Arrhythmia, digitalis-induced

The antiepileptic drug phenytoin, an orally available class DB antiarrhythmic, is mainly effective in digitalis-induced arrhythmias. This diug exhibits nonlinear pharmacokinetics and a number of side effects including neuropathy, gingival hypetplasia, hepatitis, immunological disorders and suppression of white blood cells. 

Cardiovascular manifestations include hypertension and cardiac arrhythmias (e.g., heart block, atrial flutter, paroxysmal atrial tachycardia, ventricular fibrillation, and digitalis-induced arrhythmias). In severe hypokalemia (serum concentration <2.5 mEq/L), ECG effects include ST-segment depression or flattening, T-wave inversion, and U-wave elevation. 

IB (tocainide, lidocaine, phenytoin, mexiletine) - Depress phase 0 slightly and may shorten the action potential duration. Although arrhythmia is not a labeled indication for phenytoin, it is commonly used in treatment of digitalis-induced arrhythmias. 

Parenteral therapy The dangers of parenteral use of quinidine are increased in the presence of AV block or absence of atrial activity. Administration is more hazardous in patients with extensive myocardial damage. Use of quinidine in digitalis-induced cardiac arrhythmia is extremely dangerous because the cardiac glycoside may already have caused serious impairment of intracardiac conduction system. Too rapid IV administration of as little as 200 mg may precipitate a fall of 40 to 50 mm Hg in arterial pressure. 

Digitalis intoxication Exercise caution in the use of procainamide in arrhythmias associated with digitalis intoxication. Procainamide can suppress digitalis-induced arrhythmias however, if there is concomitant marked disturbance of AV conduction, additional depression of conduction and ventricular asystole or fibrillation may result. Consider use of procainamide only if discontinuation of digitalis, and therapy with potassium, lidocaine, or phenytoin are ineffective. 

Procainamide (Pwnestyl, Procan SR) is a derivative of the local anesthetic agent procaine. Procainamide has a longer half-life, does not cause CNS toxicity at therapeutic plasma concentrations, and is effective orally. Procainamide is a particularly useful antiarrhythmic drug, effective in the treatment of supraventricular, ventricular, and digitalis-induced arrhythmias. 

Clinically, tachyarrhythmias associated with digitalis excess (including supraventricular and ventricular extrasystoles) and ventricular tachycardia have been suppressed by propranolol. Although propranolol is highly effective in the treatment of digitalis-induced arrhythmias, phenytoin and Udocaine are preferred. 

It is also used in digitalis induced ventricular arrhythmia as it reverse the conduction block while accentuating the depression of automaticity (The detailed pharmacology is discussed in chapter Antiepdeptic agents ). 

Magnesium Poorly understood interacts with Na+,K+ ATPase, K+ and Ca2+ channels Normalizes or increases plasma Mg2+ Torsade de pointes digitalis-induced arrhythmias IV duration dependent on dosage Toxicity Muscle weakness in overdose... 

Potassium Increases K+ permeability, K+ currents Slows ectopic pacemakers slows conduction velocity in heart Digitalis-induced arrhythmias arrhythmias associated with hypokalemia Oral, IV Toxicity Reentrant arrhythmias, fibrillation or arrest in overdose... 

Calcium ion facilitates the toxic actions of cardiac glycosides by accelerating the overloading of intracellular calcium stores that appears to be responsible for digitalis-induced abnormal automaticity. Hypercalcemia therefore increases the risk of a digitalis-induced arrhythmia. The effects of magnesium ion appear to be opposite to those of calcium. These interactions mandate careful evaluation of serum electrolytes in patients with digitalis-induced arrhythmias. 

Digitalis-induced arrhythmias are frequently made worse by cardioversion this therapy should be reserved for ventricular fibrillation if the arrhythmia is glycoside-induced. 

Rapid intravenous injection of the sodium salt of EDTA depletes blood calcium levels and produces hypocalcaemic tetany, but, carefully administered, this agent can be used to treat hypercalcaemia and to overcome digitalis-induced arrhythmia by adjusting the Ca2+/K+ balance61). The ready availability of calcium ion from extracirculatory stores enables slow (drip) infusion of sodium EDTA without untoward effects. Continued over several days, calcium is mobilised from bone and calcium EDTA is excreted in the urine but plasma calcium levels are not greatly affected62). Although it has been little explored, drip infusion of sodium EDTA,... 

Which one of the following aggravates a digitalis-induced arrhythmia ... 

Wijnberg I D, van der Kolk J H, Hiddink E G 1999 Use of phenytoin to treat digitalis-induced cardiac arrhythmias in a miniature Shetland pony. Veterinary Record 144 259-261... 

Amiloride is used with thiazide or loop diuretics in hypertension, in congestive heart failure, in digitalis-induced hypokalemia, and in arrhythmias resulting from hypokalemia. Inappropriate use of amiloride may cause hyperkalemia (potassium >5.5 mEq/L), which may be fatal if not corrected, and may be more deleterious in elderly individuals and in patients with diabetes mellitus and renal impairment. The symptoms of hyperkalemia include fatigue, flaccid paralysis of the extremities, paresthesias, bradycardia, ECG abnormalities, and shock. Amiloride is not metabolized but is contraindicated in anuria, acute or chronic renal insufficiency, or in diabetic nephropathy. It should not be used with potassium preparations, and should be used cautiously with ACE inhibitors because these agents cause hyperkalemia. 

Edetate disodium, a heavy metal antagonist, is indicated in hypercalcemia (500 mg/kg daily by slow IV infusion) and in digitalis-induced cardiac arrhythmias (15 mg/kg/hour by IV infusion). Ethylenediaminetetraacetic acid (EDTA) will lower serum levels of calcium, magnesium, and zinc. It should not be used in anuria, and renal excretory functions (BUN and creatinine) should be monitored carefully. EDTA should be used cautiously in hypokalemia and in patients with limited cardiac reserve. 

Magnesium has been shown to affect the conduction of both sodium and potassium in the heart, which may be due, at least in part, to the dependence of cardiac adenosinetriphosphatase (ATPase) on magnesium. It also competes with calcium and thus decreases calcium conductance across the cardiac membranes, resulting in a prolongation of phase II of the cardiac action potential. Given intravenously, it has been shown to decrease digitalis-induced arrhythmias and torsades de pointes in susceptible patients, as well as arrhythmias produced by myocardial ischemia (e.g., due to infarction). 

D. Magnesium Ion Magnesium has not been as well studied as potassium but appears to have similar depressant effects on digitalis-induced arrh5Thmias. Magnesium also appears to be effective in some cases of torsade de pointes arrhythmia. 

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