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Haemodynamic effects of encainide, flecainide, lorcainide and tocainide.

The haemodynamic effects of encainide, flecainide, lorcainide and tocainide in man are reviewed. Most of the investigations discussed are acute intervention studies after intravenous administration of the drugs. With all four drugs, haemodynamic changes, when present, were moderate. In most studies a decrease in left ventricular maximal dp/dt is demonstrated, suggesting a negative inotropic action. Left ventricular filling pressures are unchanged or slightly increased. A small decrease in cardiac performance, as determined by measurements of cardiac output and left ventricular ejection fraction, is usually observed, while systemic vascular resistance is increased or remains unchanged. Haemodynamic deterioration and/or hypotensive reactions after intravenous administration of any of the above drugs are uncommon in patients without severe cardiac dysfunction. Conclusions relative to drug safety in frank congestive failure are not warranted, in view of the small number of patients studied. While comparative studies between the drugs discussed have not been performed, the data presented here indicate that, on the basis of haemodynamic action, no one drug can be preferred above the other.

Anilides↗

Pharmacodynamic modeling of antiarrhythmic drug effects--application to 3-methoxy-O-demethyl encainide.

The pharmacodynamic characteristics of 3-methoxy-O-demethyl encainide (MODE) were studied in instrumented, chloralose-anesthetized dogs. The HIS Purkinje conduction times (HV) were utilized to assess drug effect. Two protocols were conducted; the first protocol involved multiple pairs of loading and maintenance infusions to achieve several steady-state plasma drug concentrations. The second protocol involved a single short infusion. The data from both protocols supported a linear concentration-effect relationship for the concentration range studied. The slopes and intercepts were similar for both data sets. The data from the second protocol were also analyzed to assess the temporal aspects of the pharmacodynamics of MODE. Data analysis indicated that there is significant hysteresis in the plasma concentration-effect relationship that is characterized by a first-order rate constant corresponding to a half-life (t1/2) of approximately 10 min. These study results also demonstrated the advantages of single-infusion protocols over multiple-infusion studies for evaluating the concentration-effect relationship of antiarrhythmic drugs.

Anilides↗

Treatment of encainide proarrhythmia with hypertonic saline.

We report a case of successful treatment of encainide-induced ventricular tachycardia with 3% hypertonic saline. To our knowledge, no other report exists in the literature of this treatment for proarrhythmic ventricular tachycardia from a type 1C agent. Metabolic consequences of the treatment included severe hypernatremia, hyperosmolarity, hypocalcemia, and hypophosphatemia, which were reversible over 24 hours. In spite of the risks, treatment of incessant ventricular tachycardia induced by type 1C agents with hypertonic saline may be life saving.

Anilides↗

The antiarrhythmic action of encainide versus ventricular arrhythmias in the conscious dog following coronary artery ligation.

Encainide (MJ 9067) was given intravenously at 1, 2, or 5 mg/kg and orally at 1, 2.5, 5, or 10 mg/kg to conscious dogs 18--23 h after two-stage ligation of the left anterior descending coronary artery. Heart rate and ventricular ectopic rate were lowered in a dose-related manner by 40--70 and 55--158 beats/min, respectively, following drug administration. Ventricular arrhythmia was frequently abolished with doses of 2 mg/kg and above. The onset of antiarrhythmic activity was 1--2 min after intravenous injection and 15--30 min after oral ingestion. The duration of effect was 6--7 h or longer following either route of drug administration. Emesis occurred in 1 of 10 and 1 of 6 dogs, respectively, at the 2 and 5 mg/kg intravenous dose levels. Brief ataxia was also observed in one dog given the latter dose.

Administration, Oral↗

Reversal of proarrhythmic effects of flecainide acetate and encainide hydrochloride by propranolol.

The use of membrane-active antiarrhythmic agents may be complicated by aggravation of existing arrhythmias or development of new drug-induced arrhythmias. Four patients, referred because of out-of-hospital cardiac arrest or symptomatic sustained ventricular tachycardia, were receiving class IC antiarrhythmic agents in an attempt to prevent inducibility of sustained ventricular tachycardia. New or worsening spontaneous arrhythmias developed while they were on flecainide acetate (n = 3) or encainide hydrochloride (n = 1) therapy. Spontaneous runs of rapid nonsustained and sustained ventricular tachycardia developed in two. Increased frequency of premature ventricular contractions and repetitive forms of ventricular ectopic activity developed in one, despite the fact that inducibility of sustained ventricular tachycardia had been prevented. Salvos and nonsustained ventricular tachycardia developed in the fourth patient. Propranolol had failed to prevent inducibility of sustained ventricular tachycardia during previous programmed stimulation studies in three of the four patients, but it reproducibly suppressed drug-induced arrhythmias that appeared only after administration of the IC agents in each patient. Suppression of the proarrhythmic effects by beta-adrenergic blockade suggests a possible interaction of these drugs with autonomic function in the genesis of the observed proarrhythmic effects. Direct pharmacologic control of proarrhythmic drug effects has not previously been reported.

Aged↗

[Intravenous and oral encainide: electrophysiological effects in patients with paroxysmal reciprocating supraventricular tachycardia].

The electrophysiologic effects of encainide (E) after acute i.v. (1 mg/kg in 60') and oral administration (75 to 150 mg/die for 48-72 h) were evaluated in 10 pts with PSVT (5 men and 5 women, mean age 48 +/- 15 years). The mechanism of PSVT was related to a reentry through an accessory A-V pathway in 6 cases while in the other 4 the reentry was confined in the A-V node. PA, AH and HV intervals lengthened from 42.8 +/- 5.1, 77.8 +/- 19.7 and 38.3 +/- 6.6 msec to 50 +/- 13.5, 91.7 +/- 22.9 and 49.4 +/- 12.9 and to 48.3 +/- 7.1, 94.4 +/- 33.9 and 44.4 +/- 9.2 msec, after i.v. and oral E respectively. Atrial and ventricular refractory periods showed slight not significant variations. Wenckebach point lengthened from 316 +/- 28 msec to 354 +/- 32 and to 359 +/- 45 msec, after i.v. and oral E respectively. Tachycardia cycle length was 358 +/- 32 msec in basal conditions. After i.v. E tachycardia was inducible only in 6 cases, with a mean cycle length of 403 +/- 48 msec. After oral E tachycardia was reproduced only in 3 patients with a mean cycle length of 433 +/- 85 msec. Nine patients were treated chronically with E, at a mean dose of 89 +/- 36 mg/day. After a follow-up of 18 +/- 8 months, tachycardia recurred but with a marked reduction of the attacks, in 3 patients; only 3 patients complained of side effects (blurred vision). Thus E is highly effective in the prevention of PSVT; the drug seems well tolerated thanks to the low dosage required for the control of PSVT.

Administration, Oral↗

Mortality following ventricular arrhythmia suppression by encainide, flecainide, and moricizine after myocardial infarction. The original design concept of the Cardiac Arrhythmia Suppression Trial (CAST).

OBJECTIVE: To test the hypothesis that in survivors of myocardial infarction, the suppression of ventricular premature depolarizations improves survival free of cardiac arrest and arrhythmic death. DESIGN: International, prospective, multicenter, randomized, placebo-controlled trial. SETTING: University and community hospitals. PATIENTS: A total of 3549 patients with myocardial infarction and left ventricular dysfunction. INTERVENTION: Administration of encainide, flecainide, moricizine, or placebo to suppress ventricular premature depolarizations. MAIN OUTCOME MEASURES: Overall survival and survival free of cardiac arrest or arrhythmic death were compared in patients randomized to long-term, active antiarrhythmic drug therapy vs corresponding placebo, using the stratified log rank statistic. RESULTS: At 1 year from the time of randomization to blinded therapy, 95% of placebo-treated patients vs 90% of active drug-treated patients remained alive (P = .0006). Similarly, at 1 year, 96% of placebo-treated patients vs 93% of active drug-treated patients remained free of cardiac arrest or arrhythmic death (P = .003). CONCLUSIONS: The suppression of asymptomatic or mildly symptomatic ventricular arrhythmias after myocardial infarction does not improve survival and can increase mortality. Treatment strategies designed solely to suppress these arrhythmias should no longer be followed.

Aged↗

Clinical experience of encainide (MJ 9067): a new anti-arrhythmic drug.

Encainide is a new anti-arrhythmic drug, which is highly effective against ventricular extrasystoles, both single and coupled, in the dose range of 80--140 mg i.v. Ventricular extrasystoles were abolished in 31 out of 33 cases treated. The drug is also relatively effective against supraventricular extrasystoles, but has little effect on atrial fibrillation. Both subjects with clinically normal hearts and those with ischaemic heart disease have been successfully treated. The drug prolongs the QRS and QT duration. Its effectiveness appears to be of the same order of magnitude and the range of indications similar to those of aprindine and lorcainide. Further study of the drug seems to be warranted.

Anilides↗