Classification Of Antiarrhythmic Drugs Research Articles

Pharmacotherapy in arrhythmias: an overview of anti-arrhythmic drug therapy

The article provides an overview of the principles in anti-arrhythmic drug prescribing. The cardiac action potential is explained, followed by general principles involved in treating arrhythmias and prescribing decisions. An overview of the five classifications of anti-arrhythmic drugs is given, with examples of the main drugs in the classification and principles to consider within each. Finally, anticoagulation is reviewed, being a cornerstone prescribing decision-making in the most common arrhythmia, atrial fibrillation.

Pharmacotherapy in arrhythmias: an overview of anti-arrhythmic drug therapy

The article aims to give an overview of the principles in anti-arrhythmic drug prescribing. Practitioners assessing cardiac patients are highly likely to review anti-arrhythmic drug therapies and need an understanding of the principles of therapy. The cardiac action potential is explained, followed by general principles involved in treating arrhythmias and prescribing decisions. An overview of the five classifications of anti-arrhythmic drugs is given, with examples of the main drugs in the classification and principles to consider within each. Finally anticoagulation is reviewed being a cornerstone prescribing decision in the most common arrhythmia, atrial fibrillation.

ArrhythmoGenoPharmacoTherapy.

This review is focusing on the understanding of various factors and components governing and controlling the occurrence of ventricular arrhythmias including (i) the role of various ion channel-related changes in the action potential (AP), (ii) electrocardiograms (ECGs), (iii) some important arrhythmogenic mediators of reperfusion, and pharmacological approaches to their attenuation. The transmembrane potential in myocardial cells is depending on the cellular concentrations of several ions including sodium, calcium, and potassium on both sides of the cell membrane and active or inactive stages of ion channels. The movements of Na+, K+, and Ca2+ via cell membranes produce various currents that provoke AP, determining the cardiac cycle and heart function. A specific channel has its own type of gate, and it is opening and closing under specific transmembrane voltage, ionic, or metabolic conditions. APs of sinoatrial (SA) node, atrioventricular (AV) node, and Purkinje cells determine the pacemaker activity (depolarization phase 4) of the heart, leading to the surface manifestation, registration, and evaluation of ECG waves in both animal models and humans. AP and ECG changes are key factors in arrhythmogenesis, and the analysis of these changes serve for the clarification of the mechanisms of antiarrhythmic drugs. The classification of antiarrhythmic drugs may be based on their electrophysiological properties emphasizing the connection between basic electrophysiological activities and antiarrhythmic properties. The review also summarizes some important mechanisms of ventricular arrhythmias in the ischemic/reperfused myocardium and permits an assessment of antiarrhythmic potential of drugs used for pharmacotherapy under experimental and clinical conditions.

The Impact of Teaching Up‐to‐Date Medical Pharmacology Material. Who Wins? The Board Preparation Resources!!

IntroductionPharmacology faculty are faced with the challenge of preparing medical students to become doctors but are also challenged with preparing the students to successfully complete the USMLE Step‐1, and or COMLEX Level‐1 (for osteopathic medical schools). Faculty student evaluations can help highlight the student perspective on this high‐stakes exam and the pressure it brings. But what is a pharmacology faculty to do when traditional resources such as textbooks and even some board preparation resources are not in agreement with the most current therapeutic guidelines.MethodsMost recently in 2017 and 2018 there were updates in the management of hypertension (2017) and hyperlipidemias (2018), and even the classification of antiarrhythmic drugs (2018). Those updates, amongst others, were most recently addressed in a second‐year cardiovascular system pharmacology course in our institution. Revisions required updating the pharmacology content of the course and sharing the updates on the scope of pharmacology with the physician faculty who also teach about the drugs. We then compared the student feedback in the course from the previous five years using a thematic analysis approach.ResultsThe number of times words such as: “clinical”, “integration”, and/or “boards” appeared in course‐evaluation surveys was two to three‐fold higher in 2019 compared to that of previous 5 years. Presenting updated content caused more frustration and discontent among some medical students. When the content did not necessarily match that found in the popular board preparation resources it led to a distrust in the instructor.ConclusionsThe latest pharmacology information may not necessarily support the information found in board preparation resources. In addition, clinical faculty may present therapeutic information based on their own clinical experience. Often it is the case that the pharmacology faculty is solely responsible for the overall content in the curriculum even when it may be presented at different levels from different sources. Students need to succeed on the boards and in our pharmacology courses but what are the faculty to do when the AMSPC knowledge objectives, which have traditionally been used as the standard of what to teach in pharmacology, become outdated. There is a need for updated pharmacology knowledge objectives.Support or Funding InformationNAComparison of the Cardiovascular System End‐of‐Course Evaluations as it pertains to PharmacologyFigure 1

Антиаритмические препараты: механизмы действия, клинические эффекты, показания к применению

The lecture is devoted to one of the most difficult problems of modern cardiology – the use of antiarrhythmic therapy in clinical practice. The basic mechanisms of arrhythmias, aspects of their onset, maintenance and termination are briefly described. The current evidence on the electrophysiological mechanisms of cardiac arrhythmias – re-entry, abnormal impulse formation, and trigger activity – is presented. The article contains information about the remodeling of ion channels properties. The Sicilian gambit is analyzed, in which the mechanisms of arrhythmias are compared to the mechanisms of anti-arrhythmic action of drugs. Classification of anti-arrhythmic drugs, their mechanisms of action, indications and contraindications, side effects, and interaction with other drugs are presented.

Antiarrhythmic drugs: mechanisms of action, indications for use, side effects

The lecture is devoted to one of the most difficult problems of modern cardiology – the use of antiarrhythmic therapy in clinical practice. The basic mechanisms of arrhythmias, aspects of their onset, maintenance and termination are described briefly. The current evidence on the electrophysiological mechanism of cardiac arrhythmias - re-entry, enhanced or abnormal impulse formation, and trigger activity – is presented. The article contains information about the remodeling of ion channels properties. The Sicilian gambit, in which the mechanisms of arrhythmias are corresponded to the mechanisms of action of anti-arrhythmic drugs, is discussed. There are described the classification of anti-arrhythmic drugs, their mechanisms of action, indications and contraindications, side effects, and the drug interaction.

Vaughan Williams classification of antiarrhythmic drugs

Denise Drummond Hayes is a Basic Life Support/Advanced Cardiovascular Life Support instructor at Temple University Hospital System, American Heart Association Training Center in Philadelphia, Pa., and the senior clinical editor for Nursing2018. Unless otherwise specified, the information in the preceding summaries applies to adults, not children. Consult the package insert for information about each drug's safety during pregnancy and breastfeeding. Also consult a pharmacist, the package insert, or a comprehensive drug reference for more details on precautions, drug interactions, and adverse reactions.

Modernized Classification of Cardiac Antiarrhythmic Drugs.

Among his major cardiac electrophysiological contributions, Miles Vaughan Williams (1918-2016) provided a classification of antiarrhythmic drugs that remains central to their clinical use. We survey implications of subsequent discoveries concerning sarcolemmal, sarcoplasmic reticular, and cytosolic biomolecules, developing an expanded but pragmatic classification that encompasses approved and potential antiarrhythmic drugs on this centenary of his birth. We first consider the range of pharmacological targets, tracking these through to cellular electrophysiological effects. We retain the original Vaughan Williams Classes I through IV but subcategorize these divisions in light of more recent developments, including the existence of Na+ current components (for Class I), advances in autonomic (often G protein-mediated) signaling (for Class II), K+ channel subspecies (for Class III), and novel molecular targets related to Ca2+ homeostasis (for Class IV). We introduce new classes based on additional targets, including channels involved in automaticity, mechanically sensitive ion channels, connexins controlling electrotonic cell coupling, and molecules underlying longer-term signaling processes affecting structural remodeling. Inclusion of this widened range of targets and their physiological sequelae provides a framework for a modernized classification of established antiarrhythmic drugs based on their pharmacological targets. The revised classification allows for the existence of multiple drug targets/actions and for adverse, sometimes actually proarrhythmic, effects. The new scheme also aids classification of novel drugs under investigation. We emerge with a modernized classification preserving the simplicity of the original Vaughan Williams framework while aiding our understanding and clinical management of cardiac arrhythmic events and facilitating future developments in this area.

О классификации и принципах действия антиаритмических средств

В обзоре представлены данные об основных патофизиологических механизмах аритмий и сведения об электрофизиологических механизмах действия антиаритмических препаратов. Проводится анализ развития классификации антиаритмических средств до настоящего времени.

Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

The aim of this study was to classify antiarrhythmic drugs based on their effectiveness on 6 in vivo arrhythmia models, mainly using dogs. The models were produced by two-stage coronary ligation, digitalis, halothane-adrenaline, programmed electrical stimulation in old myocardial infarction dogs, coronary artery occlusion/reperfusion, or chronic atrioventricular block. Na+-channel–blocking drugs suppressed two-stage coronary ligation and digitalis arrhythmias. Ca2+-channel blockers and β-blockers suppressed halothane-adrenaline arrhythmia. Positive inotropic drugs aggravated halothane-adrenaline arrhythmia, but did not aggravate digitalis arrhythmia. K+-channel blockers suppressed programmed electrical stimulation induced arrhythmia, but induced torsades de pointes type arrhythmia in chronic atrioventricular block dogs and aggravated halothane-adrenaline arrhythmia. Na+/H+-exchange blockers suppressed coronary artery occlusion/reperfusion arrhythmias. This classification may be useful for predicting the clinical effectiveness in the preclinical stage of drug development.

Complications during vascular surgery: basic principles and management of arrhythmias

This chapter focuses on the anatomy and physiology of arrhythmias and specifically only on supraventricular arrhythmias, as these are the most common requiring treatment in the perioperative period. Rational treatment of arrhythmias requires an understanding of the anatomy of the conduction system, the pathophysiological and electrophysiological basis of arrhythmias, and the basic mechanisms of anti-arrhythmic drug action. This chapter reviews the basic anatomy of the conduction system and then focuses on both abnormal impulse generation and conduction. The conventional classification of anti-arrhythmic drugs is then discussed, followed by some newer approaches to classification based on a more detailed understanding of the mechanisms of action. Finally, management of common supraventricular arrhythmias is presented.

Classification of Antiarrhythmic Drugs

Classification of Antiarrhythmic Drugs

Evolution, mechanisms, and classification of antiarrhythmic drugs: focus on class III actions

Since the use of cinchona bark to treat heart palpitations in the 1700s, antiarrhythmic drug therapy has developed with the discovery of new compounds and the identification of ionic, cellular, and tissue mechanisms of action. Classifications have been developed that organize the large amount of information available about antiarrhythmic drugs around groups of compounds with common mechanisms of action. Despite important and well-recognized limitations, antiarrhythmic drug classification is still widely used. In particularly broad use is the system developed by Singh and Vaughan Williams in the early 1970s and subsequently modified by Singh and Hauswirth and by Harrison. This classification divides drug actions into class I for sodium-channel blockade (with subclasses IA, IB and IC), class II for adrenergic antagonism, class III for action-potential prolongation, and class IV for calcium-channel blockade. The development of class I drugs was curtailed when studies showed that potent sodium-channel blockers (particularly IC agents) can increase mortality in patients with active coronary artery disease. The emphasis in drug development shifted to class III agents, but their use has been limited by the risk of ventricular tachyarrhythmia induction associated with QT prolongation. Current research focuses on the development of new class III drugs that may have improved safety by virtue of greater selectivity of action at faster rates (like those of arrhythmia) or for atrial tissue. Alternative approaches include the modification of existing molecules (like amiodarone) to maintain positive properties while removing undesirable ones, and treatments that target development of the arrhythmia substrate instead of the final electrical product.

The impact of recent ion channel science on the development and use of antiarrhythmic drugs.

In the past 20 years in the basic laboratory, tools have been developed to further our understanding of the mechanism of arrhythmias and of the effect of compounds on these or their substrates. Patch clamp studies have better defined the cardiac channels. A new classification of antiarrhythmic drugs was devised, coined the Sicilian Gambit. Drugs, aimed at blocking specific channels, are now being developed. With the cloning of channels, information about their molecular structure became available. One can begin to understand the molecular determinants of antiarrhythmic drug action on specific ion channels, and how this is modulated by effectors. Molecular and electrophysiologic techniques also have been used to collect information about the way disease states affect the cardiac channels, and how this can alter the response to ion channel blockers. This has proceeded utilizing a few technologies. Diseased heart cells from patients, from animal models of disease, or from transgenic mice are studied to examine the change in current expression and channel protein quantity in different stages of disease. Hopefully this new information will make drug therapy more target-oriented.

Chaos and the Transition to Ventricular Fibrillation

Sudden cardiac death resulting from ventricular fibrillation can be separated into 2 components: initiation of tachycardia and degeneration of tachycardia to fibrillation. Clinical drug studies such as CAST and SWORD demonstrated that focusing exclusively on the first component is inadequate as a therapeutic modality. The hope for developing effective pharmacological therapy rests on a comprehensive understanding of the second component, the transition from tachycardia to fibrillation. We summarize evidence that the transition from tachycardia to fibrillation is a transition to spatiotemporal chaos, with similarities to the quasiperiodic transition to chaos seen in fluid turbulence. In this scenario, chaos results from the interaction of multiple causally independent oscillatory motions. Simulations in 2-dimensional cardiac tissue suggest that the destabilizing oscillatory motions during spiral-wave reentry arise from restitution properties of action potential duration and conduction velocity. The process of spiral-wave breakup in simulated cardiac tissue predicts remarkably well the sequence by which tachycardia degenerates to fibrillation in real cardiac tissue. Modifying action potential duration and conduction velocity restitution characteristics can prevent spiral-wave breakup in simulated cardiac tissue, suggesting that drugs with similar effects in real cardiac tissue may have antifibrillatory efficacy (the Restitution Hypothesis). If valid for the real heart, the Restitution Hypothesis will support a new paradigm for antiarrhythmic drug classification, incorporating an antifibrillatory profile based on effects on cardiac restitution and the traditional antitachycardia profile (classes 1 through 4).

Pharmacological effects of antiarrhythmic drugs. Review and update.

Most antiarrhythmic drugs are potent compounds with a relatively narrow therapeutic index. When prescribed judiciously, they can have a key role in enhancing or prolonging the lives of patients with most common arrhythmias. But when misprescribed, through selection of an inappropriate drug or dosage regimen, the end result may range from inadequate control of the arrhythmia to a proarrhythmic effect. Ultimately, the optimal use of antiarrhythmic drug therapy depends in large part on understanding the pharmacodynamics and pharmacokinetics of each antiarrhythmic drug. Despite the common classification of antiarrhythmic drugs into class I, II, III, or IV, each drug has a unique pharmacological profile and must not be considered interchangeable with other members of its class. Likewise, each patient is unique with respect to the innumerable factors that can alter the pharmacokinetics of an antiarrhythmic drug, including coexisting diseases, concurrent drug therapies, and endogenous or age-related metabolic variations. This article provides an overview of the key pharmacodynamic and pharmacokinetic characteristics of the major antiarrhythmic drugs in use. It also offers specific examples that may be used to ensure that patients receive the most appropriate therapy.

Section Review: Cardiovascular & Renal: Developments in antiarrhythmic drugs: An overview

In the more industrialised part of the world, sudden cardiac (arrhythmic) death has remained, throughout recent years, the leading cause of mortality. Preventing lethal arrhythmias has been a top priority in medical research and the literature abounds with reports describing the mechanisms of action of anti- or pro-arrhythmic agents and their cardiac electrophysiological effects. Studies such as the Cardiac Arrhythmia Suppression Trials (CAST-I and -II) [1], CASCADE (Cardiac Arrest in Seattle, Conventional versus Amiodarone Drug Evaluation) [2], CASH (Cardiac Arrest Study Hamburg), CAMIAT (Canadian Amiodarone Myocardial Infarction Arrhythmia Trial) [3], ESVEM (Electrophysiologic Study versus Electrocardiographic Monitoring Trial) [4], CAPS (Cardiac Arrhythmia Pilot Study) and DAVIT (Danish Verapamil Infarction Trial) [5] for example, and new approaches to the classification of antiarrhythmic drugs, based on their actions on arrhythmogenic mechanisms and studies of ‘cardioprotective’ agents and potassium c...

Classification and mechanism of action of antiarrhythmic drugs.

The present paper reviews classification and mode of action of agents that suppress extrasystoles and tachyarrhythmias. These are classified according to their electrophysiological effects observed in isolated cardiac tissues in vitro (Vaughan Williams, 1989). Fast sodium channel blockers (class I) which reduce the upstroke velocity of the action potential are usually subclassified into three groups, class I A-C, according to their effect on the action potential duration. Beta-adrenergic antagonists (class II) exert their effects by antagonizing the electrophysiological effects of beta-adrenergic catecholamines. Class III antiarrhythmic agents (eg amiodarone) prolong the action potential and slow calcium channel blockers (class IV) suppress the calcium inward current and calcium-dependent action potentials. The classification of antiarrhythmic drugs is still under debate. This particularly applies to agents of class I and III. The effect of class I agents is frequency-dependent because the binding affinity of these drugs to the sodium channel is modulated by the state of the channel (modulated receptor hypothesis). Class I agents bind to the channel in the activated and inactivated state and dissociate from the channel in the rested state. This occurs at a drug-specific rate so that class I agents can be subclassified into only two groups, namely in those of the slow- and fast-recovery type respectively (time constant of reactivation greater or smaller than 1 s). Slow-recovery class I agents affect regular action potentials at normal heart rates which can more easily lead to a lengthening of the QRS duration in the ECG, to conduction disturbances and hence to pro-arrhythmic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiarrhythmic drug classifications and the clinician: A gambit in the land of chaos

Several classifications of antiarrhythmic drugs have appeared and all suffer considerable limitations. Recently a Task Force of the Working Group on Arrhythmias of the European Society of Cardiology proposed a novel classification of antiarrhythmic drugs (the so-called Sicilian Gambit) based on their action on the most vulnerable parameter of an arrhythmogenic mechanism. The present article attempts a critical reappraisal of the antiarrhythmic drug actions and the relationship of vulnerable parameters with cellular mechanisms such as ion channels. The clinical applicability of these concepts, the implications of the new classification in the pharmacologic therapy of arrhythmias, and its potential limitations are discussed.

Comparative mechanisms of action of antiarrhythmic drugs

The most widely used classification of antiarrhythmic drugs, formulated by Singh and Vaughan Williams, divides antiarrhythmic agents into 4 categories: (1) sodium channel blockers; (2) sympatholytic agents; (3) drugs that delay repolarization; and (4) calcium antagonists. Despite some controversy regarding its value, the available evidence indicates that this classification relates well to the most important clinically relevant mechanisms of antiarrhythmic drug action. Amiodarone is unique in that it possesses properties belonging to all 4 of the Singh and Vaughan Williams classes; moreover, all 4 properties contribute to the beneficial actions of the drug. Class 1 effects are responsible for amiodarone's ability to slow ventricular tachycardias, making them hemodynamically better tolerated, and are likely important in amiodarone's premature ventricular complex-suppressing properties. Class 2 effects may contribute to atrioventricular (AV) node-suppressing actions and may confer protection against sudden death in the postmyocardial infarction population. Class 3 actions contribute to amiodarone's ability to prevent reentrant atrial and ventricular arrhythmias, and may be responsible for a superior ability to maintain sinus rhythm after cardioversion of atrial fibrillation. Class 4 properties contribute to amiodarone's ability to stow the ventricular response in atrial fibrillation and to prevent AV node reentrant arrhythmias. Calcium channel antagonism may also suppress arrhythmias (such as torsades de pointes) caused by early after-depolarizations and contribute to the apparent infrequency of torsades, despite substantial QT prolongation, among patients treated with amiodarone. Consideration of the link between amiodarone's pharmacologic properties and clinical effects illustrates well the various mechanisms of antiarrhythmic drug action.