Anti-Arrhythmic Drugs

Antiarrythmic drugs

The drugs used for arrhythmias fall into five major groups or classes:-

1.       Group 1

  • Membrane stabilizing agents
  • Sodium channel blockers

      i.      Group1A- Quinidine, Procainamide, Disopyramide

      ii.      Group1B-lidocaine, Mexiletine

      iii.      Group1C-Propafenone, Flecainide

 

2.       Group 2

  • Antiadrenergic agents
  • β blockers
  • Propanolol, Esmolol, Sotalol (also group 3)

 

3.       Group 3

  • Agents widening AP (prolong repolarization and ERP)
  • Potassium channel blockers
  • Amiodarone, Dronedarone, Dofetilide, Ibutilide

 

4.       Group 4

  • Calcium channel blockers
  • Verapamil, Diltiazem

5.       Group 5

  • Miscellaneous group

            i.      Adenosine

            ii.      K+

            iii.      Mg2+

 

 

Group 1

Membrane stabilizing agents-Local anesthetics

Sodium channel blockers

  1. Prototype drugs and mechanism of action

 

  • Procainamide-prolong the AP
  • lidocaine-shorten the AP in some cardiac tissues.
  • Flecainide-have no effect on AP duration.

 

  • All group 1 drugs slow conduction in ischemic and depolarized cells and slow or abolish abnormal pacemakers wherever these processes depend on sodium channels.
  • The most selective agents (Group1B) have significant effects on sodium channels in ischemic tissue, but negligible effects on channels in normal cells
  • In contrast, less selective agents (group1A & 1C) cause some reduction of INa even in normal cells.
  • These group 1 drugs bind to their receptors much more readily when the channel is open or inactivated than when it is fully repolarized and resting. Therefore, they block channels in abnormal tissue more effectively than channels in normal tissue.
  • They are use dependent or state dependent in their action-ie, they selectively depress tissue that is frequently depolarizing, eg, during a fast tachycardia; or tissue that is relatively depolarized during rest, eg, by hypoxia).

 

 

Drugs with group 1A action- (Procainamide, Quinidine, Disopyramide)-

  • These drugs affect both atrial and ventricular arrhythmias.
  • They block INa and therefore slow conduction velocity in the atria, Purkinje fibers, and ventricular cells.
  • At high doses they may slow AV conduction.
  • Amiodarone (group 3 agent) also has typical group 1A actions –has similar effects on sodium current (INa block) and has the greatest AP-prolonging effect (Ik block).
  • Procainamide is also commonly used in arrhythmias during the acute phase of myocardial infarction.
  • Procainamide may cause hypotension and a reversible syndrome similar to lupus erythematosus.
  • Procainamide can induce systemic lupus erythematosus in patients. (1)
  • When the oral administration of procainamide is indicated for the management of vantricular arrhythmias after myocardial infarction, a sustained release preperation should be used. (2)
  • Procainamide may interact with lymphocyte membrane, producing a lupus syndrome directly, by altering lymphocyte function, or indirectly by generating autoantibodies reactive with normal membrane structures. (3)
  • Flecainide is a highly effective drug, superior to procainamide for the treatment of paroxysmal atrial fibrillation. (4)
  • Procainamide is used to treat recurrent ventricular fibrillation or ventricular tachycardia, paroxysmal supraventricular tachycardia uncontrolled by vagal maneuvers and adenosine, stable wide complex tachycardia of unknown origin and rapid rate atrial fibrillation in patients with Wolff-Parkinson-White syndrome. (5)
  • HYperkalemia strongly enhances procainamide induced conduction slowing by increasing the interaction between the drug and sodium channels during the rested phase of the cardiac cycle. (6)
  • Neutrophils mediates the metabolism of procainamide and there is a role of myeloperoxidase during degranulation and H2O2 derived from the respiratory burst in the direct cooxidation of procainamide to PAHA. (7)
  • Levofloxacin and ciprofloxacin decrease procainamide renal clearance. (8)
  • Agranulocytosis arises from a different mechanism than that underlying procainamide induced lupus. (9)
  • Procainamide may produce electrophysiologic features of sick sinus syndrome in patients with chronic renal failure even when its blood levels are being monitored. (10)
  • Abnormal changes in repolarization may contribute to pro-arrhythmic effects of procainamide. (11)
  • Short elimination half life and rapid plasma clearance of procainamide in children suggest that continuous intravenous infusion may be necessary to maintain therapeutically effective plsama concentrations. (12)
  • Procainamide potentiates the blockade caused by rocuronium. (13)
  • Procainamide is a specific inhibitor of DNA Methyltransferase 1. It may be a useful drug in the prevention of cancer. (14)
  • Myotonia of respiratory muscles can cause sevre dyspnea in patients with myotonic dystrophy. This can be improved by antimyotonic therapy like procainamide. (15)
  • Procainamide could be used as a possible therapeutic potential in type 2 diabetics as an epigenetic demethylating agent to increase insulin levels. It is better to be used in combination with oral hypoglycemic agent like metformin to decrease insulin resistance. (16)
  • Quinidine causes cinchonism (headache, vertigo, tinnitus); cardiac depression; GI upset; and autoimmune reactions (eg, thrombocytopenic purpura).
  • Quinidine reduces the clearance of digoxin and may increase the serum concentration of glycoside significantly.
  • Quinidine reduce significantly the recurrence of atrial fibrillation during a 1-year follow up period after successful electric shock conversion. (17)
  • The increase in serum digoxin concentrations an ddecrease in volumes of digoxin distribution when quinidine is administered to digoxin treated patients reflects a decrease in affinity of tissue receptors for digoxin. (18)
  • Amiodarone and quinidine interacts with each other, raises the plasma quinidine concentration, prolongs the QT interval and causes atypical ventricular tachycardia (torsades de pointes). (19)
  • Quinidine is an effective antimalarial drug for plasmodium falciparum infections and may be more potent than quinine. (20)
  • The marked prolongation of A-V conduction time produced by quinidine is antagonized by low K+ and enhnced by high  K+ concentration. Quinidine or high K+ concentration prolongs the A-V interval by slowing intra-atrial and His-Purkinje-ventricular conduction. Low K+ concentration depresses conduction in the N region of the AV node. Quinidine and high K+ concentration increases the action potential amplitude in the nodal and the node-His regions of the AV node while low K+ concentration shows the opposite effects. (21)
  • The antiadrenergic actions of quinidine can be explained by occupancy and competitive blockade of alpha-1 and alpha 2 adrenergic receptors. (22)
  • Syncope due to quinidine induced ventricular tachycardia and fibrillation can be abolished by intravenous administration of a bolus of 25-50 mg lidocaine infusion. (23)
  • Approximately half of the patients receiving dextromethorphan 20 mg/ quinidine 10 mg (DMQ) experience the pseudobulbar affect (PBA) during 12 week period. (24)
  • Thrombocytopenia occurs due to hypersensitivity to quinidine. (25)
  • KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine. (26)
  • Quinidine can induce acute lymphadenopathy syndrome in some patients. (27)
  • Quinidine does not significantly alter the toxicity profile, response rate or survival after epirubicin chemotherapy in patients with advanced breast cancer. This may be due to ineffective modulation of P-glycoprotein by quinidine or the lack of expression of mdr-1 in a sufficient proportion of cells in these tumors, or alternative mechanisms underlying resistance to epirubicin. (28)
  • Both electrical cardioversion and pharmacological cardioversion with quinidine are valid and effective in patients with atrial fibrillation. The decision to choose one or the other depends on the exprience of the cardiologist. (29)
  • Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with amyotrophic lateral sclerosis, Alzheimer's disease, stroke, multiple sclerosis, Parkinson's disease and traumatic brain injury. Dextromethorphan/quinidine (DM/Q) product is indicated for the treatment of PBA. (30)
  • Quinidine has a low toxic-therapeutic, prolong ventricular repolarization, causes sudden death due to torsades de pointes. Apart from temporary pacemaker for symptomatic bradycardia, sodium bicarbonate is effective in reversing cardiotoxicity. (31)
  • Clarithromycin causes reduced CYP3A4 activity leading to increased plasma level of Quinine/ Quinidine to produce enhanced antimalarial activity. (32)
  • QQuinidine produces twitch potentiation and contracture by interfering with intracellular calcium sequestration. In cardiac sarcoplasmic reticulum, following inhibition of calcium transport there will be less calcium available for coupling. (33)
  • Dextromethorphan-Quinidine is effective for Pseudobulbar affect. (34)
  • Disopyramide has marked antimuscarinic effects and may precipitate heart failure.
  • The mean plasma levels of disopyramide and mono-N-dealkyldisopyramide is high in patients with renal impairment. In patients with effective treatment of ventricular arrhythmias, the level of disopyramide is higher than those with ineffective treatment. Average protein binding of disopyramide is 82% and that of mono-N-dealkyldisopyramide is 22-35%. The protein binding is not altered in renal insufficiency, but slightly decreased by high concentrations of mono-N-dealkyldisopyramide. (35)
  • The concentrations of free disopyramide is little affected by temperature, is decreased as the pH is increased from 7.0 to 7.8. The concentration of free disopyramide is strongly and directly related to total drug concentration. (36)
  • At therapeutic concentrations, diopyramide is not appreciably dialyzed. (37)
  • Pyridostigmine selectively reverses the troublesome anticholinergic side efefcts of disopyramide without affecting its electrophysiologic or antiarrhythmic properties. (38)
  • Disopyrmaide breaks atrioventricular nodal re-entrant tachycardia by specific blockade os the retrograde fast pathway though the effect on anterograde atrioventricular nodal conduction is variable. (39)
  • Disopyramide is useful in preventing ventricular fibrillation which result from a rapid ventricular response to atrial fibrillation in patients with Wolff-Parkinson-White syndrome. (40)
  • Disopyramide slows the conduction through all parts of the conducting system to approximately the same degree with perhaps a slightly greater slowing through the atrioventricular node. (41)
  • Disopyrmaide induces ventricular tachycardia in patients with ischemic cardiomyopathy and congestive heart failure. (42)
  • There is a synergic effect of fludrocortisone and disopyramide in an elderly patient with orthostatic syncope. (43)
  • Disopyramide can induce neuropathy in patients. (44)
  • Two-third of obstructed HCM patients treated with disopyramide can be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over > 3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternative strategies. (45)
  • All group1A drugs may precipitate new arrhythmias.
  • Torsades de pointes is particularly associated with quinidine and other drugs that prolong AP duration (except amiodarone).
  • Hyperkalemia usually exacerbate the cardiac toxicity of group 1 drugs.
  • Treatment of overdose with these agents is often carried out with sodium lactate (to reverse drug-induced arrhythmias) and pressure sympathomimetics (to reverse drug-induced hypotension) if indicated.

B.     Drugs with group 1B action-(Lidocaine, Mexiletine)

  • Lidocaine is used exclusively by iv or im routes as it has a very high first-pass effect and its metabolites are potentially cardiotoxic.
  • Mexiletine is an orally active 1B agent.
  • These drugs selectively effect ischemic or depolarized Purkinje and ventricular  tissue and have little effect on atrial tissue
  • The drugs reduce AP duration in some cells, but because they slow recovery of sodium channels from inactivation, they do not shorten (and may even prolong) the effective refractory period.
  • As they have little effect on normal cardiac cells, they have little effect on the ECG.
  • Phenytoin, an anticonvulsant and not a true local anesthetic, is sometimes classified with the group 1B antiarrhythmic agents because it can be used to reverse digitalis –induced arrhythmias.
  • It resembles lidocaine in lacking significant effects on the normal ECG.
  • They are useful in acute ischemic ventricular arrhythmias for eg. after MI.
  • They causes typical local anesthetic toxicity (ie, central nervous system {CNS} stimulation, including convulsions); cardiovascular depression (usually minor); and allergy (rashes, anaphylaxis).
  • They also precipitate arrhythmias but less common than with group 1A drugs.
  • Hyperkalemia increases cardiac toxicity.
  • Lidocaine is used exclusively by iv or im routes as it has a very high first-pass effect and its metabolites are potentially cardiotoxic.
  • LIdocaine toxicity can be misinterpreted as stroke. The risk factors for lidocaine toxicity are hepatic dysfunction, cardiac dysunction, advanced age and other drug administration. (46)
  • Lidocaine has the ability to reduce the vulnerability of the heart to fibrillation during supraventricular rhythm, acute ischemia and premature ventricular beats. (47)
  • LIdocaine binds preferentially to inactivated sodium channels and the dissociation from resting channels is voltage dependent. (48)
  • Local lidocaine injections into the myofascial trigger points located in the pericranial muscles could be considered as an effective treatment for episodic tension type headache. (49)
  • Despite the potential benefit of using lidocaine and fentanyl in patients undergoing neuroprotectibe rapid sequence intubation (RSI) in the mergency department, there is a significant underultilization of optimal premedication. The identification of barrier to use and the implementation of strategies to optimize use are necessary. (50)
  • Intra-articular lidocaine represents a useful alternative to facilitate the reduction of shoulder dislocations, particularly in patients at higher risk for complications from sedation. (51)
  • 1% lidocaine should be used when multiple procedured are performed and potential toxicity in the young dental patient is a concern. (52)
  • Topical lidocaine-epinephrine-tetracaine is effective in reducing pain during laceration repair with tissue adhesive in children. (53)
  • Topical lidocaine suppresses the trigemino-cardiac reflex. (54)
  • Lidocaine inhibits epidermal cell-derived thymocyte activating factor (ETAF) production in vitro. The conventional procedures such as lidocaine anesthesia, which are acceptable for morphologic techniques, might not be suitable for functional studies of the cellular components of the skin. (55)
  • Painful disks exhibiting diskographic leakage tend to be highly responsive to intradiskal lidocaine administration, whereas painful diks without diskographic leakage tend not to improve. (56)
  • Lidocaine administered during post cardiac arrest phase may reduce the incidence of refibrillation in adult victims of witnessed out of hospital cardiac arrest presumed to be of cardiac nature. More research is needed to definitely determine the value of lidocaine administration during the post cardiac period. (57)
  • Intrathyroid injection using an insulin pen with a mixture of lidocaine and dexamethasone could produce therapeutic benefit in patients with subacute thyroiditis. (58)
  • Thre is reduction of lidocaine clearance by dl-propanolol. Beta adrenergic blockade due to dl-propanolol decreases cardiac output and liver blood flow with a resultant reduction in the rate of delivery of lidocaine to its major site of elimination in the liver. (59)
  • Mexiletine is an orally active 1B agent.
  • Intravenous mexiletine is efefctive in the treatment of acute ventricular arrhythmias. Its main potential appears to be as a long term oral antiarrhythmic agent. (60)
  • Mexoletine shares some elctrophysiological properties with procainamide and quinidine, when given to patients with conduction defects. The drug should not be used in patients with pre-existing impairment of impulse formation or conduction. It has additional effects on AV nodal conduction whihc may be of value in the treatment of re-entrant tachycardias involving the AV node. (61)
  • Mexiletine is used in the treatment of refractory ventricular arrhythmias. (62)
  • Mexiletine in a dosage of 675 mg daily can reduce pain caused by diabetic neuropathy and the effect appears to have a rapid onset. (63)
  • Mexiletene is an efefctive antiarrhythmic in some patients with life threatening ventricular arrhythmias refractory to conventional drugs. Adverse effects significantly limit its use. (64)
  • Mexiletine toxicity is manifested by ECG prolongation of ventricular depolarization. It is important to monitor mexiletine therapy by plasma levels in patients with impaired renal function to avoid mexiletine therapy. (65)
  • Mexiletine is effective in the treatment of primary erythromelalgia. It has a noemalizing effect on pathological gating properties of the L858F gain of function mutation in Nav1.7 which might in part explain the benficial effects of systemic treatment with mexiletine in patients with gain of function sodium channel disorders. (66)
  • Mexiletine shortens QTc, attenuates QT-RR slope, abolishes 2:1 AV block and TWA in a Timothy Syndrome (TS) patients and TS model via inhibition of late INa. (67)
  • Mexiletine decreases the amplitude of or abolishes either early or delayed after depolarizations induced by ouabain. (68)
  • Mexiletine overdose can be misdiagnosed because of non specific result of urinary toxicologic screeing. Thus urinary drug screening results must be confirmed with more specific tests. (69)
  • The combination of low concentrations of tetrodotoxin and quinidine produces enhanced anti-arrhythmic efficacy and enhanced prolongation of ventricular refractoriness and conduction which mimicks the effect of mexiletine and quinidine in combination. (70)
  • Mexiletine reduce the compound muscle action potential (CMAP) amplitude transitory depression (TD) in patients with recessive myotonia congenita. (71)
  • Oral mexiletine and intravenous lidocaine block reflex-induced bonchoconstrction. Mexiletine may have additional airway benefits when selcted for the treatment of dysrrhythmias or chronic pain in patients with coexisting lung diseases. (72)
  • Mexiletine is used in te treatment of chronic daily headache. Lidocaine is a novel treatment for chronic daily headache with medication use and SUNCT syndrome. Mexiletine is a similar but orally active anti-arrythmic that is an effective analgesic in various tyoes if neuropathic pain. (73)
  • These drugs selectively effect ischemic or depolarized Purkinje and ventricular  tissue and have little effect on atrial tissue
  • The drugs reduce AP duration in some cells, but because they slow recovery of sodium channels from inactivation, they do not shorten (and may even prolong) the effective refractory period.
  • As they have little effect on normal cardiac cells, they have little effect on the ECG.
  • Phenytoin, an anticonvulsant and not a true local anesthetic, is sometimes classified with the group 1B antiarrhythmic agents because it can be used to reverse digitalis –induced arrhythmias.
  • It resembles lidocaine in lacking significant effects on the normal ECG.
  • They are useful in acute ischemic ventricular arrhythmias for eg. after MI.
  • They causes typical local anesthetic toxicity (ie, central nervous system {CNS} stimulation, including convulsions); cardiovascular depression (usually minor); and allergy (rashes, anaphylaxis).
  • They also precipitate arrhythmias but less common than with group 1A drugs.
  • Hyperkalemia increases cardiac toxicity.

 

C. Drugs with group 1C action- (Flecainide, Propafenone)

  • These drugs have no effect on ventricular AP duration or the QT interval.
  • They are powerful depressant of sodium current, however, and can markedly slow conduction velocity in atrial and ventricular cells.
  • They increase the QRS duration of the ECG.
  • They are useful for refractory ventricular tachycardias and for certain intractable supraventricular arrhythmias.
  • These drugs exacerbate or precipitate arrhythmias (proarrhythmic effect) more likely than other antiarrhythmic drugs.
  • Now they are restricted to use in persistant arrhythmias that fail to respond to other drugs.
  • Local anesthetic-like CNS toxicity.
  • Hyperkalemia increases cardiac toxicity.
  • There is an excess of deaths due to arrhythmia and due to shock after acute recurrent myocardial infarction in patients treated with encainide and flecainide. The mechanism underlying the excess mortality remain unknown. (74)
  • Intravenous flecanide restores sinus rhythm more rapidly than oral flecainide but at 2 hours and 8 hours after treatment, there is no difference in the proportion of patients cardioverted by the two approaches. There us a role for oral loading doses of flecainide in the treatment of acute or symptomatic paroxysmal atrial fibrillation. (75)
  • In pediatric patients with supra-ventricular tachycardia, an intravenous dose of 2,g/kg over at least 10 minutes and an initial oral dose of 6 mg/kg/day in three divided doses is recommended. Treatment should be started in hospital so that children in whom the drug is arrhythmogenic can be identified and plasma concentrations measured to identify patients in whomlack of efficacy is caused by underdosage. (76)
  • Flecainide is recommended as one of the first line treatment in restoring and maintaining sinus rhythm in patients with atrial fibrillation under current treatment guidelines. (77)
  • There is a dual mode of felcainide action in catecholaminergic polymorphic ventricular tachycardia (CPVT): suppression of spontaneous Ca2+ release from sarcoplasmic reticulum by RyR2 inhibition and suppression of triggered beats by Na+ channel block. (78)
  • Flecainide induced ventricular tachycardia can be successfully treated with lidocaine. (79)
  • Flecainide overdose results in a large QRS complex and in prolongation of the QTc interval. Sodium bicarbonate may be useful in the treatment of widened QRS and to stabilize the overdose of the drug. (80)
  • Flecainide use can cause the absence of accelerations and poor variability in the fetal heart rate. (81)
  • Amiodarone and flecainide may have additive or synergistic effects in maintaining sinus rhythm in atrial fibrillation. The antiarrhythmic property of amiodarone is likely to minimize or nullify the proarrhythmic reactions of flecainide during combination therapy. (82)
  • The administration of a single enantiomer of flecainide rather than the racemic drug does not offer any advantage. (83)
  • The use of an intra-aortic balloon pump is a useful supportive measure during the acute phase of flecainide overdose associated with severe myocardial depression. (84)
  • There is a disparate response of Brugada patients to flecainide and ajmaline, with a failure of flecainide in 32% patients Greater inhibition of Ito by flecainide may render it less effective. (85)
  • Flecainide is safe and effective for the treatment of atrial fibrillation. It is not associated with increased mortality and improves the quality of life in these patients. (86) 
  • Propafenone effectively suppresses ventricular arrhythmias and that nonlinear drug accumulation and intersubject variability in elimination of half life, steady state mean plasma concentration, and therapeutic concentration indicate a need for individual therapy. (87)
  • A younger age, low spontaneous arrhythmia variability and particularly low titration dose are the best predictors of the short and long term efficacy of propafenone. All other responders should have repeated Holter recordings during the first year of treatment. (88)
  • Syncope, a widened QRS interval and depressed left ventricular systolic function is seen during propafenone therapy for atrial fibrillation. (89)
  • An approximately two-fold decrease of the oral clearance of metoprolol is seen when propafenone is given in addition to the patient. The dose of metoprolol should be reduced when propafenone is given in addition. (90)
  • Flecainide and propafenone are safe in the long term treatment of patients with paroxysmal supraventricular tachyarrhythmias and without clinical evidence of clinically significant heart disease. (91)
  • Propafenone is a very promising agent for emergency intravenous therapy as well as long term oral therapy in patients with Wolff-Parkinson-White syndrome. (92)
  • Propafenone as an oral loading dose is an efficacious and fast way of treating atrial fibrillation of recent onset and due to its simplicity of administration and safety canbe preferred to the intravenous route. (93)
  • A patient with propafenone overdose develops coma, seizure, bradycardia, hypotension and conduction delay. (94)
  • Propafenone therapy can cause unstable wide complex tachycardia. (95)
  • Propafenone has a depressing effect on the contractile function of lattisimus dorsi muscle isolated from rats and studies in an organ chamber. (96)
  • Propafenone therapy can cause an attack of variegate porphyria (VP) with syndrome of inappropriate antidiuretic hormone secretion (SIADH). (97)
  • Propafenone prolongs sinusnode effective refractory period (SNERP) and Atriosinus conduction time (ASCT) in an isolated sinus node preperation in rabbit heart. (98)
  • Oral loading dose of propafenone or amiodarone are safe with similar conversion rate of recent onset atrial fibrillation. Propafenone has a faster action. (99)
  • Propafenone causes bradycardia and bronchospasm. It is metabolized in liver and its bioavailability and plasma concentration differ among patients under long term therapy. Hepatic toxicity is highly uncommon. A new case has been reported presenting with new onset liver enzymes abnormalities with propafenone therapy. (100)

 

Group 2 antiarrhythmics

β blockers –( Propanolol, Esmolol)

  • Mechanism-cardiac β-adrenoceptor blockade and reduction in cAMP, which results in reduction of both sodium and calcium currents and the suppression of abnormal pacemakers.
  • The AV node is particularly sensitive & PR interval is usually prolonged by them.
  • Sotalol and amiodarone (group 3 drugs) also have group 2 β- blocking effects.
  • Esmolol, a very short acting β blocker for intravenous administration, is used exclusively in acute arrhythmias.
  • Propranolol, metoprolol and timolol are commonly used as prophylactic drugs in patients who have had a myocardial infarction.
  • Toxicities of β blockers are the same in patients with arrhythmias as in patients with other conditions except that they are more prone for depression of cardiac output than other patients.
  • They reduce progression of chronic heart failure and reduces the incidence of potentially fatal arrhythmias.
  • During the 45 min of occlusion and re-perfusion, the incidence of ventricular fibrillation is significantly reduced in propanolol treated dogs. Propanolol reduces the incidence of both ventricular premature depolarizations and ventricular tachycardia during occlusion, but the incidence of ventricular fibrillation is not reduced in propanolol treated pigs. (101)
  • The anti-arrhythmic effects of propanolol in acute myocardial ischemia is due to slowing conduction in the ischemic zone, in prolonging refractoriness, in reducing APD/ERP and in reducing the disparity in APD between ischemic and normal zones. (102)
  • Propanolol appears to control ventricular arrhythmia safely and effectively in many patients. (103)
  • The anti-arrhythmic effect ofpropanolol on ischemic myocardium is due to its cardioprotective action and this effect appear to be unrelated to the ancillary pharmacological properties of the drug. (104)
  • Propanolol administration has no significant effect on serum total cholestrol, low density lipoprotein (LDL) cholestrol, HDL cholestrol, total cholestrol:HDL cholestrol ratio or triglyceride levels. in patients with heart disease and complex ventricular arrhythmias. (105)
  • d-propanolol may be a useful antiarrhythmic agent in selected clinical situations in which beta-adrenergic blockade is unnceccessary or undesirable. (106)
  • TPranolium chloride (dimethylpropanolol chloride) has anti-arrhythmic effects but do not exert undesirable effects on the  on the adrenergic nervous system. (107)
  • Propanolol suppresses ventricular arrhythmias by both beta- and non-beta-adrenergic receptor mediated effects. (108)
  • The long acting formulation of propanolol is an effective anti-arrhythmic treatment which may improve patient compliance with treatment. (109)
  • Propanolol is well tolerated and effective in ventricular extrasystoles. It does not affect the systolic blood pressure at rest, decreases it at peak exercise and reduce the heart rate both at rest and at peak exercise. (110)
  • Intermittent anti-arrhythmic therapy (propanolol) in children with refractory atrioventricular nodal renentry tachycardia (AVNRT) could be very efficacious and useful treatment option which significantly improves their quality of life. (111)
  • Acebutolol is a safe and effective antiarrhythmic agent and compares favorably with propanolol. (112)
  • Esmolol is useful in the evaluation and management of pediatric tachyarrhythmias. The weight-adjusted dosage required to induce beta blockade in children is larger than the adult dosage and the effects of esmolol dissipate rapidly. (113)
  • Esmolol is antiarrhythmic in doxorubicin induced arrhythmia. Its pre-treatment can protect the culture from doxorubicin-induced arrhythmia. (114)
  • Esmolol is safe and effective in the treatment of supraventricular tachyarrhythmias. Mojority of the patients successfully treated with esmolol can be safely and effectively transferred to oral therapy with alternate antiarrhythmic agents. (115)
  • Esmolol has the ability to raise ventricular fibrillation threshold as measured by the train-of-pulses technique due to beta-adrenergic blockade. (116)
  • Esmolol is both the least costly and the most cost effective treatment in comparison with metoprolol, dilitazem and amiodarone in the treatment of supraventricular tachycardia in perioperative or other emergent circumstances. (117)
  • Esmolol may be useful as an antiarrhythmic agent in the management of epinephrine related ventricular arrhythmias during anesthesia in man. (118)
  • Administration of esmolol before intubation prevents tachycardia and an increase in MAP, Pwd and QTc duration caused by laryngoscopy and tracheal intubation. (119)
  • Esterification can be promising tool for enhancing the skin permeability of esmolol, which is an essential requirement for transdermal development. (120)
  • The role of esmolol in the acute treatment of supraventricular tachycardia is that of rate control. Its advantage rest in its pharmacokinetic profile of rapid onset, easy titration and rapid dissipation of effect once the infusion has been ceased. It is the agent of choice when beta-blockade is required rapidly or when beta-blockade needs to be carefully controlled. (121)

Group 3 antiarrhythmic

Potassium IK channel blockers (Amiodarone, Dronedarone, Dofetilide, Ibutilide)

  • Agents widening AP (prolong repolarization and ERP)
  • Reduces the ability of the heart to respond to rapid tachycardias.
  • The action of these drugs is apparent in the ECG as an increase in QT interval.
  • Amiodarone is useful in most types of arrhythmias and is most efficacious of all antiarrhythmic drugs.
  • It has a broad spectrum: it blocks sodium, calcium, and potassium channels and β adrenoceptors.
  • Because of its toxicities it is approved for use mainly in resistant arrhythmias.
  • Amiodarone causes microcrystalline deposits in the cornea and skin, thyroid dysfunction hyper or hypothyroidism), paresthesias, tremor and pulmonary fibrosis.
  • Amiodarone rarely causes new arrhythmias as it block calcium and β receptors as well as sodium and potassium channels.
  • Amiodarone is used to manage virtually all forms of supraventricular and ventricular tachycardia particularly sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and atrial fibrillation (AF). (122)
  • Amiodarone is more effective in treating both supraventricular and ventricular arrhythmias. It has few negative ionotropic side effects. Its use is limited due ti serious and potentially life threatening side effects. (123)
  • Cutaneous side effects and abnormal thyroid function tests (without overt gland dysfunction) are more likely to occur with increasing duration of treatment and cumulative dosage of amiodarone therapy. (124)
  • Amiodarone as part of a strategy to achieve and maintain sinus rhythm, appears to be safe and effective in patients with persistent atrial fibrillation. Some patients may not tolerate the adverse effects of this agent. (125)
  • Current data indicates that treating 1000 patients with amiodarone for 1 year will result in 54 cases of hypothyroidism, 8 cases of hyperthyroidism, 3 of peripheral neuropthy and 10 cases of pulmonary infiltration. The risk of adverse events is independent of the risk of cardiac sudden death and is high when compared with the modest reduction in cradiac sudden death. Treatment of 1000 high risk patients with amiodarone for 1 year would prevent only 35 cases of sudden cardiac death. (126)
  • The systematic prophylactic use of amiodarone should not be done in all patients with depressed left ventricular function after myocardial infarction. The lack of proarrhythmia and the reduction in arrhythmic death support the use of amiodarone in patients for whom antiarrhythmic therapy is indicated. (127)
  • Amiodarone therapy can induce pulmonary toxicity in patients. The patients can be successfully managed with pulse high dose steoid therapy. (128)
  • Amiodarone can induce pulmonary toxicity. The symptoms include progressive dyspnea, dry cough, malaise and pleuritic chest pain. Radiographic features include interstitial or alveolar (ground glass) shadows that may be localized or diffuse, and traction bronchiectasis with a honeycoomb pattern. Pulmonary function test may show reduced carbon monoxide diffusing capacity. Corticosteroid may help patients with acute disease. The prognosis is usually good in cases of chronic or subacute disease. (129)
  • Amiodarone is a commonly used drug in primary care practice to treat serious cardiac arrhythmias. While efficacious, this drug places patients at risk for serious adverse events and ongoing surveillance is essential. (130)
  • The American Heart Association guidelines for the treatment of patients with Wolff-Parkinson-White (WPW) syndrome suggests that intravenous amiodarone is a first line therapy for Atrial Fibrillation with WPW syndrome. However the evidence suggests this is a potentially dangerous myth. (131)
  • High dose IV or combined IV and oral administration of amiodarone may be effective as early as 8 hours in patients with recent onset Atrial Fibrillation of 3/4 48 hour duration in patients without contraindications to these high dose regimens. There are no data to support the use of IV amiodarone for acute conversion in patients with an ejection fraction of <40% or clinical heart failure. So its use in these scenarios should be limited to symptomatic patients who are refractory to electrical cardioversion. (132)
  • Amiodarone induced thyroid dysfunction occurs because of both its iodine content and the direct toxic effects of the compound on thyroid parenchyma. Amiodarone induced hyperthyroidism is more common in iodine deficient regions of the world, whereas amiodarone induced hypothyroidism is usually seen in iodine sufficient areas. (133)
  • The pulmonary toxicity associated with amiodarone therapy is clinically complex and results from direct toxic effects of the drug (or its metabolites) as well as indirect inflammatory and immunologic processes induced by the drug therapy. (134)
  • Dronedarone , an amiodarone analog is less toxic, is also approved at present only for the treatment of atrial fibrillation and flutter.
  • Dronedarone reduces the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation. (135)
  • Dronaderone is approved in adult clinically stable patients with a history of or current non-permanent atrial fibrillation (AF) to prevent recurrence of AF or to lower ventricular rate. (136)
  • Dronaderone is safe but less effective in management of patients with atrial fibrillation. (137)
  • Dronaderone can be used as a second or third line agent for the treatemnt of atrial fibrillation. (138)
  • Dronaderone is less effective than amiodarone for maintenance of sinus rhythm but has fewer adverse effects. For every 1000 patients treated with dronaderone instead of amiodarone, 228 more recurrences of AF are estimated in exchange for 9.6 fewer deaths and 62 fewer adverse events requiring discontinuation of drug. (139)
  • Dronaderone should be contraindicated in patients with NYHA class IV or unstable NYHA classes II and III congestive heart failure. (140)
  • Dronaderone reduces the incidence of AF recurrences, hospitalization and death in patients with paroxysmal or persistent AF. Dronadarone should not be used in high risk patients with permanent AF or patients with unstable chronic heart failure (HF) due to safety concerns. (141)
  • Dronaderone is effective in the treatment of ventricular arrhythmias who were unresponsive or intolerant to other anti-arrhythmic agents. (142)
  • Patient treated with dronaderone can develop interstitial lung disease. (143)
  • Dronedarone, which is concentrated in myocardial tissue, reduces ventricular rate during AF by slowing AV conduction. Absence of this effect after ivabradine administration implicates If inhibtion as a mechanism. (144)
  • Dronaderone decreases AF recurrence by approximately 25% and reduce the incidence of the combined end point of hospitalization for cardiac cuases and all cause mortality. Dronaderone should not be used in patients with severe (class III or IV) heart failure. Worsening renal function is also associated with dronaderone. (145)

 

Group 4 antiarrhythmics

Calcium channel blockers:( Verapamil, Diltiazem)

  • They are effective in arrhythmias that must traverse calcium-dependent cardiac tissue such as the AV node.
  • They cause a state and use-dependent selective depression of calcium current.
  • AV conduction velocity is decreased, and effective refractory period and PR interval are increased by these drugs.
  • They are effective for converting AV nodal reentry (nodal Tachycardia) to normal sinus rhythm.
  • The major use is in the prevention of these nodal arrhythmias in patients prone to recurrence.
  • These drugs are orally active and also available for parenteral use.
  • The most important toxicity is excessive depression of cardiac contractility, AV conduction and blood pressure.
  • These agents should be avoided in ventricular tachycardias.
  • The addition of verapamil to class Ic or III antiarrhythmic drug significantly reduces the atrial fibrillation recurrences, that were more frequent in older patients and in patients with longer lasting AF; moreover, verapamil is effective in reducing the secondary AF recurrences, too. (146)
  • Verapamil slows the conduction of atrial impulses thrugh the AV node. It prolongs the effective reractory period of the AN vode, thus slowing or blocking conduction of premature impulses. Verapamil prevents AV nodal reentry and initiation of atrial tachycardia by causing premature impulses to block rather than to conduct with the delay needed to initiate reentry. It has no effect on the rate of depolarization, action potential amplitude or maximum diastolic potential of atrial or His bundle fibers. (147)
  • Flecainide and verapamil substantially inhibit fKv1.4ΔN channels expressed in Xenopus oocytes by binding to the open state of the channels. Therefore, caution should be taken when these drugs are administered in combination with K+ channel blockers to treat arrhythmia. (148)
  • Verapamil can be used as an antiarrhythmic agent in patients with congestive heart failure. (149)
  • The dosage tds with conventional tablets of verapamil or once daily with the slow release formulation gave the same antiarrhythmic efficacy over 24 h and was associated with equal trough serum concentrations of verapamil. (150)
  • Verapamil plus antiarrhythmic drugs reduce atrial fibrillation recurrences after an electrical cardioversion. (151)
  • Verapamil's antiarrhythmic effect may be secondary to its anti-ischemic action, or by inhibiting slow channel conduction (with its propensity for anhanced automaticity and reentry) induced by ischemia and the sympathetic response to exercise, exerts a primary antiarrhythmic action. (152)
  • The incidence of schemia induced arrhythmia is decreased in nifedipine, verapamil and nitroglycerin. The incidence of reperfusion induced arrhythmia is also decreased in verapamil and nitroglycerin. Verapamil and nitroglycerin rather than nicardipine dis afford significant protection to the heart subjected to ischemia and reperfusion in a rabbit model. (153) 
  • Verapamil inhibits the second phase of platelet aggregation induced by adenosine diphosphate (ADP) and inhibits the aggregation induced by collagen. (154)
  • The antiarrhythmic effect of verapamil in isolated hearts can be attenuated by increasing the calcium content of the perfusion solution, but a twofold increase in the calcium concentration failed to fully restore susceptibility to ventricular fibrillation to that observed in verapamil free controls. (155)
  • Verapamil slows the conduction through the AV node, is negatively inotropic. It is used in tghe treatment of definite SVT. It is contraindicated if beta blockrs have taken by the patient. It should not be used for SVTs associated with WOlff-Parkinson-White syndrome. (156)
  • Verapamil suppresses sinus nodal and AV nodal re-entry but exerted no selective depression between fast and slow AV nodal pathways. It has no significant effect on the accessory AV bypass tract but was effective in terminating AV reciprocating tachycardia by its depressive action on the AV node. (157)
  • Calcium channels on neurons in teh CNS play an important role in the modulation of epinephrine-induced cardiac arrhythmias. Diltiazem can suppress arrhythmias through CNS mechanisms. Activation of parasympathetic nervous system mediates some of the effect of diltiazem. The mechanism of action of diltiazem is modulated through endogenous opioids. (158)
  • The rate dependent atrioventricular node depression by diltiazem results in greater tachycardia slowing and higher rates of termination during atrioventricular reentrant tachycardias with faster initial rates and shorter retrograde conduction intervals. (159)
  • Calcium channel antagonist diltiazem is recommended as a standard adjunct to perioperative medication in cardiac surgery as it significantly lowers the ventricular arrhythmias. (160)
  • During the early postreperfusion period, diltiazem is able to accelerate significantly the increase in the ventricular fibrillation threshold. Late phase of ventricular errhythmias is not influenced by the drug even when high doses are applied. This difference is due to differences in the arrhythmogenesis at the very onset of myocardial ischemia compared to the stage of myocardial necrosis. (161)
  • Diltiazem is effective in reducing incidence and extent of arrhythmias and myocardial ischemia perioperatively and provides potent postoperative antiischemic and antiarrhythmic protection in patients after coronary artery bypass surgery. (162)
  • The antiarrhythmic effects of diltiazem is due in part to direct electrophysiologic effects on cardiac tissue to block sodium and calcium channels to an antiischemic effect associated with bradycardia and vasodepression. (163)
  • Diltiazem is likely to prevent the loss and even the reversal of the antifibrillatory properties of flecainide due to myocardial ischemia in dosages that do not adversely affect myocardial contractility or atrioventricular conduction to a large extent. (164)
  • Diltiazem reduces the cardiac events in majority of patients without left ventricular dysfunction and increases such events in the minority of patients with left ventricular dysfunction. (165)
  • Amiodarone and diltiazem has no differences for treating atrial tachyarrhythmias in non cardiac surgical patients based on safety and efficacy. (166)
  • The combination therapy of ditiazem and nifedipine is more effective in patients who donot maximally respond to diltiazem or nifedipine alone with respect to anginal and exercise variables and in reducing blood pressure at rest and during exercise. Diltiazem may increase nifedipine drug levels when the drugs are combined. Fewer side effects are observed with diltiazem than nifedipine. (167)

Group 5 antiarrhythmics  

MIscellaneous group 

Adenosine

  • It is a normal component of the body but when given in high doses (6-12mg) as an intravenous bolus, the drug markedly slows or completely blocks conduction in the AV node, probably by hyperpolarizing this tissue (through increased IK1) and by reducing calcium current.
  • It is extremely effective in abolishing AV nodal arrhythmia, and because of its very low toxicity it has become the drug of choice for this arrhythmia.
  • It has extremely short duration of action.
  • Toxicity includes flushing and hypotension, but because of its short duration these effects do not limit the use of the drug.
  • Transient chest pain and dyspnea (probably due to bronchoconstriction) may also occur.
  • Adenosine is efficqacious in treating SVT bit no more efficacious than the cheaper alternatives. (168)
  • The administration of adenosine or potentiators of adenosine production in the ischemic myocardium may be beneficial for the attenuation of ischemic and reperfusion injuries. (169)
  • Adenosine produces acute inhibition of sinus node and atrioventricular (AV) nodal function, thus is a suitable agent for treating supraventricular tachycardias (SVT) that incorporates the sinus node or AV node as part of the arrhythmia circuit or for masing atrial tachyarrhythmias or ventricular pre-excitation. (170)
  • Adenosine may function as an endogenous antiarrhythmic metabolite. (171)
  • Adenosine appears to have an antiarrhythmogenic effect both in supraventricular and ventricular rhythm disturbances. During myocardial infarction, where huge amounts of adenosine are present in ischemic regions, asystole may respond to adenosine antagonists. (172)
  • Through activation of adenosine A1 receptors, BN-063 can suppress ventricular arrhythmias induced by myocardial ischemia and catecholamines. The antiarrhythmic action of BN-063 may be mediated by reducing heart rate and antagonizing the stimulatory effects of catecholamines in myocardial ischaemia. (173)
  • The antiarrhythmic action of adenosine is not only seen in ventricular tachycardia due to aconitine (triggered activity), but also in tachycardia induced by the myocardial damage (microreenteries). (174)
  • Adenosine is an effective, safe drug for the diagnosis and treatment of paroxysmal tachycardias in adult and pediatric patients. Rare but possible life threatening side effects (prolonged sinus arrest and complete AV block, atrial fibrillation, acceleration of vantricular tachycardia, apnea) necessitate proper monitoring of the patients. (175)
  • The lesser electrophysiological effects of adenosine following distal intravenous injections were associated with delay in transit time and dispersion of the bolus. The correlation of adenosine induced heart block with bolus activity in the left heart indicated dependence on coronary arterial delivery of adenosine to the atrioventricular node. (176)
  • Adenosine is a unique new agent for th acute treatment of paroxysmal supraventricular tachycardia (PSVT). Its short duration and high efficacy in converting select forms of PSVT make adenosine an excellent alternative to verapamil in patients with compromised hemodynamics. (177)
  • The antiarrhythmic properties of adenosine are independent of the coronary blood flow. (178)
  • Adenosine can be used in the treatment of neonatal and pediatric supraventricular tachycardia. (179)

Potassium ion 

  • Potassium depress ectopic pacemakers, including those caused by digitalis toxicity.
  • Hypokalemia is associated with an increased incidence of arrhythmias, especially in patients receiving digitalis while hyperkalemia depress conduction and can cause reentry arrhythmias.
  • Therefore when treating arrhythmias serum potassium should be measured and normalized if abnormal.
  • Cesium, through potassium blockade, reverses lidocaine induced elevation in defibrillation threshold values. Inhibiting outward potassium conductance and prolonging repolarization decreases defibrillation threshold values independent of sodium channel blockade. (180)
  • AZ13395438 can be characterized as a mixed potassium ion channel blocking agent that selectively prolongs atrial versus ventricular refractoriness and shows promising antiarrhythmic efficacy in a clinically relevant animal model of atrial fibrillation. (181)
  • Agents that modulate cardiac and smooth muscle K+ channels have a therapeutic potential in number of cardiovascular diseases. Class III antiarrhythmic agents acts by prolonging cardiac action potentials while K+ channel openers hyperpolarize and thereby relax smooth muscle cells. (182)

Magnesium ion 

  • It has similar depressant effects as potassium on digitalis- induced arrhythmias.
  • Also appears to be effective in some cases of torsades de pointes arrhythmia.
  • The mechanism by which high Mg2+ quickly suppresses cardiac arrhythmias are related to an extracellular action of MG2+ and do not include a block of ICa or an increase in outward current Mg2+ can be antiarrhythmic by decreasing Vos amplitude and possibly by screening the fixed negative charges at the external surface of sarcolemma. (183)
  • Intravenous magnesium sulphate is a simple, safe and widely applicable treatment. Its efficacy in reducing early mortality of myocardial infarction is comparable to but independent of, that of thrombolytic or antiplatelet therapy. (184)
  • Magnesium may be used as adjunct for dofetilide and ibutilide due to potential improved efficacy and minimal toxicity in patients with atrial fibrillation. (185)
  • Extracellular Mg2+ ecerts antiarrhythmic activities. (186)
  • Magnesium is effective against long QT Torsades de Pointes. In rapid atrial fibrillation magnesium produces rate control slowing AV nodal conduction. Magnesium prevents digitalis toxicity due to associated hypomagnesemia. (187)
  • The advantage of magnesium sulphate in the treatment of torsades de pointes are: innocuity, simplicity and rapidity of administration and almost immediate efficacy. (188)
  • Higher plasma concentrations and dietary magnesium intakes is associated with lower risks of sudden cardiac death. (189)
  • The rationale behind the use of magnesium for management of refractory ventricular fibrillation is benefit of magnesium in the management of intractable tachyarrhythmias as well as its myocardial protective action in the setting of ischemia-reperfusion injury. (190)

 

Clinical Classification of Anti-arrhythmic drugs

 
 

Supraventricular arrhythmias

Supraventricular and ventricular arrhythmias

Ventricular arrhythmias only

Adenosine

Amiodarone

Lidocaine

Verapamil

β blockers- Propanolol, Sotalol, Esmolol

Mexiletine

Diltiazem

Procainamide

 

Dronedarone

Disopyramide

 

Digoxin

Quinidine

 

 

Flecainide

 

 

Propafenone

 

 
 
 
Drug summary table
 

Subclass

Mechanism of action

Clinical applications

pharmacokinetics

Toxicities, interactions

Group 1A

 

 

 

 

Procainamide

Use and state dependent block of INa channels

Some block of IK channels

Slowed conduction velocity and pacemaker activity

Prolonged action potential duration and refractory period.

Atrial and ventricular arrhythmias, especially after myocardial infarction

Oral and parenteral

Oral slow release forms available

Duration: 2-3 h

Increased arrhythmias, hypotension, lupus like syndrome

Disopyramide

Similar

 

Longer duration of action

Also antimuscarinic effects and heart failure.

Quinidine

Similar

 

 

Also cinchonism (tinnitus head ache, gastrointestinal disturbance) & thrombocytopenia

Group 1B

 

 

 

 

Lidocaine

Highly selective use and state dependent INa  block; minimal effect in normal tissue; no effect on IK

ventricular arrhythmias; post- myocardial infarction and digitalis-induced arrhythmias

IV and IM

Duration: 1-2 h

 

Central nervous system (CNS)-sedation or excitation

Mexiletine

Similar

 

Oral; longer duration of action

 

Group 1C

 

 

 

 

Flecainide

Selective use and state dependent INa  block; slowed conduction velocity and pacemaker activity

Refractory arrhythmias

Oral

Duration: 20 h

Increased arrhythmias;

CNS excitation

Group 2

 

 

 

 

Propanolol

Block of β receptors; slowed pacemaker activity

Postmyocardial infarction as prophylaxis against sudden death ventricular fibrillation; thyrotoxicosis

Oral, parenteral

Duration: 4-6 h

Brochospasm, cardiac depression, AV block, hypotension etc.

Metoprolol

Similar but β1-selective

 

 

 

Esmolol

Similar but β1-selective

Perioperative and thyrotoxicosis arrhythmias

IV only,

Duration: 10 min

 

Group 3

 

 

 

 

Amiodarone

Strong IK block produces marked prolongation of action potential and refractory period. Group 1 activity slows conduction velocity; group 2 & 4 activity confer additional antiarrhythmic activity

Refractory arrhythmia; used off label in many arrhythmia (broad spectrum of therapeutic action)

Oral, parenteral

Half-life and duration of action: 1-10 wk

Thyroid abnormalities, deposits in skin and cornea, pulmonary fibrosis, optic neuritis, torsades is rare with amiodarone

Sotalol

IK block and β adrenoceptor block

Ventricular arrhythmias and atrial fibrillation

Oral

Duration: 7 h

 

Dose related torsades de pointes; cardiac depression

Ibutilide

 

Selective IK block; prolonged action potential and QT interval

Treatment of acute atrial fibrillation

 

IV only

Duration: 6 h

 

Torsades de pointes

 

Dofetilide

Like ibutilide

Treatment and prophylaxis of atrial fibrillation

Oral

Duration: 7 h

Torsades de pointes

Group 4

 

 

 

 

Verapamil

State and use dependent ICa block; slows conduction in AV node and pacemaker activity; PR interval prolongation

AV nodal arrhythmias; especially in prophylaxis

 

Oral, parenteral

Duration: 7 h

 

Cardiac depression; Constipation, hypotension

 

Diltiazem

 

Like verapamil

 

Rate control in atrial fibrillation

Oral, parenteral

Duration: 6 h

Like verapamil

Miscellaneous

 

 

 

 

Adenosine

 

Increase in diastolic Ik of AV node that causes marked hyperpolarization and conduction block; reduced Ica

Acute nodal tachycardias

 

IV only

Duration: 10-15 s

 

Flushing, bronchospasm, chest pain, headache

 

Potassium ion

Increase in all K currents, decreased automaticity,

Decreased digitalis toxicity

Digitalis toxicity and other arrhythmias if serum K is low

 

Oral or IV

 

Both hypokalemia and hyperkalemia are associated with arrhythmogenesis. Severe hyperkalemia causes cardiac arrest.

Magnesium ion

Poorly understood possibly increase in Na+/K+ ATPase activity

Digitalis arrhythmias and other arrhythmias if serum Mg is low

IV

Muscle weakness

Severe hypermagnesemia can cause respiratory paralysis.

 
 
 
 
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