Cardiac action potentials

There are two main pathologic mechanisms to change action potential;

1) Ischemia & Electrolyte imbalances → More positive resting membrane potential bringing it closer to the threshold potential → Abnormal Automaticity


2) Extrusion of potassium → Effect on duration of the action potential, the cell’s refractory period and the length of the QT interval

Pic from; Chapter 24 ANTIARRHYTHMIC DRUGS Geoffrey W. Abbott and Roberto Levi

Mechanisms of Arrhythmia By Antiarrhythimic agent

1) Triggered Activity;

• As an example Sotalol from class III → Prolongation of ventricular repolarization / Long QT → Triggered activity originate during phase 2 or 3 → early afterdepolarizations → TDP

• Digoxin toxicity → Phase 4 → delayed afterdepolarization


2) Reentry

• As an example Flecainide from class IC → Na+ channel blockade → slowed down enough for the unidirectional block to recover → proarrhythmia

Pic from; Introduction to Antiarrhythmic Agents Munther K. Homoud, MD Tufts-New England Medical Center Spring 2008



Principles of terminating reentrant arrhythmias

1) As an example Amiodarone from class III → K+ channel blockade → lengthening the refractory period → preclude reentry in the limb of the reentrant

2) As an example Flecainide from class IC → Na+ channel blockade → slowing conduction → traveling retrogradely block

• As you see "Class I" can treat reentry-arrhythmia and also can generate arrhythmia by reentry mechanism! When there is CAD or structural disease, the proarrhythmia risk by this mechanism is significant. When you have proarrhythmia by this mechanism, logically you are not allowed to use "Class I" to treat proarrhythmia.

Torsade de Pointes

• See the risk factor table! Proarrhythmic events 5% to 10%! HF increases this risk!

• One of interesting risk factors is genetic basis that cause subclinical congenital long QT. You can use exercise test to evaluate that.

• Some drugs could effect on QT time; Especially Macrolide & quinolone antibiotics & Diuretics. Also concurrent use of more than one drug that can prolong QT interval, is important risk factor. Advanced age & hepatic and renal dysfunction could be a risk factor.

• Interaction between concomitant drugs can lead to prolonged QT interval if they have additive or potentiating effect, for example combination of antiarrhythmic agents. Pharmacokinetic interactions may occur if one drug reduces the clearance of the other or if both the drugs compete for the same hepatic enzyme. Co-administering a drug with cytochrome CYP3A4 inhibitors such as ‘-azoles’, ‘-mycins’ or grapefruit juice will increase its level. Haloperidol and thioridazine share the same enzyme CYP2D6 for clearance resulting in increased levels of both. (From NCBI Journal, Ther Adv Drug Saf. 2012 Oct; 3(5): 241253. "Drug-induced QT interval prolongation" Senthil Nachimuthu, Manish D. Assar, and Jeffrey M. Schussler)



Treatment is directed at withdrawal of the offending agent, infusion of magnesium sulfate and potassium (K+), and temporary pacemaker in need. Because of the polymorphic nature of torsades de pointes, synchronized cardioversion may not be possible, and the patient may require an unsynchronized shock. Raising the heart rate by pacing or drug such Isoprenaline or Atropine could help. Because in higher heart rate the TdP risk is smaller.

Drug-induced QT prolongation and TdP are more prevalent than previously thought. Accurate calculation of baseline QT interval, careful review of a patient’s medication list, and obtaining a thorough family history are paramount to avoiding iatrogenic QT prolongation. When TdP occurs it is imperative to identify the potential offending agent, discontinue it, and to take steps to treat the life-threatening rhythm disturbances.


Table from; Standard Antiarrhythmic Drugs, Dawood Darbar



Compilation by Dr. Samad Ali Moradi, According to Duodecim Finnish cardiology reference book & author work experience.