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Query: CAS:41708-72-9 (Tocainide)
 93 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of metabolic enzyme induction by rifampin on the pharmacokinetics of tocainide were studied in eight healthy volunteers. In an open, unrandomized fashion, volunteers received tocainide hydrochloride 600 mg orally. Blood samples were obtained immediately before and at various time intervals up to 48 hours after the dose. Urine samples were collected before and at various intervals up to 72 hours after the dose. Serum and urine samples were assayed for tocainide content by high-performance liquid chromatography. After a four-week washout period, volunteers ingested 300 mg of rifampin by mouth every 12 hours. After 10 doses, subjects received a second oral dose of tocainide hydrochloride 600 mg, and blood and urine samples were collected as before. During the sampling period, subjects continued to ingest rifampin 300 mg orally every 12 hours. Significant differences in elimination rate constant (average increase, 0.0545 to 0.0748 hr-1), elimination half-life (average reduction, 13.2 to 9.4 hours), oral clearance, and area under the concentration-time curve (average reduction, 76.8 to 55.0 mg.hr/L) between the control and rifampin treatment phases were observed. Volume of distribution and renal clearance of tocainide were not significantly different after rifampin treatment. Tocainide appears to be susceptible to significant drug-drug interactions mediated by metabolic enzyme induction.
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PMID:Influence of rifampin on tocainide pharmacokinetics in humans. 249 79

Thirty patients received one of the lidocaine analogues--mexiletine or tocainide--orally for treatment of symptomatic ventricular arrhythmias. Crossover to the other analogue was allowed if initial drug treatment was unsuccessful, and the controlled use of other marketed oral antiarrhythmic agents was permitted. After follow-up of 7 +/- 3 months (SD), mexiletine was successful in 5 of 13 patients initially and in 5 of 14 patients who failed to respond to tocainide. Tocainide was successful in 1 of 17 patients initially and in 2 of 7 who did not respond to mexiletine. Combination therapy was used in nearly half of all ultimately successful drug trials. A common cause of drug trial failure for both drugs was the occurrence of adverse effects that frequently appeared well after hospital discharge. Response to lidocaine was a sensitive but nonspecific predictor of clinical outcome with mexiletine or tocainide that helped to identify drug-resistant patients. Finally, although mexiletine provided effective antiarrhythmic therapy more often than tocainide, response to one lidocaine analogue did not predict response to the other.
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PMID:Mexiletine and tocainide: a comparison of antiarrhythmic efficacy, adverse effects, and predictive value of lidocaine testing. 249 25

The effect of therapy with atenolol and tocainide, separately or in combination, was studied in 20 patients with hypertension and concomitant ventricular arrhythmias. Patients were given 400 mg tocainide, three times daily, 100 mg atenolol, once daily (plus 25 mg hydrochlorothiazide and 2.5 mg amiloride diuretics if required) and a combination of these treatments. Tocainide alone significantly reduced the incidence of ventricular arrhythmias without affecting atrial arrhythmias. It also controlled exercise-induced arrhythmias in 7/13 (54%) patients. Atenolol significantly reduced atrial arrhythmias and had a good effect on exercise-induced arrhythmias (reduced in 75% of patients), but it did not have a significant effect on ventricular arrhythmias. In 13 patients, despite normalization of blood pressure by atenolol, it was necessary to combine antihypertensive therapy (atenolol) with anti-arrhythmic therapy (tocainide) in order to reduce ventricular arrhythmias. All drugs were well tolerated. It is concluded that, in certain patients, specific anti-arrhythmic treatment may be necessary to control ventricular arrhythmias in hypertensive patients despite normalization of blood pressure by beta-blockers.
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PMID:Treatment of hypertensive patients with ventricular arrhythmias: comparison and combination of beta-blocker and anti-arrhythmic therapy. 249 41

Tocainide, mexiletine and moricizine belong to class IB of Vaughan Williams system of classification of antiarrhythmic drugs. Mexiletine and tocainide have little or no effect on Phase 0 of action potential and conduction velocity. Their principal effect is to shorten the action potential duration. Moricizine does not fit precisely into the Vaughan Williams system of classification, but has been categorized with class IB agents because in vitro its effects are similar to those of lidocaine. In this article, the pharmacokinetics, electrophysiologic effects, and clinical uses of these three agents are reviewed.
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PMID:Class IB antiarrhythmic drugs: tocainide, mexiletine, and moricizine. 249 45

During the past decade, advances in basic and applied cardiology have led to the introduction of several new antiarrhythmic drugs that have distinct clinical advantages over their older counterparts. These therapeutic advantages comprise either a more favorable pharmacokinetic disposition in the patient or new and perhaps novel mechanisms of antiarrhythmic actions. The class IV agent verapamil, for example, selectively blocks the slow inward Ca++ current in excitable tissues and this action is proving to be quite effective in controlling supraventricular tachyarrhythmias. Tocainide is a newly approved class I agent that exerts lidocaine-like effectiveness in treating serious ventricular arrhythmias. Unlike lidocaine, however, tocainide is not restricted to intensive care because it is effective after oral administration and has comparatively longer duration of antiarrhythmic action. Other recently approved or investigational agents include bretylium and amiodarone (class III), and aprindine, mexiletine, and disopyramide (class I). Along with clinical advantages, however, each drug has a characteristic pharmacologic-toxicologic profile and resulting spectrum of therapeutic application for only particular cardiac dysrhythmias. The advantages and disadvantages of each compound should be weighed equally when the new antiarrhythmic drugs are assessed as therapeutic alternatives for the older ones.
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PMID:New perspectives in cardiology: recent advances in antiarrhythmic drug therapy. 287 85

Tocainide is a primary analog of lidocaine with antiarrhythmic properties used to treat ventricular rhythm disorders. A 76-year-old man with benign paroxysmal premature ventricular contractions was treated with tocainide and developed a generalized maculopapular lupoid eruption, bleeding from the lips and gingivae, vertigo, gross tremors of the extremities, fever, and short-term memory loss, which required hospitalization. The patient recovered slowly over three months with no permanent sequelae after discontinuing the drug and receiving rigorous supportive care. His excellent physical status and absence of concomitant illness contributed to an uneventful recovery. Tocainide is a potent cardioactive drug with a long biological half-life and should be used with caution.
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PMID:Tocainide: a severe adverse reaction. 296 3

Tocainide was administered to 228 patients referred for treatment of recurrent ventricular tachyarrhythmias that were refractory to therapy with conventional antiarrhythmic drugs. After baseline studies, 1200 to 2400 mg tocainide/day was given for 4 days. Tocainide was effective in 49% of 180 patients evaluated with monitoring and exercise testing and in 35% of 48 patients undergoing electrophysiologic testing. No clinical parameter predicted the response to tocainide, although there was a correlation with the effect of lidocaine. Tocainide was selected for long-term treatment in 73 patients who were followed for an average of 26.4 months (range 1 to 92 months). The incidence of sudden death was 4.3% per year and two patients had nonfatal recurrence of arrhythmia. It is concluded that tocainide is effective and well tolerated during long-term use if therapy is evaluated carefully and is individualized.
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PMID:Short- and long-term therapy with tocainide for malignant ventricular tachyarrhythmias. 307 77

Twenty-nine patients with acute myocardial infarction (AMI) were studied in a randomized double-blind trial of intravenous lidocaine and tocainide, followed by either oral tocainide or placebo without regard to previous therapy, for the prophylaxis of arrhythmias associated with acute infarction. No patient had symptomatic ventricular tachycardia or fibrillation, although 1 patient taking lidocaine was withdrawn from therapy because of breakthrough arrhythmias. One patient in each group died from mechanical complications of AMI. Tocainide was administered to 16 patients and lidocaine to 13. Seven of the 13 patients receiving lidocaine had ventricular tachycardia or accelerated idioventricular rhythm, compared with 2 of 16 receiving tocainide (p less than 0.05). Adverse effects were noted in 11 of the 13 patients receiving lidocaine and 6 of the 16 patients receiving tocainide. The infusions used provided therapeutic levels of lidocaine or tocainide and the transition to oral tocainide was accomplished safely with maintenance of therapeutic antiarrhythmic levels. Thus, tocainide appears to be at least as efficacious and may be safer than lidocaine for the prophylaxis of ventricular arrhythmias associated with AMI. The transition to oral tocainide is well tolerated and can be accomplished with minimal difficulty.
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PMID:Prophylactic tocainide or lidocaine in acute myocardial infarction. 308 75

The effects of 10 and 20 mg/l of tocainide on transmembrane action potential characteristics were examined in Purkinje fibers surviving infarction. Infarcted tissue was obtained from canine hearts 24 h after coronary artery ligation. The preparation was stimulated at basic cycle lengths (BCL) of 1000-300 ms. Tocainide reduced the overshoot and amplitude of Purkinje fibers surviving infarction. The maximum upstroke velocity (Vmax) was decreased by tocainide in a dose dependent manner. This effect was more prominent at the shorter BCL. Statistical analysis revealed a significant interaction of the BCL with the drug effect on overshoot, amplitude, Vmax and action potential durations (APD50% and APD90%). Tocainide reduced the effective refractory period (ERP) at the BCL of 1000 ms, but had no significant effect at the BCL of 300 ms. Membrane responsiveness and steady state characteristics of Vmax were shifted significantly to more negative membrane potentials by tocainide. Investigation of the recovery kinetics of Vmax in the presence of tocainide showed an exponential recovery of Vmax with a time constant of 514 ms. These results support the finding that the effect of tocainide on Vmax and conductions is enhanced at faster rates of stimulation. Thus tocainide may be able to depress conduction to produce bidirectional block in the termination of ventricular tachycardia caused by reentry, while having minimal effect on conduction at normal heart rates.
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PMID:Electrophysiological effects of tocainide on canine subendocardial Purkinje fibers surviving infarction. 308 61

The left anterior descending coronary artery was occluded in anesthetized dogs. Dogs were sacrificed after 24 hours and the experimental preparations, which included both normal and infarcted tissues, were dissected from the left ventricles. Effects of tocainide in concentrations of 15-40 mg/l on action potentials of Purkinje fibers from normal and infarcted zones were studied using conventional microelectrode techniques. In the normal zone cells, tocainide superfusion produced a significant decrease in maximum diastolic potential, action potential amplitude, action potential duration to 50% and 90% repolarization and the rate of phase O depolarization, and no significant change in effective and functional refractory periods. In the infarct zone cells, it produced a significant decrease in action potential amplitude and the rate of phase O depolarization, a significant increase in effective and functional refractory periods, and no significant changes in the other parameters. The unequal actions of tocainide resulted in selective depression of maximum diastolic potential and action potential duration to 50% repolarization in the normal cells only, reducing the disparity in these parameters between normal and infarcted tissues. Tocainide increased the refractoriness (ratio of effective refractory period to action potential duration) in both cell types but this change was greater in the infarct zone. This decreased disparity of membrane potential and repolarization combined with increased refractoriness may help to block the arrhythmias observed in infarcted preparations following closely coupled stimuli.
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PMID:Effects of tocainide on Purkinje fibers from normal and infarcted ventricular tissues. 309 83


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