Arrhythmias, cardiac antiarrhythmic

Cardiac arrhythmias are an important cause of morbidity and mortality approximately 400,000 people per year die from myocardial infarctions (MI) in the United States alone. Individuals with MI exhibit some form of dysrhythmia within 48 h. Post-mortem examinations of MI victims indicate that many die in spite of the fact that the mass of ventricular muscle deprived of its blood supply is often quite small. These data suggest that the cause of death is ventricular fibrillation and that the immediate availability of a safe and efficacious antiarrhythmic agent could have prolonged a number of Hves. The goals of antiarrhythmic therapy are to reduce the incidence of sudden death and to alleviate the symptoms of arrhythmias, such as palpitations and syncope. Several excellent reviews of the mechanisms of arrhythmias and the pharmacology of antiarrhythmic agents have been pubflshed (1,2). 

Antiarrhythmic drugs are substances that affect cardiac ionic channels or receptors, thereby altering the cardiac action potential or its generation or propagation. This results in changes of the spread of activation or the pattern of repolarization. Thereby, these drugs suppress cardiac arrhythmia. 

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

The aiitiarrhytlimic drug s are primarily used to treat cardiac arrhythmias. A cardiac arrhy thmia is a disturbance or irregularity in the heart rate, rhythm, or both, which requires administration of one of the antiarrhythmic dragp. Some examples of cardiac arrhythmias are listed in Table 40-1. 

Some cardiac arrhythmias result from many stimuli present in the myocardium. Some of these are weak or of low intensity but are still able to excite myocardial tissue Lidocaine, by raising the threshold of myocardial fibers, reduces the number of stimuli that will pass along these fibers and therefore decreases the pulse rate and corrects the arrhythmia Mexiletine (Mexitil) and tocadnide (Tonocard) are also antiarrhythmic drag s with actions similar to those of lidocaine... 

The uses of the antiarrhythmic drug are given in the Summaiy Drug Table Antiarrhythmic Drug3. In general these drugp are used to prevent and treat cardiac arrhythmias, such as premature ventricular contractions (PVCs), ventricular tachycardia (VT), premature atrial contractions (PACs), paroxysmal atrial tachycardia (PAT), atrial fibrillation, and atrial flutter. Some of the antiarrhythmic dru are used for other... 

Antiarrhythmic dragp are used to treat various types of cardiac arrhythmias. There are initial preadministration assessments the nurse performs before starting therapy that are the same for all antiarrhythmic drags. These assessments include ... 

Singh, B.N. (1990) in A Symposium ControlUng Cardiac Arrhythmias with Sotalol, a Broad-Spectrum Antiarrhythmic with Beta-Blocking Effects and Class III Activity (Singh, B.N., ed.). Am. J. Cardiol. 65 No. 2 pp. 3A-11 A. 

Optimal therapy of cardiac arrhythmias requires documentation, accurate diagnosis, and modification of precipitating causes, and if indicated, proper selection and use of antiarrhythmic drugs. These drugs are classified according to their effects on the action potential of cardiac cells and their presumed mechanism of action. 

In the National Heart, Lung, and Blood Institute s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had an Ml more than 6 days but less than 2 years previously, an increased rate of death or reversed cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide (Class 1C antiarrhythmics) compared with that seen in patients assigned to placebo... 

Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The cardiac arrhythmia suppression trial II investigators. N Engl J Med. Jul 23 1992 327(4) 227-233. 

Antiarrhythmic drugs are used with the aim to prevent or suppress those conditions of cardiac arrhythmias which are considered harmful or dangerous. 

The Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on... 

For systemic use in the treatment of cardiac arrhythmias (Details are given in chapter Antiarrhythmic agents ). 

Cardiac arrhythmias are a common problem in clinical practice, occurring in up to 25% of patients treated with digitalis, 50% of anesthetized patients, and over 80% of patients with acute myocardial infarction. Arrhythmias may require treatment because rhythms that are too rapid, too slow, or asynchronous can reduce cardiac output. Some arrhythmias can precipitate more serious or even lethal rhythm disturbances for example, early premature ventricular depolarizations can precipitate ventricular fibrillation. In such patients, antiarrhythmic drugs may be lifesaving. On the other hand, the hazards of antiarrhythmic drugs—and in particular the fact that they can precipitate lethal arrhythmias in some patients—has led to a reevaluation of their relative risks and benefits. In general, treatment of asymptomatic or minimally symptomatic arrhythmias should be avoided for this reason. 

In small doses, local anesthetics can depress posttetanic potentiation via a prejunctional neural effect. In large doses, local anesthetics can block neuromuscular transmission. With higher doses, local anesthetics block acetylcholine-induced muscle contractions as a result of blockade of the nicotinic receptor ion channels. Experimentally, similar effects can be demonstrated with sodium channel-blocking antiarrhythmic drugs such as quinidine. However, at the doses used for cardiac arrhythmias, this interaction is of little or no clinical significance. Higher concentrations of bupivacaine (0.75%) have been associated with cardiac arrhythmias independent of the muscle relaxant used. 

Krinsky VI Mathematical models of cardiac arrhythmias (spiral waves) in Szekeres L (ed) Pharmacology of Antiarrhythmic Agents. Oxford, Pergamon Press, 1981, pp 105-124. 

The polypeptide ATX II has been found to have class III antiarrhythmic activity, indicating its potential in the management of cardiac arrhythmias [32]. A positive inotropic drug that was also effective as an antiarrhythmic might offer significant advantages therapeutically [33,34]. 

The cardiac arrhythmias are life-threatening, so the patient must be closely monitored, with facilities available for possible resuscitation. Drugs such as quinidine and procainamide are contraindicated, but lidocaine, propranolol, or phenytoin has been used safely and effectively. The arterial blood gas levels, pH, and electrolyte concentrations should be monitored so that metabolic acidosis or hypokalemia can be identified that would further aggravate the arrhythmias. Electrical pacing may be required if the antiarrhythmic drugs fail. Hyperpyrexia is treated by cooling. Seizures may be managed by intravenous doses of diazepam. 

In addition to their antianginal (see Chapter 12 Vasodilators the Treatment of Angina Pectoris) and antiarrhythmic effects (see Chapter 14 Agents Used in Cardiac Arrhythmias), calcium channel blockers also dilate peripheral arterioles and reduce blood pressure. The mechanism of action in hypertension (and, in part, in angina) is inhibition of calcium influx into arterial smooth muscle cells. 

Premature ventricular contractions (PVCs) are commonly recorded in patients convalescing from myocardial infarction. Since such arrhythmias have been associated with an increased risk of sudden cardiac death, it had been the empiric practice of many physicians to treat PVCs, even if asymp-tomatic, in such patients. In CAST (Cardiac Arrhythmia Suppression Trial [CAST], Echt et al, 1991), an attempt was made to document the efficacy of such therapy in a controlled clinical trial. The effects of several antiarrhythmic drugs on arrhythmia frequency were first evaluated in an open-label fashion. Then, patients in whom antiarrhythmic therapy suppressed PVCs were randomly assigned, in a double-blind fashion, to continue that therapy or its corresponding placebo. 

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