Class 1A Antiarrhythmics: How They Block Sodium and Potassium Channel

Class 1A antiarrhythmics like quinidine, procainamide, and disopyramide target both sodium and potassium channels. In this detailed video, we focus on how these drugs bind to the Nav1.5 sodium channel during the open and inactivated states, why they cause prolonged Phase 0 and delayed repolarization, and what that means for clinical use. We explain their binding location, affinity, and effects on conduction velocity and refractory periods, including why they are useful in re-entry arrhythmias—but risky in ischemic tissue.

Perfect for advanced pharmacology learners, paramedics, and physicians 🫀💊

00:01 Class 1A overview and examples
00:12 Nav1.5 and IKr channel targets
00:31 Channel structure and relevant subunits
01:00 Resting state and channel closure
01:52 Voltage change and S4 activation
02:14 Sodium influx during open state
02:57 Time and voltage promote inactivation
03:33 IFM motif blocks the channel
04:01 Class 1A binds in the S6 subunit
04:17 Lipophilicity and intracellular access
04:33 Binding requires an open pore
04:57 Binding does not depend on IFM motif
05:23 Class 1A fits hydrophobic binding pocket
05:49 Goldilocks zone: intermediate binding duration
06:14 Effects of binding: Phase 0 flattening
06:47 Blockade of potassium channels delays repolarization
07:20 QRS widening as a clinical consequence
07:36 Why Phase 0 and repolarization matter
08:02 Suppressing re-entry circuits through delayed conduction
08:23 Ideal use cases: atrial fibrillation and VT
08:41 Not preferred in ischemia due to conduction risks ⚠️
09:14 Recap: dual channel blockade and state-dependent binding
10:02 Goldilocks binding and one-beat stabilization
10:24 Clinical outcome: delayed refractory and QRS widening
10:49 Risks of intracellular calcium accumulation
11:07 Early afterdepolarizations and torsades risk ⚡
11:18 Next up: Class 1B antiarrhythmics