AssessmentsClass I antiarrhythmics: Sodium channel blockers
Class I antiarrhythmics: Sodium channel blockers
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A 62-year-old man comes to the emergency department because he fainted while grocery shopping. He says that all he recalls is feeling light-headed in addition to a fluttering feeling in his chest. His medical history includes "a heart condition." His temperature is 37.0°C (98.6°F), pulse is 162/min, respirations are 24/min, and blood pressure is 118/82 mm Hg. Physical examination shows a hyperdynamic precordium and bibasilar crackles on pulmonary auscultation. ECG shows ventricular tachycardia and left axis deviation. He is started on an antiarrhythmic. 15 minutes later, he has another episode of syncope. Physical examination now shows a blood pressure of 86/58 mm Hg and a notable increase in jugular vein distention. Laboratory studies show an elevated brain natriuretic protein level. An echocardiogram performed one month ago showed a left ventricular ejection fraction of 35%. Which of the following medications is the most likely cause of this patient's acute decompensation?
Antiarrhythmic drugs 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.
We’ll focus on class I antiarrhythmics which are further broken down into 1a, 1b, and 1c. All three groups work on Na+ channels in the cardiac myocytes, so class I medications are also called Na+ channel blockers.
When a heartbeat doesn’t follow this path, it’s 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.
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.
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.
Class 1 antiarrhythmic drugs act on Na+ channels and they’re state dependent, meaning that they bind more tightly to cardiac tissue that’s depolarizing a lot.
In other words, they are even more effective when an arrhythmia is severe and are more selective for abnormally over-reactive parts of the heart.
Class 1a antiarrhythmics inhibit the Na+ channels and the K+ channels on atrial and ventricular myocytes and cells of the purkinje fibers.
When Na+ channels are blocked, it decreases the amount of sodium entering the cell so this causes a slower depolarization, which means a decrease in the slope during phase 0.
When the K+ channels are blocked, there’s less K+ leaving the cell and it leads to a slower rate of repolarization and a longer phase 1, 2, and 3, which means a longer effective refractory period.
On the ECG, this shows up as a longer QRS complex and a longer Q-T segment.
All three drugs can be used to treat both supraventricular and ventricular arrhythmias, but should be avoided in people with heart failure since they have a negative inotropic effect on the heart and could lead to hypotension.
In addition, procainamide is very effective in treating Wolff-Parkinson-White syndrome.
Since these drugs prolong the QT, 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.
For other side effects, quinidine can cause cinchonism, which include headaches, tinnitus, and blurry vision.
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