Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning

In the present study, we aimed to compare the detoxifying effects of two fat emulsions containing either long-chain triglyceride or a mixture of medium-chain and long-chain triglycerides in the propafenone-poisoned rat model. Rats were randomly divided into 3 groups according to the fat emulsions used: long-chain triglyceride-based fat emulsion (LL) group; medium-chain and long-chain triglyceride-based fat emulsion (ML) group; normal saline (NS) group. Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was added to plasma (3.5 μg/mL) in vitro, mixed with three doses of LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of propafenone was measured. Rats treated with LL exhibited accelerated recovery, characterized by higher blood pressure and heart rate. Rats in both the LL and ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and 60 min). However, rats that received LL showed lower propafenone in myocardial tissue at the end of detoxification treatment. Rats in the ML group had the lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the in vitro experiments, propafenone decreased more dramatically in the LL group compared to the ML group. Long-chain triglyceride fat emulsion had a better effect on treating propafenone poisoning in rats.

Cost-Effectiveness of Rate- and Rhythm-Control Drugs for Treating Atrial Fibrillation in Korea

PURPOSE: Although the economic and mortality burden of atrial fibrillation (AF) is substantial, it remains unclear which treatment strategies for rate and rhythm control are most cost-effective. Consequently, economic factors can play an adjunctive role in guiding treatment selection. MATERIALS AND METHODS: We built a Markov chain Monte Carlo model using the Korean Health Insurance Review & Assessment Service database. Drugs for rate control and rhythm control in AF were analyzed. Cost-effective therapies were selected using a cost-effectiveness ratio, calculated by net cost and quality-adjusted life years (QALY). RESULTS: In the National Health Insurance Service data, 268149 patients with prevalent AF (age ≥18 years) were identified between January 1, 2013 and December 31, 2015. Among them, 212459 and 55690 patients were taking drugs for rate and rhythm control, respectively. Atenolol cost $714/QALY. Among the rate-control medications, the cost of propranolol was lowest at $487/QALY, while that of carvedilol was highest at $1363/QALY. Among the rhythm-control medications, the cost of pilsicainide was lowest at $638/QALY, while that of amiodarone was highest at $986/QALY. Flecainide and propafenone cost $834 and $830/QALY, respectively. The cost-effectiveness threshold of all drugs was lower than $30000/QALY. Compared with atenolol, the rate-control drugs propranolol, betaxolol, bevantolol, bisoprolol, diltiazem, and verapamil, as well as the rhythm-control drugs sotalol, pilsicainide, flecainide, propafenone, and dronedarone, showed better incremental cost-effectiveness ratios. CONCLUSION: Propranolol and pilsicainide appear to be cost-effective in patients with AF in Korea assuming that drug usage or compliance is the same.

Arritmias na sala de emergência e UTI. Taquicardias de QRS estreito: fundamentos para a abordagem / Arrythmias in the emergency room and ICU Narrow QRS rachycardias: bases for clinical approach

As taquicardias de QRS estreito apresentam origem supraventricular. O histórico clínico, exame físico e eletrocardiograma na sala de emergência constituem-se nas principais ferramentas para o tratamento do quadro. As taquicardias que apresentam instabilidade hemodinâmica devem ser, imediatamente, revertidas através de cardioversão elétrica sincronizada. Aquelas que se apresentam como estáveis hemodinamicamente podem, se regulares, ser tratadas através de manobras vagais ou através do uso de fármacos endovenosos. Se irregulares, podem caracterizar fibrilação e flutter atrial, sendo, então, avaliados a duração do episódio e o risco de tromboembolismo para determinar não apenas a necessidade de anticoagulação, mas também a estratégia para tratamento do quadro, seja através do controle da frequência cardíaca ou do controle do ritmo, este último podendo ser alcançado através do uso de fármacos (propafenona oral ou amiodarona endovenosa) ou da cardioversão elétrica sincronizada. Dessa forma, o papel do clínico na sala de emergência é fundamental para garantir a condução adequada dos episódios de taquicardia supraventricular, especialmente, na prevenção ou pronta intervenção em caso de deterioração hemodinâmica relacionada ao quadro

Narrow QRS tachycardias are supraventricular in origin. The clinical history, physical exam, and electrocardiogram in the emergency room are the main tools used to manage this condition. Tachycardias that present haemodynamic instability must be promptly reverted through synchronized electrical cardioversion. Those that present haemodynamic stability may be treated with vagal maneuvers or intravenous drugs. If irregular, they may take the form of atrial fibrillation or atrial flutter, and in this case, the duration of the episode and the thromboembolic risk are evaluated to determine not only the need for anticoagulation, but also the treatment strategy, whether through heart rate or rhythm control. The latter may be achieved through the use of drugs (oral propafenone or intravenous amiodarone) or synchronized electrical cardioversion. The role of the clinician in the emergency room is therefore fundamental in ensuring adequate conduct of episodes of supraventricular tachycardia, especially in prevention or prompt intervention in case of haemodynamic deterioration related to the condition

Inhibition of voltage-dependent K⁺ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone

In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent K⁺ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent IC₅₀ value of 5.04±1.05 µM and a Hill coefficient of 0.78±0.06. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of Na⁺ channel inhibition.

Supraventricular Tachycardia by Concealed Bypass Tract

Concealed bypass tract (CBT) results from incomplete development of the atrioventricular (AV) annulus. CBT conducts only in a retrograde direction, and therefore does not cause pre-excitation on standard electrocardiograms. The most common tachycardia associated with CBT is an orthodromic atrioventricular reentrant tachycardia (AVRT): a pathway involving anterograde circuitry through the AV node and His Purkinje system and retrograde conduction over the accessory pathway. Orthodromic AVRT accounts for approximately 90%-95% cases of AVRT. Most incidences of CBT occur at the left free wall. Vagal maneuvers and/or intravenous (IV) adenosine are recommended for first line acute management of AVRT. However, pharmacological therapy with IV diltiazem, verapamil, or beta blockers can also be effective for acute treatment for orthodromic AVRT in patients who do not show pre-excitation on their resting ECG during sinus rhythm. The first-line ongoing therapy for AVRT is catheter ablation of CBT; when catheter ablation is not indicated or preferred, oral beta blockers, diltiazem, verapamil, flecainide, propafenone, or amiodarone are recommended.

Abordagem das arritmias na Doença de Chagas Crônica / Approach of arrhythmias in chronic Chagas Disease

As arritmias na cardiopatia chagásica (CCH) são responsáveis por incapacitação física e morte em indivíduos adultos em faixa etária precoce e produtiva, decorrendo daí a necessidade de sua abordagem criteriosa e, às vezes, mais agressiva para se obter controle completo. As arritmias cardíacas mais encontradas na CCH são as bradiarritmias e as taquicardias. Entre as bradicardias estão as alterações sinoatriais e os bloqueios atrioventriculares, cujo tratamento padrão é o emprego de implante de marcapasso definitivo. Entre as taquiarritmias, encontram-se as supraventriculares ­ extrassístoles atriais, taquicardia atrial ectópica, "flutter" atrial e fibrilação atrial ­ que provocam morbidades como progressão para disfunção ventricular esquerda e fenômenos tromboembólicos, e as ventriculares, cujo desfecho pode ser a morte súbita instantânea. A abordagem deve ser, inicialmente, por meio de eletrocardiograma de 12 derivações, pela gravação ambulatorial (Holter), ecocardiograma, teste ergométrico, e por fim, o estudo eletrofisiológico e a ressonância nuclear magnética. O tratamento farmacológico pode ser conduzido com o uso dos fármacos existentes em nosso mercado, como amiodarona, propafenona e sotalol. O tratamento invasivo, pode consistir em ablação por cateter, embora com resultados ainda abaixo de índices confortadores, devido à possibilidade de recidivas. O uso de cardiodesfibrilador implantável é a última alternativa, que também tem suas limitações

Arrhythmias in Chagas cardiomyopathy (CCM) are responsible for physical disability and death in adults in early and productive age group, from which arises the need for a judicious and sometimes more aggressive approach to achieve the complete control. The arrhythmias most common in CCM are bradyarrhythmias and tachycardias. Among the bradycardias are the sinoatrial changes and atrioventricular blocks, whose standard treatment is the use of permanent pacemaker implantation. Among tachyarrhythmias are the supraventricular ones - atrial extrasystoles, ectopic atrial tachycardia, atrial flutter and atrial fibrillation - causing morbidity and progression of left ventricular dysfunction and thromboembolic events, and the ventricular ones, whose outcome can be the instantaneous sudden death. The approach should be initially through 12-lead electrocardiogram, by ambulatory ECG recording (Holter), echocardiogram, stress testing, and finally the electrophysiological study and magnetic resonance imaging. Pharmacological treatment can be conducted with the use of marketed drugs such as amiodarone, propafenone and sotalol. The invasive treatment may consist of catheter ablation, although the results are still below comforting rates due to the possibility of recurrence. The use of implantable cardioverter defibrillator is the last alternative, which also has its limitations

Bioequivalência de cloridrato de propafenona 300mg em comprimido revestido em administração pós-prandial em adultos saudáveis / Bioequivalence of propafenone hydrochloride 300mg film coated tablets in healthy adults

OBJETIVO: Avaliar a bioequivalência de duas formulações de cloridrato de propafenona 300mg em comprimido revestido.MÉTODOS: Estudo randomizado, cruzado, aberto, com dois tratamentos, duas sequências e quatro períodos com 60 participantes sadios de ambos os sexos. Os voluntários foram internados em quatro oportunidades durante 24 horas; em cada período, os sujeitos receberam a formulação teste ou a formulação referência, em regime pós-prandial. Foram coletadas 23 amostras de sangue após administração da droga para determinação plasmática da propafenona. Para quantificação da droga, foi utilizada técnica de cromatografia líquida acoplada à espectrometria de massas sequencial. RESULTADOS: As formulações foram consideradas clinicamente bem toleradas. A concentração máxima e a área sob a curva de zero a 36 horas foram comparadas: a média geométrica da razão entre as formulações teste e referência para concentração máxima foi de 110,16%, com intervalo de confiança de 99,44% a 122,04% e coeficiente de variação de 33,95%. A média geométrica da razão entre as formulações teste e referência para a área sob a curva de zero a 36 horas foi de 107,92%, com intervalo de confiança de 99,58% a 116,96% e coeficiente de variação de 26,39%. A média geométrica da razão entre o medicamento teste e referência para área sob a curva de zero ao infinito foi de 107,12%, com intervalo de confiança de de 99,11% a 115,78% e coeficiente de variação de 25,48%. CONCLUSÃO: As formulações teste e referência foram estatisticamente bioequivalentes, de acordo com sua taxa e extensão de absorção.

OBJECTIVE: To evaluate the bioequivalence of two 300mg profanone hydrochloride coated tablets. METHODS: Randomized, cross-over, openstudy, with two treatments, two sequences, and four periods with 60 healthy participants of both genders. The volunteers were admitted in four opportunities over 24 hours; on each period, the subjects received a test formulation, or a reference formulation, in a postprandial administration. Twenty-three samples of blood were collected after oral administration of the drug for determining plasma level of propafenone. Liquid chromatography-mass spectrometry was used for quantifying propafenone. RESULTS: The formulations were considered clinically well tolerated. The maximum concentration and the area under the curve from zero to 36 hours were compared: the geometric mean of the ratio between the test and reference formulations for maximum concentration was 110.16%, with confidence interval of 99.44% - 122.04%), coefficient of variation of 33.95%. The geometric mean of the ratio between the test and reference formulations for the area under the curve of zero to 36 hours was 107.92%, with confidence interval of 99.58% - 116.96%, and coefficient of variation of 26.39%. The geometric mean of the ratio between the formulations for area under the curve of zero to infinitum as 107.12% with confidence interval of 99.11% - 115.78%),and coefficient of variation of 25.48%. CONCLUSION: According to the rate and extension of absorption, the test and reference formulations are statistically bioequivalent.

Amiodarone Versus Propafenone to Treat Atrial Fibrillation after Coronary Artery Bypass Grafting: A Randomized Double Blind Controlled Trial

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. Several therapeutic and preventive strategies have been introduced for postoperative AF, but the treatment and prophylaxis of AF remain controversial. We aimed to compare the efficacy of intravenous amiodarone and oral propafenone in the treatment of AF after coronary artery bypass grafting (CABG). METHODS: This was a randomized controlled trial performed in two hospitals in Shiraz, Iran from 2009 to 2012. We included all patients who underwent elective CABG and developed AF postoperatively. The patients were randomly assigned to receive propafenone or amiodarone. The duration of AF, the success rate of the treatment, the need for cardioversion, the frequency of repeated AF, and the need for repeating the treatment were compared. RESULTS: The duration of the first (p=0.361), second (p=0.832), and third (p=0.298) episodes of AF, the need for cardioversion (p=0.998), and the need to repeat the first and second doses of drugs (p=0.557, 0.699) were comparable between the study groups. Repeated AF was observed in 17 patients (30.9%) in the propafenone group and 23 patients (34.3%) in the amiodarone group (p=0.704). CONCLUSION: Oral propafenone and intravenous amiodarone are equally effective in the treatment and conversion of recent-onset AF after CABG.

Falha de estimulação ventricular por variação aguda do limiar de comando induzida pela propafenona em portadora de marcapasso definitivo: relato de caso / Ventricular stimulation failure due to acute propafenone-induced command threshold variation in a patient with permanent pacemaker: case report

Relata-se o caso de uma paciente que, durante troca do gerador do marcapasso definitivo, foi tratada com propafenona após desenvolver fibrilação atrial no período intraoperatório. Os limiares eram moderadamente aumentados no pré-operatório, entretanto, estáveis. Horas após a administração de 600 mg de propafenona, a paciente apresentou síncope justificada pela perda de comando ventricular. A avaliação do dispositivo mostrava perda de captura por aumento do limiar ventricular medido em 5,0V/0,6 ms, corrigida por estimulação com energia máxima de saída do gerador. No dia seguinte, após nova avaliação, o limiar havia retornado ao valor previamente aferido e a energia de saída do gerador diminuiu, mantendo-se estável após seis meses de seguimento...

This is the case report of a patient who was treated with propafenone during the exchange of a permanent pacemaker generator, after the development of atrial fibrillation during the procedure. The thresholds were moderately increased in the preoperative period, however, they were stable. Hours after the administration of 600 mg of propafenone, the patient had a syncope which was explained by the loss of ventricular command. The evaluation of the device showed there was loss of capture due to the ventricular threshold increase, which as measured as 5.0V/0.6 ms and was adjusted by stimulation with maximum outlet energy of the generator. On the following day, after a new assessment, the values had returned to normal, the generator outlet energy decreased, and remained stable after six months of follow-up...

A Concealed Brugada Electrocardiogram Pattern Revealed after Administering Propafenone to a Patient with Atrial Fibrillation / 대한내과학회지

Brugada syndrome is characterized by sudden cardiac death associated with ventricular tachyarrhythmia in patients without structural heart disease. We recently observed a case of concealed Brugada ECG pattern, which appeared after oral propafenone administration for atrial fibrillation. A 34-year-old male patient who experienced syncope was admitted to the emergency department with acute atrial fibrillation (AF). Three hundred milligrams of propafenone that were administered to convert AF to sinus rhythm unmasked the Brugada ECG pattern that had remained concealed. The patient showed a type 1 Brugada ECG pattern after taking propafenone.

Interações medicamentosas em cardiologia: Fármacos antiárritmicos / Drugs interactions in cardiology: Antiarrhythmics drugs

As arritmias cardíacas são geradas por diferentes mecanismoseletrofisiológicos que atuam isoladamente ou interagem entresi para a formação e condução do impulso anormal. Com baseno conhecimento da eletrofisiologia celular e dos mecanismosgeradores de arritmias, diversos fármacos antiarrítmicos foramdesenvolvidos com objetivo de propiciar terapias cada vez maiseficazes e seguras. A necessidade de se agrupar os antiarrítmicos deacordo com seu mecanismo de ação e efeitos no impulsocardíaco, resultou na classificação de Vaughan- Williams que,apesar de amplamente difundida, não contempla algumasmedicações classicamente utilizadas como antiarrítmicos, taiscomo a adenosina e os digitálicos. Os antiarrítmicos são, emgeral, metabolizados pelo fígado por meio dos citocromos.Fármacos que interagem no mesmo sítio de ação em que sãometabolizados podem resultar em potencialização ou inibiçãodos efeitos antiarrítmicos. A redução ou o aumento do nívelsérico do antiarrítmico causado pelo fármaco utilizado concomitantemente,em decorrência da alteração na velocidade demetabolização, da redução na absorção ou somatório de efeitos,pode aumentar o potencial para efeitos colaterais deletérios eefeitos pró-arrítmicos e resultar em efeitos tóxicos potencialmentegraves. O objetivo deste capítulo é revisar os diversosmecanismos de interação medicamentosa que podem ocorrerenvolvendo as classes de antiarrítmicos...

Cardiac arrhythrnias are generated by different electrophysiologicalmechanisms that act alone or interact for the formation andconduction of the abnormal impulse. Based on the knowledge ofcellular electrophysiology and arrhythmia mechanisms, severalantiarrhythrnics were developed in order to provide therapiesincreasingly effective and safe. The need of grouping the antiarrhythmicagents according to their mechanism of action andeffects on cardiac impulse have led to the development of theVaughan- Williams c1assification. Although widespread used,this c1assification does not include some drugs c1assically usedas antiarrhythmics such as adenosine and digitalis.Antiarrhythmic agents are generaUy metabolized by the livervia the cytochrome. Drugs that interact at the same site of actionthat are metabolized may result in potentiation or inhibition ofantiarrhythmic effects. The reduction or increase in serum levelscaused by antiarrhythmic drug used concomitantly, due to thechange in the metabolism, reduction in absorption or summationeffects may increase the potential for deleterious side effects andproarrhythmic effects and result in potentiaUy serious toxic effects.The purpose of this chapter is to review the variousmechanisms of drug interactions that may occur involving theantiarrhythmic drugs...

Efficacy and safety of ibutilide for conversion of atrial fibrillation/flutter / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of intravenous ibutilide for conversion of atrial fibrillation (AF) and flutter (AFL) to sinus rhythm.</p><p><b>METHODS</b>Ninety-nine consecutive patients aged 18-75 y with AF/AFL were included. The duration of arrhythmia was <90 d (1 h-90 d) and ventricular rate was >60 beats/min. Patients were assigned randomly into two groups: 49 patients in ibutilide group received ibutilide 1 mg, then repeated if AF/AFL was not converted after 10 min; 50 patients in propafenone group received propafenone 70 mg, then repeated if AF/AFL persisted after 10 min. Two drugs were diluted by 50 ml of 5% glucose and injected intravenously within 10 min.</p><p><b>RESULTS</b>Ventricular rates were decreased in both groups. AF/AFL were converted in 34 of 49 patients (69.4 % ) in ibutilide group and in 22 of 50 patients (44.0 %) in propafenone group (P <0.05). The converting time of ibutilide was significantly shorter than that of propafenone [(16.79 ± 12.31) min compared with (36.92 ± 11.38)min, P <0.01]. The most serious adverse effect of ibutilide was non-sustained monomorphic ventricular tachycardia (3/49,6.12 %). Transient hypotension and heart pause were the main adverse events in patients who received propafenone, acute left heart failure occurred in one patient of propafenone group.</p><p><b>CONCLUSION</b>Intravenous ibutilide is a safe and effective agent for cardioversion of recent-onset AF/AFL. Furthermore,strict processing under electrocardio-monitoring is important.</p>

An Iatrogenically Unmasked Life Threatening Disease: Brugada Syndrome

Brugada syndrome is a life threatening disease that is usually overlooked during emergency service admissions. It is characterized by typical electrocardiography resembling right bundle branch block, static or dynamic ST-segment elevation in leads V 1-3. There is familial tendency in some cases. A majority of patients have a structurally normal heart and are likely to remain asymptomatic, however they may present to emergency departments with syncope and various serious arrhythmias. Therefore it is crucially important for emergency medicine physicians not to omit this potential diagnosis. Herein we report a case with Brugada syndrome which was iatrogenically unmasked after propafenone administration for atrial fibrillation.

Differing Electrophysiological Effects of Various Antiarrhythmic Drugs on the Cardiac Chamber in Atrial Fibrillation / 대한내과학회지

BACKGROUND/AIMS: Long-term antiarrhythmic drug therapy remains the principal approach for suppressing atrial fibrillation (AF) and maintaining sinus rhythm. In this study, we examined the differing electrophysiological effects of various antiarrhythmic drugs on the cardiac chamber and atrial selectivity in patients with AF. METHODS: We analyzed 134 patients (60.4 +/- 12.5 years, M:F = 1.14:1) who were administered a single antiarrhythmic agent for AF over 6 months: amiodarone (group A), flecainide (group F), or propafenone (group P). The P wave, QRS complex duration and dispersion, and QT interval and its dispersion were evaluated using a standard 12-lead electrocardiogram. RESULTS: There was no significant difference in age, gender ratio, or associated diseases among the three groups. In group A, Pmax, Pmin, P dispersion, QRSmax, QRSmin, and QRS dispersion were shorter than in groups F and P, whereas Pmax/QRSmax was the highest in group A (A = 1.2, F = 0.9, P = 1.0; p < 0.01). QTcmax and QTcmin were longer in group A, whereas QTc dispersion and the QT peak to end (A = 13.3 +/- 11.2, F = 30.7 +/- 24.9, P = 31.8 +/- 21.6; p < 0.01) were shorter in group A than in the other groups. CONCLUSIONS: Amiodarone had a weaker, but more selective, inhibitory effect on intra-atrial conduction, and inhibited ventricular repolarization more effectively and homogenously than flecainide or propafenone. These differing electrophysiological effects may contribute to the superior effectiveness and safety of amiodarone over flecainide or propafenone.