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2.
Anal Bioanal Chem ; 411(30): 8023-8032, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31776643

RESUMO

Within drug development and pre-clinical trials, a common, significant and poorly understood event is the development of drug-induced lipidosis in tissues and cells. In this manuscript, we describe a mass spectrometry imaging strategy, involving repeated analysis of tissue sections by DESI MS, in positive and negative polarities, using MS and MS/MS modes. We present results of the detected distributions of the administered drug, drug metabolites, lipid molecules and a putative marker of lipidosis, di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP). A range of strategies have previously been reported for detection, isolation and identification of this compound, which is an isomer of di-docosahexaenoic (22:6 n-3) phosphatidylglycerol (di-22:6 PG), a commonly found lipid that acts as a surfactant in lung tissues. We show that MS imaging using MS/MS can be used to differentiate these compounds of identical mass, based upon the different distributions of abundant fragment ions. Registration of images of these fragments, and detected drugs and metabolites, is presented as a new method for studying drug-induced lipidosis in tissues. Graphical abstract.


Assuntos
Biomarcadores/metabolismo , Lipidoses/induzido quimicamente , Pulmão/diagnóstico por imagem , Espectrometria de Massas/métodos , Amiodarona/efeitos adversos , Animais , Antiarrítmicos/efeitos adversos , Masculino , Ratos Wistar , Roedores
3.
Eur J Endocrinol ; 181(5): 519-524, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31536966

RESUMO

Objectives: Amiodarone-induced thyrotoxicosis (AIT) affects up to 3% of treated patients. Type 2 AIT (AIT2) is a destructive thyroiditis and is usually treated with medium-high oral doses of prednisone. As AIT may worsen the underlying heart disease, a rapid control of thyroid function is desirable. We aimed to determine whether a combined intravenous methylprednisolone (IVMP) pulses therapy associated to prednisone in the interpulse period can represent an efficient and safe alternative to urgent total thyroidectomy in patients with AIT2 not responsive to prednisone alone. Design and methods: Patients presenting with a severe AIT2 studied in a tertiary referral Center from August 2018 to April 2019. We included four patients requiring a rapid improvement of thyroid function for their underlying cardiac disorders. The baseline doses of oral prednisone (range: 5-12.5 mg/day) and IVMP (range: 250-500 twice a week) were determined according to the severity of the thyrotoxicosis and were titrated based on clinical response. Results: Combined treatment was effective in all patients in the prompt restoration of euthyroidism and no major adverse events were reported during the follow-up. In all cases, FT4 and FT3 levels normalized at 3-5 weeks of treatment. A permanent hypothyroidism was observed in one patient, 3 months after the discontinuation of treatment. Conclusions: We report for the first time that the combined intravenous and oral steroid therapy is effective in patients with AIT2. The treatment is well tolerated and leads to a rapid improvement of thyroid function, avoiding urgent total thyroidectomy and favoring a quick functional recovery and rehabilitation of cardiac patients.


Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Tireotoxicose/induzido quimicamente , Tireotoxicose/tratamento farmacológico , Administração Intravenosa , Idoso , Humanos , Iodo/urina , Masculino , Pessoa de Meia-Idade , Tireoglobulina/sangue , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
4.
Medicine (Baltimore) ; 98(34): e16961, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441899

RESUMO

BACKGROUND: Owing to reports of recurrent cardiac events in some catecholaminergic polymorphic ventricular tachycardia (CPVT) patients using ß-blockers, safer alternatives are being investigated. Flecainide is an alternative adjunctive anti-arrhythmic agent known to provide incomplete protection to CPVT patients. METHODS: To investigate the efficacy and tolerability of flecainide, we searched 4 databases for retrospective cohort studies (RCs) and randomized controlled trials (RCTs) investigating the efficacy and safety of flecainide for CPVT patients. Data were extracted and analyzed (risk ratio [RR] or mean difference [MD]) using RevMan software. Seven RCs and 1 RCT (333 CPVT patients; 152 patients treated with flecainide) were identified. RESULTS: Flecainide monotherapy was superior to standard therapy in alleviating the risk of arrhythmic events (RR = 0.46, confidence interval [CI] = [0.38, 0.56], P < .00001) and exercise-induced arrhythmia scores (MD = -0.39, CI = [-0.74, -0.05], P = .03). Combination therapy of flecainide and ß-blockers was superior to ß-blocker monotherapy in reducing the risk of arrhythmic and symptomatic events (RR = 0.29, CI = [0.13, 0.69], P = .005; RR = 0.36, CI = [0.20, 0.62], P = .0003, respectively), peak heart rate (MD = -16.81, CI = [-28.21, -5.41], P = .004), and exercise-induced arrhythmia scores (MD = -1.87, CI = [-2.71, 1.04], P < .0001). Flecainide did not increase the risk of all side effects (RR = 0.76, CI = [0.42, 1.40], P = .38) compared to that with ß-blockers alone. No deaths were reported among patients treated with flecainide. CONCLUSIONS: Flecainide is an effective and safe anti-arrhythmic agent, and its use as a monotherapy might be a good alternative for CPVT patients with ß-blocker intolerance. Combination therapy was superior to ß-blocker monotherapy. More randomized clinical trials are required to explore the long-term efficacy and safety of flecainide in these patients.


Assuntos
Antiarrítmicos/administração & dosagem , Flecainida/administração & dosagem , Taquicardia Ventricular/tratamento farmacológico , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Antiarrítmicos/efeitos adversos , Feminino , Flecainida/efeitos adversos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
5.
Rev Med Liege ; 74(7-8): 382-387, 2019 Jul.
Artigo em Francês | MEDLINE | ID: mdl-31373450

RESUMO

Sotalol is a bêta-blocker and class 3 anti-arrhythmic. Ciprofloxacin is a fluoroquinolone antibiotic used against Gram - germs. Both drugs have a common adverse effect : they increase QT interval with a risk of torsade de pointe. The risk increases even more if other risk factors are present such as old age, female gender, renal failure, high blood pressure and ionic disturbances. Because a long QT interval is not associated with symptoms, only an electrocardiogram can establish the diagnosis. However, it's not rare that a torsade de pointe will reveal it. We report a clinical case of a long QT interval due to the association of sotalol and ciprofloxacin, which led to a torsade de pointe. Intravenous magnesium sulphate is the recommended treatment if haemodynamic parameters are good. If not, an external electric shock may be needed.


Assuntos
Ciprofloxacino , Interações de Medicamentos , Sotalol , Torsades de Pointes , Antiarrítmicos/efeitos adversos , Antibacterianos/efeitos adversos , Ciprofloxacino/efeitos adversos , Eletrocardiografia , Feminino , Humanos , Sotalol/efeitos adversos , Torsades de Pointes/induzido quimicamente
6.
Med Clin North Am ; 103(5): 821-834, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31378328

RESUMO

The narrow therapeutic window of antiarrhythmic drugs makes their use clinically challenging. A solid understanding of the mechanisms of arrhythmias and how antiarrhythmics affect these mechanisms is only a preliminary step in their appropriate selection. Clinical factors, side-effect profiles, and proarrhythmic risks are more important than the cellular mechanisms of actions in drug selection and monitoring. This article provides a simplified approach to understanding cellular mechanisms and provides a practical approach to the selection and use of this important class of medications.


Assuntos
Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Potenciais de Ação , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/fisiopatologia , Humanos , Ablação por Radiofrequência , Medição de Risco
7.
J Vet Intern Med ; 33(4): 1585-1592, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31222803

RESUMO

BACKGROUND: Typical atrioventricular accessory pathways (APs) are composed of myocardial cells. They provide electrical connections between atria and ventricles separate from the normal conduction system. Accessory pathways can participate in a macroreentrant circuit resulting in orthodromic atrioventricular reciprocating tachycardia (OAVRT). HYPOTHESIS: Because of ultrastructural similarities of typical AP cells to ventricular myocardial cells, we hypothesized lidocaine would be effective in blocking AP conduction, thus terminating OAVRT. ANIMALS: Thirty-two consecutive client-owned dogs presenting with narrow complex tachyarrhythmias were confirmed to have OAVRT by electrophysiologic study (EPS). METHODS: Prospective, nonrandomized, single-arm study with lidocaine administered IV to dogs during OAVRT in 2 mg/kg boluses to a cumulative dose of 8 mg/kg or development of adverse effects. Electrocardiograms were monitored continuously. Subsequent EPS was performed to confirm OAVRT and the absence of other tachycardia mechanisms. RESULTS: Twenty-seven dogs experienced OAVRT cardioversion with lidocaine, before or at the time of adverse effects. Orthodromic atrioventricular reciprocating tachycardia in 5 dogs did not cardiovert before adverse effects, precluding additional dosing. Median total lidocaine dose for cardioversion was 2 mg/kg (interquartile range, 2-5.5 mg/kg). Dogs with right free wall APs had a significantly higher rate of cardioversion than did dogs with right posteroseptal APs. CONCLUSIONS AND CLINICAL IMPORTANCE: Lidocaine successfully cardioverted OAVRT in 84.4% of dogs in our study before adverse effects precluded additional dosing. In 5 dogs with dose limited by adverse effects, it is unknown whether cardioversion would have occurred at a higher cumulative dose.


Assuntos
Antiarrítmicos/farmacologia , Doenças do Cão/tratamento farmacológico , Lidocaína/farmacologia , Taquicardia Reciprocante/veterinária , Animais , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/veterinária , Cães , Feminino , Lidocaína/administração & dosagem , Lidocaína/efeitos adversos , Masculino , Estudos Prospectivos , Taquicardia Reciprocante/tratamento farmacológico
8.
Card Electrophysiol Clin ; 11(2): 375-390, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31084857

RESUMO

Abnormalities in cardiac rhythm are caused by disorders of impulse generation, conduction, or a combination of the 2, and may be life-threatening because of a reduction in cardiac output or myocardial oxygenation. Cardiac arrhythmias are commonly classified as tachycardias (supraventricular or ventricular) or bradycardias. Bradycardias are uncommon in the critically ill patient and often are caused by an underlying reversible disorder (eg, hyperkalemia, drug toxicity). Supraventricular and ventricular tachycardias are more often encountered in the critically ill patient and often have underlying treatable disorders that precipitate their development (eg, hypokalemia, hypomagnesemia, antiarrhythmic proarrhythmia, myocardial ischemia).


Assuntos
Arritmias Cardíacas , Intoxicação Alcoólica/complicações , Intoxicação Alcoólica/fisiopatologia , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Eletrocardiografia/classificação , Humanos , Hipoglicemia/complicações , Hipoglicemia/fisiopatologia , Fatores de Risco , Desequilíbrio Hidroeletrolítico/complicações , Desequilíbrio Hidroeletrolítico/fisiopatologia
11.
J Pediatr Endocrinol Metab ; 32(6): 631-633, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31085747

RESUMO

Background Amiodarone is an iodine-rich medication used to treat maternal and fetal arrhythmias, with known effects on thyroid hormone homeostasis. Case presentation We describe a case of transient neonatal hypothyroidism following a short prenatal course of maternal amiodarone therapy resulting in neonatal TSH elevations exceeding those reported in the available literature.


Assuntos
Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Doenças do Recém-Nascido/induzido quimicamente , Exposição Materna/efeitos adversos , Amiodarona/efeitos adversos , Feminino , Humanos , Hipotireoidismo/tratamento farmacológico , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Masculino , Prognóstico , Tiroxina/administração & dosagem
12.
Pain Manag ; 9(3): 233-237, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31140915

RESUMO

Background: The effects of adenosine in acute chronic pain are not clear. Literature supports both a pronociceptive/inflammatory role of the A2aR/A2bR and antihyperalgesia/allodynia with A1Rs/A3Rs. Adenosine could participate in the reactivation of chronic regional pain syndrome (CRPS) through inflammatory pathways and via A2Rs. Plastic changes in the brain CRPS-related overlap with those seen in systemic inflammation and persist even after symptoms of CRPS resolve. Aim: To illustrate the hypothesis that intravenous adenosine can reactivate dormant CRPS. Case report: An individual with successfully treated CRPS developed supraventricular tachycardia, he was treated with intravenous adenosine. Shortly after a second dose, he developed severe pain at a lower limb from relapsed CRPS. Treatment included lumbar sympathetic block, physical therapy and pharmacological agents. Conclusion: Intravenous adenosine can reactivate dormant CRPS. Its potential pronociceptive role in CRPS calls for further studies to better elucidate the underlying mechanisms.


Assuntos
Adenosina/efeitos adversos , Antiarrítmicos/efeitos adversos , Síndromes da Dor Regional Complexa/induzido quimicamente , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Síndromes da Dor Regional Complexa/tratamento farmacológico , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , Recidiva , Tapentadol/uso terapêutico
13.
Perspect Biol Med ; 62(1): 159-187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031303

RESUMO

Financial conflicts of interest can influence the design, conduct, and dissemination of medical trials. In attempting to resist "finance bias," critics and proponents of evidence-based medicine (EBM) and its precursors have largely focused on trying to improve evidence. These efforts have led to successes ranging from the 1962 Kefauver-Harris amendments to the US Federal Drug and Cosmetic Act of 1938 to recent recommendations that all trials be published. However, there are two problems with the strategy of trying to improve evidence as a buffer against finance bias. First, without political teeth, rules of evidence can be ignored with relative impunity. This is because, as sociologist Bent Flyvbjerg has pointed out, there is an asymmetry between power (of finance bias) and rationality (evidence), tending towards victory of power in an open confrontation. Second, by improving the way evidence is produced, the process has become more expensive, and thus more susceptible to influence by finance bias. Unless they address the powers behind finance bias directly, critics and proponents may be doomed to lose the war against finance bias, even if they win some battles. For EBM to be effective, the power of finance bias influencing the production and dissemination of evidence needs to be addressed as a priority. This is starting to happen, with initiatives such as the AllTrials campaign, which identifies and exposes unpublished trials. On the other hand, there are reasons to be less optimistic, as Cochrane, the most trusted source of evidence, has become more susceptible to stronger influences from industry.


Assuntos
Ensaios Clínicos como Assunto/economia , Medicina Baseada em Evidências/economia , Antiarrítmicos/efeitos adversos , Indústria Farmacêutica/economia , Humanos , Oseltamivir/efeitos adversos , Opinião Pública , Talidomida/efeitos adversos
15.
Pediatr Cardiol ; 40(5): 925-933, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30929065

RESUMO

OBJECTIVE: To determine the incidence of cardiovascular collapse in children receiving intravenous (IV) amiodarone and to identify the population at risk. DESIGN: A multicenter study of patients ≤ 18 years of age who received intravenous amiodarone between January 2005 and December 2015. A retrospective analysis was performed to identify patients who developed cardiovascular collapse (bradycardia and/or hypotension). RESULTS: Of 456 patients who received amiodarone, cardiovascular collapse occurred in 47 patients (10%). Patient risk factors for collapse in a univariate analysis were as follows: age < 3 months (p = 0.04), depressed cardiac function (p < 0.001), blood pressure below 3rd percentile (p < 0.001), high lactate at baseline (p < 0.001). Administration risk factors included bolus administration (p = 0.04), and bolus administration over ≤ 20 min (p = 0.04). In multivariate analysis, age, baseline blood pressure less than 3rd percentile, and rapid bolus delivery were independent risk factors for cardiovascular collapse in the study group. The mortality rate was significantly higher in the collapse group (28% versus 8%). CONCLUSION: We found an association between IV amiodarone administration and the risk of developing cardiovascular collapse in a significant subset of children. Extreme caution and careful hemodynamic monitoring is recommended when using IV amiodarone in this population, especially in young infants, hemodynamically compromised patients, and in patients receiving rapid amiodarone bolus administration.


Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Taquicardia Ectópica de Junção/induzido quimicamente , Taquicardia Ventricular/induzido quimicamente , Administração Intravenosa , Adolescente , Distribuição por Idade , Amiodarona/administração & dosagem , Amiodarona/farmacologia , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/mortalidade , Criança , Pré-Escolar , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipotensão/mortalidade , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Taquicardia Ectópica de Junção/mortalidade , Taquicardia Ventricular/mortalidade
16.
Am J Ther ; 26(4): e469-e480, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30946044

RESUMO

BACKGROUND: The optimal management for the prevention of recurrent ventricular tachycardia in patients with implantable cardioverter-defibrillators (ICDs) offers a challenge with no set guidelines regarding which therapy offers a best safety and efficacy profile. STUDY QUESTION: Which therapeutic strategy, among antiarrhythmic drugs and catheter ablation (CA), offers the most effective and safe approach in patients with ICDs? DATA SOURCES: Randomized controlled trials (RCTs) comparing the efficacy and safety of antiarrhythmic drugs or CA against a placebo group. RCTs were identified from a comprehensive search in PubMed, Embase, and Cochrane library. STUDY DESIGN: Our outcomes of interest were reductions in appropriate ICD shocks, inappropriate ICD shocks, and overall mortality. We used the event rates in both groups, and then using a frequentist approach employing a graph theory methodology, we constructed a network meta-analysis model. RESULTS: Fourteen RCTs with 3815 participants and 6 different interventions treatments were included in our network meta-analysis. The most effective treatment for the prevention of recurrent ventricular tachycardia after ICD is amiodarone followed by CA. Amiodarone is most effective in the reduction of appropriate and inappropriate ICD shocks with an odds ratio (OR) of 0.29 [95% confidence interval (CI), 0.11-0.74] and 0.15 (95% CI, 0.04-0.60), respectively. CA was effective in the reduction of appropriate ICD shocks (OR, 0.41; 95% CI, 0.20-0.87), whereas sotalol was effective in the reduction of inappropriate ICD shocks (OR, 0.46; 95% CI, 0.22-0.95). There was no significant reduction in the overall mortality from any therapy. There was a trend of increased mortality associated with amiodarone therapy (OR, 2.40; 95% CI, 0.92-6.26). CONCLUSIONS: Amiodarone remains the most efficacious therapy for the reduction of appropriate and inappropriate shocks in patients with ICD. No therapy resulted in mortality reduction, but amiodarone showed a trend toward increased mortality.


Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca/prevenção & controle , Prevenção Secundária/métodos , Taquicardia Ventricular/prevenção & controle , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/métodos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Humanos , Meta-Análise em Rede , Recidiva , Taquicardia Ventricular/complicações , Taquicardia Ventricular/mortalidade , Resultado do Tratamento
18.
Am J Cardiol ; 123(11): 1859-1862, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30922542

RESUMO

In patients with hypertrophic cardiomyopathy (HC), atrial fibrillation (AF) is common, often poorly tolerated and difficult to treat. Limited data exists regarding safety or efficacy of drug therapy for AF rhythm control in HC patients. We performed a retrospective analysis of patients with HC followed >6 months, treated with amiodarone, sotalol, dofetilide, or disopyramide for rhythm control of non-postoperative AF. The duration followed on each medication, reasons for discontinuing, and incidences of adverse events were recorded. Confounding factors including maximum ventricular septal thickness, age, left ventricular ejection fraction, and gender were assessed. Ninety-eight patients had 130 drug treatments (defined as a continuous time on 1 drug); 23 patients were treated with >1 medication. The probability of remaining on a single antiarrhythmic drug at 1 year was 62% and at 3 was 42%. Maximum ventricular septal thickness (hazard ratio 1.05, p = 0.03) and presence of resting outflow gradient (hazard ratio 2.50, p = 0.002) were associated with discontinuation of therapy. Patients treated with amiodarone or sotalol had no serious safety events suggesting that these medications may be reasonably safe. Amiodarone was least likely to be discontinued for inefficacy (8.5%), but likely to be discontinued for side effects (19%). The probability of remaining on sotalol was 74% at 1 year and 50.0% at 3 and it was only discontinued for side effects in 2%. A small number of patients were treated with disopyramide and dofetilide. In conclusion, our data suggest that amiodarone and sotalol are likely safe, and that sotalol may be particularly attractive given its low rate of side effects and low rate of discontinuation.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Cardiomiopatia Hipertrófica/complicações , Adulto , Idoso , Antiarrítmicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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