In this chapter we will review how the ECG is affected by medications, both cardiac and noncardiac. We’ll pay special attention to medications that prolong the QTc interval, which may predispose to life-threatening arrhythmias. Afterwards, we’ll discuss hereditary QT syndromes and other channelopathies that may pose a similar risk.
Before we go into detail about the effect of medications on the ECG, let’s review our old friend the action potential (Figure 22-1). Antiarrhythmic medications exert their effect by altering ion channels, the opening and closing of which determine the phases of the action potential. Here is a summary of what we reviewed in detail in Chapter 3.
Action potential of a nonpacemaker (a) and pacemaker (b) cell. The flow of key ions is depicted during each phase (see text for details). Abbreviations: resting potential (RP), threshold potential (TP), maximum diastolic potential (MDP), funny current (If), depolarizing stimulus (*).
Figure 22-1a displays the typical action potential of a nonpacemaker cell of the ventricular myocardium. Remember that there are five distinct phases (phases 0-4).
Phase 0 (rapid depolarization) is the rapid upstroke of the action potential that represents depolarization. A stimulus from adjacent cells opens gated sodium (Na+) channels, causing the membrane potential to become less negative. When the voltage reaches the threshold potential, typically in the range of −60 mV to −70 mV, even more Na+ channels open to permit a rapid, self-sustaining entry of Na+ ions into the cell, coining the term “fast response.”
Phase 1 (early rapid repolarization) is the initial repolarization of the cell. It reflects the final closing of the gated Na+ channels and opening of outward K+ channels. There is a net loss of positive ions from the cell, which lowers the transiently positive membrane potential to approximately 0 mV.
Phase 2 (plateau) represents a delay in repolarization. Slow Ca2+ channels open that allow a weak, inward flow of Ca2+ into the cell. K+ continues to exit the cell as Ca2+ slowly enters. There is a near balance of inward-flowing Ca2+ ions and outward-flowing K+ ions, which produces the plateau.
Phase 3 (terminal rapid repolarization) restores the negative membrane potential. K+ ions continue to exit the cell as the slow Ca2+ channels are inactivated. The membrane potential becomes progressively more negative until repolarization is complete.
Phase 4 (resting) represents the time between action potentials. This is when a nonpacemaker cell establishes a stable resting membrane potential of −90 mV using the three-step process we reviewed in Chapter 3 that includes (1) ...