Antiarrhythmic Drugs

The myocardial conducting system
Genesis of normal heart rhythms
Surface ECG for diagnosing rhythm disturbances: tachyarrhythmias & bradyarrhythmias

• The Heartbeat
• Dysrhythmias and Congenital Heart Defects

How abnormal rhythms form

There are three main ways in which abnormal rhythms can form. Firstly, an abnormal rhythm can form via re-entry, which I'll explain in a bit. Re-entry is the most common cause of arrhythmias. Secondly, an abnormal rhythm can form if a cell that doesn't usually function as a pacemaker suddenly gains enhanced automaticity. Thirdly, some medications, such as digoxin, can cause afterpotentials, which in turn result in arrhythmias.

I'll now go into re-entry in more detail. When a part of the heart is damaged, that can block conduction of the electrical signal through that part of the heart. However, sometimes damaged parts can still receive a signal coming back up from the other direction. This is known as retrograde conduction. When retrograde conduction occurs, the action potential can re-stimulate earlier parts of the heart at the wrong time, thus forming a "re-entry circus."

It is also important to note that for re-entry to be a problem, the speed of conduction needs to be just right. If the speed of conduction is too fast, those earlier parts of the heart will still be experiencing their effective refractory period (i.e. when they have just been stimulated and cannot be re-stimulated until they have re-polarised). If the speed of conduction is too slow, then the next heartbeat will have already stimulated the earlier parts of the heart. Therefore, in order for re-entry to actually stimulate another contraction, re-entry cannot be too slow or too fast.

How drugs can correct abnormal rhythms
Antiarrhythmic classes and examples

There are four main classes of antiarrhythmics, so I will go through each one in turn.

Class I: Sodium-channel blockers

Class I antiarrhythmics block sodium channels, thus decreasing the slope of phase 0, making the action potential take longer to reach its peak. As each action potential takes longer to reach its peak, it takes longer to transmit a signal through the heart. Unfortunately, class I antiarrhythmics may actually increase the risk of arrhythmia in some cases, and for that reason they can only be prescribed by specialists. The reason why they increase the risk of arrhythmia has to do with the fact that re-entry is not a problem if it is too fast. If there are latent circuits that have a super fast re-entry circus, slowing down the conduction of these circuits could mean that the re-entry time will now hit the critical window for arrhythmia.

Examples of Class I antiarrhythmics include flecainide and lignocaine.

Class II: Beta-blockers

Class II antiarrhythmics block beta-1 adrenoceptors on the heart, which are linked to sodium and calcium channels via G-proteins. Blocking beta-1 adrenoceptors therefore slows conduction. Despite also slowing conduction, Class II antiarrhythmics don't have the same risk of worsening arrhythmia as Class I antiarrhythmics do. I'm not 100% sure why, but I've asked on the class discussion board, so hopefully I'll find out soon!

Examples of Class II antiarrhythmics include metoprolol, propranolol, and many other drugs ending in -olol.

Class III: Drugs that prolong the effective refractory period (ERP)

Class III antiarrhythmics prolong the action potential and thus also prolong the ERP, often through blocking potassium channels. Examples of Class III antiarrhythmics include sotalol (which also has some Class II activity) and amiodarone. Amiodarone is an interesting drug in that it has a bunch of iodine groups and has a reeeeeeaaaallly long half-life (around 1 month), meaning that you can get toxicity from the drug building up in various organs.

Class IV: Calcium-channel blockers

Class IV antiarrhythmics block calcium channels (!). Examples include verapamil and diltiazem. Apparently we'll learn more about these in a different lecture.

Adenosine

Adenosine is an anti-arrhythmic that doesn't fit into any of the above categories. Adenosine works by opening potassium channels, allowing potassium to leave the cell and making it harder for the cell to reach threshold. This is particularly pertinent for cells that wouldn't normally be acting as a pacemaker. Therefore, adenosine can be used to block ectopic pacemakers. However, it is only good for arrhythmias that are supraventricular (above the ventricles), as the ventricles do not have receptors for adenosine.

Adenosine breaks down very quickly in blood, so it has to be given as a rapid IV bolus. It also has some pretty nasty adverse effects: transient asystole (lack of heartbeat) and bronchospasm. Of course, just like any other drug, you have to measure up the benefits and risks when giving a drug to a patient. (Also, don't take advice from random Internet bloggers such as myself.)