Repolarization, drugs that prolong

In general, drugs that block the sodium channel and shorten the action potential tend to increase the defibrillation threshold. Drugs that prolong repolarization also tend to decrease this threshold. These changes have obvious important ramifications for patients with ICDs. 

As previously noted, the relationships between the degree of hERG block, the extent of delayed repolarization/QT prolongation, and the proclivity and incidence of proarrhythmia//oryfl(7ey are uncertain. Not all drugs that prolong QTc are... 

Type III drugs specifically prolong refractoriness in atrial and ventricular fibers and include very different drugs that share the common effect of delaying repolarization by blocking potassium channels. 

Erythromycin has antidysrhythmic properties similar to those of Class lA antidysrhythmic drugs, and causes an increase in atrial and ventricular refractory periods. This is only likely to be a problem in patients with heart disease or in those who are receiving drugs that delay ventricular repolarization (5). High-doses intravenously have caused ventricular fibrillation and torsade de pointes (6). Each episode of dysrhythmia, QT interval prolongation, and myocardial dysfunction occurred 1-1.5 hours after erythromycin infusion and resolved after withdrawal. 

Acute treatment of TdP is different from treatment for the more common acute monomorphic ventricular tachycardia (or polymorphic VT with a normal QT interval). For an acute episode of TdP, most patients will require and respond to DCC. However, TdP tends to the paroxysmal in nature and often will recur rapidly after countershock. Therefore, after the initial restoration of a stable rhythm, therapy designed to prevent recurrences of TdP should be instituted. Drugs that further prolong repolarization such as intravenous procainamide are absolutely contraindicated. Lidocaine usually is inef-... 

Drugs that demonstrate calcium inhibitory activity display different cardiac membrane effects dependent upon their structure, physical properties and concentration. Compounds which interfere with Ca + influx are expected to prolong the duration of the action potential. This prediction is supported by evidence that decreased intracellular Ca2+ activity may decrease the late increase in K+ conductance and potentially prolong the duration of repolarization (phase 3) (69). The first substances reported to inhibit I without influencing rapid depolarization (phase 0) were Mn2+, Ni2+ and Co2+ (16,... 

Answer A. Amiodarone is a highly effective antiarrhythmic drug, in part because of its multiple actions, which include Na channel block, beta adrenoceptor block, K channel block, and Ca channel block. Drugs that block channels (which include class lA and class III antiarrhythmics) prolong APD and ERP and predispose toward torsades de pointes ventricular arrhythmias. Flecamide is a class IC drug, lidocaine and phenytoin are class IB, and verapamil is class IV, none of which inhibits the delayed rectifier K+ current responsible for membrane repolarization during the cardiac action potential. 

The emphasis, in terms of drug-induced prolongation of QT interval due to a decrease in the ability of myocytes to repolarize, has been squarely placed on the notion that this is due to the inhibition of (i.e., hERG potassium channel). However, an increase in the time constant for a myocyte to repolarize can also occur for reasons other than the inhibitimi of Other reasons for the prolongation... 

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