Antiarrhythmics ventricular arrhythmias

QuinidJne. Quinidine, an alkaloid obtained from cinchona bark (Sinchona sp.), is the dextrorotatory stereoisomer of quinine [130-95-0] (see Alkaloids). The first use of quinidine for the treatment of atrial fibrillation was reported in 1918 (12). The sulfate, gluconate, and polygalacturonate salts are used in clinical practice. The dmg is given mainly by the oral (po) route, rarely by the intravenous (iv) route of adniinistration. It is the most frequentiy prescribed po antiarrhythmic agent in the United States. The clinical uses of quinidine include suppression of atrial and ventricular extrasystoles and serious ventricular arrhythmias (1 3). 

Lldoc ine. Lidocaine hydrochloride, an anilide, was originally introduced as a local anesthetic in 1943 and found to be a potent antiarrhythmic in 1960. The compound is a reverse amide of procainamide. Lidocaine is generally considered to be the dmg of choice in the treatment of ventricular arrhythmias and those originating from digitalis glycoside toxicity (1,2,15—17). 

Phenytoin. Phenytoin sodium is sodium diphenylhydantoin [630-93-3] which is stmcturally related to the barbiturates. It was originally introduced as an anticonvulsant (18) (see Hypnotics, sedatives, and anticonvulsants) and later found to have antiarrhythmic properties (19), although not approved by the PDA for any arrhythmic indications. Phenytoin is effective in the treatment of ventricular arrhythmias associated with acute MI and with digitalis toxicity (20). It is not very effective in treatment of supraventricular arrhythmias (20). 

Fleca.inide, Elecainide acetate, a fluorobenzamide, is a derivative of procainamide, and has been reported to be efficacious in suppressing both supraventricular and ventricular arrhythmias (26—29). The dmg is generally reserved for patients with serious and life-threatening ventricular arrhythmias. Elecainide depresses phase 0 depolarization of the action potential, slows conduction throughout the heart, and significantly prolongs repolarization (30). The latter effect indicates flecainide may possess some Class III antiarrhythmic-type properties (31). 

Asoc inol. Asocainol, a diben2azonine derivative, has sodium channel (Class I) and calcium channel (Class IV) blocking activity that accounts for the antiarrhythmic activity. Preliminary studies indicate that the compound is effective against ventricular arrhythmias (88). Additional studies are needed to estabUsh efficacy, toxicological potential, and pharmacokinetic profile. 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

A 5. 5-year-oId male has recurrent ventricular arrhythmias after an Ml, for which he is given an antiarrhythmic agent that blocks Na+ channels and prolongs the action potential. One year later, a blood, test is positive for circulating antinuclear antibodies. 

The most frequently used classification system is that proposed by Vaughan Williams (Table 6-1). Type la drugs slow conduction velocity, prolong refractoriness, and decrease the automatic properties of sodium-dependent (normal and diseased) conduction tissue. Type la drugs are broad-spectrum antiarrhythmics, being effective for both supraventricular and ventricular arrhythmias. 

The applicability of these results to other populations (eg, those without recent Mis) is uncertain. Considering the known proarrhythmic properties of procainamide and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of procainamide and other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias. 

Survival Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias. 

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... 

In the treatment of life-threatening ventricular arrhythmias (ie, ventricular tachycardia) which have failed to respond to first-line antiarrhythmic agents (eg, lidocaine). 

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. 

Oral - Only for treatment of the following documented life-threatening recurrent ventricular arrhythmias that do not respond to documented adequate doses of other antiarrhythmics or when alternative agents are not tolerated ... 

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. 

Amiodarone (Cordarone, Pacerone) [Ventricular Antiarrhythmic/Adrenergic Blocker] Uses RecumMit VF or hemo-dynamically unstable VT, supraventricular arrhythmias, AF Action Class III antiarrhythmic (Table VI-7) Dose Adul. Ventricular arrhythmias IV 15 mg/min... 

Sotalol (Betapace) [Antiarrhythmic, Antihypertensive/Beta Blocker] WARNING Monitor pts for 1st 3 d of Rx to 4- risks of arrhythmia Uses Ventricular arrhythmias, AF Action p-Adrenergic blocking agent Dose Adults. 80 mg PO bid may be T to 240-320 mg/d Peds. Neonates 9 mg/m tid... 

A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The antiarrhythmics versus implantable defibrillators (AVID) investigators. NEnglJMed. Nov 27 1997 337(22) 1576-1583. 

Burkart F, Pflsterer M, Kiowski W, FoUath F, Burck-hardt D. Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias Basel Antiarrhythmic Study of Infarct Survival (BASIS). J Am Coll Cardiol 1990 16 1711-8. 

As with other antiarrhythmic drugs, moricizine has proarrhythmic activity, which may manifest as new ventricular ectopic beats or a worsening of preexisting ventricular arrhythmias. These effects are most common in patients with depressed left ventricular function and a history of congestive heart failure. Cardiovascular ef-... 

Phenytoin finds its most effective use in the treatment of supraventricular and ventricular arrhythmias associated with digitalis intoxication. The ability of phenytoin to improve digitaUs-induced depression of A-V conduction is a special feature that contrasts with the actions of other antiarrhythmic agents. 

Mexiletine is useful as an antiarrhythmic agent in the management of patients with either acute or chronic ventricular arrhythmias. While it is not at present an indication for use, there is interest in using mexiletine to treat the congenital long OT syndrome when an abnormality in the SCN5A gene (LOTS 3) has been found. 

Acebutolol is effective in the management of the patient with essential hypertension, angina pectoris, and ventricular arrhythmias. Antiarrhythmic effects are observed with the patient both at rest and taking exercise. 

Amiodarone may elicit life-threatening side effects in addition to presenting substantial management difh-culties associated with its use. The oral formulation of amiodarone is indicated only for the treatment of life-threatening recurrent ventricular arrhythmias (e.g., recurrent ventricular hbrillation and/or recurrent hemo-dynamicaUy unstable ventricular tachycardia) that have not responded to other potentially effective antiarrhythmic drugs or when alternative interventions could not be tolerated. Despite its efficacy as an antiarrhythmic agent, there is no evidence from clinical trials that the use of amiodarone favorably affects survival. 

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