Contractilidad del músculo ventricular bajo la acción de prajmalina-propanolol y prajmalina-epinefrina

Los efectos de la estimulación adrenérgica alfa y beta, pueden ser logrados por agentes agonistas y antagonistas, como la epinefrina y el propranolol respectivamente. Con el objetivo de precisar aspectos relacionados con la contractilidad del músculo ventricular, se realizaron un total de trece experimentos utilizando combinaciones de prajmalina-epinefrina y prajmalina-propanolol, perfundiendo preparaciones de tiras de músculo ventricular de trece ejemplares adultos de ranas catesbeiana. La prajmalina, antiarrítmico del grupo I, se obtuvo a partir de la Rauvvolfia viridis, planta endémica de Cuba. Las preparaciones fueron estimuladas con pulsos de corriente, y la tensión desarrollada por el músculo fue registrada por un transductor fuerza-desplazamiento. Las señales eléctricas fueron convertidas en trazos por un equipo registrador. Los resultados indican que las combinaciones de prajmalina-epinefrina y prajmanina-propanolol afectan de forma diametralmente opuesta la contractilidad del músculo cardíaco, aumentando en un 40 por ciento y disminuyendo en un 15 por ciento respectivamente la fuerza de la contracción del músculo ventricular. Por otra parte se sugiere un posible mecanismo de acción de la prajmalina sobre los receptores alfa presentes en las membranas de las células ventriculares...(AU)

[Treatment of atrial fibrillation in a Hungarian hospital department of cardiologic internal medicine at the turn of the millennium]. / Törekvés a pitvarfibrilláció ritmuskontroll-kezelésére kardiológiai profilú belgyógyászati osztályon az ezredfordulón.

INTRODUCTION: The atrial fibrillation is a severe and frequent disease, which influences greatly the patients' quality of life. Only a few Hungarian studies exist which discuss the physicians' own experiences in its treatment. AIM: The description of the experiences acquired in an internal medicine department with cardiological profile during the treatment based on the actual guidelines and the review of the results of one year follow-up. METHOD: Retrospective analysis of the data of patients treated with atrial fibrillation between 1 january 1999 and 31 december 2001 and a one year follow-up was performed. The age, gender, success in cardioversion, the antiarrhythmic therapy at the discharge and the modification in it during the first year were evaluated. RESULTS: During the 3 years long period 1115 patients with atrial fibrillation were admitted (53.9% female, 46.1% male, the mean age was 72.0 +/- 10.4 years), 391 of whom were discharged with sinus rhythm. In 193 cases (49%) a spontaneous cardioversion was observed. 120 electrical (31%) and 78 pharmacological (20%) cardioversions were performed. The electrical form was carried out in 42 cases with acute atrial fibrillation (in 36 of them successfully) and in 100 cases as an elective procedure, in 84 successfully. Pharmacological cardioversion was made in 39 acute cases with the administration of propafenone (in 29 ones successfully) and in 57 elective cases with quinidine + beta-blocker + magnesium (in 49 ones successfully). For the maintenance of sinus rhythm in the 38.8% of cases amiodarone, 24.0% propafenone, 19.9% sotalol, 10.7% beta-blocker, 0.8% quinidine, 0.5% prajmaline was administered, and 5.1% of the patients didn't receive any special treatment. During the one year follow-up from the 391 patients 261 remained on sinus rhythm, in 81 cases (21%) the return of the atrial fibrillation was diagnosed (in 57 of them a successful cardioversion was performed again), 11 patients (3%) died and 38 (9%) were lost for observation. At the time of the one year control 57.8% of patients treated with amiodarone, 61.7% of those treated with propafenone, 67.9% with sotalol and 35.7% with beta-blocker remained on sinus rhythm. The amiodarone was omitted in 17 cases because of its side effects. CONCLUSIONS: The treatment of the atrial fibrillation has to be performed individually taking into account the guidelines, the comorbidity, the time of the beginning of rhythm disorder, the patients' present other drugs and the former antiarrhythmic therapy. A continuous and consistent follow-up of these patients is crucial.

[Cholestatic hepatitis caused by prajmalium treatment: case report]. / Cholestatyczne zapalenie watroby wywolane zastosowaniem prajmaliny--opis przypadku.

Prajmalium rarely causes idiosyncratic liver injury. Author describes the case of cholestatic hepatitis occurring in three weeks after cessation of short-term treatment with prajmalium. Eighteen months later, despite of good general status, physical and biochemical features of cholestasis were present. Pathologic examination of liver biopsy specimen revealed the chronic intracellular cholestasis with lymphocytic infiltration. Presented case indicate that even short-term treatment with potentially weekly hepatotoxic drug may cause the long-term intrahepatic cholestasis.

[Brugada syndrome]. / Das Brugada-Syndrom.

BACKGROUND: A high take-off descending ST segment associated with right bundle branch block is the typical ECG criterion of the Brugada-Brugada syndrome. It leads to ventricular fibrillation or syncopes in case of a familiar disposition. CASE REPORT: We describe a 56-year-old man in whom oral prajmalium bitartrate therapy previously prescribed for symptomatic ventricular extrasystoles unmasked an electrographic pattern characteristic of a Brugada syndrome. After the ongoing invasive diagnostic a right ventricular dysplasia in the same case is possible. The patient was treated with an ICD pacemaker.

The structure of the ring-opened N beta-propyl-ajmaline (Neo-Gilurytmal) at physiological pH is obviously responsible for its better absorption and bioavailability when compared with ajmaline (Gilurytmal).

Prajmaline, the semisynthetic propyl derivative of ajmaline, shows a much better bioavailability when compared with the Rauvolfia alkaloid ajmaline. Early NMR and IR-studies, fluorescence spectroscopic investigations and extraction experiments combined with ion-pair chromatography proved the thesis of a tautomeric equilibrium between an aldehyde-amine and a quaternary carbinol-ammonium component. The aim of this study was to confirm this thesis by HPLC-separation and by structure-determination of both tautomeric compounds.

[Stimulus-dependent effects of the sodium channel blockers in the C-fiber sensory units]. / Stimulozavisimye éffekty pri deistvii blokatorov natrievykh kanalov na sensornye C-edinitsy.

The data obtained suggest a use-dependent inhibition in the skin terminals of the C-fibre sensory units. The terminals are discussed in respect to search of efficient local anaesthetising agents as well as cardiac anti-arrhythmic agents with obvious neurotropic effects.

[A case of fatal poisoning with the anti-arrhythmia agents Katen and Neo-Gilurytmal]. / Letálny prípad intoxikácie antiarytmikami Katen a Neo-Gilurytmal.

The case is presented on 17-year-old student who ingested larger doses of tablets and capsules in privacy. She ingested antiarrhythmics Katen and Neo-Gilurytmal without clinical therapy by these drugs and without history of suicidal attempt. The imminent case of death was asphyxiation by aspiration of vomits from gastric contents after ingestion of excessive doses of drugs. The secondary findings as brain edema, petechiae under the serous membranes and congestion of the abdominal cavity, were relieved at autopsy. Noxae was identified by the postmortem toxicological analysis of blood, liver, kidney, gastric contents and intestinal contents. Mexiletine and prajmaline were analysed by the capillary gas chromatography with FID detection. Retention time of mexiletine was 6.66 minutes, prajmaline 15.15 minutes, respectively. Blood alcohol concentration was 0.21 mg.g-1. Concentration of prajmaline in gastric contents was 3.03 mg.g-1, mexiletine 0.11 mg.g-1, respectively.

Arritmias por Reperfusion Coronaria: Mecanismos Fisiopatologicos y Estudio Farmacologico / Coronary reperfusion arrhythmias: Physiopathologic mechanisms and pharmacological study

Las arritmias que aparecen despues de la recirculacion sanguinea de una arteria coronaria previamente obstruida, han sido objeto de estudio de multiples investigadores desde finales de la decada de los 70 hasta nuestros dias, debido a la posibilidad de que estos tipos de trastornos del ritmo cardiaco pueden llevar a la muerte a pacientes en los que se libera un espasmo coronario o se produce la lisis de un trombo coronario. Con el presente trabajo tuvimos la oportunidad de profundizar en el conocimiento fisiopatologico de estas arritmias ventriculares, para ello utilizamos un modelo experimental animal de probada eficacia en este tipo de estudio. En el empleamos tres antiarritmicos clase I: prajmalina, lidocaina y mexiletine con el objetivo de conocer y analizar los efectos de estas drogas sobre la tension arterial, la frecuencia cardiaca y la incidencia de las arritmias por reperfusion coronaria. Nuestra investigacion arrojo una disminucion notable del por ciento de incidencia de arritmias en el grupo de animales tratados con mexiletine a diferencia de los resultados obtenidos con el resto de las series. Tambien en todos los grupos experimentales se registraron hipotension y bradicardia significativas al ser comparadas con su control: se emplearon para este analisis estadistico la "t" de Student para muestras pareadas (p < 0,05)

Arritmias por Reperfusión Coronaria: Mecanismos Fisiopatológicos y Estudio Farmacológico / Coronary reperfusion arrhythmias: Physiopathologic mechanisms and pharmacological study

Las arritmias que aparecen después de la recirculación sanguínea de una arteria coronaria previamente obstruida, han sido objeto de estudio de múltiples investigadores desde finales de la década de los 70 hasta nuestros días, debido a la posibilidad de que estos tipos de trastornos del ritmo cardíaco pueden llevar a la muerte a pacientes en los que se libera un espasmo coronario o se produce la lisis de un trombo coronario. Con el presente trabajo tuvimos la oportunidad de profundizar en el conocimiento fisiopatológico de estas arritmias ventriculares, para ello utilizamos un modelo experimental animal de probada eficacia en este tipo de estudio. En él empleamos tres antiarrítmicos clase I: prajmalina, lidocaína y mexiletine con el objetivo de conocer y analizar los efectos de estas drogas sobre la tensión arterial, la frecuencia cardíaca y la incidencia de las arritmias por reperfusión coronaria. Nuestra investigación arrojó una disminución notable del por ciento de incidencia de arritmias en el grupo de animales tratados con mexiletine a diferencia de los resultados obtenidos con el resto de las series. También en todos los grupos experimentales se registraron hipotensión y bradicardia significativas al ser comparadas con su control: se emplearon para este análisis estadístico la "t" de Student para muestras pareadas (p < 0,05)(AU)

[Cardiogenic shock and ventricular fibrillation induced by prajmalium and metoprolol poisoning]. / Kardiogén shock és kamrafibrilláció kialakulása prajmalin és metoprolol mérgezés következtében.

Prajmaline is not a relatively well known and frequently used antiarrhythmic belonging to Class IA group of antiarrhythmics, which was administered to a young male with metoprolol for the treatment of parasystole. The patient took in 120 mgs prajmaline and 600 mgs metoprolol during the day of the case, which leads to cardiogenic shock, ventricular tachycardia and ventricular fibrillation. The patient's parameters were normalized after successful resuscitation, temporary pacemaker and two days long Dopamin therapy. Therapy was not regarded to be necessary for a few ventricular premature beats detected during a week observation period. The patient is without complaints now, and significant ventricular arrhythmias, or malignant ventricular ectopy hasn't been proved with ECG tests and Holter monitoring for more than three months. Due to adverse effect profile of prajmaline, even at commonly used doses it should be administered carefully and other agents should probably be considered first before beginning long term treatment with prajmaline.

[Antiarrhythmic effects of prajmaline (Neo-Gilurythmal) in stable angina pectoris in light of Holter electrocardiographic monitoring]. / Przeciwarytmiczne efekty prajmaliny (Neo-Gilurytmal) w stabilnej dusznicy bolesnej w swietle holterowskich badan elektrokardiograficznych.

40 patients with various type of arrhytmia with stable angina were treated with 3 x 20mg Prajmalin (Neo-Gilurytmal) over 6-day period. A positive antyarhytmic response was observed in 30 patients (75%). In the remaining 10 patients considering the lack of adequate response after 6 days on 60 mg the trial was continued at a dose of 100 mg/day (5 x 20mg). With this dose bringing on the desired results. In 32 patients with VE'e and SVE's Neo-Gilurytmal was used in mono therapy. While in other types of arthymia it was used as previously as a first treatment and also in cases where other antiarhytmic drugs (e.g. Propahenone, Mexitil or Beta-blockers) were unsuccessful. Antiarhytmic effects were verified using 24-hour Holter monitoring before introduction of Neo-Gilurytmal, during the first fourth and seventh day of administration and also the eleventh day of observation (in 30 patients three days after cessation of treatment and in 10 cases three days after commencing on 100 mg daily). The results, as mean of the 24-hour observation was statistically analysed using the Wilcoxon test. We analysed the mean from the first day (H1), fourth day (H2), seventh day (H3) i.e. 6 days after administration and in 10 patients three day after increasing the dose to 100 mg/day (H4). We compared this to a base value (Ho) obtained before drug administration. The results obtained showed the Neo-Gilurythmal is an effective drug significantly reducing meanly VE's and SVE's and also gigemini, trigemini, coupled, runs. It was concluded that Neo-Gilurythmal did not significantly effect the heart rate and QT intervals and also QT adjusted to the heart rate. It was also noticed that these was a lack of therapeutic effect 3 days after cessation of treatment, which was suggested that constant therapy is required. Neo-Gilurythmal was find to be effective even in the case where other previously used antiarhymics were ineffective. We also observe a positive result in treatment of paroxismal tachycardia, in treatment of WPW Syndrome and also in prophylactic againts its recurrence. In our study no adverse effects (e.g. cardiac muscle depression, hypotensive episodes or noted in other studies gepatotoxicity or cholestatic episodes) were observed.

[Magnesium or proajmaline (neogilurytmal) in treatment of recurrences of paroxysmal supraventricular tachyarrhythmias?]. / Magnez czy proajmalina (neogilurytmal) w leczeniu nawrotów napadowych tachyarytmii nadkomorowych?

In order to compare the effectiveness of magnesium with that of proajmaline in preventing of recurrences of paroxysmal tachyarrhythmias. 60 consecutive patients were studied who had been previously treated for paroxysmal arterial fibrillation (PAF) or paroxysmal supraventricular tachycardia (PSVT). For the studies the patients were qualified who had been effectively treated during acute phase with intravenous magnesium (magnesium sulphate) and ajmaline (gilurytmal). The patients were randomly divided into three groups of 20 persons in each, every group received different oral treatment: in the first group--magnesium (magnesium carbonate) 3 x 0.6, in the second--proajmaline (neogilurytmal) in dose 3 x 20 mg, and in the third--neogilurytmal 2 x 20 mg and magnesium 2 x 0.6. During three months of observation the effectiveness of treatment and incidence of adverse effects were assessed. The following was found: neogilurytmal showed higher effectiveness (60%) than magnesium (30%), while the combined treatment demonstrated similar effectiveness (65%) as neogilurytmal alone with lower drug doses and lower incidence of bad tolerance manifestations (10% vs 20%).

Chemically modified cardiac Na+ channels and their sensitivity to antiarrhythmics: is there a hidden drug receptor?

Elementary Na+ currents were recorded at 19 degrees C in inside-out patches from cultured neonatal rat cardiocytes. In analyzing the sensitivity of chemically modified Na+ channels to several class 1 antiarrhythmic drugs, the hypothesis was tested that removal of Na+ inactivation may be accompanied by a distinct responsiveness to these drugs, open channel blockade. Iodate-modified and trypsin-modified cardiac Na+ channels are noninactivating but strikingly differ from each other by their open state kinetics, a O1-O2 reaction (tau open(1) 1.4 +/- 0.3 msec; tau open(2) 5.4 +/- 1.1 msec; at -40 mV) in the former and a single open state (tau open 3.0 +/- 0.5 msec; at -40 mV) in the latter. Lidocaine (150 mumol/liter) like propafenone (10 mumol/liter), diprafenone (10 mumol/liter) and quinidine (20 mumol/liter) in cytoplasmic concentrations effective to depress NPo significantly can interact with both types of noninactivating Na+ channels to reduce the dwell time in the conducting configuration. Iodate-modified Na+ channels became drug sensitive during the O2 state. At -40 mV, for example, lidocaine reduced tau open(2) to 62 +/- 5% of the control without detectable changes in tau open(1). No evidence could be obtained that these inhibitory molecules would flicker-block the open Na+ pore. Drug-induced shortening of the open state, thus, is indicative for a distinct mode of drug action, namely interference with the gating process. Lidocaine proved less effective to reduce tau open(2) when compared with the action of diprafenone. Both drugs apparently interacted with individual association rate constants, a(lidocaine) was 0.64 x 10(6) mol-1 sec-1 and a(diprafenone) 13.6 x 10(6) mol-1 sec-1. Trypsin-modified Na+ channels also appear capable of discriminating among these antiarrhythmics, the ratio a(diprafenone)/a(lidocaine) even exceeded the value in iodate-modified Na+ channels. Obviously, this antiarrhythmic drug interaction with chemically modified Na+ channels is receptor mediated: drug occupation of such a hypothetical hidden receptor that is not available in normal Na+ channels may facilitate the exit from the open state.

[Acute anicteric hepatitis and intrahepatic cholestasis caused by administration of prajmalium bitartrate (Neo-Gilurytmal)]. / Akutní anikterická hepatitida s intrahepatální cholestázou vyvolaná podáváním prajmalium bitartarátu (Neo-Gilurytmal).

The authors draw attention to a serious drug response to the derivative of the alkaloid ajmaline prajmalium (Neo-Gilurytmal, Giulini-GFR) which causes impairment of liver functions of various grades as a result of intrahepatic cholestasis. They draw attention to the necessity of a careful pharmacological case-history, evaluation of the premorbid stage, in particular former liver disease or contemporary administration of drugs which burden liver function (hormonal contraceptives, non-steroid antirheumatic drugs). It is essential to follow-up liver functions by laboratory tests already at the onset of treatment with Neo-Gilurytmal.

[Hepatotoxic side effect of n-propylajmaline suggesting suspicion of viral hepatitis--case history]. / Hepatotoksyczny efekt uboczny Neo-Gilurytmalu uzasadniajacy podejrzenie o wirusowe zapalenie watroby--opis przypadku.

The case of 28 aged woman with cellular damage of liver is presented. Toxic side-effect of n-propylajmaline was confirmed after exclusion of Viral hepatitis or co-existed poly-parasitism (Ascaridiasis, Giardiasis), as reason of liver injury.

Fosfolipasa A2 y su papel en el funcionamiento hepático por acción de prajmalina / Phospholipase A2 and its role in liver function by projmaline action

Se estudió la influencia del tiempo de tratamiento con prajmalina sobre las concentraciones plasmáticas de la fosfolipasa A2, y se correlacionaron estos resultados con los niveles de las enzimas creatin fosfoquinasa (CPK) y transaminasa glutamicooxalacética (GOT). Los parámetros enzimáticos exhibieron tendencias semejantes, las cuales disminuían con respecto al tiempo de tratamiento con el antiarrítmico. Cuando se evaluaron las relaciones CPK/fosfolipasa A2 y GOT/fosfolipasa A2 se encontró que estas relaciones eran representativas del momento a partir del cual se producía la lesión orgánica

Hepatotoxicidad de prajmalina: diagnóstico farmacocinético por bromosulftaleina / Prajmaline hepatotoxicity: pharmaco-kinetic diagnosis by brumosulfthaleine

Escasas publicaciones abordan el efecto del primer paso de la prajmalina (N-propil ajmalina bitartrato), por lo que surgieron interrogantes sobre una posible respuesta hepatotóxica. Mediante valoraciones farmacocinéticas modelo dependiente en las que se emplean bromosulftaleína (BSP) como una medida de la función excretora del hígado, se demuestra que la prajmalina en aplicación crónica, prvoca efectos hepatotóxicos sobre un modelo experimental animal. Los valores obtenidos de la constante de depuración (K) se correlacionan con otras mediciones realizadas por el mismo colectivo de otros trabajos: variación de la fracción albúmina índices transaminasa glutamicooxalacética/fosfolipasa A2 (GOT/FPA) y creatin-fosfoquinasa/fosfolipasa A2 (CPK/FPA); se definen períodos críticos de degeneración de la capacidad excretora

Hepatotoxicidad de prajmalina. diagnóstico farmacocinético por bromosulftaleina / Prajaline hepatotoxicity: pharmaco-kinetic diagnosis by brumosulfthaleine

Escasas publicaciones abordan el efecto del primer paso de la prajmalina (N-propil ajmalina bitartrato), por lo que surgieron interrogantes sobre una posible respuesta hepatotóxica. Mediante valoraciones farmacocinéticas modelo dependiente en las que se emplean bromosulftaleína (BSP) como una medida de la función excretora del hígado, se demuestra que la prajmalina en aplicación crónica, prvoca efectos hepatotóxicos sobre un modelo experimental animal. Los valores obtenidos de la constante de depuración (K) se correlacionan con otras mediciones realizadas por el mismo colectivo de otros trabajos: variación de la fracción albúmina índices transaminasa glutamicooxalacética/fosfolipasa A2 (GOT/FPA) y creatin-fosfoquinasa/fosfolipasa A2 (CPK/FPA); se definen períodos críticos de degeneración de la capacidad excretora