Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of Class V agents work by other or unknown mechanisms. With regard to management of atrial fibrillation, classes I and III are used in rhythm control as. Class III antiarrhythmic drugs act by blocking repolarising currents and thereby prolong the effective refractory period of the myocardium. This is believed to. Antiarrhythmics are used to treat heart rhythm disorders, called arrhythmias, and to Class IV antiarrhythmic medicines work like class III medicines but act by.
an Antiarrhythmic Act as 3.
Current evidence suggests that rhythm control has no morbidity or mortality benefit compared with ventricular rate control in elderly AF patients with established cardiac co-morbidity and moderately symptomatic AF. Severely haemodynamically compromised AF patients i. In haemodynamically stable AF patients, elective cardioversion either electrical or pharmacological is performed to improve symptoms, and the choice of cardioversion mode should be based on the clinical setting.
Intravenous flecainide and propafenone are restricted to patients without altered cardiac substrate. Ibutilide is an alternative to intravenous flecainide and propafenone; however, it is torsadogenic and should be avoided in patients with long QT and the QTc interval should be carefully monitored during and immediately after the infusion.
Table 13 Antiarrhythmic drugs currently used for cardioversion of atrial fibrillation. The use of dofetilide for AF cardioversion is recommended by the US guidelines, but not by the Canadian AF guidelines, and the drug is not available in Europe.
AV, atrioventricular; HF, heart failure; i. Rarely used for cardioversion of AF not indicated in reference 8. Pharmacological restoration and maintenance of sinus rhythm in AF patients. Acute pharmacological AF cardioversion is generally performed in the hospital setting and requires continuous medical supervision and ECG monitoring during the drug infusion and afterwards for at least half of the drug half-life.
Most AADs are given intravenously, with the exception of flecainide and propafenone which could be administered orally with similar efficacy Table Oral bolus of flecainide or propafenone can also be self-administered by selected outpatients with infrequent symptomatic paroxysmal AF, provided that their safety has been previously established in the hospital setting.
Typical atrial flutter is best treated by catheter ablation, which is comparably safe and more effective than AAD. Flecainide and propafenone may slow the flutter cycle thus facilitating 1: Ibutilide is more effective in conversion of flutter than AF, whereas vernakalant is ineffective for typical atrial flutter. However, quinidine and disopyramide [OR 2. Caution is needed when using any AAD in patients with conduction system disease e.
Amiodarone is more effective in rhythm control than other AADs, but extracardiac adverse effects may limit its long-term use. In a recent European survey, beta-blockers, flecainide, propafenone, and amiodarone were most frequently used first-line AAD for rhythm control. Limited data are available on the best type of rate control therapy and optimal heart rate during AF. Pharmacological rate control strategies rely on agents prolonging AV node refractoriness including beta-blockers, non-dihydropyridine calcium channel antagonists, digitalis, and amiodarone alone or in combination.
Non-dihydropyridine calcium channel antagonists are not recommended in patients with significant left ventricular systolic dysfunction because of their negative inotropic effect. Amiodarone may slow the ventricular rate in haemodynamically unstable patients, especially in the acute setting. It may be also used for chronic treatment, but its side effects limit long-term tolerability. Dronedarone should not be used for rate control in patients with permanent AF because of safety concerns.
Medication for rate control inf atrial fibrillation adapted from Algorithm for management of the proarrhythmic risk. In patients with pre-excited AF, agents acting primarily on the AV node e.
The acute management of VT includes the use of beta-blocker therapy and typically the use of AADs such as amiodarone, lidocaine and procainamide intravenously. Antiarrhythmic drugs therapy for the prevention of SCD due to ventricular tachyarrhythmias has not been shown to be effective in randomized controlled clinical trials, and therefore should be considered as adjunct therapy to ICD or catheter ablation.
Most patients with ventricular arrhythmias have structural heart disease, and therefore pharmacologic treatment is limited to amiodarone, sotalol, or other AAD in conjunction with ICD. In patients with monomorphic VT, catheter ablation has evolved as alternative treatment and results in a significant reduction of VT recurrences.
Patients suffering from VT arising from the right ventricular outflow tract, the left ventricular fascicular system or the mitral annulus, may respond to beta-blockade and or non-dihydropyridine-calcium channel blockers i. In patients not responding to conventional beta-blocker therapy, sotalol, flecainide, mexiletine, propafenone, or amiodarone may be used as alternative treatments.
As idiopathic VT can be successfully treated by catheter ablation in the majority of cases, usually patients will undergo the procedure having failed beta-blockade. Although beta-blockers are considered the mainstay of AAD therapy, their efficacy is low in preventing monomorphic sustained VT.
Amiodarone has been shown to reduce ICD interventions when used for secondary prevention. The PVT which occurs in the setting of normal QT interval is distinct from that which occurs in the setting of QT prolongation; the last, called TdP, is characterized by QRS morphology which is twisting around the isoelectric line.
Not only the ECG appearance but also the management is different between the two forms. Deep sedation, neuraxial modulation, mechanical ventilation, and catheter ablation are recommended in unstable patients non-responding to pharmacological therapy. Immediate coronary angiography is indicated when ischaemia is the cause. In all patients, the search for and correction of reversible causes hypokalaemia, hypomagnesaemia, acute decompensated heart failure, and proarrhythmic drugs are indicated.
Hypomagnesaemia is typically associated with PVT and responds to intravenous magnesium. The addition of flecainide should be considered in patients who experience recurrent PVT or syncope while on beta-blocker, or in patients non-suitable for ICD implantation. Torsadogenic drugs differ significantly in their arrhythmic risk profile. The anti-torsadogenic mechanism of magnesium is poorly understood. Increasing heart rate with isoproterenol or repletion of potassium to serotherapeutic levels 4.
One unique situation in which prophylactic treatment with lidocaine might have a role is its use after cardiac arrest and successful resuscitation, where it has led to suppression of recurrent ventricular arrhythmias and improved survival. Early use of beta-blockers in the setting of ACS reduces mortality, and the incidence of ventricular arrhythmias and is therefore recommended.
Correction of hypomagnesaemia and hypokalaemia may help in selected patients. Amiodarone may have the most balanced efficacy-to-risk profile, and should be considered only if episodes of VT or VF are frequent, and can no longer be controlled by successive electrical cardioversion or defibrillation.
However, the effect on global mortality is neutral. Lidocaine may reduce the incidence of ventricular arrhythmias related to myocardial ischaemia, although no beneficial effect on early mortality has been demonstrated. Statin therapy reduces mortality in patients with coronary artery disease, mostly through prevention of recurrent coronary events, and is therefore part of the recommended routine medication.
Evidence does not support the use of AADs for overall mortality reduction in patients with ventricular arrhythmias post-myocardial infarction and neither as prophylactic treatment in patients without demonstrable ventricular arrhythmias.
The following statements apply for patients with stable coronary artery disease after myocardial infarction and with preserved ejection fraction: Beta-blockers improve survival in patients who have had myocardial infarction in part by reducing the incidence of SCD. A substantial part of the survival benefit seen with beta-blockers in patients with heart failure is due to a significant reduction in SCD. Amiodarone may be considered for prevention of SCD, particularly in patients who cannot receive or do not have access to ICD therapy.
Angiotensin-converting enzyme ACE inhibitors improve survival in all stages of heart failure. Antiarrhythmic drugs play a major role in the treatment of both arrhythmogenic diseases such as arrhythmogenic right ventricular cardiomyopathy ARVC , hypertrophic cardiomyopathy as well as in ion channel diseases, since catheter ablation is associated with little or no success, and because electrical storm in these patients can only be controlled by AADs.
Patients with ARVC are often well controlled with amiodarone or sotalol, since they suffer most frequently from recurrent monomorphic VT. In LQTS, there are reports on many different beta-blockers. The most frequently used drugs are propranolol, metoprolol, and bisoprolol. Nadolol, which is very efficient, is used infrequently because of its limited availability in many countries.
In Brugada syndrome, quinidine is the therapy of choice as adjunct to an ICD or if a patient refuses an ICD, with reported favourable outcome. There is a large series of patients reported from Belhassen et al. In catecholaminergic PVT, beta-blockade is first line therapy and flecainide can be added with considerable success if beta-blockade does not suppress arrhythmias effectively.
In the setting of an electrical storm accompanying early repolarization syndrome, short-QT syndrome, and Brugada syndrome, quinidine can be used. Additionally, isoproterenol infusion is recommended in Brugada syndrome. Pacemakers PM are usually indicated for patients with symptomatic or high-risk bradyarrhythmia. They may also be indicated when a mandatory antiarrhythmic or other medication causes significant chronotropic or dromotropic side effects.
Antiarrhythmic drugs blocking sodium channel currents may increase pacing thresholds and lead to loss of capture. Specifically, some type IA agents quinidine, procainamide and most type IC agents encainide, flecainide, propafenone increase the pacing threshold, especially at higher doses.
Caution is advised in PM-dependent patients, when using these drugs, either a higher safety margin or automatic output regulation is recommended. These drugs may also slow down atrial tachyarrhythmia below the mode switch rate and may lead to inadvertent rapid ventricular pacing or affect device statistics. Propranolol, a Class II agent, also has some sodium channel-blocking effect and can increase the stimulation threshold when administered intravenously.
Table 15 Effect of antiarrhythmic medications on the pacing threshold. Among AAD therapies, amiodarone plus beta-blocker is effective for reducing ICD therapy, 52 though amiodarone adverse effects need to be appreciated. Sotalol is also effective, but less than amiodarone plus a beta-blocker. Table 16 Antiarrhythmic drugs for implantable cardioverter-defibrillator patients. In the first randomized study which evaluated the effects of AAD after radiofrequency catheter ablation of AF, after month follow-up, no significant difference was observed in the rates of AF recurrences, either in patients with paroxysmal or persistent AF, but AAD increased the proportion of patients with asymptomatic AF episodes.
Antiarrhythmic drugs were discontinued in Table 17 Randomized trials of empirical antiarrhythmic drug therapy after ablation of atrial fibrillation on the recurrence rate. Randomized trials of empirical antiarrhythmic drug therapy after ablation of atrial fibrillation on the recurrence rate.
However, not all studies demonstrated a benefit of AAD therapy in patients who underwent catheter ablation. For instance, a retrospective, non-randomized, single-centre study of ablation patients demonstrated no difference in the rates of early AF recurrence among those treated with an AAD or an AV nodal blocking agent alone. With the exception of beta-blockers, AADs have not been demonstrated to prevent life-threatening ventricular arrhythmias and SCD. However, most AAD might cause proarrhythmia.
Mexiletine and disopyramide should also be avoided in post-myocardial infarction patients. Dofetilide may provoke TdP in patients with severe heart failure. Amiodarone may also cause TdP although this is a very rare effect of the drug. Digitalis may cause diverse arrhythmias [e. In addition, several drugs e. Since polypharmacy is very often necessary, drug-drug interactions and their pharmacological consequences especially QT interval modification might become crucial Table However, other forms of drug induced rhythm disturbances, as bradycardia, may occur.
The list is very long, including almost all classes of drugs other than AAD: There is an individual genetic predisposition to proarrhythmia to a specific drug, the PD sensitivity, and vulnerability due to abnormal high plasma concentration of a drug given in therapeutical dosage.
The PK sensitivity, is explained by the interference of a single metabolizing pathway e. Table 18 Mechanisms promoting proarrhythmia. This monitoring is appropriate in hospital settings. Important are also the identification and modification whenever possible of risk factors potentially associated with arrhythmia onset or worsening e. In the case of drug-related proarrhythmia, the first-line of management is to stop the offending drug; however, in selected cases, the implantation of ICD needs to be considered based on the individual characteristics of the patient and the future risk of life-threatening ventricular tachyarrhythmias.
Sodium channel blocker-related proarrhythmia, generally secondary to slowing of conduction, include atrial flutter with 1: Besides discontinuation of the offending drug, management is based on control of the ventricular response by intravenous beta-blocker or calcium antagonist whereas incessant slow VT can be reversed by intravenous administration of sodium or sodium bicarbonate.
Beta-blockers have been reported to be effective in treating ventricular arrhythmias related to flecainide. In milder cases, arrhythmias due to digitalis toxicity can be managed by discontinuation of the drug, potassium supplementation, and observation. For digitalis-induced life threatening arrhythmias, several AAD have been proposed in the past e. More recently, digitalis-specific antibodies have proven effective in reversing digitalis toxicity by rapidly binding to and acutely lowering serum digitalis.
The pharmacological management of AF and other arrhythmias requires careful consideration from a safety perspective Table The full profile of potential cardiac effects should therefore be considered for each AAD and carefully tailored to the individual patient history before treatment is initiated. Table 19 Cardiac effects, extracardiac toxicities, and contraindications for antiarrhythmic drugs.
Not only thyroid tests can be modified, but, also, hyopthyroidism or hyperthyroidism can be induced. Amiodarone-induced hypothyroidism usually develop in patients with underlying thyroid abnormalities.
Stopping amiodarone or adding hormone replacement, are acceptable strategies in AIHT. Amiodarone-induced thyrotoxicosis is encountered mainly in the regions with insufficient iodine intake and it is more prevalent in men. Type 1 amiodarone-induced thyrotoxicosis occurs in patients with abnormal thyroid function, whereas Type 2 is a direct consequence of amiodarone.
Inflammatory markers IL-6 are markedly elevated in Type 2 amiodarone-induced thyrotoxicosis and thyroid autoantibodies are typically present in Type 1. Amiodarone should be stopped in amiodarone-induced thyrotoxicosis. In Type 1 amiodarone-induced thyrotoxicosis, prophylactic thyroid ablation thyroidectomy or radioactive iodine following the restoration of the normal thyroid function is recommended. However, Dronedarone is less effective than amiodarone and has itself adverse effects discussed in previous sections.
Periodic monitoring of lung function is required, and amiodarone should be avoided in patients with impaired pulmonary function. Supplementary material is available at Europace online. Gregory Lip Chair , Prof. Bulent Gorenek Co-chair , Prof. Close mobile search navigation Article navigation. Decisions to initiate antiarrhythmic drug therapy and follow-up.
Classification of antiarrhythmic drugs and overview of clinical pharmacology. Monitoring of antiarrhythmic drugs. Individualizing recommendations for pharmacological therapy of arrhythmias. Antiarrhythmic drug therapy to prevent sudden cardiac death in high-risk patients. Antiarrhythmic drugs as adjuvant to devices and arrhythmia interventions.
Safety issues for patients treated with antiarrhythmic drugs. Antiarrhythmic drugs—clinical use and clinical decision making: Gregory Y H Lip.
A correction has been published: View large Download slide. GI, gastrointestinal; PK, pharmacokinetics; Vd, distribution volume. Effect of antiarrhythmic drugs on heart rate, conduction, and repolarization. Drugs recommended for acute management of haemodynamically stable and regular tachycardia. Antiarrhythmic drugs currently used for cardioversion of atrial fibrillation. Antiarrhythmic drugs currently used for rhythm control in atrial fibrillation.
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New approaches to antiarrhythmic therapy, Part I: Upstream therapies for management of atrial fibrillation: Upstream therapies for management f atrial fibrillation: Novel pharmacological targets for the rhythm control management of atrial fibrillation.
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Effectiveness of oral propafenone for the prevention of atrial fibrillation after coronary artery bypass grafting. Hemodynamic effects of intravenous amiodarone in patients with depressed left ventricular function and recurrent ventricular tachycardia.
Although class I AADs are generally not prescribed for patients with ischaemic heart disease or cardiomyopathy, they are occasionally used in combination with amiodarone in patients who are refractory to amiodarone monotherapy, especially those with ICDs, as this provides some protection against potential proarrhythmic side effects. Phenytoin has class IB antiarrhythmic properties due to its effects on sodium channels in cardiac myocyte and Purkinje fibre cell membranes.
Therefore, it is particularly effective in inhibiting ventricular ectopy, especially in an ischaemic or damaged myocardium. Recent case reports have documented its successful use in controlling idiopathic ventricular fibrillation in a young man 7 and refractory idiopathic ventricular tachycardia VT in a newborn, 8 but these reports have not documented the potential dangers associated with its use.
Although phenytoin was successful in suppressing VT in our patient, this case report highlights several important learning points. Class I AADs, including phenytoin, can increase pacing threshold through use-dependent inhibition of sodium channel function. AADs can also increase the defibrillation threshold, increase VT cycle length potentially resulting in VT undersensing and reduce antitachycardia pacing efficacy.
Phenytoin exhibits zero-order pharmacokinetics, is susceptible to multiple drug interactions and has a narrow therapeutic window. Vertigo, ataxia, headache and nystagmus are common early side effects. At higher plasma concentrations, marked confusion and sedation may result. All of these changes occur acutely and are rapidly reversible. Cardiovascular side effects include bradycardia, hypotension and, occasionally, exacerbation of VT.
Our patient developed side effects despite a conventional loading protocol used in treating status epilepticus. Factors that may have contributed to toxicity were the presence of severe cardiomyopathy — which may have altered tissue distribution properties and resulted in a higher availability of unbound drug — and recent lignocaine administration, although this had been ceased 6 hours earlier.
Rapid loading of phenytoin for VT has been associated with fatal arrhythmogenic complications 3 and should therefore be cautiously performed. Phenytoin, a commonly used drug in the treatment of status epilepticus, is an old but effective treatment option in patients with malignant VT or electrical storm. Although it is readily available and is successful in terminating and suppressing malignant VT, appropriate caution must be taken with its use, especially with regard to the increased likelihood of drug toxicity in patients with cardiomyopathy and its important effects on pacemaker and ICD function.
These reported effects of phenytoin on pacemaker function are not only of interest to cardiologists caring for patients with ventricular arrhythmia, but also to neurologists, and emergency and general physicians who use phenytoin to terminate seizures.
Owing to the effects of phenytoin on pacemaker threshold and the attendant risks of loss of pacemaker capture, care should be taken with loading doses of phenytoin in patients who are pacemaker-dependent. Phenytoin has class IB antiarrhythmic drug properties and is a potential treatment option for patients with refractory ventricular arrhythmia when other agents have failed or are unavailable.
However, phenytoin has a narrow therapeutic range and the potential for multiple drug interactions. Phenytoin administration may also result in elevation of pacemaker threshold.
Care should be taken with loading doses in patients with cardiomyopathy or who are pacemaker-dependent, because of the potential for loss of pacemaker capture. Publication of your online response is subject to the Medical Journal of Australia 's editorial discretion. You will be notified by email within five working days should your response be accepted.
Basic Search Advanced search search. Agents used in cardiac arrhythmias. Mortality and morbidity in patients receiving encainide, flecainide or placebo. The Cardiac Arrhythmia Suppression Trial.
New Engl J Med ; Am J Cardiol ; Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Close mobile search navigation Article navigation. Classification of antiarrhythmic agents and the two laws of pharmacology Luc M. Department of Pharmacology, K.
Leuven, B Leuven, Belgium. Antiarrhythmic agents , Conduction block , Membrane potential , Ventricular arrhythmias. View large Download slide.
Kinetics of onset of rate-dependent effects of class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification. Time and voltage dependent interactions of antiarrhythmic drugs with cardiac sodium channels. Advantages of beta blockers versus antiarrhythmic agents and calcium antagonists in secondary prevention after myocardial infarction.
Prospective study of calcium channel blocker use, cardiovascular disease, and total mortality among hypertensive women: Class III antiarrhythmic agents have a lot of potential, but a long way to go: Computer aided development of antiarrhythmic agents with class III a properties.
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might prove to be especially effective. Mechanisms Instead of Classification. Class III antiarrhythmic agents are defined as antiarrhythmic drugs that act primarily. Class III antiarrhythmics prolong the action potential and refractory period, acting primarily by Class IV drugs act primarily by blocking calcium channels. class III potassium channel blocker drugs for treatment of arrhythmias.