Class III antiarrhythmics: Potassium channel blockers
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AssessmentsClass III antiarrhythmics: Potassium channel blockers
Class III antiarrhythmics: Potassium channel blockers
Class III antiarrhythmics: Potassium channel blockers exam links
Content Reviewers:Elizabeth Nixon-Shapiro, MSMI, CMI, Marisa Pedron
Contributors:Ursula Florjanczyk, MScBMC, Evan Debevec-McKenney, Filip Vasiljević, MD
Antiarrhythmic medications help control arrhythmias, or abnormal heart beats.
There are five main groups of antiarrhythmic medications: class I, also known as sodium-channel blockers; class II, also called beta-blockers; class III, also known as potassium-channel blockers; class IV, also called calcium-channel blockers; and miscellaneous antiarrhythmics, or unclassified antiarrhythmics. Now, we’ll focus on class III antiarrhythmic medications.
Normally, an electrical signal starts at the sinoatrial or SA node in the right atrium, then propagates out through both atria, making them contract.
The signal gets delayed a bit as it goes through the atrioventricular or AV node, then goes through the Bundle of His to the Purkinje fibers of both ventricles, making them contract as well.
When the signal doesn’t follow this pathway, we get abnormal heartbeats called an arrhythmia, and there are two main causes - abnormal automaticity and abnormal reentry.
Abnormal automaticity is when an area of the heart, say, a part of the ventricle, begins to fire off action potentials at a rate that’s even faster than the SA node.
As a result, this area of the heart essentially flips roles with the SA node, firing so fast that the pacemaker cells in the SA node don’t get a chance to fire. At that point, the heartbeat is being driven by the ventricles.
Alternatively, there can be an abnormal reentry which often results from scar tissue in a ventricle after a heart attack.
Scar tissue doesn’t conduct electricity, so the signal just goes around and around the scar, and each cycle can cause the ventricles to contract.
Alternatively, there might be an accessory, or extra pathway between the atria and the ventricles, like the bundle of Kent in Wolff-Parkinson-White syndrome.
Here, the signal might move back up the accessory pathway, since oftentimes it’s bidirectional, meaning the signal can go from atrium to ventricle as well as from ventricle to atrium.
This creates a reentry circuit that causes extra contractions that occur in between the signals coming from the SA node.
Now let’s focus on a single action potential in a myocyte - it can be broken into five phases.
Here’s a graph of the membrane potential vs. time. In phase 4, which is the resting phase, the myocyte’s membrane slowly depolarizes. This is caused by the leakage of some ions - mainly calcium ions - through the gap junctions, which are openings between two neighboring cells, and that makes the membrane depolarize to the threshold potential, which marks the start of phase 0.
Phase 0 is the depolarization phase where voltage gated sodium channels open up when they reach the threshold potential, and they allow sodium to rush into the cell, creating an inward current. This rapid influx of sodium causes the myocyte’s membrane potential to become more positive.
After the membrane has depolarized, we enter Phase 1, initial repolarization. At this point the sodium channels close and the voltage-gated potassium channels open up, allowing positive potassium ions to leave the cell. This is called the outward current and the membrane potential starts to fall, and this creates a little notch on our graph.
Soon, there’s phase 2 or the plateau phase, which is when the voltage-gated calcium channels open up, and that allows positively charged calcium ions into the cell which counterbalances the potassium ions that are flowing out, so the membrane potential remains pretty stable.
During phase 3, or repolarization, the calcium channels close, but the potassium channels remain open, resulting in a net outward positive current. At the same time, ion pumps start to pump calcium ions back out of the cell and that causes the heart to relax.
Eventually the myocyte returns to the resting membrane potential and we start over with phase 4 again.
Now, class III antiarrhythmics bind and inhibit potassium (K+) channels, which are responsible for repolarization during phase 3 of the action potential in cardiomyocytes. These channels are also called cardiac delayed rectifier potassium channels, or IKr.
So, when they’re blocked, there’s less potassium leaving the cell, which leads to a slower rate of repolarization.
Ultimately, this results in the prolonged duration of action potentials and effective refractory periods, which is the period of time that the cell is unexcitable by new stimulus. On the ECG, this shows up as a longer Q-T interval.
So, longer repolarization prevents the fast conduction of the action potential throughout the heart, which eventually leads to a slower heart rate!
But, since class III antiarrhythmics prolong the QT interval, they can trigger a type of arrhythmia called torsade de pointes, which means “the twisting of points,” because the QRS complexes seem to twist around the isoelectric line.
Common medications in this class include amiodarone, dronedarone, sotalol, ibutilide, and dofetilide.
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