AssessmentsClass IV antiarrhythmics: Calcium channel blockers and others
Class IV antiarrhythmics: Calcium channel blockers and others
Content Reviewers:Yifan Xiao, MD
Antiarrhythmic medications help control arrhythmias, or abnormal heartbeats.
There are four main groups of antiarrhythmic medications: class I, sodium-channel blockers; class II, beta-blockers; class III, potassium-channel blockers; class IV, calcium-channel blockers; and miscellaneous antiarrhythmics, or unclassified antiarrhythmics. Now, we’ll focus on class IV and miscellaneous antiarrhythmics in this video.
Pacemaker cells build the electrical conduction system of the heart, which consists of the sinoatrial node, or SA node; the atrioventricular node, or AV node; the bundle of His; and the Purkinje fibers.
The current through these channels is called pacemaker current or funny current (If), and it mainly consists of sodium ions.
These sodium ions cause the membrane potential to begin to spontaneously depolarize and as the membrane potential depolarizes, voltage-dependent T-type calcium channels open up, thereby further depolarizing the pacemaker cell.
As calcium enters the cell, voltage-dependent L-type calcium channels open up, causing more calcium to rush into the cell, ultimately depolarizing the membrane to its threshold potential. This marks the start of phase 0, which is also known as the depolarization phase.
Now phase 0 is caused by an influx of calcium ions through the voltage-dependent L-type calcium channels that started opening at the end of phase 4. But, this influx of calcium ions isn’t that rapid, so the slope of phase 0 is gradual.
Also during phase 0, the pacemaker channels and voltage-dependent T-type calcium channels close.
Finally, during phase 3, which is the repolarization phase, L-type calcium channels close and potassium channels open up, resulting in a net outward positive current.
At the end of repolarization, pacemaker channels open up and we start over with phase 4 again.
During phase 4 there’s also an outward movement of potassium ions as the potassium channels responsible for the repolarization phase continue to close.
Finally, it’s important to note that besides pacemaker cells, L-type calcium channels are also found in non-pacemaker cells and they’re responsible for phase 2 or the "plateau" phase of their action potential.
Furthermore, calcium that passes through these channels, along with calcium that’s released from the sarcoplasmic reticulum, are essential for the contraction of the cardiac myocytes that make up the rest of the heart.
The SA node fires an electrical signal that propagates throughout both atria, making them contract.
When the electrical signal of the heart doesn’t follow this path, it’s called an irregular heartbeat or arrhythmia.
For example, let’s say a part of ventricle begins to fire off action potentials at a rate that’s even faster than the SA node. 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.
Alright, switching gears and moving on to pharmacology. Calcium channel blockers bind and inhibit voltage-dependent L-type calcium channels and they’re subdivided into two main groups: dihydropyridines and non-dihydropyridines.
On the other hand, non-dihydropyridines are the class IV antiarrhythmics and they include verapamil and diltiazem. These medications work by targeting the pacemaker cells and non-pacemaker cells in the heart.
On the ECG, this shows up as a longer PR interval, which is the time between the onset of atrial depolarization and the onset of ventricular depolarization.
This way, they decrease the amount of calcium available inside the cell, weakening the force generated during heart contraction.
Supraventricular tachycardia is a type of arrhythmia caused by an impulse that originates above the heart’s ventricles and there are a few different types: paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter.
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