Antiarrhythmic Drugs

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Chapter: Essential pharmacology : Antiarrhythmic Drugs

These are drugs used to prevent or treat irregularities of cardiac rhythm.



These are drugs used to prevent or treat irregularities of cardiac rhythm.


Nearly 3 out of 4 patients of acute myocardial infarction (MI) and about half of those given a general anaesthetic exhibit at least some irregularity of cardiac rhythm. Arrhythmias are the most important cause of sudden cardiac death. However, only few arrhythmias need to be treated with antiarrhythmic drugs.


Abnormal automaticity or impaired conduction or both underlie cardiac arrhythmias. The generation and propagation of cardiac impulse and properties of excitability and refractoriness are described on p. 476 to 478. Ischaemia, electrolyte and pH imbalance, mechanical injury, stretching, neurogenic and drug influences, including antiarrhythmics themselves, can cause arrhythmias by altering electrophysiological properties of cardiac fibres.


Important mechanisms of cardiac arrhythmias are:


1. Enhanced/Ectopic Pacemaker Activity


The slope of phase4 depolarization may be increased pathologically in the automatic fibres or such activity may appear in ordinary fibres. Ectopic impulse may result from current of injury. Myocardial cells damaged by ischaemia become partially depolarized: a current may flow between these and normally polarized fibres (injury current) and initiate an impulse.


2. After-Depolarizations


These are secondary depolarizations accompanying a normal or premature action potential (AP), Fig. 38.1.



Early After-Depolarization (EAD) Repolarization during phase3 is interrupted and membrane potential oscillates. If the amplitude of oscillations is sufficiently large, neighbouring tissue is activated and a series of impulses are propagated. EADs are frequently associated with long QT interval due to slow repolarization and prolonged APs. They result from depression of delayed rectifier K+ current.


Delayed After-Depolarization (DAD) After attaining resting membrane potential (RMP) a secondary deflection occurs which may reach threshold potential and initiate a single premature AP. Generally result from Ca2+ overload (digitalis toxicity, ischaemia-reperfusion).

Because an AP is needed to trigger afterdepolarizations, arrhythmias based on these have been called triggered arrhythmias.


3. Reentry


Due primarily to abnormality of conduction, an impulse may recirculate in the heart and cause repetitive activation without the need for any new impulse to be generated. These are called reentrant arrhythmias.


Circus Movement Type: It occurs in an anatomically defined circuit. A premature impulse, temporarily blocked in one direction by refractory tissue, makes a one-way transit around an obstacle (natural orifices in heart, infarcted or refractory myocardium), finds the original spot in an advanced state of recovery and re-excites it, setting up recurrent activation of adjacent myocardium (Fig. 38.2).



Reentry occurring in an anatomically fixed circuit can be permanently cured by high radiofrequency catheter ablation of the defined pathway.


Microreentry circuit:  It may form at the junction of a Purkinje fibre (PF) with ordinary ventricular fibre (gate region). One of the branches of the PF may get sufficiently depolarized to cause unidirectional block (Fig. 38.3). Extremely slow conduction at this site due to slow channel depolarization and markedly abbreviated action potential duration (APD) and effective refractory period (ERP) makes reentry possible in a short loop of tissue.


For reentry to occur, the path length of the circuit should be greater than the wave length (ERP × conduction velocity) of the impulse. Slow conduction in the reentrant circuit may be caused by:


ü Partial depolarization of the membrane—decreased slope of phase 0 depolarization, i.e. depressed fast channel response.


ü Cells changing over from fast channel to slow channel depolarization which conducts extremely slowly. When a fibre is depolarized to a RMP of about –60 mv, the Na+ (fast) channels are inactivated, but it can still develop Ca2+ (slow) channel response.


Reentry can be abolished both by marked slowing of conduction (converting unidirectional block to bidirectional block) as well as by acceleration of impulse (retrograde impulse reaches so early as to meet refractory tissue).


4. Fractionation Of Impulse


When atrial ERP is brief and inhomogeneous (under vagal overactivity), an impulse generated early in diastole gets conducted irregularly over the atrium, i.e. it moves rapidly through fibres with short ERP (which have completely recovered) slowly through fibres with longer ERP (partially recovered) and not at all through those still refractory. Thus, asynchronous activation of atrial fibres occurs atrial fibrillation (AF). This arrhythmia must be initiated by a premature depolarization, but is self sustaining, because passage of an irregular impulse leaves a more irregular refractory trace and perpetuates the inhomogeneity of ERPs.


The important cardiac arrhythmias are:


Extrasystoles (ES) are premature beats due to abnormal automaticity or afterdepolarization arising from an ectopic focus in the atrium (AES), AV node (nodal ES) or ventricle (VES). The QRS complex in VES is broader and abnormal in shape.


Paroxysmal Supraventricular Tachycardia (PSVT) is sudden onset episodes of atrial tachycardia (rate 150–200/min) with 1:1 atrioventricular conduction: mostly due to circus movement type of reentry occurring within or around the AV node or using an accessory pathway between atria and ventricle (Wolff-ParkinsonWhite syndrome).


Atrial Flutter (AFI): Atria beat at a rate of 200– 350/min and there is a physiological 2:1 to 4:1 or higher AV block (because AV node cannot transmit impulses faster than 200/ min). This is mostly due to a stable reentrant circuit in the right atrium, but some cases may be due to rapid discharge of an atrial focus.


Atrial fibrillation (AF): Atrial fibres are activated asynchronously at a rate of 350–550/min (due to electrophysiological inhomogeneity of atrial fibres), associated with grossly irregular and often fast (100–160/min) ventricular response. Atria remain dilated and quiver like a bag of worms.


Ventricular Tachycardia is a run of 4 or more consecutive ventricular extrasystoles. It may be a sustained or non-sustained arrhythmia, and is due either to discharges from an ectopic focus, afterdepolarizations or single site (monomorphic) or multiple site (polymorphic) reentry circuits.


Torsades de pointes (French: twisting of points) is a life-threatening form of polymorphic ventricular tachycardia with rapid asynchronous complexes and an undulating baseline on ECG. It is generally associated with long QT interval.


Ventricular Fibrillation (VF) is grossly irregular, rapid and fractionated activation of ventricles resulting in incoordinated contraction of its fibres with loss of pumping function. It is fatal unless reverted within 2–5 min; is the most common cause of sudden cardiac death.


Atrio-Ventricular (AV) Block is due to depression of impulse conduction through the AV node and bundle of His, mostly due to vagal influence or ischaemia.


First degree AV block: Slowed conduction resulting in prolonged PR interval.

Second degree AV block: Some supraventricular complexes are not conducted: drop beats.

Third degree AV block: No supraventricular complexes are conducted; ventricle generates its own impulse; complete heart block.


Arrhythmogenic Potential Of Antiarrhythmics


Most antiarrhythmics can themselves precipitate serious arrhythmias, especially during long-term prophylactic use. Two multicentric trials ‘Cardiac Arrhythmia Suppression Trial I and II’ (CAST I, II, 1991, 1992) have shown that postMI patients randomized to receive on a long-term basis encainide, flecainide, moricizine had higher incidence of sudden death, though initially the same drugs had suppressed VES in these patients. It is possible that during transient episodes of ischaemia, the intraventricular conduction slowing action of these drugs gets markedly accentuated resulting in VT and VF. It is therefore not prudent to try and suppress all extrasystoles/arrhythmias with drugs.





Antiarrhythmic drugs act by blocking myocardial Na+, K+ or Ca2+ channels. Some have additional or even primary autonomic effects. Classification of antiarrhythmic drugs has been unsatisfactory, because many drugs have more than one action. Vaughan Williams and Singh (1969) proposed a 4 class system which takes into account the most important property of a drug which is apparently responsible for its antiarrhythmic action in the clinical setting. This system, though arbitrary, is widely accepted.




The primary action of drugs in this class is to limit the conductance of Na+ (and K+) across cell membrane—a local anaesthetic action. They also reduce rate of phase-4 depolarization in automatic cells.





The subclass IA containing the oldest antiarrhythmic drugs quinidine and procainamide are open state Na+ channel blockers which also moderately delay channel recovery (1–10s), suppress AV conduction and prolong refractoriness. The Na+ channel blockade is greater at higher frequency (premature depolarization is affected more). These actions serve to extinguish ectopic pacemakers that are often responsible for triggered arrhythmias and abolish reentry by converting unidirectional block into bidirectional block.




It is the dextro isomer of the antimalarial alkaloid quinine found in cinchona bark. In addition to Na+ channel blockade, quinidine has cardiac antivagal action which augments prolongation of atrial ERP and minimizes RP disparity of atrial fibres. AV node ERP is increased by direct action of quinidine, but decreased by its antivagal action; overall effect is inconsistent. Quinidine depresses myocardial contractility; failure may be precipitated in damaged hearts.


ECG: It increases PR and QT intervals and tends to broaden QRS complex. Changes in the shape of T wave may be seen reflecting effect on repolarization.


Mechanism Of Action:


Quinidine blocks myocardial Na+ channels in the open state—reduces automaticity and maximal rate of 0 phase depolarization in a frequency dependent manner. Prolongation of APD is due to K+ channel block, while lengthening of ERP is caused by its moderate effect on recovery of Na+ and K+ channels. At high concentrations it also inhibits L type Ca2+ channels. Quinidine decreases the availability of Na+ channels as well as delays their reactivation.


The other actions of quinidine are fall in BP (weak α adrenergic blockade and cardiac depression), decreased skeletal muscle contractility, uterine contractions, vomiting, diarrhoea and neurological effects like ringing in ears, vertigo, deafness, visual disturbances and mental changes (Cinchonism). Like its levo isomer, it has antimalarial action, and has been used as a parenteral alternative to quinine for falciparum malaria. The important drug interactions of quinidine are:


·      Rise in blood levels and toxicity of digoxin due to displacement from tissue binding and inhibition of Pglycoprotein mediated renal and biliary clearance of digoxin.


·      Marked fall in BP in patients receiving vasodilators.


·      Risk of torsades de pointes is increased by hypokalaemia caused by diuretics.


·      Synergistic cardiac depression with βblockers, verapamil, K+ salts.


·   Quinidine inhibits CYP2D6: prolongs t½ of propafenone and inhibits conversion of codeine to morphine.




Though quinidine is effective in many atrial and ventricular arrhythmias, it is not used to terminate them because of risk of adverse effects, including that of torsades de pointes, sudden cardiac arrest or VF; idiosyncratic angioedema, vascular collapse, thrombocytopenia. It is occasionally used in a dose of 100–200 mg TDS to maintain sinus rhythm after termination of AF or AFI, and rarely in ventricular arrhythmias.


QUINIDINE SULPHATE 200 mg tab; QUININGA 300 mg tab, 600 mg/2 ml inj; NATCARDINE 100 mg tab.




It is the orally active amide derivative of the local anaesthetic procaine, with cardiac electrophysiological actions almost identical to those of quinidine, viz. slowing of 0 phase and impulse conduction, prolongation of APD, ERP, QRS complex and QT interval. Significant differences between the two are:


·      It is less effective in suppressing ectopic automaticity.

·      It causes somewhat less marked depression of contractility and AV conduction.

·      Antivagal action is minimal.

·     It is not an α blocker: causes less fall in BP; at high doses, fall in BP is due to ganglionic blockade.



Oral bioavailability of procainamide is about 75%, peak plasma concentration occurs in 1 hour. It is metabolized in liver, primarily by acetylation to N-acetyl-procainamide (NAPA) which has no Na+ channel blocking property but blocks K+ channels and prolongs repolarization: APD is lengthened. There are fast and slow acetylators of procainamide (as there are for isoniazid). More than half of procainamide is excreted unchanged in urine; plasma t½ is relatively short (3–4 hours). Thus, more frequent dosing than quinidine is required.


Dose: For abolition of arrhythmia—0.5–1 g oral or i.m. followed by 0.25–0.5 g every 2 hours; or 500 mg i.v. loading dose (25 mg/min injection) followed by 2 mg/kg/hour. Maintenance dose—0.5 g every 4–6 hours.


PRONESTYL 250 mg tab., 1 g/10 ml inj.


Adverse Effects

Gastrointestinal tolerance of procainamide is better than quinidine, but nausea and vomiting do occur.


CNS: weakness, mental confusion and hallucinations are noted at higher doses.


Flushing and hypotension are seen on rapid i.v. injection. Cardiac toxicity, ability to cause torsades de pointes are similar to quinidine.


Hypersensitivity reactions are rashes, fever, angioedema. Agranulocytosis and aplastic anaemia is rare.


More than half of patients given chronic high dose procainamide therapy develop antinuclear antibodies and about 1/5 develop systemic lupus erythematosus (SLE). It is more common in slow acetylators.



Procainamide (i.v.) can terminate monomorphic VT in upto 80–90% patients, but is less effective in preventing recurrences. Many WPW reciprocal VTs respond and it has been used to prevent recurrences of VF. However, procainamide is not suitable for prolonged oral therapy because of inconveniently frequent dosing and high risk of lupus.




It is a quinidine like Class IA drug that has prominent cardiac depressant and anticholinergic actions, but no α adrenergic blocking property. Disopyramide usually has no effect on sinus rate because of opposing direct depressant and antivagal actions. Prolongation of PR interval and QRS broadening are less marked.



Bioavailability of oral disopyramide is about 80%. It is partly metabolized in liver by dealkylation, nearly half is excreted unchanged in urine; plasma t½ is 6–8 hrs. The t½ is increased in patients of MI and in renal insufficiency.


Dose: 100–150 mg 6–8 hourly oral.


NORPACE 100, 150 mg cap, REGUBEAT 100 mg tab.


Adverse Effects

Disopyramide is better tolerated than quinidine, less g.i. effects. Anticholinergic side effects are the most prominent: dry mouth, constipation, urinary retention (especially in elderly males) and blurred vision. It can cause greater depression of cardiac contractility. Cardiac decompensation and hypotension may occur in patients with damaged hearts because it also increases peripheral resistance, so that cardiac output may be markedly decreased.


Contraindications are—sick sinus, cardiac failure and prostate hypertrophy.



The primary indication of disopyramide is as a second line drug for prevention of recurrences of ventricular arrhythmia. It may also be used for maintenance therapy after cardioversion of AF or AFl.




This Class IA drug delays Na+ channel recovery to a greater extent (also classified as Class IC), but cardio-depressant and CNS effects are less marked. It has been used to suppress VES and WPW arrhythmias, but the CAST II study has found it to increase mortality in postMI patients.





These drugs block Na+ channels more in the inactivated than in the open state, but do not delay channel recovery (channel recovery time < 1S). They do not depress AV conduction or prolong (even shorten) APD, ERP and QT.


Lidocaine (Lignocaine)


It is the most commonly used local anaesthetic. In addition, it is a popular antiarrhythmic in intensive care units.


The most prominent cardiac action of lidocaine is suppression of automaticity in ectopic foci. Enhanced phase4 depolarization in partially depolarized or stretched PFs, and afterdepolarizations are antagonized, but SA node automaticity is not depressed.


The rate of 0 phase depolarization and conduction velocity in AV bundle or ventricles is not decreased. Lidocaine decreases APD in PF and ventricular muscle, but has practically no effect on APD and ERP of atrial fibres. Atrial reentry is not affected. However, it can suppress reentrant ventricular arrhythmias either by abolishing one-way block or by producing two way block.


Lidocaine is a blocker of inactivated Na+ channels more than that of open state. As such, it is relatively selective for partially depolarized cells and those with longer APD (whose Na+ channels remain inactivated for longer period). While normal ventricular and conducting fibres are minimally affected, depolarized/damaged fibres are significantly depressed. Brevity of atrial AP and lack of lidocaine effect on channel recovery might explain its inefficacy in atrial arrhythmias.


Lidocaine has minimal effect on normal ECG; QT interval may decrease. It causes little depression of cardiac contractility or arterial BP. There are no significant autonomic actions: all cardiac effects are direct actions.



Lidocaine is inactive orally due to high first pass metabolism in liver. Action of an i.v. bolus lasts only 10–20 min because of rapid redistribution. It is hydrolysed, deethylated and conjugated; metabolites are excreted in urine. Metabolism of lidocaine is hepatic blood flow dependent.


The t½ of early distribution phase is 8 min while that of later elimination phase is nearly 2 hours. Its t½ is prolonged in CHF, because of decrease in volume of distribution and hepatic blood flow.


Dose and preparations Lidocaine is given only by i.v. route: 50–100 mg bolus followed by 20–40 mg every 10– 20 min or 1–3 mg/min infusion.

XYLOCARD, GESICARD 20 mg/ml inj. (5, 50 ml vials). These preparations for cardiac use contain no preservative. The local anaesthetic preparations should not be used for this purpose.


Ventricular ectopic activity can be titrated with the rate of administration. Propranolol prolongs t½ of lidocaine by reducing hepatic blood flow. Cimetidine also increases plasma levels of lidocaine.


Adverse Effects

The main toxicity is dose related neurological effects:


Drowsiness, nausea, paresthesias, blurred vision, disorientation, nystagmus, twitchings and fits. Lidocaine has practically no proarrhythmic potential and is the least cardiotoxic antiarrhythmic. Only excessive doses cause cardiac depression and hypotension.



Lidocaine is used only in ventricular tachyarrhythmias. It is ineffective in atrial arrhythmias. Because of rapidly developing and titratable action it is a good drug in the emergency setting, e.g. arrhythmias following acute MI, during cardiac surgery, etc. Given prophylactically by infusion in acute MI, it reduces occurrence of VF. However, metaanalysis has shown that lidocaine fails to improve survival; may even increase short term mortality. Therefore, it is no longer administered routinely to all MI patients.


Efficacy of lidocaine in chronic ventricular arrhythmia is low, but it is useful in digitalis toxicity because it does not worsen AV block.




It is a local anaesthetic and an active antiarrhythmic by the oral route; chemically and pharmacologically similar to lidocaine. It reduces automaticity in PF, both by decreasing phase4 slope and by increasing threshold voltage. By reducing the rate of 0 phase depolarization in ischaemic PF it may convert oneway block to twoway block.


Mexiletine is almost completely absorbed orally, 90% metabolized in liver and excreted in urine; plasma t½ 9–12 hours.

Bradycardia, hypotension and accentuation of AV block may attend i.v. injection of mexiletine. Neurological—tremor, nausea and vomiting are common; dizziness, confusion, blurred vision, ataxia can occur.


Dose: 100–200 mg i.v. over 10 min., 1 mg/min infusion.


Oral: 150–200 mg TDS with meals.


MEXITIL 50, 150 mg caps, 250 mg/10 ml. inj.



Parenteral mexiletine is effective in postinfarction ventricular arrhythmias as alternative to lidocaine in resistant cases. Orally it is used to keep VES and VT suppressed over long-term.




These are the most potent Na+ channel blockers with more prominent action on open state and the longest recovery times (> 10S). They markedly delay conduction, prolong PR, broaden QRS complex, but have variable effect on APD. Drugs of this subclass have high proarrhythmic potential—sudden deaths have occurred.


They have profound effect on His-Purkinje as well as accessory pathway conduction; markedly retard anterograde as well as retrograde conduction in the bypass tract of WPW syndrome.




By blocking Na+ channels propafenone markedly depresses conduction and has β adrenergic blocking property—can precipitate CHF and bronchospasm. Sinoatrial block has occurred occasionally. Propafenone is absorbed orally and undergoes variable first pass metabolism; there being extensive or poor metabolizers. Bioavailability and t½ differs considerably among individuals. Some metabolites are active. Side effects are nausea, vomiting, bitter taste, constipation and blurred vision.


Propafenone is a reserve drug for ventricular arrhythmias, reentrant tachycardias involving AV node/accessory pathway and to maintain sinus rhythm in AF.


Dose: 150 mg BD–300 mg TDS; RHYTHMONORM 150 mg tab.




It suppresses VES, VT, WPW tachycardia and prevents recurrences of AF and PSVT. But in the CAST study it was found to increase mortality in patients recovering from MI; can itself provoke arrhythmias during chronic therapy. It is reserved for resistant cases of recurrent AF, and WPW rhythms in patients not having associated CHF.




The primary action of drugs in this class is to suppress adrenergically mediated ectopic activity.




Some β blockers, e.g. propranolol have quinidine like direct membrane stabilizing action at high doses, but in the clinically used dose range—antiarrhythmic action is exerted primarily because of cardiac adrenergic blockade. Propranolol decreases the slope of phase4 depolarization and automaticity in SA node, PF and other ectopic foci when this has been increased under adrenergic influence; little action otherwise. The other most important action is to prolong the ERP of AV node (an antiadrenergic action). This impedes AV conduction (no paradoxical tachycardia can occur when atrial rate in AF or AFl is reduced).


Slow channel responses and afterdepolarizations that have been induced by catecholamines (CAs) are suppressed. Reentrant arrhythmias that involve AV node (many PSVTs) or that are dependent on slow channel/depressed fast channel response may be abolished by its marked depressant action on these modalities.


The most prominent ECG change is prolongation of PR interval. Depression of cardiac contractility and BP are less marked than with quinidine.



For rapid action, propranolol may be injected i.v. 1 mg/min (max. 5 mg) under close monitoring. The usual oral antiarrhythmic dose is 40–80 mg 2–4 times a day.



Propranolol is very useful in treating inappropriate sinus tachycardia, atrial and nodal ESs provoked by emotion or exercise. It is less effective than adenosine and verapamil for PSVT—conversion rate is about 60%.


Propranolol rarely abolishes AF or AFl, but can be used to control ventricular rate. It is highly effective in sympathetically mediated arrhythmias seen in pheochromocytoma and during anaesthesia with halothane. Digitalis induced tachyarrhythmias may be suppressed.


Efficacy in chronic ventricular arrhythmias is low, but its anti-ischaemic action may be protective. Prophylactic treatment with β blockers reduces mortality in postMI patients. Propranolol has also been used for WPW, but in some cases severe bradycardia may be precipitated.




It is a nonselective β blocker having prominent Class III action of prolonging repolarization by blocking cardiac K+ channels. It is not a Na+ channel blocker—does not depress conduction in fast response tissue, but delays AV conduction and prolongs its ERP. Sotalol is effective in polymorphic VT and for maintaining sinus rhythm in AF/AFl. Due to prolongation of APD and QT, risk of dose-dependent torsades de pointes is the major limitation. It is contraindicated in patients with long QT interval.




This quick and short acting β1 blocker administered i.v. is very useful for emergency control of ventricular rate in AF/AFl. It can terminate supraventricular tachycardia, and is mainly used for arrhythmias associated with anaesthesia.


MINIBLOCK 100 mg/10 ml, 250 mg/10 ml inj.; 0.5 mg/ kg in 1 min followed by 0.05–0.2 mg/kg/min i.v. infusion.




The characteristic action of this class is prolongation of repolarization; AP is widened and ERP is increased. The tissue remains refractory even after full repolarization: reentrant arrhythmias are terminated.




This unusual iodine containing highly lipophilic long-acting antiarrhythmic exerts multiple actions:


Prolongs APD and QT interval attributable to block of myocardial delayed rectifier K+ channels. This also appears to reduce nonuniformity of refractoriness among different fibres.


Preferentially blocks inactivated Na+ channels (like lidocaine) with relatively rapid rate of channel recovery: more effective in depressing conduction in cells that are partially depolarized or have longer APD.


Inhibits myocardial Ca2+ channels and has noncompetitive β adrenergic blocking property.


Conduction is slowed and ectopic automaticity is markedly depressed, but that of SA node is affected only slightly. Effect of oral doses on cardiac contractility and BP are minimal, but i.v. injection frequently causes myocardial depression and hypotension.


Despite prolongation of APD, the arrhythmia (torsades de pointes) provoking potential of amiodarone is low, probably because it does not exhibit ‘reverse use-dependence’ of APD prolongation or because of its multiple antiarrhythmic mechanisms. The prolongation of APD by most class III drugs is more marked at slower rates of activation (encouraging EAD) than at higher rates (reverse use-dependence), while with amiodarone it is independent of rate of activation.



Amiodarone is incompletely and slowly absorbed from the g.i.t. On daily oral ingestion the action develops over several days, even weeks. However, on i.v. injection, action develops rapidly. It accumulates in muscle and fat from which it is slowly released and then metabolized in liver mainly by CYP3A4. One metabolite is active. The duration of action is exceptionally long; t½ 3–8 weeks.


Dose: Amiodarone is mainly used orally 400–600 mg/ day for few weeks, followed by 100–200 mg OD for maintenance therapy. 100–300 mg (5 mg/kg) slow i.v. injection over 30–60 min.


CORDARONE, ALDARONE, EURYTHMIC 100, 200 mg tabs, 150 mg/3 ml inj.



Amiodarone has been found effective in a wide range of ventricular and supraventricular arrhythmias. Resistant VT and recurrent VF are the most important indications. It is also used to maintain sinus rhythm in AF when other drugs have failed. Rapid termination of ventricular and supraventricular arrhythmias can be obtained by i.v. injection. WPW tachyarrhythmia is terminated by suppression of both normal and aberrant pathways.


Its long duration of action makes it suitable for long-term prophylactic therapy; has been found to reduce sudden cardiac death. Because of high and broad spectrum efficacy and relatively low proarrhythmic potential, amiodarone is a commonly used antiarrhythmic, despite its organ toxicity in the long-term.


Adverse Effects

These are dose-related and increase with duration of therapy. Fall in BP, bradycardia and myocardial depression occurs on i.v. injection and on drug cumulation.


Nausea, gastrointestinal upset may attend oral medication, especially during the loading phase. Photosensitization and skin pigmentation occurs in about 10% patients. Corneal microdeposits are common with long-term use, but are reversible on discontinuation.


Pulmonary alveolitis and fibrosis is the most serious toxicity of prolonged use, but is rare if daily dose is kept below 200 mg.


Peripheral neuropathy generally manifests as weakness of shoulder and pelvic muscles. Liver damage is rare. Amiodarone interferes with thyroid function in many ways including inhibition of peripheral conversion of T4 to T3: goiter, hypothyroidism and rarely hyperthyroidism may develop on chronic use.



Amiodarone can increase digoxin and warfarin levels by reducing their renal clearance. Additive AV block can occur in patients receiving β blockers or calcium channel blockers. Inducers and inhibitors of CYP3A4 respectively decrease and increase amiodarone levels.




It is an adrenergic neurone blocking drug (see Ch. No. 10) introduced in 1960 as antihypertensive, but was soon withdrawn. It was reintroduced for parenteral use to facilitate reversal of VF, but is not available in India or the USA, and is rarely used elsewhere.


Bretylium has complex electrophysiological effects which are partly a result of initial NA release from adrenergic terminals in heart, and later blockade of NA release, but major direct action is prolongation of APD and ERP, due to K+ channel blockade.




This newer antiarrhythmic prolongs APD and ERP by selectively blocking rapid component of delayed rectifier K+ current without affecting other channels or receptors; has no autonomic or peripheral actions. It is therefore labelled as pure class III antiarrhythmic.


Oral dofetilide can convert AF or AFl to sinus rhythm in ~30% cases, but is more effective in maintaining sinus rhythm in converted patients—its primary indication. Significantly, chronic therapy with dofetilide in patients with high risk of sudden cardiac death/post MI cases has not increased mortality, despite provoking torsades de pointes in some recipients. It is mainly excreted unchanged in urine and produces few side effects.


Ibutilide is another new class III antiarrhythmic used i.v. for pharmacological conversion of AFl and AF to sinus rhythm.




The primary action of this class of drugs is to inhibit Ca2+ mediated slow channel inward current.





Of the many Ca2+ channel blockers, verapamil has the most prominent cardiac electrophysiological action (Table 38.1). It blocks L type Ca2+ channels and delays their recovery. Its antiarrhythmic aspects are described here, while other aspects are covered in Ch. No. 39 and 40.



The basic action of verapamil is to depress Ca2+ mediated depolarization. This suppresses automaticity or reentry dependent on slow response. Phase4 depolarization in SA node and PFs is reduced resulting in bradycardia and extinction of latent pacemakers. Reflex sympathetic stimulation due to vasodilatation partly counteracts the direct bradycardia producing action. Delayed afterdepolarizations in PFs are dampened.


The most consistent action of verapamil is prolongation of AV nodal ERP. As a result AV conduction is markedly slowed and reentry involving AV node is terminated. Intraventricular conduction, however, is not affected. Verapamil has negative inotropic action due to interference with Ca2+ mediated excitation-contraction coupling in myocardium.


Uses and Precautions


ü PSVT—Verapamil can terminate attacks of PSVT; 5 mg i.v. over 2–3 min is effective in 80% cases, but marked bradycardia, AV block, cardiac arrest and hypotension can occur. Verapamil should not be used if PSVT is accompanied with hypotension or CHF. It is also useful for preventing recurrences: 60 to 120 mg TDS orally.


ü To control ventricular rate in AF or AFl; it may be used as an alternative to, or in addition to digitalis: 40–80 mg TDS oral. In few cases the AF or AFl may revert to sinus rhythm, but this is an unusual happening.


Reentrant supraventricular and nodal arrhythmias (WPW) are susceptible to verapamil, but it should not be used because of risk of increased ventricular rate due to reflex sympathetic stimulation and reduction of ERP of the bypass tract in some cases.


Verapamil has poor efficacy in ventricular arrhythmias. In contrast to β blockers, verapamil prophylaxis does not reduce mortality in post-MI patients. In some patients of VT, i.v. injection of verapamil has precipitated VF: therefore contraindicated. It is also not recommended for digitalis toxicity, because additive AV block may occur. It is contraindicated in partial heart block and sick sinus.


CALAPTIN 40, 80 mg tab; 120, 240 mg SR tab, 5 mg/2 ml inj.




The direct cardiac actions of diltiazem are similar to those of verapamil. However, they are less marked. It is an alternative to verapamil for PSVT.


For rapid control of ventricular rate in AF or AFl, i.v. diltiazem is preferred over verapamil, because it can be more easily titrated to the target heart rate, causes less hypotension and myocardial depression—can be used even in the presence of mild-to-moderate CHF.


DILZEM 30, 60, 90 mg tabs, 25 mg/5 ml inj.


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