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

The conditions for the heptafluorobutyrylation of tocainide have been studied. An almost instantaneous reaction was obtained with 0.01% of heptafluorobutyric anhydride in toluene at 40 degrees C. Higher anhydride concentration caused degradation of the initially formed derivative, mainly by the loss of water, as shown by mass spectral analysis. Tocainide was isolated from plasma by extraction into dichloromethane at alkaline pH. Gas chromatographic separation was performed with a fused-silica capillary column coated with a methyl silicone gum. The enantiomers were separated on a glass capillary column coated with Chirasil-Val. Upon analysing 0.1 ml of plasma eight times the precision was 4.7% at the 10 mumol/1 level for the S-form of tocainide.
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PMID:Monitoring of S- and R-tocainide in human plasma after heptafluorobutyrylation, separation on Chirasil-Val and electron-capture detection. 643 Sep 40

The widespread use of antiarrhythmic agents to control severe life-threatening arrhythmias evidenced the possibility of a worsening of arrhythmias induced by the same drugs. We performed a retrospective analysis studying the worsening phenomenon in patients who underwent pharmacological invasive and non invasive antiarrhythmic tests to choose the drug to be administered in the chronic treatment. Particularly we reviewed: 101 acute pharmacologic non invasive tests for "stable" ventricular ectopic beats using computerized automatic continuous recording system which allows quantitative and qualitative evaluation of arrhythmias. The drugs tested were: Propafenone (25 patients), Disopiramide (25 patients), Tocainide (11 patients), Lorcainide (8 patients), Lorajmine (13 patients), Nadolol (9 patients). In accordance with Vallebit et al., we considered arrhythmias worsening criteria: the onset of non sustained or sustained ventricular tachycardia; an increase of four fold the number of ventricular ectopic beats and/or ten fold the repetitive forms. A worsening of arrhythmias was observed in 4/101 (3.9% patients); 1/9 treated with Nadolol, 1/25 with Propafenone, 1/35 with Disopiramide, 1/13 with Lorajmine. For one young patient the worsening phenomenon could be considered a toxic picture, because of the very high drug plasmatic levels (Lorajmine) observed for the whole duration of the sustained VT induced from the drug. For the remaining 3 patients the response resambles a paradox effect. 34 pharmacologic invasive tests in 30 patients with common recurrent ventricular tachycardia, during electrophysiologic endocavitary study. The drugs tested were: Propafenone (12 patients), Amiodarone (11 patients), Ajmaline (4 patients), Tocainide (3 patients), Lorcainide (2 patients), Lorajmine (1 patient), Disopiramide (1 patient).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Worsening of arrhythmias during pharmacological treatment. 644 Aug 27

In this ultrastructural study, the simple model of cultured rat peritoneal macrophages was used to examine whether local anaesthetics can induce lipidosis-like alterations. Exposure (24h) of macrophages to 1 X 10(-5) M dibucaine, or to 5 X 10(-5) M tetracaine, quinidine, and quinine, respectively, led to the occurrence of lamellated cytoplasmic inclusions in most cells. This is interpreted as indicating lipidosis. Type and degree of alterations were similar to those induced by the reference compound chlorphentermine (5 X 10(-5) M) for which lipidosis has previously been shown by biochemical methods. Tocainide (5 X 10(-5) M) caused weak alterations only; procaine (5 X 10(-5) M) was without effect. The differential potencies presently observed are paralleled by differential affinities of the local anaesthetics towards polar lipids as determined by other authors. The present results support the hypothesis that the lipidosis-inducing potency inherent to an amphiphilic cationic drug can be tentatively predicted on the basis of its affinity to polar lipids, although it may be obscured by secondary factors when the drug is administered to intact organisms. The present communication emphasizes the advantage of cell cultures over animal experiments for studying the structure-response relationships underlying drug-induced lipidosis, and to reliably ascertain that a given drug has only low lipidosis-inducing potency or none at all as found for tocainide and procaine, respectively.
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PMID:Lipidosis-like alterations in cultured macrophages exposed to local anaesthetics. 651 99

Tocainide, a congener of lidocaine, was used to treat symptomatic ventricular arrhythmias in 19 patients resistant to or unable to tolerate conventional agents. In this highly selected group, 15 showed good initial responses to oral therapy. Ventricular tachycardia was suppressed to a greater extent than isolated ventricular ectopic depolarizations at any plasma concentration, and upward dose-ranging showed progressive suppression of both. Arrhythmia responsiveness to lidocaine was found to be an excellent predictor of tocainide response. Of the 15 responders, one died 24 hours after stopping therapy, three died while receiving tocainide, nine stopped because of adverse reactions (five allergic), and two continue on therapy at 1 and 4 years. We conclude that tocainide is an effective agent for the short-term suppression of ventricular arrhythmias, particularly ventricular tachycardia sensitive to lidocaine, but a high incidence of adverse effects limits its application to chronic therapy in many patients.
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PMID:Tocainide therapy for refractory ventricular arrhythmias. 677 Jun 66

The antiarrhythmic efficacy and pharmacokinetics of tocainide, an oral analog of lidocaine, was evaluated in 18 hospitalized convalescing myocardial infarction patients. Holter ECG tapes were recorded daily during two-day placebo therapy preceding and succeeding two days of tocainide treatment. Left ventricular function was characterized from prior or subsequent arteriographic studies (ten cases) or from radionuclide scanning (eight cases). Tocainide dosage was 17.7 +/- 4.9 SD mg/kg/day. Plasma half-time of elimination was 19.1 +/- 6.8 hours (r = 0.9). Tocainide had no significant effect on heart rate, pulse rate, or QTC intervals and did not worsen chronic heart failure, even in patients with ejection fraction < 30%. In seven of 18 patients, tocainide significantly reduced ventricular premature beat (VPB) frequency as compared to predrug and postdrug placebo periods. Drug responders averaged a 200 to 545% reduction in VPB frequency at tocainide blood levels of > 3.5 microgram/ml.
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PMID:Antiarrhythmic efficacy, pharmacokinetics and clinical safety of tocainide in convalescent myocardial infarction patients. 677 81

Tocainide, a lidocaine congener with low hepatic clearance, is eliminated predominantly by formation of a novel glucuronide conjugate. This suggested the possibility of metabolic interactions with enzyme inducers or competitive substrates for glucuronyl transferase. The time course of tocainide blood concentration as well as the urinary excretion-time profiles of drug and principal metabolite (a glucuronide of tocainide carbaminic acid, TOCG) were examined in six subjects before and after 15 days on phenobarbital (100 mg/day). In another study, the effect of salicylamide and clofibrate on the time courses of tocainide and TOCG urinary excretion were examined in four of the same six subjects. After 600 mg tocainide HCl by mouth, the area under the tocainide blood concentration-time curve was 48.2 +/- 11.9 hr micrograms/ml for the control dose and 49.6 +/- 4.2 hr micrograms/ml (mean = SD) after phenobarbital. Percent of dose excreted unchanged in urine (46.0 +/- 4.9 and 43.4 +/- 5.6) and percent of dose excreted as TOCG (30.6 +/0 3.3 and 27.7 +/- 7.2) were not affected by phenobarbital (data presented as control and after phenobarbital). Because salicylamide has been reported to be a potent inhibitor of the glucuronidation of some drugs and because clofibrate yields metabolites that may be competitive inhibitors of tocainide conjugation, the two were given together with tocainide. Average percent of dose recovered in urine as unchanged tocainide in 24 hr was 26.8%, 28.3%, and 29.7% in the control, salicylamide, and clofibrate studies. The urinary excretion of TOCG was also not affected. It is concluded that under the conditions of our investigation, the principal urinary metabolite of tocainide, a glucuronide of tocainide carbaminic acid, is formed by a mechanism not subject to induction by phenobarbital or competitive inhibition by salicylamide or clofibrate.
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PMID:Tocainide kinetics and metabolism: effects of phenobarbital and substrates of glucuronyl transferase. 677 7

In order to evaluate the hemodynamic and antiarrhythmic efficacy of tocainide, studies were performed in patients suffering acute myocardial infarction. Intravenous tocainide was administered over a 15-minute period in order to determine its acute effects and subsequently, in a randomized double-blind study with placebo control, to determine its effects over a 24-hour period in acute myocardial infarction. Tocainide resulted in a significant decrease of frequent and complex ventricular arrhythmias acutely and had only minimal effects of hemodynamics in most patients. In the long-term studies, tocainide produced no adverse hemodynamic effects when compared with placebos.
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PMID:Hemodynamic and antiarrhythmic effects of tocainide in patients with acute myocardial infarction. 677 86

In a double-blind placebo controlled study, tocainide, 750 mg i.v. during a 15-minute period directly followed by 800 mg orally and later 400 mg t.i.d., was administered to patients wiht acute myocardial infarction (AMI). Treatment was started as soon as possible following onset of symptoms; the follow-up period was 6 months. The patient groups consisted of 56 tocainide and 56 placebo patients. There was no significant effect on the incidence of ventricular fibrillation or symptomatic ventricular tachycardia. The mortality rates were similar and low in both groups. Tocainide suppressed ventricular arrhythmias, including ventricular tachycardia, both in the acute stage of AMI and during convalescence. Tocainide also suppressed exercies-induced ventricular arrhythmias. Side effects were in general mild or moderate.
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PMID:Prophylaxis of ventricular tachyarrhythmias with intravenous and oral tocainide in patients with and recovering from acute myocardial infarction. 677 87

Tocainide therapy has been evaluated in 38 patients with ventricular arrhythmias. Thirty-one had recurrent sustained ventricular tachycardia and/or fibrillation and 29 required prior cardioversions. These arrhythmias could not be managed with quinidine, procainamide, disopyramide, or propranolol. Tocainide doses averaged 1,500 mg/day (range 600 to 2,400) and the majority of patients had plasma concentrations from 6 to 12 micrograms/ml. Twenty-two patients (61%) had their arrhythmias controlled with tocainide and 16 (39%) did not. Tocainide dose and plasma concentrations were similar for responders and nonresponders. Lidocaine was effective in 26 patients and 16 (63%) of these had their arrhythmias controlled with tocainide. Of 12 patients in whom lidocaine was known to be ineffective or who had not been previously treated, only two (17%) had arrhythmias controlled with tocainide (P < 0.02). Side effects occurred in approximately two thirds of patients but required discontinuation of long-term tocainide in only three patients.
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PMID:Tocainide for drug-resistant ventricular arrhythmias: efficacy, side effects, and lidocaine responsiveness for predicting tocainide success. 677 91

This is a report of the safety evaluation of tocainide in the first 369 patients entered into the American Tocainide Emergency Use Program. This humanitarian protocol has made tocainide available for emergency use in the treatment of life-threatening, intractable ventricular arrhythmias in patients who were unresponsive to or unable to take the approved antiarrhythmic drugs. TAhe most frequent adverse experiences reported were neurologic and gastrointestinal in nature and included dizziness, lightheadedness, tremors, nausea, vomiting, and anorexia. Adverse experiences resulted in the discontinuation of tocainide in 16% of these patients and were transient and reversible with no conclusive evidence of permanent organ injury. Adverse experiences having special relevance to the safety assessment of new antiarrhythmic agents are discussed, including congestive heart failure, arrhythmias and conduction disturbances, convulsions, lupus erythematosus-like illness, and deaths while on therapy. No significant abnormal trends were observed in routine hematologic and biochemical laboratory screening tests or in ophthalmologic or chest x-ray examinations. An evaluation of the effects of chronic tocainide administration of ECG intervals showed no significant change in P-R or QRS intervals but demonstrated a statistically significant decrease in Q-T duration. It is concluded that in patients with life-threatening ventricular arrhythmias, tocainide is a safe agent with a favorable risk-benefit ratio.
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PMID:Safety evaluation of tocainide in the American Emergency Use Program. 677 92


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