ANTIARRHYTHMICS : SYNTHESIS SHEET
CLASSIFICATION OF MEDICINES.
To talk about antiarrhythmic treatments is to talk about a set of drugs. However, in medicine, there are hundreds or even thousands of drugs used for the treatment of various conditions. Thus, in order to simplify the classification, it is customary to distribute them by families. These generally group the drugs according to their spectrum of action. In addition, within the same family, many sub-families can be broken down according to various criteria (chemical structure, target organs, target molecules, etc.). Therefore, this makes a universal and harmonious classification particularly complex to establish. Antiarrhythmics belong to one of these families. As the name suggests, this set includes cardiological treatments whose function is to prevent cardiac arrhythmias. An arrhythmia or rhythm disorder is a generic and imprecise term which refers to many conditions. The different scenarii are the following:
- Cases when the heart beats too fast: tachycardia.
- And / or cases when the heart beats irregularly / abnormally: extrasystoles, fibrillation, flutter,…
Let’s note, however, that arrhythmia does not include cases when the heart beats too slowly (bradycardia). Antiarrhythmic drugs are, therefore, not an indication for the treatment of bradycardia.
HOW ANTIARRHYTHMICS WORK
Antiarrhythmics are intended to prevent or reduce heart rhythm disorders. Their common mode of action is to block (directly or indirectly) the channels regulating the heart rate.
PHYSIOLOGY AND PHYSIOPATHOLOGY OF THE HEART RATE.
The heart is a muscular organ activated by a set of specialized “electrical” cells. These cells, which are integrated in the heart muscle, make up what is called the cardionector tissue. Their function is to regularly and synchronously activate the entire heart muscle which can then contract effectively and homogeneously. To do so, these cells have special electrical channels located on their surface. They are called ion channels. There are several types, such as:
- Sodium channels (carry sodium ions)
- potassium channels (carry potassium ions)
- Calcium channels (carry calcium ions)
Thus, ion channels, thanks to complex mechanisms, make it possible to regulate ionic flows through the electrical cells. The ion channels and flows allow the heart to beat through regular electrochemical pulses which, at the cellular level, constitute what is called the membrane action potential. Then, the action potential generated by electrical cells spreads throughout the heart muscle through a well-defined network (a little like electrical circuits).
Therefore, a defect in the ion channels will disrupt the function of the electrical cells. Consequently, this disruption will be likely to result in arrhythmia. The abnormalities of the cardiac ion current can have multiple origins, which are the cause of arrhythmias. They can be innate (certain genetic diseases such as congenital long QT syndrome or Brugada disease), or they can be acquired (intake of a toxic drug, cell death by asphyxiation following a myocardial infarction, metabolic dysfunction, etc.).
MECHANISM OF ACTION OF ANTIARRHYTHMIC TREATMENTS.
Antiarrhythmic drugs are chemical molecules that interact directly or indirectly (via other cellular receptors) with these ion channels. Thus, they will correct / rectify a rhythm disorder by regulating the ion channels whenever they are defective. However, these treatments may have a counter-productive effect if they are not used correctly. They can then be pro-arrhythmogenic (causing arrhythmias), which can be particularly dangerous or even fatal in certain cases. It is therefore very important to emphasize the fact that antiarrhythmic drugs are not innocuous. They must be handled with the utmost care by specialist doctors (usually cardiologists) and under strict supervision.
CLASSIFICATION OF ANTIARRHYTHMICS.
Each antiarrhythmic drug has molecular targets whose purpose is to regulate cardiac ion flows, as mentioned above. However, these targets can be multiple and the same molecule can block several channels. This makes it particularly complex to establish a universal classification. Currently /To date, the most frequently used classification is that of VAUGHAN WILLIAMS. It is by no means perfect, but it has the advantage of being fairly / quite simple. It regroups the different molecules according to their “main” target ion channel. This classification includes 4 major families / classes.
- Class 1 antiarrhythmics
o Target: sodium channel(s?) (calcium ions)
o Example: flecainide, quinidine, disopyramide
- Class 2 antiarrhythmics
o Target: beta adrenergic receptors = family of beta-blockers
o Example: bisoprolol, atenolol, propranolol, acebutolol, metoprolol
- Class 3 antiarrhythmics
o Target: potassium channels
o Example: amiodarone
- Class 4 antiarrhythmics
o Target: calcium channels = family of calcium channel blockers
o Example: verapamil, diltiazem
Let’s note that some molecules can belong to several classes at the same time:
- Sotalol: class 2 and class 3 effect
- Propafenone: class 1 and class 2 effect
INDICATION OF ANTIARRHYTHMIC TREATMENTS.
The indications for antiarrhythmic therapy include all heart rhythm disorders. However, given the various diagnoses and potential side effects, choosing the treatment / therapy is often complex and may require specialist advice (cardiologist or rhythmologist).
Many different parameters are taken into account when choosing the most appropriate treatment. For example:
- Origin of rhythm disorder: atrial (which comes from the atria) or ventricular
- Its nature: tachycardia, premature beat …
- Intensity of the symptoms described by the patient
- Presence or not of an underlying heart disease (previous myocardial infarction, dilated heart disease, …)
- Contra-indication to certain treatments (thyroid problems for amiodarone, asthma for beta-blockers, …)
- Poor tolerance to certain drugs/ intolerance to
SIDE EFFECTS OF ANTIARRHYTHMICS.
As with all medicines, antiarrhythmics can have side effects which can be divided into 2 groups: cardiac and non-cardiac effects.
- CARDIAC EFFECTS OF ANTIARRHYTHMICS.
As previously mentioned, antiarrhythmic drugs have a direct action on the ion channels of the heart. However, in some cases they can have an unexpected reverse effect Indeed, an excessive blockage (overdose) or inappropriate (wrong indication) may lead to a counter-productive effect sometimes causing life threatening rhythm disorders such as major tachycardia or bradycardia. This applies to all antiarrhythmic drugs. These rhythm disorders are of particular severity and may, in some extreme cases, be fatal to the patient. However, these effects are rare and are often the result of an overdose. These potentially dangerous drugs must therefore always be prescribed by a specialist (cardiologist, rhythmologist) and handled with great care.
- NON-CARDIAC SIDE-EFFECTS.
Unlike the cardiac effects which are common to all antiarrhythmics (to a greater or lesser extent), non-cardiac effects vary widely from one treatment to another. Some treatments are rather well tolerated, such as class 1 or 2 antiarrhythmics (beta blockers). On the contrary, others are much less well tolerated, as for example amiodarone which has a number of side effects. Here is a non-exhaustive list of classic extracardiac complications caused by frequently used drugs:
- Flecainide: dizziness, tingling, tremors
- Quinidine: cinchonism, skin disorders, visual disorders, liver disease
- Beta blockers (class 2): asthma (episodes), Raynaud syndrome, psoriasis
- Amiodarone: thyroid disorders (hypo- or hyperthyroidism), interstitial lung disease, neuropathy, hepatopathy, eye disorders
- Verapamil: constipation
Anti arrhythmics belong to a large family of drugs. They include many molecules with different targets but a common purpose: to prevent heart rhythm disorders. Antiarrhythmics are however potentially dangerous drugs. They require careful and specialized management. In addition, their toxicity can sometimes lead to choose an alternative strategy such as catheter ablation, a particularly interesting technique whose results and safety often make it the best choice.