Ventricular tachycardia antiarrhythmics

Indeca.inide. Indecainide hydrochloride is a po active antiarrhythmic agent that received PDA approval in 1989, but it has not been marketed as of this writing. Chemically, it is 9-[3-(isopropylamino)propyl]fiuorine-9-carboxamide [74517-78-5]. The dmg has potent activity against premature ventricular complexes (PVCs) and ventricular tachycardias. Indecainide has no effect on sinus node function, atrial or ventricular effective refractory periods (32,33). 

Other Glass III Antiarrhythmic Agents. Clofihum phosphate is a benzene-butanaminium derivative that has highly specific Class III antiarrhythmic activity. It is orahy active, has a rapid onset of action, and a reasonably long duration of antiarrhythmic activity. In preliminary clinical studies, clofihum has shown efficacy against spontaneous ventricular tachycardias (69). 

Besides the class I-typical proarrhythmic risk class IA antiarrhythmics possess a marked proarrhythmic risk for the induction of torsade depointes arrhythmia (life-threatening polymorphic ventricular tachycardia observed with most action potential prolonging drugs). 

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... 

Procainamide (Class IA antiarrhythmic drug) is an effective agent for ventricular tachycardia. Its mechanism of action involves blockade of the fast Na+ channels responsible for phase 0 in the fast response tissue of the ventricles. Therefore, its effect is most pronounced in the Purkinje fibers. The effects of this drug s activity include a decrease in excitability of myocardial cells and in conduction velocity. Therefore, a decrease in the rate of the phase 0 upstroke and a prolonged repolarization are observed. As a result, duration of the action potential and the associated refractory period is prolonged and the heart rate is reduced. These effects are illustrated by an increase in the duration of the QRS complex. 

FIGURE 6-2. Algorithm for the treatment of acute (top portion) paroxysmal supraventricular tachycardia and chronic prevention of recurrences (bottom portion). Note For empiric bridge therapy prior to radiofrequency ablation procedures, calcium channel blockers (or other atrioventricular [AV] nodal blockers) should not be used if the patient has AV reentry with an accessory pathway. (AAD, antiarrhythmic drugs AF, atrial fibrillation AP, accessory pathway AVN, atrioventricular nodal AVNRT, atrioventricular nodal reentrant tachycardia AVRT, atrioventricular reentrant tachycardia DCC, direct-current cardioversion ECG, electrocardiographic monitoring EPS, electrophysiologic studies PRN, as needed VT, ventricular tachycardia.)... 

Reid, P.R. (1985) Flecainide electrophysiologic and antiarrhythmic properties in refractory ventricular tachycardia. The American Journal of Cardiology, 55, 956-962. 

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. 

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. 

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. 

Mechanism of Action An antiarrhythmic that directly affects myocardial cell membranes. Therapeutic Effect Contributes to suppression of ventricular tachycardia. Pharmacokinetics Absorption is not expected to be present in peripheral blood at recommended doses. Protein binding l%-6%. Not metabolized. Excreted unchanged in urine. Removed by hemodialysis. Half-life 6-13.5 hr. 

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. 

As noted above, the antiarrhythmic drugs can modify impulse generation and conduction. More than a dozen such drugs that are potentially useful in treating arrhythmias are currently available. However, only a limited number of these agents are clinically beneficial in the treatment of selected arrhythmias. For example, the acute termination of ventricular tachycardia by lidocaine or supraventricular tachycardia by adenosine or verapamil are examples in which antiarrhythmic therapy results in decreased morbidity. In contrast, many of the antiarrhythmic agents are now known to have lethal proarrhythmic actions, that is, to cause arrhythmias. 

In contrast, amiodarone and sotalol are effective in most supraventricular and ventricular tachycardias. Amiodarone displays electrophysiologic characteristics consistent with each type of antiarrhythmic drug, ft is a sodium channel blocker with relatively fast on-off kinetics, has nonselec-tive j8-blocking actions, blocks potassium channels, and has slight calcium antagonist activity. The impressive effectiveness and low proarrhythmic potential of amiodarone have challenged the notion that selective ion channel blockade is preferable. Sotalol is a potent inhibitor of outward... 

Duff HJ, Mitchell LB, Kavanagh KM, Manyari DE, GUlis AM, Wyse DG. Amiloride. Antiarrhythmic and elec-trophysiologic actions in patients with inducible sustained ventricular tachycardia. Circulatiou 1989 79(6) 1257-63. 

Kowey PR, Marinchak RA, Rials SJ, Bharucha DB. Intravenous antiarrhythmic therapy in the acute control of in-hospital destabilizing ventricular tachycardia and fibrillation. Am J Cardiol 1999 84(9A) R46-51. 

Hoffmann E, Mattke S, Haberl R, Steinbeck G. Randomized crossover comparison of the electrophysiolo-gic and antiarrhythmic efficacy of oral cibenzoline and sota-lol for sustained ventricular tachycardia. J Cardiovasc Pharmacol 1993 21(1) 95-100. 

Cocco G, Strozzi C, Pansini R, Rochat N, Bulgarelli R, Padula A, Sfrisi C, Kamal A1 Yassini A. Antiarrhythmic use of cibenzohne, a new class 1 antiarrhythmic agent with class 3 and 4 properties, in patients with recurrent ventricular tachycardia. Eur Heart J 1984 5(2) 108-14. 

Bashir Y, Thomsen PE, Kingma JH, Moller M, Wong C, Cobbe SM, Jordaens L, Campbell RW, Rasmussen HS, Camm AJ. Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia. Dofetilide Arrhythmia Study Group. Am J Cardiol 1995 76(14) 1040-4. 

Maloney JD, Nissen RG, McColgan JM. Open clinical studies at a referral center chronic maintenance tocainide therapy in patients with recurrent sustained ventricular tachycardia refractory to conventional antiarrhythmic agents. Am Heart J 1980 100(6 Pt 2) 1023-30. 

Sustained ventricular tachycardia is defined as consecutive premature ventricular contractions lasting more than 30 seconds. Nonsustained ventricular tachycardia (VT) usually self-terminates and lasts for less than 30 seconds. The acute treatment of SuVT depends on the hemodynamic stability and symptoms of the patient. Unstable patients should receive immediate cardioversion. If patients are stable with mild symptoms, they can be treated with IV antiarrhythmics. 

A 57-year-old woman recently started on an antiarrhyth-mic for her ventricular tachycardia returns 2 days later complaining of shortness of breath. PMH VT, s/p Ml, hyperlipidemia, asthma, and osteoporosis. Which of the following antiarrhythmic drugs was probably prescribed for this patient ... 

Class la antiarrhythmic agents block fast sodium channels and prolong the action potential (class III effect), thereby lengthening the effective refractory period. They can cause QT interval prolongation, which may in turn be proarrhythmic, promoting re-entry. In the horse, they are useful for the treatment of a wide variety of arrhythmias, including both supraventricular and ventricular tachycardias. 

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