Recently, I was part of a short discussion between fellow healthcare providers of different levels of care, about Amiodarone and its expected effects on the heart during Ventricular Tachycardia (VT). I figured, I could break it down and write a short summary of how it works.
Most healthcare providers are familiar, or at least have heard of AMIODARONE. We also know that it is one of the leading antiarrhythmics used for treating ventricular dysrhythmias. But the reality is that, it can be used for more than just ventricular tachyarrhythmias.
Amiodarone is a Class III antiarrhythmic of the Vaughan-Williams Classification system. Class III antiarrhythmics, are Potassium Channel Blockers. This means they partially block Potassium efflux (intracellular to extracellular) by inhibiting Na-KAtpase channels, adenosine triphospatase mediated channels (utilizes ATP breakdown for opening) . However, Amiodarone has other familiar properties such as:
- Beta Adrenergic Receptor Blocking
- Slow Calcium Channel Blocking
- Fast Sodium Channel Blocking
- Potassium (K+), which is a positive ion, is responsible for cardiac repolarization (rest). As Sodium and Calcium channels become inactivated, Potassium channels open, allowing Potassium to exit the cell, causing the cell to return to its predominantly negative voltage state, leading to cardiac relaxation. This portion is seen on the surface ECG as a the end of the ST segment and the entire T wave.
The initial portion of the T wave (the upslope), represents the Absolute or Absolute Refractory Period (ARP), where it is physiologically impossible to stimulate another cardiac cycle, while the terminal portion (downslope), is the Relative Refractory Period (RRP), where the ventricles can be stimulated again, if a premature impulse causes ventricular depolarization.
“You can’t jump again (depolarization), until you have at least one foot back on the ground (RRP)”… a simple example I often use!
- Potassium Channel Blocking leads to increased repolarization phase, which is the Phase 3 of the Action Potential (AP). This means that since Potassium efflux is delayed, there is a prolonged positive gradient intracellular, which delays the next AP, while delaying repolarization. The result is a prolonged QT interval on the surface ECG, which is the beginning of ventricular depolarization, until the end of ventricular repolarization. Prolonged QT is the main electrophysiologic change secondary to Amiodarone administration, typically with prolonged use.
- Amiodarone also delays fast Sodium Channel opening, again, by Na-Katpase inhibition, which delays fast sodium influx. This means that, Phase 0 of the Action Potential (which is the fast upstroke caused by sodium influx) is slowed down. This slows down the initiation of ventricular depolarization.
- Because of the above mechanism, slow L-Type Calcium Channels are also inhibited, leading to slow calcium influx which reduces automaticity in SA and AV node, as Calcium helps maintain depolarization and transmission. This also reduces contractility of cardiac tissue (decreased Cardiac Output), as well as decreasing systemic vascular resistance (decreased preload).
- Because of Amiodarone’s effect on the Thyroid gland, hormonal and adrenergic receptor proteins, there is a “Beta blocker like” effect. That is, it does not bind to Beta adrenergic receptors, but can lead to reduced inotropic and chronotropic effect.
Because changes is heart rate such as tachycardias shortening the QTI (QT Interval) and bradycardias appearing as prolonged QTI, the QTc (QT Corrected) should be evaluated over the QTI during abnormal rates.
My goal is that more healthcare providers realize that, because of all these actions mentioned above, Amiodarone can be use for more than just VT, such as atrial arrhythmias (i.e. Atrial fibrillation), Cardiomyopathies or Heart Failure. It can also be effective terminating ventricular dysrhythmias in the presence of Hyperkalemia, as long as the Hyperkalemia is being treated.