Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.021
Filtrar
1.
Int Heart J ; 62(2): 427-431, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33731522

RESUMO

In this study, we present a case of a 22-year-old female with a family history of syncope, suffering from recurrent syncope since childhood. She had an obvious prolonged QTc interval of up to 651 ms, a bifid T wave pattern on electrocardiogram, and torsade de pointes, corresponding to a syncope episode. Additionally, her echocardiogram showed left ventricular non-compaction in the apex. After treatment with mexiletine, the QTc interval has been observed to shorten immediately, and the T wave morphology recovered. A similar effect was also observed in her mother and young sister. Administration of propranolol prolonged her QTc interval. Target sequencing of candidate genes revealed a missense mutation in the pore area of the hERG protein, coded by KCNH2. We diagnosed this as a case of type 2 long QT syndrome in which mexiletine could be effective in shortening the QTc interval.


Assuntos
Eletrocardiografia/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Síndrome do QT Longo/tratamento farmacológico , Mexiletina/farmacologia , Taquicardia Ventricular/complicações , Função Ventricular Esquerda/fisiologia , Antiarrítmicos/farmacologia , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Síndrome do QT Longo/etiologia , Síndrome do QT Longo/genética , Linhagem , Taquicardia Ventricular/fisiopatologia , Adulto Jovem
2.
Cardiovasc Ther ; 2021: 6683098, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688374

RESUMO

Background: Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. Methods: This study was a retrospective cohort study. One hundred seventy-two confirmed COVID-19 patients were included in this study, hospitalized at Babol University of Medical Sciences hospitals between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. Results: 83.1% of patients received hydroxychloroquine plus azithromycin vs. 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2 ± 15.4.The mean of posttreatment QTc interval in the monotherapy group was shorter than the mean of posttreatment QTc interval in the combination therapy group, but it had no significant statistical difference (462.5 ± 43.1 milliseconds vs. 464.3 ± 59.1 milliseconds; p = 0.488). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc ≥ 450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, fourteen patients did not continue therapy after four days. Conclusions: Hospitalized patients treated by hydroxychloroquine with or without azithromycin had no significant difference in prolongation of QT interval and outcome. The numbers of patients with prolonged QT intervals in this study emphasize careful cardiac monitoring during therapy, especially in high-risk patients.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Azitromicina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Adulto , Idoso , Azitromicina/administração & dosagem , Eletrocardiografia/efeitos dos fármacos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Cardiovasc Toxicol ; 21(4): 314-321, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33387252

RESUMO

Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment. We analyzed the (change in) QRS and QTc interval using the one-sample t-test. Of the 106 patients treated with chloroquine, 70 met the inclusion criteria. The average change in QRS interval was 6.0 ms (95% CI 3.3-8.7) and the average change in QTc interval was 32.6 ms (95% CI 24.9-40.2) corrected with the Bazett's formula and 38.1 ms (95% CI 30.4-45.9) corrected with the Fridericia's formula. In 19 of the 70 patients (27%), the QTc interval was above 500 ms after start of chloroquine treatment or the change in QTc interval was more than 60 ms. A heart rate above 90 bpm, renal dysfunction, and a QTc interval below 450 ms were risk factors for QTc interval prolongation. Chloroquine prolongs the QTc interval in a substantial number of patients, potentially causing rhythm disturbances. Since there is no substantial evidence for a beneficial effect of chloroquine, these results discourage its use in COVID-19 patients.


Assuntos
/tratamento farmacológico , Cloroquina/efeitos adversos , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Idoso , Estudos de Coortes , Eletrocardiografia/tendências , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Risco
4.
Ann Pharmacother ; 55(1): 123-126, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32536291

RESUMO

Acute care pharmacists play an integral role in identifying drug-drug interactions that may predispose patients to QT prolongation. Although most pharmacists are equipped with a baseline understanding of drug interactions and the risks of QTc prolongation, few understand the limitations of QTc calculation and interpretation. In this commentary, we put forth the notion that at times health care providers, including pharmacists, place an overemphasis on the QTc interval. In the context of using the QTc to guide pharmacotherapy decisions, unintended consequences may include a cascade of effects leading to delays in treatment, suboptimal medication selection, alert fatigue, and overutilization of resources.


Assuntos
Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/diagnóstico , Farmacêuticos/normas , Torsades de Pointes/prevenção & controle , Sistemas de Apoio a Decisões Clínicas , Interações Medicamentosas , Feminino , Humanos , Síndrome do QT Longo/induzido quimicamente
5.
Medwave ; 20(7): e8008, 2020 Aug 28.
Artigo em Espanhol | MEDLINE | ID: mdl-32877391

RESUMO

In December 2019, a new strain of the SARS-CoV-2 coronavirus was reported in Wuhan, China, which produced severe lung involvement and progressed to respiratory distress. To date, more than seventeen million confirmed cases and more than half a million died worldwide from COVID-19. Patients with cardiovascular disease are more susceptible to contracting this disease and presenting more complications. We did a literature search on the association of cardiovascular disease and COVID-19 in databases such as Scopus, PubMed/MEDLINE, and the Cochrane Library. The purpose of this review is to provide updated information for health professionals who care for patients with COVID-19 and cardiovascular disease, given that they have a high risk of complications and mortality. Treatment with angiotensin-converting enzyme inhibitors and receptor blockers is controversial, and there is no evidence not to use these medications in patients with COVID-19. Regarding treatment with hydroxychloroquine associated or not with azithromycin, there is evidence of a higher risk with its use than clinical benefit and decreased mortality. Likewise, patients with heart failure are an important risk group due to their condition per se. Patients with heart failure and COVID-19 are a diagnostic dilemma because the signs of acute heart failure could be masked. On the other hand, in patients with acute coronary syndrome, the initial therapeutic approach could change in the context of the pandemic, although only based on expert opinions. Nonetheless, many controversial issues will be the subject of future research.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/terapia , Algoritmos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Quimioterapia Combinada , Eletrocardiografia/efeitos dos fármacos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Hidroxicloroquina/efeitos adversos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Prognóstico , Sistema Renina-Angiotensina/fisiologia
6.
Open Heart ; 7(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32817375

RESUMO

The outbreak of COVID-19 in Wuhan, China and its declaration as a global pandemic by WHO has left the medical community under significant pressure to rapidly identify effective therapeutic and preventative strategies. Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were found to be efficacious against SARS-CoV-2 when investigated in preliminary in vitro experiments. Reports of success in early clinical studies were widely publicised by news outlets, politicians and on social media. These results led several countries to approve the use of these drugs for the treatment of patients with COVID-19. Despite having reasonable safety profiles in the treatment of malaria and certain autoimmune conditions, both drugs are known to have potential cardiotoxic side effects. There is a high incidence of myocardial injury and arrhythmia reported with COVID-19 infection, and as such this population may be more susceptible to this side-effect profile. Studies to date have now demonstrated that in patients with COVID-19, these drugs are associated with significant QTc prolongation, as well as reports of ventricular arrhythmias. Furthermore, subsequent studies have failed to demonstrate clinical benefit from either drug. Indeed, clinical trials have also been stopped early due to safety concerns over HCQ. There is an urgent need for credible solutions to the global pandemic, but we argue that in the absence of high-quality evidence, there needs to be greater caution over the routine use or authorisation of drugs for which efficacy and safety is unproven.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Pneumonia Viral/tratamento farmacológico , Medição de Risco , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Infecções por Coronavirus/epidemiologia , Saúde Global , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Incidência , Síndrome do QT Longo/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia
7.
Medwave ; 20(7)31-08-2020.
Artigo em Inglês, Espanhol | LILACS | ID: biblio-1122676

RESUMO

En diciembre de 2019 se reportó en Wuhan, China, la aparición de una nueva cepa de coronavirus SARS-CoV-2 que producía un compromiso pulmonar severo y progresaba a estrés respiratorio agudo. A la fecha, son más de diecisiete millones los casos confirmados y más de medio millón los fallecidos en todo el mundo a causa de COVID-19. Los estudios reportan que los pacientes con enfermedad cardiovascular son más susceptibles a contraer esta enfermedad y a presentar más complicaciones. El propósito de esta revisión es proporcionar información actualizada para los profesionales de la salud que atienden a pacientes con COVID-19 y que tienen además enfermedad cardiovascular y por ende un riesgo elevado de complicaciones y mortalidad. Realizamos una búsqueda de bibliografía científica acerca de la asociación de enfermedad cardiovascular y COVID-19 en diferentes bases de datos como Scopus, MEDLINE vía PubMed y Cochrane Library. El tratamiento con inhibidores de la enzima convertidora de angiotensina y bloqueadores del receptor de angiotensina ha sido motivo de discusión y no hay evidencia sólida para contraindicarlo en pacientes con COVID-19. Respecto al tratamiento con hidroxicloroquina asociado o no con azitromicina, hay evidencia que demuestra un mayor riesgo con su utilización, que beneficio clínico y/o disminución de mortalidad. En este contexto, los pacientes con insuficiencia cardíaca representan un grupo importante de riesgo por su condición per se y por el dilema diagnóstico generado al evaluar un paciente con COVID-19, en el que los signos de insuficiencia cardíaca aguda podrían enmascararse. Por otro lado, en los pacientes con síndrome coronario agudo, el enfoque terapéutico inicial podría cambiar en el contexto de la pandemia, aunque sólo sobre la base de opiniones de expertos. Quedan, sin embargo, muchos temas en controversia que serán motivo de investigaciones futuras.


In December 2019, a new strain of the SARS-CoV-2 coronavirus was reported in Wuhan, China, which produced severe lung involvement and progressed to respiratory distress. To date, more than seventeen million confirmed cases and more than half a million died worldwide from COVID-19. Patients with cardiovascular disease are more susceptible to contracting this disease and presenting more complications. We did a literature search on the association of cardiovascular disease and COVID-19 in databases such as Scopus, PubMed/MEDLINE, and the Cochrane Library. The purpose of this review is to provide updated information for health professionals who care for patients with COVID-19 and cardiovascular disease, given that they have a high risk of complications and mortality. Treatment with angiotensin-converting enzyme inhibitors and receptor blockers is controversial, and there is no evidence not to use these medications in patients with COVID-19. Regarding treatment with hydroxychloroquine associated or not with azithromycin, there is evidence of a higher risk with its use than clinical benefit and decreased mortality. Likewise, patients with heart failure are an important risk group due to their condition per se. Patients with heart failure and COVID-19 are a diagnostic dilemma because the signs of acute heart failure could be masked. On the other hand, in patients with acute coronary syndrome, the initial therapeutic approach could change in the context of the pandemic, although only based on expert opinions. Nonetheless, many controversial issues will be the subject of future research.


Assuntos
Humanos , Pneumonia Viral/complicações , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Betacoronavirus , Antivirais/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Prognóstico , Sistema Renina-Angiotensina/fisiologia , Algoritmos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Azitromicina/efeitos adversos , Peptidil Dipeptidase A/metabolismo , Quimioterapia Combinada , Eletrocardiografia/efeitos dos fármacos , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/terapia , Pandemias , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Hidroxicloroquina/efeitos adversos , Hipertensão/complicações , Hipertensão/tratamento farmacológico
10.
J Am Heart Assoc ; 9(12): e017144, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32463348

RESUMO

Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We analyzed a case series of COVID-19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs. We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID-19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448±29 ms and increased to 459±36 ms (P=0.005) with medications. Significant prolongation was observed only in men (18±43 ms versus -0.2±28 ms in women; P=0.02). A total of 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17±39 ms versus 0.5±40 ms; P=0.07). No patients manifested torsades de pointes. Conclusions Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.


Assuntos
Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Eletrocardiografia/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Pandemias , Pneumonia Viral/tratamento farmacológico , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Infecções por Coronavirus/complicações , Quimioterapia Combinada , Feminino , Humanos , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Prognóstico , Fatores de Risco
11.
Circ Arrhythm Electrophysiol ; 13(6): e008662, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32347743

RESUMO

BACKGROUND: The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the global coronavirus disease 2019 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine±azithromycin for the treatment of coronavirus disease 2019. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes and sudden cardiac death. METHODS: Hospitalized patients treated with chloroquine/hydroxychloroquine±azithromycin from March 1 to the 23 at 3 hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in Torsade de pointes. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation, and arrhythmogenic death. RESULTS: Two hundred one patients were treated for coronavirus disease 2019 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine, and 119 (59.2%) also received azithromycin. The primary outcome of torsade de pointes was not observed in the entire population. Baseline corrected QT interval intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) versus those treated with combination group (chloroquine/hydroxychloroquine and azithromycin; 440.6±24.9 versus 439.9±24.7 ms, P=0.834). The maximum corrected QT interval during treatment was significantly longer in the combination group versus the monotherapy group (470.4±45.0 ms versus 453.3±37.0 ms, P=0.004). Seven patients (3.5%) required discontinuation of these medications due to corrected QT interval prolongation. No arrhythmogenic deaths were reported. CONCLUSIONS: In the largest reported cohort of coronavirus disease 2019 patients to date treated with chloroquine/hydroxychloroquine±azithromycin, no instances of Torsade de pointes, or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Azitromicina/efeitos adversos , Betacoronavirus , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Eletrocardiografia/efeitos dos fármacos , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Arritmias Cardíacas/complicações , Arritmias Cardíacas/epidemiologia , Azitromicina/uso terapêutico , Cloroquina/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Quimioterapia Combinada , Seguimentos , Humanos , Hidroxicloroquina/uso terapêutico , Incidência , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
13.
Toxicol Appl Pharmacol ; 396: 114994, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32251685

RESUMO

Anticholinergic treatment is key for effective medical treatment of nerve agent exposure. Atropine is included at a 2 mg intramuscular dose in so-called autoinjectors designed for self- and buddy-aid. As patient cohorts are not available, predicting and evaluating the efficacy of medical countermeasures relies on animal models. The use of atropine as a muscarinic antagonist is based on efficacy achieved in studies in a variety of species. The dose of atropine administered varies considerably across these studies. This is a complicating factor in the prediction of efficacy in the human situation, largely because atropine dosing also influences therapeutic efficacy of oximes and anticonvulsants generally part of the treatment administered. To improve translation of efficacy of dosing regimens, including pharmacokinetics and physiology provide a promising approach. In the current study, pharmacokinetics and physiological parameters obtained using EEG and ECG were assessed in naïve rats and in sarin-exposed rats for two anticholinergic drugs, atropine and scopolamine. The aim was to find a predictive parameter for therapeutic efficacy. Scopolamine and atropine showed a similar bioavailability, but brain levels reached were much higher for scopolamine. Scopolamine exhibited a dose-dependent loss of beta power in naïve animals, whereas atropine did not show any such central effect. This effect was correlated with an enhanced anticonvulsant effect of scopolamine compared to atropine. These findings show that an approach including pharmacokinetics and physiology could contribute to improved dose scaling across species and assessing the therapeutic potential of similar anticholinergic and anticonvulsant drugs against nerve agent poisoning.


Assuntos
Atropina/uso terapêutico , Substâncias para a Guerra Química/envenenamento , Sarina/envenenamento , Escopolamina/uso terapêutico , Animais , Atropina/sangue , Atropina/farmacocinética , Atropina/farmacologia , Química Encefálica/efeitos dos fármacos , Antagonistas Colinérgicos , Eletrocardiografia/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Masculino , Camundongos , Ratos Wistar , Sarina/antagonistas & inibidores , Escopolamina/sangue , Escopolamina/farmacocinética , Escopolamina/farmacologia , Telemetria/métodos
14.
J Pharmacol Sci ; 143(1): 39-44, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151542

RESUMO

We investigated effects of isoflurane and sevoflurane on sparfloxacin-induced QT-interval prolongation in guinea pigs under the monitoring of electrocardiogram and monophasic action potential (MAP), which was compared with those of halothane or non-inhaled anesthetics ketamine/xylazine. Intravenous administration of sparfloxacin at 3 and 10 mg/kg prolonged the QT interval and MAP duration together with bradycardic action under 4 different anesthetic conditions. The order of extent of prolongation of corrected QT interval after the administration of sparfloxacin was isoflurane ≈ sevoflurane ≈ halothane >> ketamine/xylazine, whereas that of the MAP90 at a pacing cycle length of 300 ms was halothane ≥ isoflurane ≈ sevoflurane >> ketamine/xylazine. These results suggest that isoflurane and sevoflurane as well as halothane could sensitize the heart to sparfloxacin-induced QT interval prolongation in guinea pigs.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Isoflurano/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Sevoflurano/efeitos adversos , Potenciais de Ação/efeitos dos fármacos , Animais , Eletrocardiografia/efeitos dos fármacos , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/efeitos adversos , Cobaias , Halotano/efeitos adversos , Síndrome do QT Longo/fisiopatologia , Masculino
15.
Int Heart J ; 61(2): 338-346, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32173709

RESUMO

Sympathetic nerve activity has arrhythmogenic potential for ventricular arrhythmias associated with structural heart diseases. However, a sufficient amount of beta-blockers occasionally cannot be prescribed in some patients.An experimental study was performed to clarify the therapeutic effects of bepridil, a multiple ionic current inhibitor that does not affect beta-adrenergic receptors, for premature beats occurring during enhanced sympathetic nerve activity. Cardio-sympathetic nerve activity was augmented via stellate-ganglion (SG) stimulation in a canine model (n = 8), and the arrhythmogenic potential and anti-arrhythmic effects of bepridil (2 and 4 mg/kg intravenously) were assessed. For safe use, vagal-stimulation-induced slow HR and programmed electrical stimulation were applied to evaluate possible pro-arrhythmic effects of the drug. Heart rate variability (HRV) indexes were used to estimate cardio-autonomic nerve activity.Either side of the SG-stimulation increased BP and HR. Premature beats were induced in 10/16 SG-stimulations and it was more frequent in left (8/8) rather than right stimulation (2/8). Following 2 mg/kg drug administration, premature beats were still inducible in 8/16 stimulations (7/8 in left and 1/8 in right), but burden of the premature beats decreased from 87.1 ± 46.8 to 62.1 ± 42.6 beats. After 4 mg/kg administration, premature beats were inducible in one SG-stimulation. Proarrhythmic effects were not observed in all experiments. Steady-state HRV indexes and percent increases in SG-stimulation-induced BP-elevation and HR-acceleration were similar among the 3 periods (before, 2 and 4 mg/kg of the drug).Bepridil may be an option for ventricular arrhythmias developed during enhanced cardio-sympathetic nerve activity with minimal effect on autonomic nerve responses.


Assuntos
Antiarrítmicos/uso terapêutico , Bepridil/uso terapêutico , Complexos Ventriculares Prematuros/tratamento farmacológico , Animais , Antiarrítmicos/farmacologia , Bepridil/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Cães , Avaliação Pré-Clínica de Medicamentos , Estimulação Elétrica , Eletrocardiografia/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Gânglio Estrelado
16.
Toxicol Lett ; 324: 1-11, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035120

RESUMO

α-asarone is a natural phenylpropene found in several plants, which are widely used for flavoring foods and treating diseases. Previous studies have demonstrated that α-asarone has many pharmacological functions, while some reports indicated its toxicity. However, little is known about its cardiovascular effects. This study investigated developmental toxicity of α-asarone in zebrafish, especially the cardiotoxicity. Zebrafish embryos were exposed to different concentrations of α-asarone (1, 3, 5, 10, and 30 µM). Developmental toxicity assessments revealed that α-asarone did not markedly affect mortality and hatching rate. In contrast, there was a concentration-dependent increase in malformation rate of zebrafish treated with α-asarone. The most representative cardiac defects were increased heart malformation rate, pericardial edema areas, sinus venosus-bulbus arteriosus distance, and decreased heart rate. Notably, we found that α-asarone impaired the cardiac function of zebrafish by prolonging the mean QTc duration and causing T-wave abnormalities. The expressions of cardiac development-related key transcriptional regulators tbx5, nkx2.5, hand2, and gata5 were all changed under α-asarone exposure. Further investigation addressing the mechanism indicated that α-asarone triggered apoptosis mainly in the heart region of zebrafish. Moreover, the elevated expression of puma, cyto C, afap1, caspase 3, and caspase 9 in treated zebrafish suggested that mitochondrial apoptosis is likely to be the main reason for α-asarone induced cardiotoxicity. These findings revealed the cardiac developmental toxicity of α-asarone, expanding our knowledge about the toxic effect of α-asarone on living organisms.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anisóis/toxicidade , Apoptose/efeitos dos fármacos , Eletrocardiografia/efeitos dos fármacos , Cardiopatias Congênitas/induzido quimicamente , Mitocôndrias Cardíacas/efeitos dos fármacos , Animais , Cardiotoxicidade/etiologia , Embrião não Mamífero/efeitos dos fármacos , Mitocôndrias Cardíacas/patologia , Peixe-Zebra
17.
Anesthesiology ; 132(4): 636-651, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31972655

RESUMO

BACKGROUND: Remimazolam (CNS 7056) is a new ultra-short-acting benzodiazepine for intravenous sedation and anesthesia. Its pharmacokinetics and pharmacodynamics have been reported for bolus administration. This study aimed to investigate the pharmacokinetics and pharmacodynamics of remimazolam after continuous infusion. METHODS: Twenty healthy male volunteers (20 to 38 yr, 64 to 99 kg) received remimazolam as continuous intravenous infusion of 5 mg/min for 5 min, 3 mg/min for the next 15 min, and 1 mg/min for further 15 min. Pharmacokinetics of remimazolam and its metabolite were determined from arterial plasma concentrations. Sedation was assessed using the Modified Observer's Assessment of Alertness and Sedation scale. Pharmacokinetic-pharmacodynamic modeling was performed by population analysis. Hemodynamics and the electrocardiogram were also investigated. RESULTS: Pharmacokinetics was best described by a three-compartment model for remimazolam and a two-compartment model with transit compartment for the metabolite. Remimazolam showed a high clearance (1.15 ± 0.12 l/min, mean ± SD), a small steady-state volume of distribution (35.4 ± 4.2 l) and a short terminal half-life (70 ± 10 min). The simulated context-sensitive halftime after an infusion of 4 h was 6.8 ± 2.4 min. Loss of consciousness was observed 5 ± 1 min after start, and full alertness was regained 19 ± 7 min after stop of infusion. Pharmacodynamics of Modified Observer's Assessment of Alertness and Sedation score was best described by a sigmoid probability model with effect site compartment. The half-maximum effect site concentration for a Modified Observer's Assessment of Alertness and Sedation score less than or equal to 1 was 695 ± 239 ng/ml. The equilibration half-time between central and effect compartment was 2.7 ± 0.6 min. Mean arterial blood pressure decreased by 24 ± 6%, and heart rate increased by 28 ± 15%. Spontaneous breathing was maintained throughout the study. There was no significant prolongation of the QT interval of the electrocardiogram observed. CONCLUSIONS: Remimazolam was characterized by a pharmacokinetic-pharmacodynamic profile with fast onset, fast recovery, and moderate hemodynamic side effects.


Assuntos
Benzodiazepinas/administração & dosagem , Benzodiazepinas/sangue , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/sangue , Adolescente , Adulto , Estudos Cross-Over , Relação Dose-Resposta a Droga , Eletrocardiografia/efeitos dos fármacos , Eletrocardiografia/métodos , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Masculino , Estudos Prospectivos , Adulto Jovem
18.
Toxicol Lett ; 324: 86-94, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954867

RESUMO

Organophosphorus nerve agents (NA) inhibit acetylcholinesterase (AChE) which results in the over-stimulation of both the central and peripheral nervous systems, creating a toxic syndrome that can be lethal if left untreated (Cannard, 2006). It is standard practice to treat Sarin (GB) intoxication with an oxime, an antimuscarinic such as atropine and an anticonvulsant. Three common oximes are available: HI-6, Pralidoxime (2-PAM) and Obidoxime (Obi), all possess a nucleophile that can break the NA-AChE covalent bond. However, each oxime's efficacy profile against various agents is different (Thiermann and Worek, 2018). In an effort to broaden therapeutic efficacy against a range of possible NA's, consideration should be given to the use of two oximes in combination. Using a guinea pig model, the first arm of this study was to determine the pharmacokinetics (PK) of HI-6 DMS, 2-PAM chloride and Obi chloride (at autoinjector equivalent doses) following intramuscular (i.m.) co-administration along with atropine to replicate either a single isometrically scaled dose (referred to in this study as a single autoinjector equivalent) of 2-PAM (and equimolar doses of Obi and HI-6) or double doses (referred to in this study as two autoinjector equivalents). The second arm of the study evaluated the efficacy of Obi and 2-PAM individually at a single or double autoinjector dose and also in combination against GB exposure. Pharmacokinetic profiles of each oxime were evaluated for both arms of the study and no significant change in parameters were reported. Improved cholinesterase reactivation was observed in a dose dependent manner with combined therapy showing similar reactivation to individual oximes alone at a two autoinjector equivalent dose. Seizure activity was reduced when combined oxime therapy was administered. This improvement was also reflected in the Racine seizure index score assigned at the end of the experimental period. To the best of our knowledge, this study is the first to evaluate and compare the pharmacokinetics of three oximes and the combination of two oximes (2-PAM and Obi) administered in naïve animals or those exposed to GB. Combined oxime therapy (Obi and 2-PAM) resulted in improved seizure control, increased cholinesterase reactivation peripherally and centrally and improved behavioral signs (Racine score). This study provides evidence that combination of oximes is effective, does not result in adverse events and that the pharmacokinetics of each oxime are not affected when administered in combination.


Assuntos
Agentes Neurotóxicos/envenenamento , Oximas/farmacocinética , Oximas/uso terapêutico , Sarina/envenenamento , Acetilcolinesterase/metabolismo , Animais , Quimioterapia Combinada , Eletrocardiografia/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Cobaias , Masculino , Oximas/administração & dosagem
19.
Am J Cardiol ; 125(6): 894-900, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31980141

RESUMO

Randomized data suggest lenient rate control (resting heart rate <110 beats/min) is noninferior to strict rate control (resting heart rate <80 beats/min) in patients with atrial fibrillation (AF). However, the optimal rate control strategy in patients with AF and heart failure (HF) remains unknown. Accordingly, we performed an observational analysis using data from the Get With The Guidelines-HF Program linked with Medicare data from July 1, 2011, to September 30, 2014. Of 13,981 patients with AF and HF, 9,100 (65.0%) had strict rate control, 4,617 (33.0%) had lenient rate control, and 264 (1.9%) had poor rate control by resting heart rate on the day of discharge. After multivariable adjustment, compared with strict rate control, lenient rate control was associated with higher adjusted risks of death (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.11 to 1.33, p <0.001), all-cause readmission (HR 1.09, 95% CI 1.03 to 1.15, p <0.002), death or all-cause readmission (HR 1.11, 95% CI 1.05 to 1.18, p <0.001), but not cardiovascular readmission (HR1.08, 95% CI 1.00 to 1.16, p = 0.051) at 90 days. Associations were comparable in patients with poor rate control and with heart rate modeled as a continuous variable. The presence or absence of reduced ejection fraction did not impact the magnitude of most observed associations. In conclusion, in patients with HF and AF, 2 of 3 patients had a heart rate that met strict-control goals at discharge. Heart rates >80 beats/min were associated with adverse outcomes irrespective of left ventricular ejection fraction.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Eletrocardiografia/efeitos dos fármacos , Fidelidade a Diretrizes , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Adulto , Idoso , Fibrilação Atrial/mortalidade , Causas de Morte , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Risco , Análise de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...