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1.
Expert Opin Drug Saf ; 19(1): 59-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31795777

RESUMO

Introduction: The objective of this study was to review the current status of drug-induced hypomagnesemia and its adverse effects on cardiovascular disease (CVD) and hypertension. Since magnesium is a potent vasodilator, which modulates vasomotor tone, peripheral blood flow, and hypertension, its deficiency could have significant cardiovascular and blood pressure (BP) effects.Areas covered: Studies have shown that several factors can contribute to magnesium deficiency including age, diet, disease, and certain drugs such as diuretics and proton-pump inhibitors (PPIs). For an updated perspective of drug-induced hypomagnesemia, a Medline search of the English language literature was conducted between 2010 and 2019 using the terms diuretics, proton-pump inhibitors, hypomagnesemia, cardiovascular disease, hypertension, and 35 pertinent papers were retrieved.Expert opinion: The data showed that magnesium deficiency is difficult to occur since it is plentiful in green leafy vegetables, cereals, nuts, and the drinking water. However, magnesium deficiency can occur with the use of diuretics for the treatment of hypertension and heart failure, or the use of PPIs for the treatment of gastroesophageal reflux disease. Therefore, magnesium deficiency should be detected and treated to prevent the aggravation of hypertension and the onset of CVD and serious cardiac arrhythmias including torsades de points.


Assuntos
Diuréticos/efeitos adversos , Deficiência de Magnésio/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Animais , Arritmias Cardíacas/induzido quimicamente , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Diuréticos/administração & dosagem , Humanos , Hipertensão/etiologia , Deficiência de Magnésio/complicações , Deficiência de Magnésio/diagnóstico , Inibidores da Bomba de Prótons/administração & dosagem
2.
Emerg Med J ; 36(10): 635-638, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31551305

RESUMO

A shortcut review was carried out to establish the incidence of arrhythmia after prescription of a fluoroquinolone antibiotic. 332 papers were found using the reported searches, of which 14 presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that the incidence of arrhythmia after prescription of a fluoroquinolone antibiotic is low (<3%), but estimates are imprecise.


Assuntos
Antibacterianos/efeitos adversos , Arritmias Cardíacas/epidemiologia , Infecções Bacterianas/tratamento farmacológico , Fluoroquinolonas/efeitos adversos , Adulto , Idoso , Arritmias Cardíacas/induzido quimicamente , Medicina de Emergência Baseada em Evidências/estatística & dados numéricos , Feminino , Humanos , Incidência
3.
Biomed Res Int ; 2019: 5269074, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317032

RESUMO

Adriamycin (Adr) is a cytotoxic anthracycline agent that is utilized to manage many types of tumors, but its clinical use is undesirable due to severe cardiotoxicity. The present study aimed to investigate the cardioprotective effect of Achillea fragrantissima (A. fragrantissima) against Adr-induced cardiotoxicity through the antioxidant and anti-inflammatory metabolic pathways. A single dose of Adr was injected in rats to induce cardiotoxicity. Rats are divided into 5 groups, control, A. fragrantissima 800, Adr, A. fragrantissima 400 + Adr, and A. fragrantissima 800 + Adr. 72 h after Adr administration, electrocardiographic (ECG) study was performed for all rats. Serum and hearts were then collected for biochemical and histopathological studies. A. fragrantissima ameliorated Adr-induced ST-segment elevation. It reduced Adr-induced elevation in lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), thiobarbituric acid reactive substance (TBARS), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and IL-6. It also protected against Adr-induced histopathological changes. Pretreatment with the extract increased heart tissue contents of glutathione peroxidase (GSH-PX) and reduced glutathione (GSH). Phytochemical analysis of the extract revealed that it is rich in phenolic and flavonoid active constituents. The results of this study revealed that A. fragrantissima extract ameliorates Adr-induced cardiotoxicity via an antioxidant and anti-inflammatory mechanisms. Further studies are warranted in order to recognize the precise active constituents of this natural extract which are responsible for the antioxidant and anti-inflammatory actions.


Assuntos
Achillea/química , Antioxidantes/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Cardiotoxicidade/tratamento farmacológico , Inflamação/tratamento farmacológico , Animais , Antioxidantes/química , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/patologia , Doxorrubicina/toxicidade , Glutationa , Coração/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos
4.
Clin Drug Investig ; 39(11): 1057-1066, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31325111

RESUMO

BACKGROUND AND OBJECTIVE: Risk-minimization measures (RMM), including label revisions were implemented in Europe for domperidone because of evidence of increased incidence of cardiac arrhythmia and sudden cardiac death. In accordance with the guideline on good pharmacovigilance practices, the European Medicines Agency Pharmacovigilance Risk Assessment Committee requested to conduct two studies to evaluate the effectiveness of these risk minimization measures. METHODS: In Belgium, France, Germany, Spain, and the UK, surveys were conducted to assess physicians' knowledge on the updated domperidone labeling information, and a drug-utilization study (DUS) was conducted using healthcare databases to assess domperidone prescribing patterns before and after the RMM. Four DUS sensitivity analyses (scenarios) evaluated uncertainty regarding domperidone treatment duration and indication. RESULTS: Among 1805 physicians participating in the survey, most were aware of the approved indication (nausea and vomiting, 80%), treatment duration (≤ 7 days, 70%), and maximum adult daily dose (10 mg three times daily, 84%). Only 33% selected the on-label indication from a list of indications for which they would prescribe domperidone. Awareness was low for medications contraindicated for concomitant use (26%) and contraindicated conditions (4%). In the DUS, under the optimistic scenario, a large improvement in labeling compliance from pre- to post-implementation period was observed in France (27% vs. 69%), while Belgium, Germany, Spain, and the UK showed small improvements (< 10%). In the other scenarios, there was little to no improvement in compliance with the revised labeling from the pre- to post-implementation periods in most countries. CONCLUSIONS: The survey findings documented that most physicians in all five countries were aware of the main aspects of the revised labeling. Results of the DUS were inconclusive regarding the effect of the RMM and compliance with the revised labeling for all countries except France.


Assuntos
Antieméticos/uso terapêutico , Domperidona/uso terapêutico , Rotulagem de Medicamentos/normas , Uso de Medicamentos/normas , Médicos/normas , Adulto , Antieméticos/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/prevenção & controle , Doença do Sistema de Condução Cardíaco/induzido quimicamente , Doença do Sistema de Condução Cardíaco/epidemiologia , Doença do Sistema de Condução Cardíaco/prevenção & controle , Estudos Transversais , Morte Súbita Cardíaca/etiologia , Domperidona/efeitos adversos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Náusea/epidemiologia , Estudos Retrospectivos , Medição de Risco , Inquéritos e Questionários , Vômito/tratamento farmacológico , Vômito/epidemiologia
6.
Anesth Analg ; 129(1): 63-72, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31210652

RESUMO

BACKGROUND: Bupivacaine cardiotoxicity mainly manifests as inhibition of the cardiac sodium channel, which slows conduction, particularly at the ventricular level. Experimental studies have demonstrated that intravenous lipid emulsions (ILEs) can reduce the cardiotoxic effects of bupivacaine, but the extent of these effects is controversial. Sodium bicarbonate (B) represents the standard treatment of toxicity related to sodium channel-blocking drugs. The aim of this study was to compare the effects of ILEs and B on the speed of recovery from bupivacaine-induced effects on the electrocardiographic parameters. METHODS: Bupivacaine 4 mg/kg was administered to 24 anesthetized pigs. Three minutes after delivering the bupivacaine bolus, the animals were given the following: ILE 1.5 mL/kg followed by 0.25 mL/kg/min (ILE group) and B 2 mEq/kg followed by 1 mEq/kg/h (B group). Controls (C group) were given saline solution, 50 mL followed by 1 mL/kg/h. Electrophysiological parameters were evaluated in sinus rhythm and during right ventricular pacing at several time intervals up to 30 minutes. Data were analyzed as the area under the curve (AUC) for the first 10 minutes (AUC10) or 30 minutes (AUC30). RESULTS: Bupivacaine increased the sinus cycle length, PR interval, and QRS duration. AUC30 of the sinus rhythm QRS duration after antidote administration was significantly different among the 3 groups (P = .003). B group experienced faster recovery from intoxication than the C group (AUC10, P = .003; AUC30, P = .003) or the ILE group (AUC10, P = .018). During the first minute, 50% of the B group (versus 0% of the ILE and C groups) had recovered >30% of QRS duration (P = .011). The trend toward faster recovery in the ILE group than in the C group did not reach significance (AUC10, P = .23; AUC30, P = .06). Effects on the paced QRS duration at a rate of 150 bpm were more intense but with similar results (B versus C group: AUC10, P = .009; AUC30, P = .009; B versus ILE: AUC10, P = .015; AUC30, P = .024). The recovery process of the paced QRS tended to be slower for all antidotes. CONCLUSIONS: In a closed-chest swine model, B was an effective treatment for electrophysiological alterations caused by established bupivacaine toxicity. At clinical doses, B ameliorated bupivacaine electrocardiographic toxicity faster than ILE. Use-dependent effects of bupivacaine are prominent and delay the effects of both antidotes, but B produces faster recovery than ILE.


Assuntos
Anestésicos Locais , Antídotos/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Bupivacaína , Emulsões Gordurosas Intravenosas/administração & dosagem , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Bicarbonato de Sódio/administração & dosagem , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Cardiotoxicidade , Modelos Animais de Doenças , Sistema de Condução Cardíaco/fisiopatologia , Recuperação de Função Fisiológica , Sus scrofa , Fatores de Tempo
7.
Afr Health Sci ; 19(1): 1647-1656, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31148994

RESUMO

Purpose: To determine the cumulative incidence of anthracycline induced cardiotoxicity (AIC), its predictors, and associated electrocardiographic and echocardiographic manifestations in adult cancer patients at Uganda Cancer Institute (UCI). Methods: We enrolled 160 participants between June 2013 and April 2014 and followed them up for a median of 146 days. Data on clinical, electrocardiographic and echocardiographic findings was obtained at baseline, and at completion of chemotherapy. The Pearson chi square test was used to identify the predictors associated with cardiotoxicity. Results: Of the 64 patients who were accessible for follow-up electrocardiography (ECG) and echocardiography (ECHO), fourteen participants developed cardiotoxicity hence a cumulative incidence rate of 21.9% with 95% CI 13.5%-33.43%. The predictors of AIC were female gender (p=0.025), LVEF (p=0.014) and LVFS (P=0.019). Anthracycline therapy was associated with shortening of the QRS duration (84.3±7.9 Vs 82.1±11.8 ms, p=0.005), prolongation of the QTc interval (411.9±30.7 Vs 447.2±39.4 ms, p=<0.001) and reduction in the LVEF (66.4±7.7 Vs 63.9±8.4%, p=0.026) and LVFS (36.9±6.2 Vs 35.1±6.6%, p=0.03). Conclusion: The cumulative incidence of AIC in this study cohort was high. Our findings emphasize the need for early monitoring for AIC.


Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Arritmias Cardíacas/diagnóstico , Cardiotoxicidade/diagnóstico , Ecocardiografia/métodos , Eletrocardiografia/métodos , Coração/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Cardiotoxicidade/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Prospectivos , Uganda/epidemiologia
8.
Environ Sci Pollut Res Int ; 26(18): 18200-18207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041709

RESUMO

Previous studies have shown that exposure to particulate matter (PM) increased variety of health problems, particularly cardiovascular diseases leading to premature mortality. The cardiac effects of particulate matter containing PM10 include increased infarct size, decreased heart function, and increased arrhythmias in experimental ischemia-reperfusion models in rats. The aim of this study was to evaluate the effects of particles with an aerodynamic diameter smaller than 10 µm (PM10) on isolated-rat heart and also to determine the efficacy of gallic acid (GA) as a preventive agent in oxidative damage. The healthy rats were divided into 8 equal groups which served as, control, GA, PM10 (0.5, 2.5, and 5 mg/kg), and PM10+GA groups. PM10 administered into the lungs via the trachea in two stages with 48-h interval. After all experiments, the electrocardiogram was recorded. Then, the hemodynamic parameters and ventricular arrhythmias in rat isolated-hearts were assessed using Langendorff apparatus and according to the Lambeth conventions. In addition, the inflammation and oxidative stress factors in cardiac tissues were evaluated in all groups. The obtained results showed that the exposure to PM caused to decrease in cardiac hemodynamic and electrocardiogram parameters. Also, in PM10 rat groups, the IL-6, TNF-α, and oxidative stress parameters were increased. Gallic acid preserved the value of cardiac parameters and inflammation in rat hearts. In summary, we added a novel therapeutic effect of gallic acid for cardiac dysfunction induced by particulate matter. These findings could be related to antioxidant and antiinflammation properties and the obtained results suggest that natural antioxidant like gallic acid could be a therapeutic agent in prevention and management of health issues in the polluted areas of the world.


Assuntos
Poluentes Atmosféricos/toxicidade , Ácido Gálico/farmacologia , Coração/efeitos dos fármacos , Material Particulado/toxicidade , Substâncias Protetoras/farmacologia , Animais , Arritmias Cardíacas/induzido quimicamente , Eletrocardiografia , Inflamação/induzido quimicamente , Inflamação/complicações , Masculino , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley
9.
Am J Emerg Med ; 37(8): 1600.e5-1600.e6, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31053371

RESUMO

INTRODUCTION: This report describes changes in blood and urine concentrations of glyphosate potassium over time and their correlations with clinical symptoms in a patient with acute glyphosate potassium poisoning. CASE REPORT: A 67-year-old man visited the emergency center after ingesting 250 mL of a glyphosate potassium-based herbicide 5 h before. He was alert but presented with nausea, vomiting, and bradyarrhythmia with atrial fibrillation (tall T waves). Laboratory findings revealed a serum potassium level of 6.52 mEq/L. After treatment with an injection of calcium gluconate, insulin with glucose, bicarbonate, and an enema with polystyrene sulfonate, the patient's serum potassium level normalized and the bradyarrhythmia converted to a normal sinus rhythm. During admission, the blood and urine concentration of glyphosate and urine aminomethylphosphonic acid (AMPA, a glyphosate metabolite) was measured at regular time intervals. The patient's glyphosate blood concentration on admission was 11.48 mg/L, and it had decreased rapidly by 16 h and maintained about 1mgl/L by 70 h after admission. Urine glyphosate and AMPA levels had also decreased rapidly by 6 h after admission. DISCUSSION: Glyphosate potassium poisoning causes hyperkalemia. Blood concentrations of glyphosate were decreased rapidly by 16 h after admission, and urine concentrations were also decreased by 6 h after admission.


Assuntos
Glicina/análogos & derivados , Herbicidas/sangue , Herbicidas/envenenamento , Hiperpotassemia/induzido quimicamente , Idoso , Arritmias Cardíacas/induzido quimicamente , Glicina/sangue , Glicina/envenenamento , Glicina/urina , Herbicidas/urina , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/tratamento farmacológico , Masculino , Náusea/induzido quimicamente , Potássio/sangue , Tentativa de Suicídio , Resultado do Tratamento , Vômito/induzido quimicamente
11.
Am J Case Rep ; 20: 758-763, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31138776

RESUMO

BACKGROUND Diphenhydramine is a commonly available over-the-counter antihistamine; however, there are few documented cases of treatment when ingested in toxic quantities, where it can cause a sodium channel blockade leading to wide-complex tachycardia, seizures, and death. Conventional treatment includes sodium bicarbonate infusion, but few cases have documented the addition of lipid emulsion therapy. CASE REPORT A 24-year-old African American female ingested 18 g (360 pills of 50 mg) over-the-counter diphenhydramine. She presented comatose, with hemodynamic instability and hypotension, intubated with pupil dilation to 6 to 7 mm, and initial electrocardiography findings showing a type 1 AV block with a QT/QTc of 360/402 ms which progressed into sinus tachycardia with widened QRS intervals of 134 ms and prolonged QT/QTc intervals of up to 638/759 ms. Treatment using sodium bicarbonate and magnesium was initiated; however, the intraventricular conduction delay persisted. Infusion of 20% intravenous lipid emulsion was administered; following this, the patient developed narrow complex QRS with sinus rhythm and shortened the QT/QTc interval to 448/516 ms. She recovered quickly and was transferred to inpatient psychiatric unit for further evaluation, and discharged 1 month later. CONCLUSIONS Lipid emulsion therapy has been utilized in treatment of various medication overdoses, but there are few documented cases in the treatment of diphenhydramine overdose. With the amount of diphenhydramine ingested by the patient in this case report, the use of combined conventional and lipid emulsion therapy was utilized in the stabilization and management of the patient, and should be considered in scenarios where conventional treatments have not improved the clinical outcome.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/terapia , Difenidramina/efeitos adversos , Overdose de Drogas/terapia , Emulsões Gordurosas Intravenosas/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Feminino , Humanos , Adulto Jovem
12.
Aust Vet J ; 97(6): 202-207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31136688

RESUMO

BACKGROUND: Intoxication following ingestion of the popular garden shrub 'Yesterday, today, tomorrow' (Brunfelsia sp.) is known to result in gastrointestinal and central nervous system clinical signs in dogs. CASE REPORT: A 2-year-old dog developed acute-onset vomiting, profuse diarrhoea and ptyalism after unsupervised access to an enclosed backyard that contained a Brunfelsia sp. shrub. During initial assessment the watery diarrhoea contained plant material and the dog appeared painful on abdominal palpation. Soon after admission, severe neurological abnormalities developed. Decontamination was undertaken by gastric and colonic lavage under general anaesthesia, but on recovery the patient had generalised seizures that were unresponsive to benzodiazepines. Following treatment with multiple antiepileptic medications and endotracheal intubation for loss of gag reflex, the patient developed respiratory failure requiring mechanical ventilation. Four days after initial presentation, the patient developed cardiac dysrhythmia leading to fatal cardiac arrest. Plant material recovered from the shrub and the patient's gastrointestinal tract were identified as Brunfelsia spp. CONCLUSION: This is the first report of hypoventilation, severe cardiac dysrhythmia and cardiac arrest associated with Brunfelsia sp. intoxication in a dog. Previous reports described clinical signs of gastrointestinal disease and mild cardiac dysrhythmia progressing to seizure activity and opisthotonus. Electrocardiography should form part of patient monitoring and mechanical ventilation considered for patients that develop respiratory failure, especially if massive ingestion is suspected.


Assuntos
Arritmias Cardíacas/veterinária , Doenças do Cão/etiologia , Parada Cardíaca/veterinária , Hipoventilação/veterinária , Intoxicação por Plantas/veterinária , Solanaceae/envenenamento , Animais , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/etiologia , Doenças do Cão/terapia , Cães , Feminino , Parada Cardíaca/etiologia , Hipoventilação/etiologia , Intoxicação por Plantas/terapia , Convulsões/veterinária
13.
Expert Rev Cardiovasc Ther ; 17(5): 345-351, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092056

RESUMO

Introduction: Magnesium is the third most common intracellular ion after potassium and calcium and is an important element in the functions of the body, since it participates in more than 300 enzyme systems. It also, plays a significant role in the transport of calcium and potassium across the cell membranes and protects against cardiac arrhythmias and is useful for their treatment due to hypomagnesemia induced from the proton pump inhibitors (PPIs). Areas covered: PPIs are used for the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD), but have been associated with hypomagnesemia with serious cardiac arrhythmias including torsades de pointes (TdP). To better understand the magnitude of this problem, a Medline search of the English language literature was conducted from 2010 to 2018 and 35 papers with pertinent information were selected. Expert commentary: The review of these papers suggests that PPIs cause hypomagnesemia, which could be associated with serious cardiac arrhythmias including TdP. However, its incidence is not very common considering the millions of people taking PPIs, but the FDA has advised the physicians to be watchful about this serious adverse effect of PPIs and check the magnesium levels before initiation of PPI treatment.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Magnésio/sangue , Inibidores da Bomba de Prótons/efeitos adversos , Cálcio/metabolismo , Humanos , Torsades de Pointes/induzido quimicamente
14.
Cardiovasc Toxicol ; 19(3): 191-197, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31030341

RESUMO

Synthetic cannabinoids (SCBs) are widely used recreational substances especially among adults. Although they have been considered as safe during the marketing process, our knowledge about their adverse effects has evolved since years. SCBs are associated with various cardiac events including acute myocardial infarction and sudden cardiac death. There is also growing evidence that SCBs are associated with cardiac arrhythmia development both in acute and chronic exposure. SCBs have been shown to be associated with both supraventricular and ventricular arrhythmias. However, the exact mechanism of the SCB related arrhythmia remains unknown. Understanding the exact association and possible mechanisms may help us to identify high risk patients at an early stage and to develop treatment modalities to prevent or reverse the arrhythmic effects of SCBs.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Canabinoides/efeitos adversos , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/fisiopatologia , Canabinoides/síntese química , Cardiotoxicidade , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Medição de Risco
15.
Biofactors ; 45(4): 495-506, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30937979

RESUMO

Environmental noise is a well-recognized health risk and part of the external exposome-the World Health Organization estimates that 1 million healthy life years are lost annually in Western Europe alone due to noise-related complications, including increased incidence of hypertension, heart failure, myocardial infarction, and stroke. Previous data suggest that noise works through two paired pathways in a proposed reaction model for noise exposure. As a nonspecific stressor, chronic low-level noise exposure can cause a disruption of sleep and communication leading to annoyance and subsequent sympathetic and endocrine stress responses leading to increased blood pressure, heart rate, stress hormone levels, and in particular more oxidative stress, being responsible for vascular dysfunction and representing changes of the internal exposome. Chronic stress generates cardiovascular risk factors on its own such as increased blood pressure, blood viscosity, blood glucose, and activation of blood coagulation. To this end, persistent chronic noise exposure increases cardiometabolic diseases, including arterial hypertension, coronary artery disease, arrhythmia, heart failure, diabetes mellitus type 2, and stroke. The present review discusses the mechanisms of the nonauditory noise-induced cardiovascular and metabolic consequences, focusing on mental stress signaling pathways, activation of the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system, the association of these activations with inflammation, and the subsequent onset of oxidative stress and vascular dysfunction. © 2019 BioFactors, 45 (4):495-506, 2019.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Doença da Artéria Coronariana/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Poluentes Ambientais/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Hipertensão/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Coagulação Sanguínea/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Viscosidade Sanguínea/efeitos dos fármacos , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia
16.
Cardiology ; 142(1): 4-6, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30852576

RESUMO

The uptake of sacubitril/valsartan since the PARADIGM study confirmed its beneficial effects on outcomes over enalapril in chronic systolic heart failure has inevitably led to potential interactions with co-prescribed medications in real-world patients. We report two cases that raise the possibility of an interaction between sacubitril/valsartan and the class Ib anti-arrhythmic mexiletine resulting in proarrhythmic effects. We discuss the pharmacokinetics of both agents and posit potential mechanistic interactions that suggest caution should be used and careful monitoring for (ventricular) arrhythmias applied in patients receiving sacubitril/valsartan and mexiletine.


Assuntos
Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Mexiletina/efeitos adversos , Tetrazóis/efeitos adversos , Idoso , Aminobutiratos/farmacocinética , Antagonistas de Receptores de Angiotensina/farmacocinética , Interações de Medicamentos , Feminino , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Masculino , Mexiletina/farmacocinética , Tetrazóis/farmacocinética
17.
Int J Clin Pharm ; 41(2): 387-390, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30864085

RESUMO

European Medicines Agency (EMA) issued a final decision on September 01, 2014 that restricts the maximum daily dose of domperidone to 30 mg and treatment duration to 7 days. This paper presents a critical review of the scientific basis of the literatures having a role in the decision of EMA on domperidone with an approach based on statistical and epidemiological perspective. Although observational studies used by EMA were published, the EMA didn't use an algorithm including "randomized clinical trials" according to evidence-based medicine when presenting their results. In conclusion, the results obtained from published studies are controversial, especially for the bias. From these publications, it cannot be concluded that domperidone exposure definitely increases the risk of "sudden cardiac death", "death associated with ventricular arrhythmia" or "ventricular arrhythmia" The most concrete result of these studies is that the risk is higher with metoclopramide exposure compared to domperidone exposure.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Morte Súbita Cardíaca , Domperidona/efeitos adversos , Medição de Risco/estatística & dados numéricos , Antieméticos/efeitos adversos , Humanos , Metoclopramida/efeitos adversos
18.
Medicine (Baltimore) ; 98(7): e14466, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762762

RESUMO

RATIONALE: Amiodarone, a broad-spectrum antiarrhythmic drug, is widely used for the clinical treatment of tachyarrhythmias because of its safety and efficacy. PATIENT CONCERNS: A 30-year-old woman presented with known paroxysmal atrial tachycardia and severe preeclampsia. Two days before admission, she had given birth to twins. She described her symptoms as a sudden palpitation at 10:20 accompanied by chest tightness and shortness of breath. DIAGNOSIS: Cardiac arrhythmia and acute left heart failure. INTERVENTIONS: Furosemide and sodium nitroprusside were administered to control the heart failure. At 16:20, 150 mg amiodarone (15 mg/min) was injected intravenously and continued at 1 mg/min. At 16:50, her electrocardiogram showed possible atrial tachycardia or atrial flutter with a ventricular rate of 206 beats/min. Administration of amiodarone was stopped at 17:23, and the medication was changed to esmolol. OUTCOMES: After 3 minutes, the palpitations stopped, the heart rate changed to a sinus rhythm, and the ventricular rate was 100 beats/min. Four days later, the patient underwent an electrophysiologic study and radiofrequency ablation. LESSONS: When amiodarone is used to treat atrial arrhythmia, the ventricular rate may accelerate, which can cause patients with borderline heart failure to develop acute heart failure or further deterioration of acute heart failure. For heart failure induced or mediated by atrial arrhythmias, short-term ß-blockers may be used to control the ventricular rate more quickly and effectively and to prevent the progression of heart failure.


Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Insuficiência Cardíaca/induzido quimicamente , Pré-Eclâmpsia/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/induzido quimicamente , Taquicardia Paroxística/tratamento farmacológico , Adulto , Feminino , Humanos , Gravidez
19.
Epileptic Disord ; 21(1): 48-54, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30782581

RESUMO

Several recent studies have reported potassium sodium-activated channel subfamily T member 1 (KCNT1) mutations in epilepsy patients on quinidine therapy. The efficacy and safety of quinidine for epilepsy treatment, however, remains controversial. We herein report the cases of four patients with KCNT1 mutations treated with quinidine. A reduction in seizures of more than 50% after quinidine treatment was observed in one patient with epilepsy of infancy with migrating focal seizures (EIMFS), whereas two patients with EIMFS and one with focal epilepsy did not achieve apparent seizure reduction. The relationship between quinidine dose and serum quinidine concentration was inconsistent, particularly at high quinidine doses. One patient with EIMFS developed ventricular tachycardia the day after an increase in quinidine dose from 114 to 126 mg/kg/day. The serum trough quinidine concentration and the corrected QT interval (QTc) before arrhythmia onset were 2.4 µg/ml and 420 ms, respectively, and peak serum quinidine concentration after arrhythmia onset was 9.4 µg/ml. Another patient with EIMFS showed aberrant intraventricular conduction with a quinidine dose of 74.5 mg/kg/day and a serum trough concentration of 3.2 µg/ml. Given that serum quinidine levels may elevate sharply after a dose increase, careful monitoring of electrocardiographs and serum concentrations is required. Based on a review of previous reports and our experience with this case, quinidine should be considered as a promising drug for patients with EIMFS harbouring KCNT1 mutations, however, its efficacy remains controversial due to the limited number of cases, and more information on optimal serum concentrations and appropriate titration methods is required.


Assuntos
Anticonvulsivantes/farmacologia , Arritmias Cardíacas/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Proteínas do Tecido Nervoso/genética , Canais de Potássio/genética , Quinidina/farmacologia , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/sangue , Criança , Pré-Escolar , Monitoramento de Medicamentos , Eletrocardiografia , Feminino , Humanos , Lactente , Masculino , Quinidina/administração & dosagem , Quinidina/efeitos adversos , Quinidina/sangue
20.
Mol Pharmacol ; 95(5): 537-550, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30770456

RESUMO

Current guidelines around preclinical screening for drug-induced arrhythmias require the measurement of the potency of block of voltage-gated potassium channel subtype 11.1 (Kv11.1) as a surrogate for risk. A shortcoming of this approach is that the measured IC50 of Kv11.1 block varies widely depending on the voltage protocol used in electrophysiological assays. In this study, we aimed to investigate the factors that contribute to these differences and to identify whether it is possible to make predictions about protocol-dependent block that might facilitate the comparison of potencies measured using different assays. Our data demonstrate that state preferential binding, together with drug-binding kinetics and trapping, is an important determinant of the protocol dependence of Kv11.1 block. We show for the first time that differences in IC50 measured between protocols occurs in a predictable way, such that machine-learning algorithms trained using a selection of simple voltage protocols can indeed predict protocol-dependent potency. Furthermore, we also show that the preference of a drug for binding to the open versus the inactivated state of Kv11.1 can also be inferred from differences in IC50 values measured between protocols. Our work therefore identifies how state preferential drug binding is a major determinant of the protocol dependence of IC50 values measured in preclinical Kv11.1 assays. It also provides a novel method for quantifying the state dependence of Kv11.1 drug binding that will facilitate the development of more complete models of drug binding to Kv11.1 and improve our understanding of proarrhythmic risk associated with compounds that block Kv11.1.


Assuntos
Bioensaio/métodos , Canal de Potássio ERG1/genética , Canal de Potássio ERG1/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Animais , Arritmias Cardíacas/induzido quimicamente , Células CHO , Linhagem Celular , Cricetulus , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Cinética , Bloqueadores dos Canais de Potássio/efeitos adversos
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