Generality
Antiarrhythmic drugs are medicines that are used in the treatment of cardiac arrhythmias.
The heart rhythm is normally controlled by a peacemaker site called the sinoatrial node and consists of specialized cells that contract generating action potentials.
The speed of cardiac contraction at rest should be within an interval ranging, approximately, from 60 to 100 beats per minute. If the sinus velocity is lower than this interval, we can speak of bradycardia; on the contrary, if the sinus velocity is higher than the aforementioned values, then one speaks of tachycardia. However, in these cases there is always talk of cardiac arrhythmias, whether they are bradycardic or tachycardic.
The antiarrhythmic drugs currently used in therapy can be divided into various classes, depending on the effect they have on the action potential of myocardial cells. These classes will be briefly described below.
However, to better understand the type of classification and the mechanism of action of antiarrhythmic drugs, it is necessary to make a short introduction about what the aforementioned cardiac action potential is and how it is generated.
Cardiac action potential
As mentioned, the cells of the myocardium contract by generating an action potential, whose course, under normal conditions, is absolutely predictable.
The aforementioned cardiac action potential can be divided into five phases:
- Phase 0 or rapid depolarization phase : in this phase the permeability of the cell membrane for sodium ions increases, allowing the rapid entry of this cation into the cell and causing rapid depolarization. When the cardiac cell is at rest, in fact, the internal potential of the membrane is more electronegative than the external one (this is defined as a resting membrane potential). When the impulse arrives and you enter the zero phase, instead, we see a rapid inversion of the inner membrane potential, which becomes positive with respect to the outside.
- Phase 1 : in phase 1 the permeability of the membrane is reduced to sodium ions and there is the entry of chlorine ions into the cell and to the exit of potassium ions.
- Phase 2 : phase 2, also called plateau phase, is characterized by a slow entry into the calcium ion cell, counterbalanced by the leakage of potassium ions. This phase is called a plateau precisely because there is little or no change in the membrane potential.
- Phase 3 : in this phase the entry speed of calcium ions slows down in conjunction with a continuous efflux of potassium ions. All this brings the membrane back to the initial resting potential.
- Phase 4 : finally, at this stage, ionic concentrations inside and outside the cell are restored, thanks to the action of the membrane Na + / K + ATPase pump.
Summing up briefly, we can state that the action potential is generated by an initial entry of sodium ions into the cardiac cell, followed then by the entry of calcium and, finally, by the output of potassium which brings the action potential back to the condition rest.
Class I anti-arrhythmics
The antiarrhythmics belonging to class I carry out their action through the bond and the consequent block of the sodium channels.
These antiarrhythmics can in turn be subdivided into subclasses. Therefore, we can distinguish:
- Class IA antiarrhythmics: the active ingredients belonging to this class of antiarrhythmics block the sodium channel by inhibiting the rapid depolarization phase 0, thus prolonging the action potential. This type of antiarrhythmics dissociates from the sodium channels with an intermediate speed. This class includes active ingredients such as quinidine, disopyramide and procainamide .
- Class IB antiarrhythmics: the antiarrhythmics belonging to this class always act by blocking the sodium channels, but they dissociate from the latter much faster than the class IA antiarrhythmics and give rise to a short phase 3 of repolarization, thus reducing also the duration of the action potential. Thanks to their rapid onset of action, they are used especially in emergencies.
This class of antiarrhythmics includes lidocaine (effective only if administered parenterally), tocainide, mexiletine and phenytoin .
- Class IC antiarrhythmics: these antiarrhythmics have a low rate of dissociation from the sodium channels and give rise to a very slow initial phase 0 depolarization.
Active ingredients such as flecainide, propafenone and moricizine belong to this category.
Side effects
Being a rather heterogeneous class, the side effects deriving from the use of class I antiarrhythmics can vary greatly, depending both on the type of active ingredient chosen, and on the route of administration (parenteral or, where possible, oral) that intends to employ.
For example, the main side effects that may occur following the use of quinidine are gastrointestinal (abdominal pain, vomiting, diarrhea and anorexia), while the main undesirable effects resulting from the use of parenteral lidocaine are vertigo, delusions, paresthesia and confusion.
Class II antiarrhythmics
Class II antiarrhythmics are active ingredients with β-blocking action. More in detail, these active ingredients are able to block the β1-adrenergic receptors present in the heart. The stimulation of these receptors, in fact, causes an increase in the frequency, contractility and speed of conduction of the impulse of myocardial cells.
The blockade of this type of receptors, on the other hand, causes a blockage of the influx of calcium ions inside the cell, thus inducing a prolonged repolarization. The following principles belong to this class of antiarrhythmic drugs such as propranolol, sotalol, nadolol, l ' atenolol, acebutolol and pindolol .
Side effects
Also in this case the type of undesirable effects that can occur depends very much on the active ingredient used and on the sensitivity of each patient to the drug.
However, the main side effects of taking β-blocking antiarrhythmics are: dyspnoea, headache, dizziness, fatigue, bradycardia and Raynaud's syndrome.
Class III antiarrhythmics
Class III antiarrhythmics are active ingredients that exert their activity by inhibiting the repolarization of cardiac cell membranes. More in detail, these antiarrhythmics interfere with phase 3 of the action potential through the blockage of the potassium channels.
Active substances such as ibutilide and amiodarone belong to this class of antiarrhythmics.
The main side effect deriving from the use of this type of antiarrhythmics is hypotension, including orthostatic type.
Class IV antiarrhythmics
Class IV antiarrhythmics exert their activity by blocking the calcium channels, thus giving rise to a slow phase of repolarization of the cell membrane.
Among the various active ingredients belonging to this class of antiarrhythmics we mention verapamil and diltiazem .
The side effects that may arise following the use of class IV antiarrhythmics consist substantially in hypotension, confusion, headache, peripheral edema, pulmonary edema and, in some cases, constipation.
Other antiarrhythmic drugs
There are other antiarrhythmic drugs that do not fall under the classification just carried out. This is the case, for example, of adenosine and digitalis glycosides.
Adenosine is a nucleoside that can be used - at appropriate dosages and intravenously - in the treatment of paroxysmal supraventricular tachycardias. Adenosine performs its action by acting directly on the atrioventricular node of the heart.
Among the digitalis glycosides, however, we recall digoxin, an active ingredient used mainly in the treatment of fibrillation and atrial flutter. Digoxin exerts its antiarrhythmic activity through inhibition of the membrane Na + / K + ATPase pump, with consequent increase in intracellular sodium levels.
