Ventricular fibrillation antiarrhythmics

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). 

Proarrhythmia refers to development of a significant new arrhythmia (such as VT, ventricular fibrillation [VF], or TdP) or worsening of an existing arrhythmia. Proarrhythmia results from the same mechanisms that cause other arrhythmias or from an alteration in the underlying substrate due to the antiarrhythmic agent. TdP is a rapid form of polymorphic VT associated with evidence of delayed ventricular repolarization due to blockade of potassium conductance. TdP may be hereditary or acquired. Acquired forms are associated with many clinical conditions and drugs, especially type la and type III IKr blockers. 

The analogous 4- (19, X = H2) and 5-phenyltetrahydro-l-benzazepines are less active than the 3-phenyl isomers [30]. The corresponding 4-phenyl-benzazepin-2-one (19, X = O) shows moderate antiarrhythmic activity [30] and is claimed to be useful for the treatment of neurogenic or carcinogenic auricular and ventricular fibrillation and as an antihistaminic or local anaesthetic agent [37]. Introduction of an aminoalkyl group, such as 2-piperidinyl-... 

Keep patient supine during therapy or closely observe for postural hypotension. The optimal dose has not been determined. Dosages greater than 40 mg/kg/day have been used without apparent adverse effect. As soon as possible, and when indicated, change patient to an oral antiarrhythmic agent for maintenance therapy. Immediate life-threatening ventricular arrhythmias (eg, ventricular fibrillation, hemodynamically unstable ventricular tachycardia) Administer undiluted, 5 mg/kg by rapid IV injection. If ventricular fibrillation persists, increase dosage to 10 mg/kg and repeat as necessary. 

Bepridil has Class I antiarrhythmic properties and, like other such drugs, can induce new arrhythmias, including ventricular tachycardia/ventricular fibrillation (VTA/F). In addition, because of its ability to prolong the QT interval, bepridil can cause torsades de pointes type VT. Because of these properties, reserve bepridil for patients in whom other antianginal agents do not offer a satisfactory effect (see Warnings). P.285... 

Proarrhythmia Like other antiarrhythmic agents, sotalol can provoke new or worsened ventricular arrhythmias in some patients, including sustained ventricular tachycardia or ventricular fibrillation, with potentially fatal consequences. Because of its effect on cardiac repolarization, is the most common form of proarrhythmia associated with sotalol, occurring in approximately 4% of high-risk patients. 

Following resuscitation from ventricular fibrillation (VF) or pulseless VT, ICD implantation is a proven strategy for the prevention of recurrent SCD. Three prospective, randomized, controlled trials, the Antiarrhythmics Versus Implantable Defibrillators (AVID) study, the Canadian Implantable Defibrillator Study (CIDS), and the Cardiac Arrest Study Hamburg (CASH), support this strategy [27-29]. 

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. 

Exner, D., Reiffel, J., Epstein, A., Ledingham, R., Reiter, M., Yao, Q., Duff, H., Follmann, D., Schron, E., Greene, H., Carlson, M., Brodsky, M., Akiyama, T., Baessler, C., and Anderson, J., Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, Journal of American College of Cardiology, Vol. 34, No. 2, 1999, pp. 325-333. 

Other class III antiarrhythmics include sotalol, ibutilide, and dofetilide. These agents do not have a role in the acute treatment of ventricular fibrillation. 

Trade names Aratac Corbionax Cordarex Cordarone (Wyeth) Cordarone X Pacerone (Upsher-Smith) Tachydaron Indications Ventricular fibrillation, ventricular tachycardia Category Antiarrhythmic class III Half-life 26-107 days... 

Interest in the antiarrhythmic activity of quaternary ammonium compounds continues. Unlike bretylium (11a). its o-iodobenzyl trimethyl-ammonium analog (UM-360, lib) did not inhibit release of norepinephrine from sympathetic nerve endings and did not cause adrenergic stimulation on its own.UM-36O effectively antagonized ventricular arrhythmias produced by ouabain in dogs, an action bretylium did not possess. Both agents elevated the threshold to electrically induced ventricular fibrillation. The same group of workers also studied the profile of a quaternary propan-2-ol derivative (UM- 2h, 12). ° In contrast to tertiary compounds of... 

FIGURE 17-16. Example of an approach to the management of survivors of cardiac arrest (resuscitated VT/VF). Reversible causes of cardiac arrest (e.g., electrolyte abnormalities, acute phase of Ml) should be treated with specific therapy. AADs = antiarrhythmic drugs BBs = /i-blockers EPS = invasive electrophysio-logic studies ICD = implantable cardioverter-defibrillator VT/VF = ventricular tachycardia/ventricular fibrillation Ml = myocardial infarction. 

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