of the underlying pathophysiology. Hypoxemia may be explained in part by the loss of hypoxic pulmonary vasoconstriction. The present study assessed the effect of almitrine, a selective pulmonary vasoconstrictor, on arterial oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome. DESIGN: Single-center retrospective observational study. SETTING: ICU of Lille Teaching Hospital, France, from February 27, 2020, to April 14, 2020. PATIENTS: Patients with coronavirus disease 2019 pneumonia confirmed by positive reverse transcriptase-polymerase chain reaction for severe acute respiratory syndrome-coronavirus 2 and acute respiratory distress syndrome according to Berlin definition. Data focused on clinicobiological features, ventilator settings, therapeutics, outcomes, and almitrine-related adverse events. INTERVENTIONS: Almitrine was considered in patients with severe hypoxemia (Pao2/Fio2 ratio < 150 mm Hg) in addition to the recommended therapies, at an hourly IV delivery of 10 µg/kg/min. Comparative blood gases were done before starting almitrine trial and immediately after the end of the infusion. A positive response to almitrine was defined by an increase of Pao2/Fio2 ratio greater than or equal to 20% at the end of the infusion. MEASUREMENTS AND MAIN RESULTS: A total of 169 patients were enrolled. Thirty-two patients with acute respiratory distress syndrome received an almitrine infusion trial. In most cases, almitrine was infused in combination with inhaled nitric oxide (75%). Twenty-one patients (66%) were responders. The median Pao2/Fio2 ratio improvement was 39% (9-93%) and differs significantly between the responders and nonresponders (67% [39-131%] vs 6% [9-16%], respectively; p < 0.0001). The 28-day mortality rates were 47.6% and 63.6% (p = 0.39) for the responders and nonresponders, respectively. Hemodynamic parameters remained similar before and after the trial, not suggesting acute cor pulmonale. CONCLUSIONS: Almitrine infusion improved oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome without adverse effects. In a multistep clinical approach to manage severe hypoxemia in this population, almitrine could be an interesting therapeutic option to counteract the loss of hypoxic pulmonary vasoconstriction and redistribute blood flow away from shunting zones.


Assuntos
Almitrina/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Medicamentos para o Sistema Respiratório/uso terapêutico , COVID-19/complicações , Cuidados Críticos/métodos , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Troca Gasosa Pulmonar/efeitos dos fármacos , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos
5.
Brasília; S.N; 23 jul. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117682

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 21 artigos e 8 protocolos.


Assuntos
Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Esteroides/uso terapêutico , Avaliação da Tecnologia Biomédica , Vacina BCG/uso terapêutico , Heparina/uso terapêutico , Almitrina/uso terapêutico , Estudos de Coortes , Corticosteroides/uso terapêutico , Enoxaparina/uso terapêutico , Azitromicina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Darunavir/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ipilimumab/uso terapêutico , Fondaparinux/uso terapêutico , Nivolumabe/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticoagulantes/uso terapêutico
9.
Mol Genet Genomics ; 295(5): 1305-1314, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32583015

RESUMO

Identifying the cause-and-effect mechanism behind the drug-disease associations is a challenging task. Recent studies indicate that microRNAs (miRNAs) play critical roles in human diseases. Targeting specific miRNAs with drugs to treat diseases provides a new aspect for drug repositioning. Drug repositioning provides a way to identify new clinical applications for approved drugs. Drug discovery is expensive and complicated. Therefore, computational methods are necessary for predicting the potential associations between drugs and diseases based on the target miRNAs. Our approach bilateral-inductive matrix completion (BIMC) performed two rounds of inductive matrix completion algorithm, one on the drug-miRNA and another on the miRNA-disease, association matrices, and integrated the results for predicting the drug-disease relationships through the target miRNAs. The fundamental idea of inductive matrix completion (IMC) is to fill the unknown entries of the association matrices by utilizing existing associations and side information. In our study, the integrated similarities of drugs, miRNAs, and diseases were utilized as side information. Our method predicts drug-miRNA and miRNA-disease associations, as intermediate results. To estimate the performance of our approach, we conducted leave-one-out cross-validation (LOOCV) experiments. The method could achieve AUC scores of 0.792, 0.759, and 0.791 in drug-disease, drug-miRNA, and miRNA-diseases association predictions. The results and case studies indicate the prediction ability of our method, and it is superior to previous models with high robustness. The proposed approach predicts new drug-disease relationships and the causal miRNAs. The top predicted relationships are the promising candidates, and they are released for further biological tests.


Assuntos
Almitrina/farmacologia , Ácido Aminolevulínico/farmacologia , Biologia Computacional/métodos , MicroRNAs/metabolismo , Algoritmos , Reposicionamento de Medicamentos , Humanos , MicroRNAs/antagonistas & inibidores , Terapia de Alvo Molecular
10.
Brasília; s.n; 9 jun. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1100308

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 16 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Vitamina D/uso terapêutico , Imunoglobulinas/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Almitrina/uso terapêutico , Cloroquina/uso terapêutico , Corticosteroides/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Infliximab/uso terapêutico , Hidroxicloroquina/uso terapêutico
12.
Anesth Analg ; 129(2): e48-e51, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29337729

RESUMO

This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%-75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.


Assuntos
Almitrina/administração & dosagem , Oxigenação por Membrana Extracorpórea , Respiração/efeitos dos fármacos , Síndrome do Desconforto Respiratório/terapia , Medicamentos para o Sistema Respiratório/administração & dosagem , Adulto , Almitrina/efeitos adversos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/fisiopatologia , Medicamentos para o Sistema Respiratório/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
14.
J Cardiothorac Vasc Anesth ; 28(4): 919-24, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24016684

RESUMO

OBJECTIVE: Almitrine enhances hypoxic pulmonary vasoconstriction (HPV) and can improve hypoxemia related to one-lung ventilation (OLV). Studies using almitrine have been conducted without inhaled anesthetics because they could inhibit HPV, counteracting the effect of almitrine. This hypothesis, however, has not been confirmed. This study's aim was to evaluate whether almitrine could improve oxygenation when administered during OLV with sevoflurane anesthesia. DESIGN: A prospective, randomized, double-blind, placebo-controlled trial. SETTING: A tertiary care, university teaching hospital. PARTICIPANTS: Thirty adult patients undergoing open-chest thoracic surgery. INTERVENTIONS: Patients were assigned randomly to receive almitrine or placebo during OLV. Respiratory and hemodynamic variables were recorded continuously. Anesthesia was maintained with sevoflurane and remifentanil. Intraoperative techniques and medical teams were the same all over the study. MEASUREMENTS AND MAIN RESULTS: Respiratory and hemodynamic variables were measured during two-lung ventilation and during open-chest OLV. Two-way repeated-measures analysis of variance was used to compare the effects of almitrine and placebo. During OLV, PaO2 and shunt fraction worsened in all patients without significant differences between groups. At 30-minutes of OLV, PaO2 was 184±67 mmHg in the almitrine group and 145±56 mmHg in the placebo group, while shunt fraction were 31%±6% and 36%±13%, respectively. Mean pulmonary artery pressure was higher in the almitrine group (31±5 v 24±5 mmHg, p<0.001). CONCLUSIONS: During anesthesia with sevoflurane for open-chest OLV, almitrine failed to improve oxygenation and increased pulmonary artery pressure. The combination of sevoflurane and almitrine should, therefore, be avoided.


Assuntos
Almitrina/administração & dosagem , Anestesia Geral/métodos , Hemodinâmica/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Éteres Metílicos/administração & dosagem , Ventilação Monopulmonar/métodos , Consumo de Oxigênio/efeitos dos fármacos , Adolescente , Adulto , Idoso , Anestésicos Inalatórios/administração & dosagem , Gasometria , Método Duplo-Cego , Feminino , Humanos , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Estudos Prospectivos , Medicamentos para o Sistema Respiratório/administração & dosagem , Sevoflurano , Procedimentos Cirúrgicos Torácicos , Adulto Jovem
15.
Minerva Anestesiol ; 80(5): 517-25, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24299918

RESUMO

BACKGROUND: Lung ultrasound can be used at bedside to assess initial lung morphology in hypoxemic patients. We hypothesized that blood flow in consolidated lung and therefore effects of inhaled nitric oxide (iNO) and intravenous almitrine could be directly assessed using Doppler transesophageal echocardiography (TEE). METHODS: We conducted a prospective study including 13 ALI patients with consolidated left lower lobe (LLL). Regional arterial and venous flow signals within the consolidation were recorded with TEE using Doppler at baseline, after iNO (5 ppm), almitrine (4 µg/kg/min) and their combination. Pulmonary shunt (Qs/Qt) was measured using a Swan-Ganz catheter. Arterial and venous velocity time integral (VTI), peak velocity (Vmax) and mean velocity (Vmean) were measured. Patients were responders if PaO2 basal value increased by 20% after iNO or almitrine. RESULTS: In 7 NO responders, iNO decreased regional arterial VTI (8.1±1.9 vs. 6.7±1.6, P<0.05). In 8 almitrine responders, almitrine decreased regional arterial and venous VTI (from 6.7±2.0 to 4.5±2.3 cm and from 12.3±5.4 to 7.5±3.8 cm, respectively, P<0.05). For all patients, combination of iNO and almitrine decreased regional arterial and venous VTI (from 7.3±0.3 to 4.1±0.3 cm and from 12.6±0.7 to 6.7±0.8 cm, respectively, P<0.05). Arterial and venous Vmean and Vmax significantly decreased. Variations of arterial VTI and venous Vmean were correlated to variations of Qs/Qt (r=.71, P<.001 and r=.62, P<.01, respectively). CONCLUSION: Doppler of consolidated LLL allows assessment of regional pulmonary circulation in ICU settings. It detects changes in flow profiles resulting from the administration of NO and/or almitrine. Further applicability remains to be determined.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/fisiopatologia , Almitrina/uso terapêutico , Broncodilatadores/uso terapêutico , Óxido Nítrico/uso terapêutico , Circulação Pulmonar/efeitos dos fármacos , Medicamentos para o Sistema Respiratório/uso terapêutico , Lesão Pulmonar Aguda/diagnóstico por imagem , Administração por Inalação , Idoso , Almitrina/administração & dosagem , Broncodilatadores/administração & dosagem , Ecocardiografia Transesofagiana , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/administração & dosagem , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/fisiopatologia , Medicamentos para o Sistema Respiratório/administração & dosagem
17.
Cochrane Database Syst Rev ; (3): CD008068, 2011 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-21412915

RESUMO

BACKGROUND: Almitrine-raubasine combination (brand name Duxil), has been considered as an alternative treatment for dementia. OBJECTIVES: To determine the clinical efficacy and safety of Duxil in the treatment of patients with dementia. SEARCH STRATEGY: We searched the Cochrane Dementia and Cognitive Improvement Group Specialised Register (now known as ALOIS) (September 2009), the China Biological Medicine Database (CBM-disc 1979 to December 2009), the Chinese National Knowledge Infrastructure (www.cnki.net 1979 to December 2009), the Stroke Trials Registry at www.strokecentre.org/trials/index.aspx. We searched identified citations for additional trials, contacted the first author of identified trials for additional references and unpublished data. We also contacted the pharmaceutical company manufacturing Duxil (Servier Pharmaceutical Co Ltd) for additional unpublished data. SELECTION CRITERIA: Randomised controlled trials studying the efficacy and safety of Duxil for dementia were included, irrespective of blinding, publication status, or language. If the trial was cross-over in nature, only data from the first period were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Three trials involving a total of 206 participants were included, all patients with vascular dementia. All three included studies were assessed as being at high risk of bias. When analysing these trials together, there was significant beneficial effect of Duxil on the improvement of cognitive function measured by MMSE (WMD 2.04, 95% CI 1.43 to 2.66). No data on behaviour and death at the end of treatment and follow-up were available from the included trials. Two trials failed to show an improvement of functional performance measured by ADL (WMD -1.68; 95% CI -3.70 to 0.35). Of the three included trials, all described the adverse events in detail, there were no statistically significant differences across the trials (OR 4.84, 95%CI 0.55 to 42.67). Behaviour disturbance, quality of life, caregiver burden were not undertaken in the included trials. AUTHORS' CONCLUSIONS: Due to the low methodological quality of included trials, small number of trials and probable publication bias, this review did not provide sufficient evidence to support the routine use of Duxil for the treatment of patients with dementia. High-quality and large-scale randomised controlled trials are needed to confirm or refute these results.


Assuntos
Almitrina/uso terapêutico , Demência/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Ioimbina/uso terapêutico , Idoso , Combinação de Medicamentos , Humanos , Pessoa de Meia-Idade
18.
Drug Test Anal ; 1(6): 279-85, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20355207

RESUMO

A second-derivative spectrophotometric method ((2)D) and a derivative ratio spectrum zero crossing ((1)DD) method were used to determine raubasine and almitrine dismesylate in the presence of raubasine degradation product, using methanol as a solvent. Linear relationships were obtained in the range from 6-20 microg ml(-1) raubasine for the ((2)D) method and 12-24 microg ml(-1) almitrine dismesylate for the ((1)DD) method. By applying these methods it was possible to determine raubasine in its pure powdered form with an accuracy of 99.93 +/- 1.116 (n = 8) for the ((2)D) method and almitrine dismesylate with an accuracy of 99.98 +/- 0.602 (n = 7) for the ((1)DD) method.Laboratory-prepared mixtures containing different ratios of raubasine, almitrine dismesylate and raubasine degradation product were analysed and the proposed methods were valid up to 50% of raubasine degradation product. They were found to be suitable stability-indicating assay methods for raubasine and almitrine dismesylate in pharmaceutical formulations.


Assuntos
Almitrina/química , Alcaloides de Triptamina e Secologanina/química , Espectrofotometria/métodos , Combinação de Medicamentos , Estabilidade de Medicamentos , Metanol/química , Medicamentos para o Sistema Respiratório/química , Solventes/química , Vasodilatadores/química
19.
Ter Arkh ; 80(3): 28-33, 2008.
Artigo em Russo | MEDLINE | ID: mdl-18441680

RESUMO

AIM: To elucidate efficacy of a combination almitrine+thiotropium bromide (TB)+pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) of stage II-III complicated with chronic respiratory failure (CRF). MATERIAL AND METHODS: Efficacy of therapy was compared in two groups of patients: group 1 (n = 22) received TB in a dose 18 mcg/day for one year, almitrine in a dose 10 mg/kg/day for 3 months, an 8 week course of PR, group 2 (n = 17) received TB and PR. The treatment efficacy was determined by spirometric parameters of external respiration function, blood gases, dyspnea indices, exercise tolerance assessed by 6-min walk test, quality of life (St. George Hospital Respiratory Questionnaire). RESULTS: Group 1 patients walked longer distance after a course of PR and 1 year later (by 90.5 +/- 25.4 and 44.5 +/- 10.2 m, respectively, p < 0.05), had reduced desaturation measured by pulsoxym-etry at the end of 6-min walk test, increased PaO2 in baseline under 70 mmHg (by 5.8 +/- 1.2 mmHg, p > 0.05), decreased exacerbation rate per 1 patient a year (by 25%). CONCLUSION: Combination treatment with TB, almitrine and PR is indicated for COPD patients with moderate hypoxemia.


Assuntos
Almitrina/administração & dosagem , Broncodilatadores/administração & dosagem , Terapia por Exercício/métodos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/reabilitação , Derivados da Escopolamina/administração & dosagem , Administração por Inalação , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Brometo de Tiotrópio , Resultado do Tratamento
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