Pharmacokinetics and antiarrhythmic efficacy of intravenous ajmaline in ventricular arrhythmia of acute onset

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.

Cardiac arrhythmias in acute coronary syndromes: position paper from the joint EHRA, ACCA, and EAPCI task force

“…The antiarrhythmic potential of these AADs for the suppression and termination of VA has been mainly studied until the 1990s. [34][35][36][37] However, in the setting of ACS, these drugs may cause an aggravation of VT/VF. After the publication of the CAST trial that has shown an increased mortality in patients after MI treated with encainide, flecainide, or moricizine as compared with placebo, further research to class IAAD and VA has largely been abandoned.…”

Computational Analysis of “-omics” Data to Identify Transcription Factors Regulating Secondary Metabolism in Rauvolfia serpentina

“…Reserpine is the principle component of R. serpentina used to treat hypertension (Hutcheon 1971;Nammi et al 2005), tachycardia (Jerie 2007), and allergy (Lelek and Furedi Szabo 1961). Other compounds such as ajmaline (Bazika 1969;Köppel et al 1989), serpentine (Beljanski and Beljanski 1982), rescinnamine (Hutcheon 1971;Nammi et al 2005), and yohimbine (Singh et al 2004) have also been reported in treatment of various diseases. Despite their broad pharmacological properties, limited information is available about regulatory factors involved in the synthesis of secondary metabolites (Chou and Kutchan 1998;Wink 2010) which further affect the yield and spectrum of such pharmacologically important compounds (De Luca and St Pierre 2000;Vom Endt et al 2002).…”

Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus

“…Reserpine is the principle component of R. serpentina which is used to treat hypertension (Nammi et al, 2005 ), tachycardia (Jerie, 2007 ), and allergy (Lelek and Furedi Szabo, 1961 ). Other compounds such as ajmaline (Köppel et al, 1989 ), serpentine (Beljanski and Beljanski, 1982 ), rescinnamine (Nammi et al, 2005 ), and yohimbine (Singh et al, 2004 ) are also used as therapeutics in the treatment of different diseases. Catharanthus roseus , a closely related medicinal plant to R. serpentina of same family, is also known for its anti-cancerous properties, where vinblastine and vincristine are the most important molecules that are effectively used in treatment of several cancers (van Der Heijden et al, 2004 ).…”