The Efficacy of Ajmaline in Ventricular Arrhythmias after Failure of Lidocaine Therapy in the Acute Phase of Myocardial Infarction

Grenadier, Ehud; Alpan, Gad; Keidar, Shlomo; Weiss, Dov; Marmor, Alon; Palant, A

doi:10.1177/000331978303400307

Cited by 13 publications

(3 citation statements)

References 17 publications

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“…Hemodynamics were not affected in the patients of Groups 1-6. This is in agreement with the resnlts published by other authors (5,6). The only adverse effect observed in the patients was a transient left bundle branch block.…”

Section: Discussionsupporting

confidence: 93%

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

Köppel

Wagemann

Martens

1989

Eur. J. Drug Metab. Pharmacokinet.

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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.

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Section: Discussionsupporting

confidence: 93%

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

Köppel

Wagemann

Martens

1989

Eur. J. Drug Metab. Pharmacokinet.

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“…There is evidence also supportive of the view that PAF may contribute to myocardial ischaemia and reperfusion-induced arrhythmias by activated platelets (Wainwright et al 1989;Koltai et al 1989). Ajmaline is beneficial against ventricular arrhythmias not controlled by other anti-arrhythmic drugs (Grenadier et al 1983) and is found to be effective against reperfusion-induced arrhythmia (Okumura et al 1988).…”

Section: Discussionmentioning

confidence: 71%

Dual Inhibition of Platelet-activating Factor and Arachidonic Acid Metabolism by Ajmaline and Effect on Carrageenan-induced Rat Paw Oedema

Saeed

Simjee

Mahmood

et al. 1993

Journal of Pharmacy and Pharmacology

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The effects of ajmaline on human platelet aggregation, arachidonate metabolism and platelet activating factor (PAF)-induced lethality in rabbits were examined. Platelet aggregation induced by several stimuli (ADP, collagen, and PAF) was inhibited by increasing concentrations of ajmaline. The potency of ajmaline was higher when PAF was employed as stimulating agent in comparison with other agonists (IC50 70, 270 and 380 microM for PAF, ADP and collagen, respectively) whereas ajmaline had no effect against arachidonic acid-induced aggregation. In contrast however, ajmaline inhibited arachidonate metabolism by platelet homogenates. The formation of both thromboxane A2 and 12-hydroxy-eicosatetraenoic acid was inhibited by ajmaline with comparable potencies. Pretreatment of rabbits with ajmaline (50 mg kg-1) completely abolished the lethal effects of PAF (11 micrograms kg-1) given intravenously (P < 0.001). In addition, ajmaline at doses ranging from 50 to 100 mg kg-1 inhibited carrageenan-induced rat paw oedema (P < 0.001). In this test ajmaline was three times more potent than aspirin. In the light of these results we conclude that ajmaline, a known anti-arrhythmic agent is a PAF antagonist and a dual inhibitor of platelet cyclo-oxygenase and lipoxygenase enzymes with anti-inflammatory properties.

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“…1) is a class Ie antiarrhythmic with class IA properties which is clinically used in ventricular arrhythmia of acute onset refractory to lidocaine or in pre-excitation syndromes (1)(2)(3)(4)(5)(6). The clinical pharmacokinetics of ajmaline have recently been studied in intensive care patients m. After an infusion of 50 mg/5 min, a distribution half-life of 6 min and an elimination half-life of 95 min have been determined.…”

Section: Introductionmentioning

confidence: 99%

Metabolic disposition of ajmaline

Köppel

Tenczer

Arndt

1989

Eur. J. Drug Metab. Pharmacokinet.

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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.

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The Efficacy of Ajmaline in Ventricular Arrhythmias after Failure of Lidocaine Therapy in the Acute Phase of Myocardial Infarction

Cited by 13 publications

References 17 publications

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

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

Dual Inhibition of Platelet-activating Factor and Arachidonic Acid Metabolism by Ajmaline and Effect on Carrageenan-induced Rat Paw Oedema

Metabolic disposition of ajmaline

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