Arrhythmia is a common disorder of cardiac excitation, which may be benign but may also be fatal ( e.g., ventricular fibrillation following a heart attack).
Antiarrhythmic drugs are used to control or correct cardiac rhythm.
Four types of arrhythmias are:
1) Atrial fibrillation,
3) Tachycardia, and
4) Ventricular arrhythmias.
The symptoms of arrhythmias are:
1) Shortness of breath,
2) Feeling tired or light-headed,
3) Rapid thumping in chest or palpitations,
4) Chest pain, and
5) Losing consciousness.
Sodium Channel Blockers (Class I)
Sodium channel blockers are the most wi dely used antiarrhythmic agents. They act by blocking myocardial Na +
ion channels. They are mainly used for the treatment of supraventricular, nodal and ventricular arrhythmias , especially after MI and DC shock.
Mechanism of Action
Antiarrhythmic activity of sodium channel blockers is due to:
1) Decrease in inflow of sodium during phase 0 which slo ws the maximum rate of depolarisation,
2) Decrease in excitability and conduction velocity,
3) Prolongation of effective refractory period, and
4) Decrease in slope of phase 4 spontaneous depolarisation (automaticity).
The sodium channel blockers have the following therapeutic uses:
1) Treatment of supraventricular, nodal and ventr icular arrhythmias, especially after MI and DC shock.
2) After treatment of atrial flutter and fibrillation to maintain sinus rhythm.
The adverse effects of sodium channel blockers are marked depression of AV
conduction, hypotension, bradycardia, anorexia, nausea, and vomiting.
Class I antiarrhythmic agents are further classified into:
1) Moderate (Class IA): These drugs slow the rate of rise of action potential
and prolong the duration of action potential. They block Na+ ion channels and prolong the repolarisation time.
i) Quinidine: It is the prototype of Class IA drug. Because of its concomitant Class III activity, it can precipitate arrhythmias such as polymorphic ventricular tachycardia ( torsades de pointes ), which can degenerate into ventricular fibrillation. Due to the toxic effects, the clinical uses of quinidine are replaced with calcium antagonists (like amiodarone and verapamil).
Mechanism of Action: Quinidine binds to open and inactivated Na+ ion
channels to pr event the influx of Na+ ions; thus slowing down the rapid upstroke during phase 0. It also reduces the slope of phase 4 spontaneous depolarisation and inhibits potassium channels. These actions result in
slow conduction velocity and increased refractoriness.
Therapeutic Uses: Quinidine is used in the treatment of a wide variety of arrhythmias including atrial, AV -junctional, and ventricular tachyarrhythmia. It is used to maintain sinus rhythm after direct -current cardioversion of atrial flutter or fibrilla tion and to prevent frequent ventricular tachycardia.
a) A potential adverse effect of quinidine is development of arrhythmia (torsades de pointes).
b) It may cause SA and AV blockage or asystole.
c) At toxic levels, it may induce ventricular tachycardia.
d) Nausea, vomiting, and diarrhoea are commonly observed.
e) In l arge doses , it may induce the symptoms of cinchonism ( e.g., blurred vision, tinnitus, headache, disorientation, and psychosis).
f) It has a mild α-adrenergic blocking action as well as an atropine-like effect.
g) It can increase the steady -state concentration of digoxin by displacement of digoxin from tissue -binding sites (minor effect) and by decreasing digoxin renal clearance (major effect).
ii) Procainamide: It is a derivative of the local anaesthetic procaine and shows actions similar to those of quinidine.
Mechanism of Action: Procainamide stabilises the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby affecting local anaesthetic action.
Therapeutic Uses: Procainamide can be given in place of quinidine as it is better tolerated in the treatment of atrial fibrillation and flutter. It is an alternative to lidocaine in preventi on and treatment of frequent VPBs (Ventricular Premature Beats) and sustained tachycardia after MI. Its use is also declining because of frequent dosing and unacceptable adverse effects.
Adverse Effects: With chronic use, procainamide causes a high incidence of side effects, including a reversible lupus erythematous -like syndrome. Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias. CNS side effects include depression, hallucination, and psychosis.
2) Weak (Class IB): The characteristic effects of these drugs are reduced rate
of rise of action potential and reduced or unchanged APD ( Action Potential Duration). The drugs of Class IB rapidly associate and dissociate from the sodium channels. Thus , their actions are m anifested when the cardiac cells are depolarised or firing rapidly.
i) Lidocaine: It is a local anaesthetic which shortens phase 3 repolarisation and decreases the duration of action potential . Lidocaine is useful in treating ventricular arrhythmias. It was the drug of choice for emergency treatment of cardiac arrhythmias. It does not slow down conduction, thus has a little effect on the AV junction arrhythmia.
Lidocaine in higher doses causes cardiac and CNS manifestations. SA nodal arrest and hypotension may also occur. Paraesthesia, tremor (facial twitching), vomiting, light headedness, slurred speech, and convulsions also occur commonly.
ii) Phenytoin: It is an antiepileptic drug used in tonic -clonic seizures. It produces unique cardiac electrophys iological effects, thus is used in digoxin-induced arrhythmia.
Phenytoin blocks the inactivated sodium channels, thus recovery occurs rapidly and depresses automaticity in ventricular tissues and PF, thus suppresses DAPs (Delayed After -Polarisations). It facilitates AV nodal conduction, therefore can be suitably used in supraventricuar arrhythmia
associated with AV blocks such as digitalis -induced atrial tachycardia
and digoxin-induced ventricular tachycardia.
Phenytoin is mainly used in children with con genital heart disease and
congenital prolonged QT syndrome to treat ventricular tachycardia. Some common adverse effects of phenytoin include decreased coordination, mental confusion, nervousness, slurred speech, trouble
with breathing, speaking, or swal lowing, unsteadiness, trembling, and
other problems with muscle control or coordination.
3) Strong (Class IC): Drugs of this class are powerful blockers of fast Na +
ion channels, and thus reduce upstroke of AP in normal and diseased myocardium. There is dela yed inactivation of slow Na +
ion channels during down slope of AP , and this result in prolongation of APD. In addition, there is inhibition of delayed rectifier K +
current (less K +
efflux), so the APD is prolonged in His Bundle and Purkinje fibre system.
These changes create heterogeneity of impulse conduction, non -uniform slowing and unidirectional block predisposing to development of re -entry (proarrhythmic potential). Arrhythmias are more likely to occur in structural heart disease, sympathetic over activity and at faster heart rates.
i) Flecainide: It blocks Na +
ion channels in normal and ischemic myocardium, t hus slow ing down the recovery of blocked Na +
ion channels. It further slows down the conduction of electrical impulse in
the heart, i.e., reduces excitability.
Flecainide is useful in terminating PSVT, and treating atrial fibrillation and atrial flutter occurring in normal heart. It stabilises the heart rhythm when the heart beats too fast or beats irregularly.
Common adverse effects of flecainide are:
a) During Cardiac Arrhythmia Suppression Trial (CAST), it causes serious ventricular arrhythmias and even sudden death.
b) During the treatment of atrial fibrillation, it should be administered with a rate -reducing drug (digoxin) otherwise paradoxical tachycardia may occur.
c) It is contraindicated in sick sinus syndrome, bundle branch block and should be avoided in acute MI.
ii) Propafenone: It blocks fast Na +
ion channels and gives a mild β-
blocking action (1/10 of propranolol) and class -IV action (Ca ++ ion channel block age). QT interval does not change but QRS and PR intervals are prolonged. It is effective orally and is metabolised by CYP 2D6 (in persons with CYP 2D6 deficiency, it is slowly metabolised).
Propafenone acts by slowing down the influx of Na+ ions into the cardiac muscle cells, thus decreasing the excitability of the cells.
Propafenone is used in life -threatening ventricular tachyarrhythmias, for suppressing supraventricular tachycardia in Wolff -Parkinson-White (WPW) syndrome, i n recurrent atrial fibrillation, and in suppression of paroxysms of atrial fibrillation.
The main adverse effects of propafenone are constipation, and sometimes
it worsens CHF. Serious ventricular arrhythmias, sudden death, and increased mortality have also been reported.