Intraindividual comparison of intravenous ajmaline and quinidine in patients with sustained ventricular tachycardia: Effects on normal myocardium and on arrhythmia characteristics
Intraindividual comparison of the acute response to intravenous quinidine and to intravenous ajmaline was performed in 23 patients with sustained ventricular tachycardia (VT) who underwent serial electrophysiological studies. In each patient, sustained VT could be reproducibly initiated by programmed ventricular stimulation during control studies. Inducibility of sustained VT was prevented after quinidine in 6 of the 23 patients (26%) and after ajmaline in 8 of the same 23 cases (35%). Agreement between the effects of both drugs was not significant: 2 patients had a similar response to both quinidine and ajmaline and 11 patients did not have a response to either of the two drugs, resulting in a total of only 13 patients (57%) who had a similar response to both drugs. In the 11 non-responders with inducible sustained VT before and after both drugs, quinidine and ajmaline caused qualitatively and quantitatively similar alterations of VT characteristics including a significant prolongation of the interval between the initiation extrastimulus and the first beat of VT by 38 and 42% (P less than 0.01), an increase in VT cycle length by 15 and 22% (P less than 0.01) and a prolongation of the QRS duration during VT by 15 and 18% (P less than 0.01), respectively. In all 23 patients, quinidine and ajmaline caused a quantitatively similar prolongation of ventricular refractoriness by 11 and 9% (P less than 0.05), of the QRS duration at sinus rhythm by 10 and 15% (P less than 0.01) and of the QTc interval by 13 and 10% (P less than 0.05), respectively. Thus, ajmaline and quinidine appear to have similar electrophysiological effects on both normal myocardium and on indirect parameters of reentry; in individual patients with sustained VT, however, such electrophysiological similarities do not result in significant agreement of preventive responses.
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ABSTRACT: 21 patients with acute myocardial infarction and ventricular arrhythmia of Lown class II-IIIB of acute onset received a short infusion of (50 mg/5 min) ajmaline (Gilurytmal). 6 of the patients had normal kidney and liver function (Group 1), 4 patients had acute renal failure and hemodialysis treatment (Group 2), 4 patients had impaired hepatic function (Group 3), 3 patients had cardiogenic shock (Group 4), and 4 patients had been pretreated with phenobarbital for seizures for at least 5 days (Group 5). A distribution half-life of 6 +/- 1 min and an elimination half-life of 95 +/- 6 min was determined in Group 1. The total plasma clearance was significantly lower in patients with impaired liver or cardiac function and significantly higher in Group 5, whereas impaired renal function did not affect total plasma clearance. After short infusion, ventricular arrhythmia of Lown II-IIIB completely disappeared for at least 16 to 36 min (mean: 19 min), which was associated with an ajmaline plasma level of 0.1-0.45 micrograms/ml. Additionally, steady-state plasma levels of ajmaline were determined after continuous infusion of 10-50 mg/h to 16 patients (Group 6) with ventricular arrhythmia of acute onset (Lown class IVA-V). Ventricular arrhythmia completely disappeared or at least changed to lower Lown classes at ajmaline plasma levels of 0.4-2.0 micrograms/ml. The ajmaline plasma protein binding was 76 +/- 9%. Ajmaline had a special affinity to alpha 1-acid glycoprotein.European Journal of Drug Metabolism and Pharmacokinetics 04/1989; 14(2):161-7. DOI:10.1007/BF03190857 · 1.56 Impact Factor
Article: Metabolic disposition of ajmaline[Show abstract] [Hide abstract]
ABSTRACT: Urine was collected from six patients receiving a continuous infusion of 20 mg/h ajmaline. Pooled urine was extracted with and without enzymatic conjugate cleavage or hydrolysis with concentrated hydrochloric acid. The extracts were analyzed by gas chromatography/mass spectrometry. Ajmaline and its metabolites in urine were identified in the form of their acetylated derivatives. Twenty two different acetylated derivatives of ajmaline and its metabolites could be detected. Three of these derivatives were artifacts generated by acetylation and/or thermal decomposition. The major metabolic pathways were mono- and di-hydroxylation of the benzene ring with subsequent O-methylation, reduction of the C-21, oxidation of the C-17 and C-21-hydroxyl function, N-oxidation, and a combination of these metabolic steps. Ajmaline and its metabolites were mainly excreted in the form of their conjugates. Furthermore, the interference of sparteine, debrisoquine, quinidine, and nifedipine with ajmaline metabolism was studied with semiquantitative thin-layer chromatography. Ajmaline metabolism was inhibited by co-administration of sparteine or quinidine, but not by debrisoquine or nifedipine. Sparteine most likely competed with ajmaline metabolism. Quinidine probably bound competitively to ajmaline-metabolizing enzymes without being metabolized itself. Additionally, the metabolic ratio of hydroxyajmaline/ajmaline in urine was determined in 9 extensive metabolizers and one poor metabolizer of dextromethorphan. The poor metabolizer had a significantly reduced metabolic ratio of hydroxyajmaline/ajmaline, which indicates that ajmaline metabolism probably co-segregates with polymorphic sparteine/debrisoquine/dextromethorphan metabolism.European Journal of Drug Metabolism and Pharmacokinetics 10/1989; 14(4):309-16. DOI:10.1007/BF03190117 · 1.56 Impact Factor
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ABSTRACT: Episodes of sustained paroxysmal supraventricular tachycardias can be terminated by antiarrhythmic drugs given intravenously. The cardiodepressive effects of these drugs are an important limitation of this therapeutic procedure. The dose-dependent circulatory and myocardial effects of the nucleoside adenosine (0.5, 2.0, 5.0 mg/kg/minute) and the class I antiarrhythmic drug ajmaline (1.0, 2.0, 4.0 mg/kg) were investigated in 73 open-chest rats. Hemodynamic measurements in the intact circulation and isovolumic registrations (peak isovolumic left ventricular systolic pressure and peak isovolumic dP/dtmax) were compared with saline controls. Adenosine has a short-lasting, negative, chronotropic effect that causes a dose-dependent reduction of cardiac output (–34%, –54%, –65% vs control). The peak isovolumic left ventricular systolic pressure (LVSP) is not changed significantly by adenosine (–6%, –4%, +5% vs control). The negative chronotropic effect of ajmaline with consecutive reduction of cardiac output is less pronounced (cardiac output: –18%, –20%, –38% vs control). The highest dose of ajmaline causes a significant reduction of peak isovolumic LVSP (–2%, –1%, –7% vs control). Adenosine has an impressive negative chronotropic effect with a consequent marked decrease of cardiac output. The reduction of cardiac output by adenosine is more pronounced compared with ajmaline. Nevertheless, adenosine has—in contrast to ajmaline—no cardiodepressive effectsin vivo.International Journal of Angiology 01/1998; 7(3):197-201. DOI:10.1007/BF01617392
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