[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.

[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.

[Anti-arrhythmic effectiveness of neogilurhythmal in extrasystolic arrhythmia]. / Antiaritmicheskaia éffektivnost' neogiluritmala pri ékstrasistolicheskoi aritmii.

The paper provides the results of differential neogilurythmal therapy in 20 patients with high-grade atrial and ventricular premature contractions in the presence of coronary heart disease. The detection of cardiac arrhythmias and evaluation of the antiarrhythmic efficacy of neogilurythmal were performed by Holter monitoring and transesophageal electrophysiological study. After the baseline studies, the antiarrhythmic efficacy of the drug was evaluated during an acute drug test and then during a 8-day course of the therapy. In the acute drug test, the dose of neogilurythmal was 50% of the daily dosage. The studies indicated that neogilurythmal in a dose of 80 mg/day was beneficial in affecting both the atrial and ventricular extrasystolic arrhythmia. The agent failed to alter heart rate, sinus nodal function and atrioventricular conduction. Thus, neogilurythmal is low toxic and produces no adverse effects when given in the definite dosage range.

[Transient liver damage due to prajmalium bitartrate].

3 patients developed transient cholestatic jaundice after administration of prajmalium bitartrate, a class I antiarrhythmic drug. The leukocyte inhibition tests showed 4%, 12% and 15% inhibition, respectively, while eosinophilia was seen in all 3, supporting the assumption that the transient hepatic damage was due to drug exposure. Discontinuing the drug resulted in improvement in the clinical and biochemical findings.

[Diagnostic difficulties in prajmaline-induced intrahepatic cholestasis]. / Trudnosci diagnostyczne sródwatrobowego zastoju zólci wywolanego zazywaniem prajmalium.

A case of prajmalium-induced intrahepatic cholestasis is presented. A proper diagnosis was delayed because differential diagnosis did not include toxic liver damage. Pathogenetic considerations included immunological background of the disease which improved completely within one year. No clinical and biochemical complications were seen.

[Intrahepatic cholestasis and aplastic anemia following administration of prajmaline]. / Intrahepatische Cholestase und aplastische Anämie nach Prajmalin-Einnahme.

Intrahepatic cholestasis and aplastic anemia after N-propylajmaline. A 43 year old female patient taking oral contraceptives for more than five years received the antiarrhythmic drug N-propylajmaline for treatment of ventricular arrhythmia. After twelve days (total dosage 510 mg N-propyl-ajmaline) acute severe intrahepatic cholestasis and aplastic anemia developed. The erythropoeisis improved after three weeks of treatment with corticosteroids. However, despite treatment with phenobarbital the jaundice receded very slowly. Even after nine years of follow-up cholestatic enzymes are still significantly elevated although serum bilirubin levels are in the normal range. This case report demonstrates that antiarrhythmic drugs may induce nearly irreversible intrahepatic cholestasis and severe hematological disturbances.

[Comparative study of the anti-arrhythmia effect of flecainide acetate and prajmalium bitartrate in patients with tachycardiac ventricular rhythm disorders]. / Vergleichende Untersuchung über den antiarrhythmischen Effekt von Flecainidacetat und Prajmaliumbitartrat bei Patienten mit tachykarden ventrikulären Rhythmusstörungen.

In an open randomized therapeutic study, 20 patients known to have frequent ventricular premature beats (VPB) and/or ventricular pairs (VP) were treated with both 2 X 200 mg flecainide (F) and 4 X 20 mg prajmalium-bitartrate (P) for 3 months each. There was a drug-free interval of one week between the two therapy phases. 24-hour long-term ECG-registrations were carried out before the start of the therapy phases as well as 1 week, 1 month, 2 months and 3 months after the initiation of antiarrhythmic therapy. After one week, the group as a whole evidenced a VPB reduction of 94% under F and only 57% under P (p less than or equal to 0.05). The percentage of individual patients in whom there was a statistically significant VPB reduction was also higher under F than under P (65% vs. 40%). In the group as a whole, there was a VP reduction of 99% under F and 88% under P (p less than or equal to 0.05) after one week. Of the 13 individuals with frequent VP (over 16 VP/24 h), a significant reduction was seen in 77% under F and only 38% under P. The difference between the two antiarrhythmic agents registered after one week was also observed in the further course of therapy but could no longer be statistically confirmed for the ventricular pairs. An aggravation of ventricular arrhythmias was observed in 2 patients under F and in 3 under P.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oral prajmaline bitartrate on exercise test responses in patients with coronary artery disease.

The safety, tolerability and haemodynamic effects of oral prajmaline bitartrate were assessed in a double-blind, randomized, placebo-controlled, crossover trial in 21 patients with stable angina pectoris and coronary artery disease. No serious side-effects occurred. Prajmaline bitartrate produced no statistically significant changes in resting heart rate or systolic blood pressure or in work capacity on the treadmill, or in heart rate or systolic blood pressure at maximum exercise compared to placebo values. No new arrhythmias or conduction abnormalities were produced in any patient. We conclude that oral prajmaline bitartrate is well tolerated and can be given safely to patients with coronary artery disease without producing deleterious haemodynamic effects or changes in exercise capacity.

Prajmaliumbitartrate-associated liver damage. Report on seven further cases with follow-up for two to five years.

Seven further cases with n-propyl-ajmaliumbitartrate (NPAB)-associated liver damage observed between 1976 and 1980 in two collaborating institutions are reported. The cause/effect relationship could be classified as probable in three cases and as potential in the remaining four patients. No drug rechallenge was carried out. In the clinical management, definite exclusion of biliary tract obstruction had a clear priority over histologic documentation of the degree of the transient liver damage. Follow-up data after 2 years 8 months to 5 years 9 months by personal reinvestigation of three patients and by questionnaire to family physicians and patients in the remaining four cases gave no clinical or serologic indication of persisting or relapsing liver damage. Liver biopsies were not considered to be warranted in the follow-up of these asymptomatic patients with normal liver function tests.

Acute haemodynamic effects of ajmaline and prajmaline in patients with coronary heart disease.

Thirty patients undergoing cardiac catheterisation for coronary artery disease received parenteral ajmaline (15 patients) or prajmaline (15 patients). There were no statistically significant induced changes in left ventricular systolic or end diastolic pressures, indirect left atrial pressure, pulmonary artery mean pressure, cardiac output or left ventricular ejection fraction compared to control values. Intravenous prajmaline bitartrate in 15 patients with angina did not significantly alter work capacity, maximum exercise heart rate or systolic blood pressure compared to control values. Five patients developed transient minor conduction defects ( 2LBBB , 1 RBBB, 2 prolonged PR interval): all five were also receiving long-term treatment with beta blockers and nifedipine.

Comparison of tocainide and prajmalium bitartrate for the treatment of ventricular arrhythmias.

The antiarrhythmic efficacy of tocainide, a new antiarrhythmic substance, has been compared with that of prajmalium bitartrate, a drug in clinical use for many years in the German speaking countries. The investigation was performed as a double-blind cross-over study in 20 patients with ventricular arrhythmias (VA) of various origin. The efficacy was assessed by serial Holter monitoring. Plasma levels were measured to study the dose-effect relationship. Applying to the criterion of a reduction of VA of more than 75% or an improvement according to the Lown grading 8 pts. under tocainide and 7 under prajmalium bitartrate were responders. Side effects were few and under tocainide only 2 pts. had to discontinue the therapy. From the present findings tocainide and prajmalium bitartrate have the same efficient antiarrhythmic effects in the majority of patients.

Prajmalium bitartrate in chronic ventricular arrhythmias: comparison with disopyramide.

24-h ECG recordings were used to assess the efficacy of prajmalium bitartrate (PB) in reducing the incidence and the severity of premature ventricular complexes (PVCs), and to compare its antiarrhythmic action with that of Disopyramide. 13 patients with frequent PVCs were distributed randomly into 2 groups. The first group of 7 patients received PB 80 mg/day for 4 days as their first treatment, and disopyramide 400 mg/day for a further 4 days as the second therapy. The succession of the drugs was reversed in the other group of 6 patients. Analysis of the Holter recordings showed that PB and disopyramide reduced PVC frequency to a similar extent as compared to the corresponding wash-out period, viz. by 56.7% (p less than 0.05) and 62.1% (p less than 0.01), respectively. Thus, PB appears to be an effective antiarrhythmic drug and comparable to disopyramide. It may be used to prevent premature ventricular complexes and runs of ventricular tachycardia.

Evaluation of prajmalium-induced cholestasis by immunologic tests.

Cholestatic jaundice developed in four patients after the administration of prajmalium bitartrate. The clinical, histologic, ultrastructural, and immunologic findings were determined. In all patients, the clinical and morphologic features indicated idiosyncrasy. Two antibodies distributed in a granular pattern along the bile canaliculi were detected by immunofluorescence in all patients. In one patient, autoimmune markers were found in the serum, and in two instances, the migration-inhibition factor assay against the offending drug was found to be positive. The data support the concept that immunologic processes may participate in the production of the cholestatic syndrome.