Antiarrhythmics long-term effects

The most notable electrophysiological effect of amiodarone after long-term administration is prolongation of repolarization and refractoriness in all cardiac tissues, an action that is characteristic of class III antiarrhythmic agents. 

The benefits of antiarrhythmic therapy are actually relatively difficult to establish. Two types of benefits can be envisioned reduction of arrhythmia-related symptoms, such as palpitations, syncope, or cardiac arrest or reduction in long-term mortality in asymptomatic patients. Among drugs discussed here, only 3 blockers have been definitely associated with reduction of mortality in relatively asymptomatic patients, and the mechanism underlying this effect is not established (see Chapter 10). 

Although sedative antihistamines do not potentiate the effect of alcohol, they should be avoided in excess quantity. Overdose of astemizole can be treated with gastric lavage and supportive measures.86 Coadministration of astemizole and ter-fenadine with antiarrhythmics, antipsychotics, cisapride, and diuretics should be avoided. Chlorpheniramine maleate has been found to be incompatible with phe-nobarbitone sodium, kanamycin sulfate, and calcium chloride. Cyclizines have been used alone or with opioids in tablets or in injectable form for euphoric effects. Cyproheptadine has shown dependence in long-term use. Diphenhydramine is reported to be incompatible with amphotericin, cephalothin sodium, and hydrocortisone sodium succinate. Diphenhydramine and pheniramine maleate are sometimes used as drugs of abuse. Studies have shown that promethazine is adsorbed onto glass, plastic containers, and infusion systems.87... 

Effect of long-term antiarrhythmic therapy on mortality based on placebo-controlled, randomized trials. 

Regardless of the method for choosing long-term therapy, chronic antiarrhythmic drug treatment in these often young, otherwise healthy patients is problematic. Besides the necessity of taking daily medication possibly for life, antiarrhythmic drugs are not weU tolerated, sometimes precipitate severe side effects, and commonly... 

When intravenous ibutilide 2 mg was used for cardioversion of atrial fibrillation or flutter in 70 patients taking long-term amiodarone the QT interval was further prolonged (iiom 371 to 479 milliseconds). However, only one patient had an episode of non-sustained torsade de pointes. Ibutilide was effective within 30 minutes of infusion in 39% of patients with atrial flutter, and 54% of patients with fibrillation. Both amiodarone and ibutilide are class III antiarrhythmics and prolong the QT interval, with the consequent risk of torsade de pointes. The manufacturer recommends that they should not be used concurrently. However, the authors of the above report suggest that ibutilide may be useful for cardioversion in those already taking amiodarone. Combined use should be very well monitored. 

Antiarrhythmic drugs are widely used in clinical practice. They differ by potency, mechanisms of antiarrhythmic action, and also by manifestations of side effects [ 1-3]. Many of currently used preparations are either insufficiently effective or exhibit the antiarrhythmic action during a long-term treatment [4, 5]. In some cases effective antianhythmic therapy (AAT) is even impossible for patients with ventricular anhythmias due to fatal heart ihythm disturbances. Thus, a search for new biologically active compounds exhibiting high antiarrhythmic activity (AAA) still represents an important task. 

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