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Cardiovascular Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
A lidocaine-related antiarrhythmic medication, encainide, was not teratogenic in rats and rabbits when given at doses up to 9 and 13 times the human dose (Manufacturer’s package insert). Encainide is an FDA category B drug. The Swedish Birth Defects Registry contained no infants exposed to encainide during the first trimester.
Antidysrhythmic Drugs in Pediatrics
Published in Sam Kacew, Drug Toxicity and Metabolism in Pediatrics, 1990
Howard C. Mofenson, Thomas R. Caraccio, Kathleen Mimnagh, Peter Bruzzo
Encainide is a Class 1C oral agent which is very effective in the treatment of both supraventricular (especially those associated with accessory pathways) and ventricular dysrhythmias. It has little inotropic effect and modest incidence of side effects. In a large multicenter trial (double-blind, placebo-controlled crossover trial) including 187 patients, encainide therapy resulted in a 70% or greater reduction in the frequency of PVCs in 80% of the patients as determined by 24-h halter monitoring.187 In the same study, 75% of patients exhibited complete elimination of nonsustained VT. Encainide was shown to be more effective and to have less side effects than quinidine in the treatment of ventricular ectopy.188 As is true for the other available antidysrhythmics, the effectiveness of encainide in preventing dysrhythmias during programmed electrical stimulation is low (23%).189 See FDA’s recommendations for current use under flecainides.
Substrates of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Encainide, a benzanilide derivative, is a class Ic (sodium channel blocking) antiarrhythmic agent (Antonaccio et al. 1989) but no longer used because of its frequent proarrhythmic side effects. Encainide is particularly effective in patients with excessive premature ventricular complexes and less so in patients with sustained ventricular tachycardia (Antonaccio et al. 1989). After encainide labeled on the carbonyl carbon with 14C and at the benzylic (2′-1-ethyl) carbon with 13C is administered to healthy subjects, 42.0% of the radioactive dose is excreted in the urine in the first 24 h and the total urinary excretion is 47.0% and total fecal excretion is 38.7% over 5 days (Jajoo et al. 1990). At least six metabolites of encainide are identified from the hydrolyzed urine together with unchanged drug, including O-demethylencainide, 3-methoxy-O-demethylencainide, and N,O-di-demethylencainide, N-demethyl-3-methoxy-O-demethylencainide, 3-hydroxyencainide, and O-demethylencainide lactam, accounting for >90% of the radioactivity excreted in the urine (Figure 3.54) (Jajoo et al. 1990). Encainide is converted by CYP2D6 to active O-demethyl metabolite (Funck-Brentano et al. 1992), which is 6–10 times more potent than the parent drug in blocking sodium channels (Roden et al. 1982). In humans, encainide undergoes extensive metabolism via four major routes: (a) O-demethylation of the aromatic methyl ether, (b) formation of methylated catechol derivatives, (c) N-demethylation of the piperidyl nitrogen, and (d) oxidation at α-carbon to the piperidyl nitrogen (Jajoo et al. 1990).
Precision medicine in cardiac electrophysiology: where we are and where we need to go
Published in Expert Review of Precision Medicine and Drug Development, 2020
Ashish Correa, Syed Waqas Haider, Wilbert S. Aronow
From the 1960s through the 1980s, arrhythmia management rested on anti-arrhythmic drugs. However, over time, there was gradual recognition that any putative benefits brought on by these drugs were counterbalanced by various adverse effects, particularly pro-arrhythmic effects. The first major trial to demonstrate this was the Cardiac Arrhythmia Suppression Trial I (CAST I) in 1989 which randomized post-myocardial infarction patients to either antiarrhythmic therapy (with Class I agents flecainide, encainide, and/or moricizine) or placebo to analyze reduction sudden cardiac death (SCD) by malignant arrhythmias [1]. The trial had to be stopped early, because while the drugs did reduce premature ventricular contractions (PVCs) and non-sustained ventricular tachycardias (NSVT), they demonstrated a significant increase in mortality, primarily by pro-arrhythmic effects. This trial was followed by several other trials assessing anti-arrhythmics for the primary prevention of SCD, particularly in heart failure (HF) and post-myocardial infarction patients. These largely demonstrated no benefit, and sometimes even harm [2–4]. For atrial fibrillation (AF) and atrial flutter, apart from beta-blockers, calcium channel blockers, and the Class III agent amiodarone, very few anti-arrhythmic agents have shown long-term benefits. One notable exception is dofetilide, which was shown to be effective in cardioverting patients, both with and without concomitant HF, to sinus rhythm and in maintaining sinus rhythm [5,6].
New methodological approaches to atrial fibrillation drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Sodium channel blockers are classified as class I AAD in the Vaughan-William’s classification. They exert their action by blocking phase 0 inward sodium current (INa). Although class 1A agents such as procainamide, disopyramide, and quinidine, and class 1 C agents such as propafenone, flecainide, encainide, and pilsicainide have modest effect against AF, they are contraindicated in certain patient groups due to their proarrhythmic risk, such as the QT prolongation effect of class 1A agents, and other extra-cardiac side effects. [24]
Current pharmacotherapeutic strategies for cardiac arrhythmias in heart failure
Published in Expert Opinion on Pharmacotherapy, 2020
Ashish Correa, Yogita Rochlani, Wilbert S. Aronow
The Cardiac Arrhythmia Suppression Trial (CAST I) showed the marked pro-arrhythmic effects of class I antiarrhythmics (flecainide, encainide, propafenone) in the post-myocardial infarction population [61]. Extrapolating this information to the HF population, these agents are generally avoided in patients with HF.